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Sample records for weight heparin anticoagulation

  1. In vitro anticoagulation monitoring of low-molecular-weight heparin

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi

    2009-01-01

    Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.

  2. High antiangiogenic and low anticoagulant efficacy of orally active low molecular weight heparin derivatives.

    Science.gov (United States)

    Park, Jin Woo; Jeon, Ok Cheol; Kim, Sang Kyoon; Al-Hilal, Taslim Ahmed; Jin, Shun Ji; Moon, Hyun Tae; Yang, Victor C; Kim, Sang Yoon; Byun, Youngro

    2010-12-20

    Heparin, an anticoagulant that is widely used clinically, is also known to bind to several kinds of proteins through electrostatic interactions because of its polyanionic character. These interactions are mediated by the physicochemical properties of heparin such as sequence composition, sulfation patterns, charge distribution, overall charge density, and molecular size. Although this electrostatic character mediates its binding to many proteins related with tumor progression, thereby providing its antiangiogenic property, the administration of heparin for treating cancer is limited in clinical applications due to several drawbacks, such as its low oral absorption, unsatisfactory therapeutic effects, and strong anticoagulant activity which induces hemorrhaging. Here, we evaluated novel, orally active, low molecular weight heparin (LMWH) derivatives (LHD) conjugated with deoxycholic acid (DOCA) that show reduced anticoagulant activity and enhanced antiangiogenic activity. The chemical conjugate of LMWH and DOCA was synthesized by conjugating the amine group of N-deoxycholylethylamine (EtDOCA) with the carboxylic groups of heparin at various DOCA conjugation ratios. The LMWH-DOCA conjugate series (LHD1, LHD1.5, LHD2, and LHD4) were further formulated with poloxamer 407 as a solubilizer for oral administration. An in vitro endothelial tubular formation and in vivo Matrigel plug assay were performed to verify the antiangiogenic potential of LHD. Finally, we evaluated tumor growth inhibition of oral LHD administration in a SCC7 model as well as in A549 human cancer cell lines in a mouse xenograft model. Increasing DOCA conjugation ratios showed decreased anticoagulant activity, eventually to zero. LHD could block angiogenesis in the tubular formation assay and the Matrigel plug assay. In particular, oral administration of LHD4, which has 4 molecules of DOCA per mole of LMWH, inhibited tumor growth in SCC7 mice model as well as A549 mice xenograft model. LHD4 was orally

  3. Engineered heparins as new anticoagulant drugs.

    Science.gov (United States)

    Vaidyanathan, Deepika; Williams, Asher; Dordick, Jonathan S; Koffas, Mattheos A G; Linhardt, Robert J

    2017-03-01

    Heparin is an anionic polysaccharide that is widely used as a clinical anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric ton quantities. Animal-sourced heparin is also widely used in the preparation of low molecular weight heparins that are gaining in popularity as a result of their improved pharmacological properties. The recent contamination of pharmaceutical heparin together with concerns about increasing demand for this life saving drug and the fragility of the heparin supply chain has led the scientific community to consider other potential sources for heparin. This review examines progress toward the preparation of engineered heparins through chemical synthesis, chemoenzymatic synthesis, and metabolic engineering.

  4. Low-molecular-weight heparin as a multipurpose anticoagulant for laboratory testing.

    Science.gov (United States)

    Kawamoto, T; Hiino, M; Takubo, T; Tatsumi, N

    2000-06-01

    The availability of low-molecular-weight heparin (LMWH) for use as an anti-coagulant for laboratory testing was studied. Hematology and chemistry tests were performed with an automated hematology analyzer and an automated chemistry analyzer, respectively. The results of hematology tests of LMWH-treated blood were similar to those obtained for blood treated with ethylenediaminetetraacetic acid (EDTA)-2K, except for platelet count. The platelet count of LMWH-treated blood was lower than that of EDTA-treated blood, and the decrease in platelet count in the former was due to platelet aggregation. Prothrombin time tests could be performed with plasma prepared from LMWH-treated blood, although with such blood the prothrombin time was prolonged. Chemistry tests could be performed for all 18 parameters. These results suggest that LMWH is a candidate for use for hematology testing (with the exception of platelet count), coagulation testing, and chemistry tests.

  5. Anticoagulant treatment of cancer patients with pulmonary embolism in the real world Actual use of low-molecular-weight heparin in cancer

    NARCIS (Netherlands)

    Kleinjan, A.; Hutten, B. A.; Di Nisio, M.; Buller, H. R.; Kamphuisen, P. W.

    2014-01-01

    Background: Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the Netherlan

  6. Anticoagulant treatment of cancer patients with pulmonary embolism in the real world Actual use of low-molecular-weight heparin in cancer

    NARCIS (Netherlands)

    Kleinjan, A.; Hutten, B. A.; Di Nisio, M.; Buller, H. R.; Kamphuisen, P. W.

    2014-01-01

    Background: Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the

  7. Prevention of Venous Thromboembolism in Major Orthopedic Surgery: Bayesian Network Meta-Analysis of 21 Randomized Trials Evaluating Unfractionated Heparins, Low-Molecular Weight Heparins, and New Oral Anticoagulants

    Directory of Open Access Journals (Sweden)

    Andrea Messori

    2014-09-01

    Full Text Available Background: In major orthopedic surgery, prevention of venous thromboembolism has been based on Unfractionated Heparins (UFHs over the past decades, then on Low-Molecular Weight Heparins (LMWHs, and on New Oral Anticoagulants (NOACs more recently. To summarize the comparative effectiveness of UFHs, LMWHs, and NOACs in this clinical indication, we applied Bayesian network meta-analysis to the clinical material (randomized studies published in two previous reviews focused on this issue.. Objectives: Our end-point was a composite of venous thromboembolism and pulmonary embolism.. Materials and Methods: Our analysis was based on standard Bayesian network meta-analysis (random-effect model.. Results: The analysis included 21 randomized trials for a total of 21,805 patients. Our results showed that the degree of effectiveness did not differ among UFHs, LMWHs, and NOACs. Although some trends emerged from an in-depth analysis of these data (e.g. according to the histogram of rankings, no significant differences were found (P > 0.05. Moreover, two agents among LMWHs proved to be adequately supported by randomized trials (enoxaparin and dalteparin, while limited evidence was available for other agents of this class.. Conclusions: Our synthesis of the effectiveness data can be useful as an overall reference in this area and can also contribute to defining the place of further innovative treatments for this clinical indication..

  8. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

    Science.gov (United States)

    Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R

    2008-06-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major

  9. Old and new applications of non-anticoagulant heparin.

    Science.gov (United States)

    Cassinelli, Giuseppe; Naggi, Annamaria

    2016-06-01

    The aim of this chapter is to provide an overview of non-anticoagulant effects of heparins and their potential use in new therapeutic applications. Heparin and heparin derivatives have been tested in inflammatory, pulmonary and reproductive diseases, in cardiovascular, nephro- and neuro-tissue protection and repair, but also as agents against angiogenesis, atheroschlerosis, metastasis, protozoa and viruses. Targeting and inhibition of specific mediators involved in the inflammatory process, promoting some of the above mentioned pathologies, are reported along with recent studies of heparin conjugates and oral delivery systems. Some reports from the institute of the authors, such as those devoted to glycol-split heparins are also included. Among the members and derivatives of this class, several are undergoing clinical trials as antimetastatic and antimalarial agents and for the treatment of labour pain and severe hereditary anaemia. Other heparins, whose therapeutic targets are non-anticoagulant such as nephropathies, retinopathies and cystic fibrosis are also under investigation.

  10. Complement inhibitory and anticoagulant activities of fractionated heparins

    NARCIS (Netherlands)

    Hennink, W.E.; Klerx, J.P.A.M.; Dijk, H. van; Feijen, J.

    1984-01-01

    Almost monodisperse heparin fractions (w/n < 1.1) were obtained by gel filtration of a commercial heparin. These fractions were assayed for anticoagulant activity (thrombin times and APTT), chromogenic anti-factor Xa activity, inhibitory activity for the human classical complement pathway, carboxyl

  11. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

    Science.gov (United States)

    Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K

    2016-01-01

    Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

  12. Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements.

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    Nielen, Johannes T H; Dagnelie, Pieter C; Emans, Pieter J; Veldhorst-Janssen, Nicole; Lalmohamed, Arief; van Staa, Tjeerd-Pieter; Boonen, Annelies E R C H; van den Bemt, Bart J F; de Vries, Frank

    2016-11-01

    There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery. This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagulants (NOAC) or low-molecular-weight heparins (LMWHs) compared with aspirin in patients undergoing total joint replacement. A population-based retrospective cohort study was performed using the Clinical Practice Research Datalink. Patients ≥18 years of age who had undergone total knee (n = 3261) or hip replacement (THR (n = 4016)) between 2008 and 2012 were included. Within this population, three cohorts were selected, based on their first prescription within the 35-day period after surgery: use of NOACs only, LMWHs only and aspirin only. Incidence rates were calculated, and Cox proportional hazard models were fitted to estimate the risk of VTE, GI bleeding and all-cause mortality with the use of NOACs and LMWHs compared with aspirin use after total knee replacement and THR. We statistically adjusted our analyses for lifestyle factors, comorbidities and concomitant drug use. Total knee replacement and THR patients currently on LMWHs had higher risk of VTE (HR = 17.2 (6.9-43.0) and HR = 39.5 (18.0-87.0), respectively), GI bleeding (HR = 20.9 (1.9-232.3) and HR = 2.0 (0.2-17.2), respectively) and all-cause mortality (HR = 4.3 (1.7-12.4) and HR = 4.0 (2.4-6.7), respectively). NOAC use was associated with an increased risk of GI bleeding in patients undergoing THR surgery. In contrast to previous studies, we found an increased risk of VTE, GI bleeding and all-cause mortality with the use of LMWHs compared with aspirin. Risk of GI bleeding was increased with the use of NOACs compared with aspirin use after THR surgery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Effect of Low Molecular Weight Heparins (LMWHs) on antiphospholipid Antibodies (aPL) - Mediated Inhibition of Endometrial Angiogenesis: e29660

    National Research Council Canada - National Science Library

    Riccardo Marana; Fiorella Di Nicuolo; Roberta Castellani; Manuela Veglia; John Stinson; Giovanni Scambia; Nicoletta Di Simone

    2012-01-01

    .... APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH). Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because...

  14. Meta analysis of the effect of continuous blood purification by no heparin and low molecular weight heparin anticoagulation for critically ill patients with bleeding tendency%无肝素抗凝与低分子肝素抗凝对有出血倾向的危重患者连续性血液净化影响的Meta分析

    Institute of Scientific and Technical Information of China (English)

    马丽丽; 许红梅

    2015-01-01

    Objective To systematically evaluate the safety and efficacy of anticoagulation therapy for critically ill patients with bleeding tendency with no-heparin anticoagulation and low molecular weight heparin anticoagulation for the continuous blood purification .Method The Pub Med ,MEDLINE ,RNAO ,OVID ,Web of Knowledge ,Nursing Consult ,EMbase ,CBM disc ,Wanfang Data and CNKI was searched to collect randomized controlled trials (RCTs) and quasi-randomized controlled trials (q-RCTs) which studied the effects of anticoagulation therapy for critically ill patients with bleeding tendency with no-heparin anticoagulation and low molecular weight heparin anticoagulation for the continuous blood purification .The quality of RCTs and q-RCT were critically appraised ,and data were extracted by 2 reviewers independently .Meta-analyses were conducted for the eligible RCTs .Result 7 RCTs were included . The meta-analysis had showed that no heparin can reduce the incidence of bleeding for critically ill patients with bleeding tendency .Conclusion No-heparin anticoagulation was effective to prevent bleeding complications of antico-agulant therapy for critically ill patients with bleeding tendency .%目的 系统评价无肝素抗凝与低分子肝素抗凝用于有出血倾向的危重患者连续性血液净化抗凝治疗的安全性和有效性.方法 计算机检索PubMed 、MEDLINE、RNAO、OVID、Web of Knowledge、Nursing Consult、EM base、中国生物医学文献数据库、万方数据库和中国学术期刊全文数据库中关于无肝素抗凝与低分子肝素抗凝用于有出血倾向的危重患者连续性血液净化抗凝治疗效果的随机对照试验(RCT)和半随机对照试验(q-RCT) ,同时筛检纳入文献的参考文献.由两名研究者对文献质量进行严格评价和资料提取 ,对符合质量标准的RCT进行Meta分析.结果 共纳入7篇文献 ,Meta分析的结果显示 :无肝素抗凝能降低有出血倾向的危重患

  15. Polyurethane modified with an antithrombin-heparin complex via polyethylene oxide linker/spacers: influence of PEO molecular weight and PEO-ATH bond on catalytic and direct anticoagulant functions.

    Science.gov (United States)

    Sask, Kyla N; Berry, Leslie R; Chan, Anthony K C; Brash, John L

    2012-10-01

    A segmented polyurethane (PU) was modified with polyethylene oxides (PEO) of varying molecular weight and end group. The PEO served as linker/spacers to immobilize an antithrombin-heparin (ATH) anticoagulant complex on the PU. Isocyanate groups were introduced into the PU to enable attachment of either "conventional" homo-bifunctional dihydroxy-PEO (PEO-OH surface) or a hetero-bifunctional amino-carboxy-PEO (PEO-COOH surface). The PEO surfaces were functionalized with N-hydroxysuccinimide (NHS) groups using appropriate chemistries, and ATH was attached to the distal NHS end of the PEO (PEO-OH-ATH and PEO-COOH-ATH surfaces). Water contact angle and fibrinogen adsorption measurements showed increased hydrophilicity and reduced fibrinogen adsorption from buffer on all PEO surfaces compared to unmodified PU. ATH uptake on NHS-functionalized PEO was quantified by radiolabeling. Despite the different PEO molecular weights and end groups, and NHS-functionalization chemistries, the surface densities of ATH were similar. The adsorption of fibrinogen and antithrombin (AT) from plasma was measured in a single experiment using dual radiolabeling. On PEO-ATH surfaces fibrinogen adsorption was minimal while AT adsorption was high showing the selectivity of the heparin moiety of ATH for AT. The PEO-COOH-ATH surfaces showed slightly greater AT adsorption than the PEO-OH-ATH surfaces. Thrombin adsorption on all of the PEO-ATH surfaces was greater than on the corresponding PEO surfaces without ATH, and was highest on the PEO-OH-ATH, suggesting potential anticoagulant properties for this surface via direct thrombin inhibition by the AT portion of ATH.

  16. Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia

    Directory of Open Access Journals (Sweden)

    Maura Poli

    2017-04-01

    Full Text Available The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs, which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability. The chemical characteristics for high anti-hepcidin activity in vitro and in vivo include the 2O-and 6O-sulfation and a molecular weight above 7 kDa. The most potent heparins have been found to be the super-sulfated ones, active in hepcidin suppression with a molecular weight as low as 4 kDa. Moreover, the alteration of endogenous heparan sulfates has been found to cause a reduction in hepcidin expression in vitro and in vivo, indicating that heparins act by interfering with the interaction between BMPs and components of the complex involved in the activation of the BMP/SMAD1/5/8 pathway. This review summarizes recent findings on the anti-hepcidin activity of heparins and their possible use for the treatment of anemia caused by hepcidin excess, including the anemia of chronic diseases.

  17. Effect of Low Molecular Weight Heparins (LMWHs) on antiphospholipid Antibodies (aPL)-mediated inhibition of endometrial angiogenesis

    National Research Council Canada - National Science Library

    D'Ippolito, Silvia; Marana, Riccardo; Di Nicuolo, Fiorella; Castellani, Roberta; Veglia, Manuela; Stinson, John; Scambia, Giovanni; Di Simone, Nicoletta

    2012-01-01

    ... HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH). Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because...

  18. Green synthesis and nanotopography of heparin-reduced gold nanoparticles with enhanced anticoagulant activity.

    Science.gov (United States)

    Kim, Hyun-Seok; Jun, Sang Hui; Koo, Yean Kyoung; Cho, Seonho; Park, Youmie

    2013-03-01

    This paper reports on the green synthesis of heparin-reduced gold nanoparticles and their nanotopography as studied with atomic force microscopy. The study also evaluated the anticoagulant activity of the newly prepared gold nanoparticles. The heparin-reduced gold nanoparticles were homogeneous, showing characteristic surface plasmon resonance bands of approximately 523-527 nm, and their shapes were mostly spherical and amorphous. The average diameter of the nanoparticles measured from atomic force microscopic images was either 20.26 +/- 3.35 nm or 40.85 +/- 8.95 nm depending on the different precursor salts and heparin concentrations. Atomic force microscopic images revealed that the topography of the heparin polymer aggregated when deposited onto mica, resembling a chain of mountains. This characteristic nanotopography of the heparin disappeared after the synthesis of the gold nanoparticles was performed. Interestingly, prolonged prothrombin time, thrombin time, and activated partial thromboplastin time were observed in the heparin-reduced gold nanoparticles when compared to a control heparin, suggesting the enhancement of anticoagulant activity in heparin-reduced gold nanoparticles. Hence, the green synthesis of gold nanoparticles with heparin using a simple reaction step could be a viable procedure for enhancing heparin's anticoagulant activity.

  19. Survival of heparins, oral anticoagulants, and aspirin after the year 2010.

    Science.gov (United States)

    Fareed, Jawed; Hoppensteadt, Debra A; Fareed, Daniel; Demir, Muzaffer; Wahi, Rakesh; Clarke, Melaine; Adiguzel, Cafer; Bick, Rodger

    2008-02-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and

  20. [Low molecular weight heparin and non valvular atrial fibrillation].

    Science.gov (United States)

    Ederhy, S; Di Angelantonio, E; Meuleman, C; Janower, S; Boccara, F; Cohen, A

    2006-12-01

    Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

  1. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    Science.gov (United States)

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  2. An Antithrombin-Heparin Complex Increases the Anticoagulant Activity of Fibrin Clots

    Directory of Open Access Journals (Sweden)

    Lesley J. Smith

    2008-01-01

    Full Text Available Clotting blood contains fibrin-bound thrombin, which is a major source of procoagulant activity leading to clot extension and further activation of coagulation. When bound to fibrin, thrombin is protected from inhibition by antithrombin (AT + heparin but is neutralized when AT and heparin are covalently linked (ATH. Here, we report the surprising observation that, rather than yielding an inert complex, thrombin-ATH formation converts clots into anticoagulant surfaces that effectively catalyze inhibition of thrombin in the surrounding environment.

  3. Heparin versus low molecular weight heparin K 2165 in chronic hemodialysis patients: a randomized cross-over study.

    Science.gov (United States)

    Borm, J J; Krediet, R; Sturk, A; ten Cate, J W

    1986-01-01

    Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight (LMW) heparin K 2165 in a single-blinded randomized cross-over study to assess: effects on hemostasis and ex vivo platelet functions, and effectiveness, i.e. prevention of fibrin formation in the extracorporeal circuit. The 20 dialysis treatments were without untoward side effects, for both drugs used. The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization. No differences between the drugs were observed regarding the Ivy bleeding time, platelet count and platelet aggregation (spontaneous, and induced by ADP and collagen). Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin. Both drugs did not influence the plasma levels of beta-thromboglobulin, thromboxane B2 and platelet serotonin content. K 2165 did not affect platelet adhesion to collagen, in contrast to heparin which substantially inhibited platelet adhesion. Under both treatments, 4 minor clots were observed in 4 artificial kidneys, despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml. K 2165 may therefore be considered as effective an anticoagulant as heparin, with less effects on ex vivo platelet functions.

  4. Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

    Science.gov (United States)

    Krisper, Peter; Tiran, Beate; Fliser, Danilo; Haditsch, Bernd; Stadlbauer, Vanessa; Otto, Ronald; Ernst, Thomas; Kretschmer, Ulrich; Stauber, Rudolf E; Haller, Hermann; Holzer, Herwig; Manns, Michael P; Rifai, Kinan

    2010-01-01

    Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

  5. Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Chang-Jiang, E-mail: panchangjiang@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China); Pang, Li-Qun [Department of General Surgery, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an 223300 (China); Gao, Fei [Zhejiang Zylox Medical Devices Co., Ltd., Hangzhou 310000 (China); Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China)

    2016-06-01

    Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents. - Highlights: • Heparin-loaded graphene oxide coating was

  6. Low molecular weight heparin impairs tendon repair.

    Science.gov (United States)

    Virchenko, O; Aspenberg, P; Lindahl, T L

    2008-03-01

    Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

  7. High sulfation and a high molecular weight are important for anti-hepcidin activity of heparin

    Directory of Open Access Journals (Sweden)

    Michela eAsperti

    2016-01-01

    Full Text Available Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins or by high sulfation (SS-Heparins, but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH and separated them in fractions of molecular weight in the range 4-16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells, in mice, and also for the capacity to bind an Heparin Binding Domain peptide. The three approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with an increase of the N-acetylation level and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites.

  8. Heparin improves BMSC cell therapy: Anticoagulant treatment by heparin improves the safety and therapeutic effect of bone marrow-derived mesenchymal stem cell cytotherapy

    Science.gov (United States)

    Liao, Li; Shi, Bingzheng; Chang, Heran; Su, Xiaoxia; Zhang, Lichao; Bi, Chunsheng; Shuai, Yi; Du, Xiaoyan; Deng, Zhihong; Jin, Yan

    2017-01-01

    Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure. Histological and homeostasis analysis confirmed that large doses of BMSCs induced disseminated intravascular thrombosis, exhaustion of platelets and coagulation factors, and prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Similar to mouse BMSCs, goat and human BMSCs also induced coagulation reactions in vitro and in vivo. The coagulation was induced mostly by tissue factor, the overexpression of which enhanced the procoagulant activity of BMSCs during in vitro culture. Notably, clinical doses of BMSCs in cell therapy also induced mild and reversible coagulation, which increased BMSC lung embolism and clearance. Anticoagulation treatment by heparin (400 U/kg) prevented BMSC-induced coagulation and the acute adverse effects of large-dose BMSCs infusion efficiently. Importantly, heparin treatment led to decreased BMSC lung embolism and enhanced migration and maintenance of BMSCs to target organs in cell therapy. Based on an experimental colitis model, we confirmed that heparin treatment enhanced the effect of BMSC therapy efficiently to reduce mortality, prevent weight loss, suppress inflammation reaction and alleviate tissue injury. In conclusion, BMSCs possess procoagulant activity that could induce disseminated coagulation and thrombosis in recipients. Anticoagulation treatment by heparin is a practical strategy to improve both the safety and therapeutic effect of BMSC therapy. PMID

  9. Fabrication of PP-g-PEGMA-g-heparin and its hemocompatibility: From protein adsorption to anticoagulant tendency

    Energy Technology Data Exchange (ETDEWEB)

    Jin Jing [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Jiang Wei, E-mail: wjiang@ciac.jl.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Shi Qiang [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Zhao Jie [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Yin Jinghua, E-mail: yinjh@ciac.jl.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Stagnaro, Paola [Istituto per Io Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, Via de Marini 6, 16149 Genova (Italy)

    2012-05-15

    We described a two-step process to fabricate the heparinized polypropylene (PP) film using cyanuric chloride (CC) as a trifunctional reagent and poly (ethylene glycol) methacrylate (PEGMA) as a spacer. The modified PP films were characterized by attenuated total reflectance FT-IR and X-ray photoelectron spectroscopy; the content of PEGMA and heparin were determined by gravimetric method and a toluidine blue assay, respectively. For the PP-g-PEGMA films, it was found that small size protein BSA tended to adsorb on the surface of low molecular weight monomer grafted PP, whereas big spindle-shaped fibrinogen tended to adsorb on the surface of high molecular weight monomer grafted PP. We gave a definition of anti-protein adsorptive factor r with two model proteins, albumin and fibrinogen. The results by platelet adhesion and plasma recalcification time (PRT) experiments indicated that the factor r could be used to quantitatively evaluate the anticoagulant tendency of PP-g-PEGMA modified films. For the PP-g-PEGMA-g-heparin modified films, the surface was proved to have a high bioactivity by the adsorption of AT III assay and very low platelet adhesion. It indicated that immobilization of heparin on the PP film with PEGMA as a spacer was an effective way to improve the hemocompatibility of PP.

  10. Fabrication of PP-g-PEGMA-g-heparin and its hemocompatibility: From protein adsorption to anticoagulant tendency

    Science.gov (United States)

    Jin, Jing; Jiang, Wei; shi, Qiang; Zhao, Jie; Yin, Jinghua; Stagnaro, Paola

    2012-05-01

    We described a two-step process to fabricate the heparinized polypropylene (PP) film using cyanuric chloride (CC) as a trifunctional reagent and poly (ethylene glycol) methacrylate (PEGMA) as a spacer. The modified PP films were characterized by attenuated total reflectance FT-IR and X-ray photoelectron spectroscopy; the content of PEGMA and heparin were determined by gravimetric method and a toluidine blue assay, respectively. For the PP-g-PEGMA films, it was found that small size protein BSA tended to adsorb on the surface of low molecular weight monomer grafted PP, whereas big spindle-shaped fibrinogen tended to adsorb on the surface of high molecular weight monomer grafted PP. We gave a definition of anti-protein adsorptive factor r with two model proteins, albumin and fibrinogen. The results by platelet adhesion and plasma recalcification time (PRT) experiments indicated that the factor r could be used to quantitatively evaluate the anticoagulant tendency of PP-g-PEGMA modified films. For the PP-g-PEGMA-g-heparin modified films, the surface was proved to have a high bioactivity by the adsorption of AT III assay and very low platelet adhesion. It indicated that immobilization of heparin on the PP film with PEGMA as a spacer was an effective way to improve the hemocompatibility of PP.

  11. Comparison of low-molecular-weight-heparin and unfractionated heparin for acute PTE

    Institute of Scientific and Technical Information of China (English)

    CHEN Li-ying; YING Ke-jing; HONG Wu-jun; ZHOU Pan

    2005-01-01

    Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagulation and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased,lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expensive.

  12. Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy

    Institute of Scientific and Technical Information of China (English)

    LIAO Yu-jie; ZHANG Ling; ZENG Xiao-xi; FU Ping

    2013-01-01

    Background Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT),but it can increase the risk of bleeding.Citrate is a promising substitute.Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT.Methods We searched the MEDLINE,the EMBASE,the Cochrane Central Register of Controlled Trials,and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT.The primary outcome was mortality and the secondary outcomes included circuit survival,control of uremia,risk of bleeding,transfusion rates,acid-base statuses,and disturbance of sodium and calcium homeostasis.Results Four trials met the inclusion criteria.Meta-analysis found no significant difference between two anticoagulants on mortality.Less bleeding and more hypocalcemic episodes were with citrate.Citrate was superior or comparable to unfractionated heparin in circuit life.Conclusions Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life,although there is more metabolic derangement.Mortality superiority has not been approved.

  13. Systemic anticoagulation related to heparin locking of non-tunnelled venous dialysis catheters in intensive care patients.

    Science.gov (United States)

    Bong, Y C; Walsham, J

    2016-07-01

    Heparin locking of venous dialysis catheters is routinely performed in intensive care to maintain catheter patency when the catheters are not being used. Leakage of heparin into the circulation can potentially cause systemic anticoagulation and may present a risk to intensive care patients. To assess the effect of 5000 units per millilitre heparin locking of non-tunnelled dialysis catheters on systemic anticoagulation, we performed a prospective observational study of ten intensive care patients receiving heparin locking of dialysis catheters in an adult tertiary intensive care unit between July and September 2015. Activated partial thromboplastin time (APTT) was measured prior to, and three minutes after, heparin locking of catheter lumens with the manufacturer's recommended locking volume to assess the effect on systemic anticoagulation. Heparin locking of venous dialysis catheters resulted in a significant rise in APTT (P=0.002). The median rise was by 56 seconds (interquartile range 30-166.5). Following heparin locking, 80% of patients had APTT values within or above the range associated with therapeutic anticoagulation. Heparin locking of non-tunnelled venous dialysis catheters can cause systemic anticoagulation in intensive care patients and therefore poses a potential risk to patient safety.

  14. Effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy rewarming in dogs with accidental hypothermia

    Directory of Open Access Journals (Sweden)

    Rui YUAN

    2016-10-01

    Full Text Available Objective  To observe the influences of regional citrate or systemic heparin anticoagulation on acid-base balance, coagulation, electrolytes, serum creatinine, alanine aminotransferase (ALT and cardiac index (CI during continuous renal replacement therapy (CRRT rewarming in accidental hypothermia dogs. Methods  Nineteen adult beagles were given abdominal trauma coupled with deep hypothermia [(28±0.5℃] induced by seawater immersion for establishing animal model of trauma. According to rewarming ways, the animal models were randomly divided into three groups, comparison group (warm bath rewarming, n=5, CRRT rewarming-systemic heparin anticoagulation group (heparin anticoagulation group, n=7 and CRRT rewarming-regional citrate anticoagulation group (citrate anticoagulation group, n=7. During the rewarming routine blood examination was performed, and blood chemistry, coagulation function, blood gas and hemodynamic status were assayed, at the same time the mortality was recorded. Results  During the rewarming, the mortality was 14.3% (1/7 in heparin anticoagulation group, 40.0% (2/5 in warm bath group and 0 in regional citrate anticoagulation group. Blood temperature in creased to 38℃, the heparin anticoagulation group showed a significant decrease of platelet compared with citrate anticoagulation group and comparison group (P0.05. Conclusions  CRRT plus warm bath rewarming have better effect on improving metabolic acidosis than warm bath rewarming alone in accidental hypothermia dogs. In comparison with systemic heparin anticoagulation, regional citrate anticoagulation has smaller influences on coagulation system and platelet when CRRT rewarming performed in accidental hypothermia dogs. DOI: 10.11855/j.issn.0577-7402.2016.10.05

  15. Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

    Directory of Open Access Journals (Sweden)

    Henning Hagmann

    Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

  16. [Practical use of low molecular weight heparins in angiology].

    Science.gov (United States)

    Plettner, J L

    1991-01-01

    The recent development of low molecular weight heparins (LMWH), obtained by the depolymerization of standard non-fractioned heparin (NFH), considerably simplifies the course of anticoagulant treatments. They now allow effectively and safely dealing with the risks of thrombosis, both in hospital and at the patient's home. Their effectiveness for both the prevention and the treatment of thromboembolic accidents has been proved by many clinical trials. In comparison to standard heparin, the LMWHs still have a high anti-Xa activity, but their anti-IIa action is much reduced, thus preserving their antithrombotic power while reducing the hemorrhagic risks. Owing to their better bioavailability and longer half-life, they allow using in priority the subcutaneous route, reducing the frequency of the injections and simplifying surveillance, without impairing the effectiveness of the treatment. The prevention of thrombosis with LMWHs requires one daily subcutaneous dose. The control of the anti-Xa activity is not necessary for the doses used. Prior to initiating a curative treatment, it is essential to confirm the existence of thrombosis. When the diagnosis is definitive, the three LMWHs currently known are used after reconversion, at a dosage of 100 IU/kg/12 hrs. The anti-Xa activity, in samples taken 3 to 4 hours after the injection, must be maintained between 0.5 and 1 IU anti-Xa/ml. It is prudent to control the platelet level at D5 and D10, although thrombocytopenia is exceptional. The changeover treatment with antivitamins K (AVK), which is essential to prevent the recurrence of venous thrombosis, is initiated very early (2nd or 3rd day).(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Venous Thromboembolism Anticoagulation Therapy

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2009-01-01

    @@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).

  18. Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

    Science.gov (United States)

    Junqueira, Daniela R; Zorzela, Liliane M; Perini, Edson

    2017-04-21

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use

  19. Heparins with reduced anti-coagulant activity reduce myocardial reperfusion injury.

    Science.gov (United States)

    Barry, William H; Kennedy, Thomas P

    2011-05-01

    Heparin which is desulfated at the 2-O and 3-O positions (ODSH) has reduced anti-coagulant properties, and reduced interaction with heparin antibodies. Because of the reduced anti-coagulant effect, ODSH can be safely administered to animals and humans intravenously at doses up to 20 mg/kg, resulting in a serum concentration of up to 250µg/ml. Administration of ODSH causes a 35% reduction in infarct size in dogs and pigs subjected to coronary artery occlusion and reperfusion when given 5 min before reperfusion. ODSH has anti-inflamatory effects, manifest as a decrease in neutrophil infiltration into ischemic tissue at high doses, but this effect does not entirely account for the reduction in infarct size. ODSH decreases Na(+) and Ca(2+) loading in isolated cardiac myocytes subjected to simulated ischemia. This effect appears due to an ODSH-induced reduction in an enhanced Na(+) influx via the Na channel in the membrane of cardiac myocyes caused by oxygen radicals generated during ischemia and reperfusion. Reduction in Na(+) influx decreases Ca(2+) loading by reducing Ca2(+) influx via Na/Ca exchange, thus reducing Ca(2+) - dependent reperfusion injury. ODSH does not appear to interact with antibodies to the heparin/platelet factor 4 complex, and does not cause heparin-induced thrombocytopenia. Because of these therapeutic and safety considerations, ODSH would appear to be a promising heparin derivative for prevention of reperfusion injury in humans undergoing thrombolytic or catheter-based reperfusion for acute myocardial infarction. The review article discussed the use of heparin and the discussion of some of the important patents, including: US6489311; US7478358; PCTUS2008070836 and PCTUS2009037836.

  20. Incidence of hypersensitivity skin reactions in patients on full-dose low-molecular-weight heparins during pregnancy

    NARCIS (Netherlands)

    Schultinge, L.; Knol, H. M.; Kluin-Nelemans, H.C.; Erwich, J. J. H. M.; Meijer, K.

    2013-01-01

    Background: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants for the treatment and prophylaxis of venous thromboembolism in pregnancy. Hypersensitivity skin reactions associated with the use of LMWH are frequently seen, but are probably underreported. Objective: To eval

  1. [Fondaparinux as an alternative anticoagulant in heparin-induced thrombocytopenia in the patient with a ventricular assist device].

    Science.gov (United States)

    Cegarra-Sanmartín, V; Paniagua, P; Galán, J; Muñoz, C; Moral, M V

    2013-11-01

    Heparin-induced thrombocytopenia is a reaction associated with the use of this drug. It occurs in up to 3% of patients treated for at least 5 days. Its treatment is to stop the heparin, and according to patient needs, replace it with another anticoagulant. We present a patient who, after a heart transplant, and the need for a ventricular assist device, required anticoagulation. The patient developed heparin-induced thrombocytopenia. Heparin was stopped and anticoagulation was replaced by fondaparinux. The peri-operative complications and the management of the coagulation are described. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  2. Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients.

    Science.gov (United States)

    Junqueira, Daniela R G; Perini, Edson; Penholati, Raphael R M; Carvalho, Maria G

    2012-09-12

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a poorly understood paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population presenting a higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by adverse reactions such as HIT. We therefore sought to determine the relative impact of UFH and LMWH specifically on HIT in postoperative patients receiving thromboembolism prophylaxis. The objective of this review was to compare the incidence of HIT and HIT complicated by thrombosis in patients exposed to UFH versus LMWH in randomised controlled trials (RCTs) of postoperative heparin therapy. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (March 2012) and CENTRAL (2012, Issue 2). In addition, the authors searched LILACS (March 2012) and additional trials were sought from reference lists of relevant publications. We were interested in comparing the incidence of HIT occurring during exposure to UFH or LMWH after any surgical intervention. Therefore, we studied RCTs in which participants were postoperative patients allocated to receive UFH or LMWH, in a blinded or unblinded fashion. Eligible studies were

  3. Manipulating the surface active and anticoagulant properties of heparin through amphiphilic molecular constructs

    Science.gov (United States)

    Mintz, Rosita Candida

    Cardiovascular devices implanted within the vasculature are subjected to non-specific adsorption of plasma proteins. This initiates the blood coagulation cascade and platelet adhesion and activation, leading to thrombus formation. In this thesis Heparin Alkyl Diblock (HAD) surfactants were developed to improve the blood compatibility of cardiovascular biomaterials. The material designs involved using heparin, a natural anticoagulant, to inhibit coagulation pathway enzymes and mimic the cell glycocalyx to provide a repulsive force field to inhibit non-specific protein adsorption. Type AB linear (HAD Cn, n = 6,10,12,18) and branched (HAD nx 18, n = 2,3,4) heparin surfactants were synthesized by end point coupling primary and secondary alkyl amines to heparin via reductive amination. Surfactant yields (83--4%) and anticoagulant activity (149.8 +/- 3.7--39.6 +/- 0.6 IU/mg) decreased with increased branching and hydrocarbon number. Surfactant adsorption, self assembly and molecular packing of HAD surfactants at the air/liquid and liquid/solid interface were a function of the number of hydrocarbons in the surfactant alkyl segment and the presence or absence of an ionic liquid phase. Increased molecular packing was observed at the air/PBS and PBS/graphite interface, relative to aqueous interfaces, resulting from buffer cations shielding heparin's negatively charged sulfate and carboxyl groups. At the PBS/graphite interface, the surfactant's apparent heparin head group cross section decreased in diameter (1.84 to 1.05 nm) and increased in tilt angle (75.7 to 81.9°) with increasing alkyl carbon number (n = 6 to 18). The heparin head group reached a minimum diameter, equivalent to the surfactant's diameter at the air/PBS interface (0.57 nm) just prior to 36 hydrocarbons in the surfactant. For surfactants with 36 to 78 hydrocarbons, the surfactant's heparin head group oriented normal to the graphite surface and alkyl overlap or interdigitation increased (0.02 to 0.59 nm

  4. Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems.

    Science.gov (United States)

    Longstaff, Colin; Hogwood, John; Gray, Elaine; Komorowicz, Erzsebet; Varjú, Imre; Varga, Zoltán; Kolev, Krasimir

    2016-03-01

    Neutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 µg/ml histones in APTT and 4.6 µg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 µg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 µg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.

  5. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    Science.gov (United States)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  6. Dissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin

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    Moon, Andrea F.; Xu, Yongmei; Woody, Susan M.; Krahn, Joseph M.; Linhardt, Robert J.; Liu, Jian; Pedersen, Lars C. (NIH); (UNC); (Rensselaer)

    2012-05-29

    Heparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that transfers a sulfo group to the 3-OH position of a glucosamine unit. 3-OST is present in multiple isoforms, and the polysaccharides modified by these different isoforms perform distinct biological functions. 3-OST isoform 1 (3-OST-1) is the key enzyme for the biosynthesis of anticoagulant heparin. Here, we report the crystal structure of the ternary complex of 3-OST-1, 3'-phosphoadenosine 5'-phosphate, and a heptasaccharide substrate. Comparisons to previously determined structures of 3-OST-3 reveal unique binding modes used by the different isoforms of 3-OST for distinguishing the fine structures of saccharide substrates. Our data demonstrate that the saccharide substrates display distinct conformations when interacting with the different 3-OST isoforms. Site-directed mutagenesis data suggest that several key amino residues, including Lys259, Thr256, and Trp283 in 3-OST-3 and Arg268 in 3-OST-1, play important roles in substrate binding and specificity between isoforms. These results deepen our understanding of the biosynthetic mechanism of heparan sulfate and provide structural information for engineering enzymes for an enhanced biosynthetic approach to heparin production.

  7. Efficacy of unfractionated heparin, low molecular weight heparin and both combined for releasing total and free tissue factor pathway inhibitor.

    Science.gov (United States)

    Altman, R; Scazziota, A; Rouvier, J

    1998-01-01

    Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0. 01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.

  8. Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface.

    Science.gov (United States)

    Pan, Chang-Jiang; Pang, Li-Qun; Gao, Fei; Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua

    2016-06-01

    Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents.

  9. A sulfated fucan from the brown alga Laminaria cichorioides has mainly heparin cofactor II-dependent anticoagulant activity.

    Science.gov (United States)

    Yoon, Seon-Joo; Pyun, Yu-Ryang; Hwang, Jae-Kwan; Mourão, Paulo A S

    2007-11-05

    The major acidic polysaccharide from the brown alga Laminaria cichorioides is a complex and heterogeneous sulfated fucan. Its preponderant structure is a 2,3-disulfated, 4-linked alpha-fucose unit. The purified polysaccharide has a potent anticoagulant activity, as estimated by APTT assay ( approximately 40 IU/mg), which is mainly mediated by thrombin inhibition by heparin cofactor II. It also accelerates thrombin and factor Xa inhibition by antithrombin but at a lower potency. Sulfated fucan from L. cichorioides is a promising anticoagulant polysaccharide and a possible alternative for an antithrombotic compound due to its preferential heparin cofactor II-dependent activity.

  10. Heparin-induced platelet aggregation (H-IPA): dose/response relationship for two low molecular weight (LMW) heparin preparations (CY 216 and CY 222)

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    Brace, L.D.; Fareed, J.

    1986-03-01

    The authors have previously demonstrated that heparin and a LMW heparin derivative (PK 10169) causes platelet aggregation in a dose-dependent manner that can be inhibited by antagonists of the thromboxane pathway. Using fractions of these agents separated on the basis of molecular weight (MW) by gel permeation chromatography, the authors showed that H-IPA was directly dependent upon the MW of the agents tested. In order to further examine this MW dependence, the authors tested two other LMW heparin preparations, CY 216 and CY 222 and subfractions of these agents separated on the basis of MW. Citrate anticoagulated whole blood was drawn from drug-free normal healthy donors whose platelets aggregated when heparin was added to their platelet-rich plasma (PRP). PRP was prepared, various concentrations of the agents or their subfractions were added and aggregation was monitored for 40 minutes at 37/sup 0/C. The results demonstrate that like heparin and PK 10169, CY 216 and CY 222 caused platelet aggregation in a dose and MW dependent manner. Fractions with MW less than 2500 daltons caused aggregation only at concentrations exceeding the therapeutic range of the agents. The authors conclude that the ability to cause H-IPA is an inherent property of heparin and its fractions.

  11. The influence of unfractionated and low-molecular weight heparins on the properties of human umbilical vein endothelial cells (HUVEC.

    Directory of Open Access Journals (Sweden)

    Michał Myśliwiec

    2009-05-01

    Full Text Available Heparins, as anticoagulants widely used in the prophylaxis and treatment of many conditions connected with hypercoagulability, have a potent effect on the vascular endothelium. Unfractionated Heparin (UFH is characterized by relatively low biological accessibility, short activity time, binding of numerous proteins, as well as unfavorable influence on endothelium and blood platelets. Low-Molecular Weight Heparins (LMWHs, formed by chemical and enzymatic UFH depolymerizations, show a significantly more favorable impact on endothelium, which was confirmed on the HUVEC cultures study models. The studies on the heparins' modulation of angiogenesis process proved the superiority of LMWHs over UFH. It was connected with a better deactivation of growth factors' receptors (e.g. for VEGF165, FGF-2. Comparing the effects of LMWHs and UFH on haemostatic and antiangiogenic properties of HUVEC, significant differences were found as well. A new effect, engaging these compounds in the pathomechanism of an excessive osteoclastogenesis via osteoprotegerin /RANKL/RANK pathway has been discovered recently.

  12. Profile of low molecular weight tinzaparin sodium for anticoagulation during hemodialysis

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    Al-Saran Khalid

    2010-01-01

    Full Text Available Low-molecular-weight heparin (LMWH has been suggested as providing safe, effi-cient, convenient, and possibly more cost-effective anticoagulation for hemodialysis (HD than un-fractionated heparin (UFH with a single bolus dose at the start of hemodialysis effectively pre-vents clot formation in the dialyzer and bubble trap with fewer side-effects and possible benefits on uremic dyslipidemia. In this study, we compared the safety, clinical efficacy, and cost effectiveness of Tinzaparin sodium (Innohep with unfractionated heparin (UFH in 23 chronic HD patients; their extracorporeal anticoagulant protocol-consisted of UFH was switched to Tinzaparin for a period of 6 months. Clinical clotting (grade 1-4 was evaluated by visual inspection after blood draining of the air trap every hour and the dialyzer after each session. Anticoagulation with Tinzaparin sodium re-sulted in less frequent dialyzer and air-trap clotting compared to UFH (P= 001 and 0.04 respec-tively. Over 24 weeks, we observed no alteration in the serum lipid profile of the patients. There was a statistically significant improvement in the dialysis single pool Kt/V after 6 months of Tinza-parin use (1.40 ± 0.28 for Tinzaparin versus 1.23 ± 0.28 for heparin without any modification in the hemodialysis prescription. The total cost for 24 weeks use of Tinzaparin sodium was 23% more expensive compared to that for UFH. We conclude that a single bolus of Tinzaparin sodium injec-tion at the start of the dialysis session was more effective and convenient in our patients than UFH, but at a higher total cost. Furthermore, at least on the short term, there was no observed benefit on the lipid profile.

  13. Selective cleavage and anticoagulant activity of a sulfated fucan: stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, preparation of oligosaccharides, and heparin cofactor II-dependent anticoagulant activity.

    Science.gov (United States)

    Pomin, Vitor H; Pereira, Mariana S; Valente, Ana-Paula; Tollefsen, Douglas M; Pavão, Mauro S G; Mourão, Paulo A S

    2005-04-01

    A linear sulfated fucan with a regular repeating sequence of [3)-alpha-L-Fucp-(2SO4)-(1-->3)-alpha-L-Fucp-(4SO4)-(1-->3)-alpha-L-Fucp-(2,4SO4)-(1-->3)-alpha-L-Fucp-(2SO4)-(1-->]n is an anticoagulant polysaccharide mainly due to thrombin inhibition mediated by heparin cofactor II. No specific enzymatic or chemical method is available for the preparation of tailored oligosaccharides from sulfated fucans. We employ an apparently nonspecific approach to cleave this polysaccharide based on mild hydrolysis with acid. Surprisingly, the linear sulfated fucan was cleaved by mild acid hydrolysis on an ordered sequence. Initially a 2-sulfate ester of the first fucose unit is selectively removed. Thereafter the glycosidic linkage between the nonsulfated fucose residue and the subsequent 4-sulfated residue is preferentially cleaved by acid hydrolysis, forming oligosaccharides with well-defined size. The low-molecular-weight derivatives obtained from the sulfated fucan were employed to determine the requirement for interaction of this polysaccharide with heparin cofactor II and to achieve complete thrombin inhibition. The linear sulfated fucan requires significantly longer chains than mammalian glycosaminoglycans to achieve anticoagulant activity. A slight decrease in the molecular size of the sulfated fucan dramatically reduces its effect on thrombin inactivation mediated by heparin cofactor II. Sulfated fucan with approximately 45 tetrasaccharide repeating units binds to heparin cofactor II but is unable to link efficiently the plasma inhibitor and thrombin. This last effect requires chains with approximately 100 or more tetrasaccharide repeating units. We speculate that the template mechanism may predominate over the allosteric effect in the case of the linear sulfated fucan inactivation of thrombin in the presence of heparin cofactor II.

  14. Effect of heparin and low-molecular weight heparin on serum potassium and sodium levels

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    Girish M Bengalorkar

    2011-01-01

    Full Text Available Introduction: To study the effects of heparin and low-molecular weight heparin (LMWH on potassium and sodium levels in patients with cardiovascular diseases (CVDs and stroke. Materials and Methods : Sixty patients were recruited with 30 patients each receiving heparin and enoxaparin. Patients with CVD and stroke receiving heparin and LMWH were compared for their demographic profile and laboratory data, and this was analyzed by descriptive statistics. Risk factors associated with the development of hyperkalemia were analyzed using multiple logistic regression model. Results : There was an increase in potassium levels and decrease in sodium levels compared with baseline in both the groups. The difference between the groups with respect to sodium and potassium levels was not statistically significant. On analysis, the risk factors for development of hyperkalemia were baseline potassium levels, serum creatinine, and creatinine clearance. The change in sodium and potassium levels on the fifth day of therapy was increased with LMWH compared with heparin, although not statistically significant. Conclusions : The clinician should anticipate hyperkalemia especially in patients with renal impairment receiving these drugs.

  15. An Anti-Coagulation Conundrum: Implantation of Total Artificial Heart in a Patient with Heparin-Induced Thrombocytopenia Type II

    Science.gov (United States)

    Cios, Theodore J.; Salamanca-Padilla, Yuliana; Guvakov, Dmitri

    2017-01-01

    Patient: Male, 44 Final Diagnosis: Heparin-induced thrombocytopenia Type II Symptoms: Congestive heart failure • short of breath Medication: — Clinical Procedure: LVAD explantation • TAH insertion Specialty: Anesthesiology Objective: Rare co-existance of disease or pathology Background: Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of heparin administration. It can present a major clinical dilemma for physicians caring for patients requiring life-saving urgent or emergent cardiac surgery. Studies have been published examining the use of alternative anticoagulants for patients undergoing cardiopulmonary bypass (CPB), however, evidence does not clearly support any particular approach. Presently, there are no large-scale, prospective randomized studies examining the impact of alternative anticoagulants on clinical outcomes for HIT-positive patients requiring cardiac surgery. Case Report: We present the case of a patient who underwent SynCardia Total Artificial Heart (TAH) implantation following a recent left ventricular assist device (LVAD) placement. The patient was receiving argatroban for type II HIT with anuric renal failure, and developed a thrombus which occluded the inflow cannula of the LVAD. Based on a published study and after establishing consensus with the surgical, anesthesiology, perfusion, and hematology teams, we decided to use tirofiban as an antiplatelet agent to inhibit the platelet aggregation induced by heparin, and ultimately used heparin as the anticoagulant for cardiopulmonary bypass. Conclusions: When selecting anticoagulation for a HIT-positive patient requiring CPB, so that benefits outweigh risks, it is of paramount importance that the decision be based on a multitude of factors. The team caring for the patient should have a shared mental model and be familiar with the pharmacology, devices used, and local practices. These three elements should be integrated with patient-specific comorbidities

  16. Heparin-induced thrombocytopenia

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    Shaikh Nissar

    2011-01-01

    Full Text Available In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT. HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock.

  17. Capillary Electrophoresis-Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin.

    Science.gov (United States)

    Sun, Xiaojun; Lin, Lei; Liu, Xinyue; Zhang, Fuming; Chi, Lianli; Xia, Qiangwei; Linhardt, Robert J

    2016-02-01

    Heparins, highly sulfated, linear polysaccharides also known as glycosaminoglycans, are among the most challenging biopolymers to analyze. Hyphenated techniques in conjunction with mass spectrometry (MS) offer rapid analysis of complex glycosaminoglycan mixtures, providing detailed structural and quantitative data. Previous analytical approaches have often relied on liquid chromatography (LC)-MS, and some have limitations including long separation times, low resolution of oligosaccharide mixtures, incompatibility of eluents, and often require oligosaccharide derivatization. This study examines the analysis of glycosaminoglycan oligosaccharides using a novel electrokinetic pump-based capillary electrophoresis (CE)-MS interface. CE separation and electrospray were optimized using a volatile ammonium bicarbonate electrolyte and a methanol-formic acid sheath fluid. The online analyses of highly sulfated heparin oligosaccharides, ranging from disaccharides to low molecular weight heparins, were performed within a 10 min time frame, offering an opportunity for higher-throughput analysis. Disaccharide compositional analysis as well as top-down analysis of low molecular weight heparin was demonstrated. Using normal polarity CE separation and positive-ion electrospray ionization MS, excellent run-to-run reproducibility (relative standard deviation of 3.6-5.1% for peak area and 0.2-0.4% for peak migration time) and sensitivity (limit of quantification of 2.0-5.9 ng/mL and limit of detection of 0.6-1.8 ng/mL) could be achieved.

  18. Comparison of hematologic values in blood samples with lithium heparin or dipotassium ethylenediaminetetraacetic acid anticoagulants in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Mitchell, Mark A; Gaunt, Stephen D; Beaufrère, Hugues; Tully, Thomas N

    2008-06-01

    Blood samples were collected from 20 Hispaniolan Amazon parrots (Amazona ventralis) and were divided into tubes that contained dipotassium ethylenediaminetetraacetic acid (K2EDTA) and lithium heparin. Complete blood cell counts were determined in each sample within 2 hours of collection. The level of agreement in results was moderate for plasma protein, packed cell volume (PCV), and leukocyte, monocyte, and lymphocyte counts between the anticoagulants. Plasma protein and PCV values were significantly lower in samples with lithium heparin than in those with K2EDTA, whereas lymphocyte numbers were significantly higher in lithium heparin samples than in K2EDTA samples. The level of agreement was good for the other cell types (heterophils, eosinophils, and basophils) when comparing the different anticoagulants. The poor level of agreement between anticoagulants with the increase in thrombocyte clumping in lithium heparin samples indicates that the use of lithium heparin as anticoagulant may affect thrombocyte count. No negative effects on morphology and staining of blood cells were apparent in smears from heparin samples compared with K2EDTA samples. Within the different values compared, the limits of agreement are small enough to be confident that lithium heparin can be used for routine CBC counts in a clinical setting. The use of the same anticoagulant should be recommended to follow trends within the same patient, especially when considering plasma protein concentration, PCV, and lymphocyte count.

  19. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin

    Science.gov (United States)

    Cheng, Wenming; Zohra Dahmani, Fatima; Zhang, Juan; Xiong, Hui; Wu, Yuanyuan; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-02-01

    Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH. The resulting LMWH-UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200-250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH-UA. Meanwhile, the in vivo antitumor effect of LMWH-UA was also evaluated using a B16F10 mouse melanoma model. LMWH-UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH-UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH-UA as a new therapeutic remedy for cancer therapy.

  20. Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Li, Daoyuan; Chi, Lequan; Jin, Lan; Xu, Xiaohui; Du, Xuzhao; Ji, Shengli; Chi, Lianli

    2014-01-01

    Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs.

  1. The use of low molecular weight heparins in patients with acute ST-elevated myocardial infarction

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    Petrović Milovan

    2006-01-01

    Full Text Available Introduction. According to the published guidelines for the management of acute coronary syndromes (ACS, treatment of acute ST-elevated myocardial infarction is based on rapid revascularization, either mechanical or pharmacological. Pharmacological revascularization consists of fibrinolytic therapy with antiplatelet and anticoagulant therapy. In regard to the anticoagulant therapy, low molecular weight heparins (LMWHs are of special importance. LMWHs cause less complications (bleeding, thrombocytopenia, better bioviability in comparison with unfractionated heparin (UFH. Some studies on use of LMWHs in ACS, show that LMWHs are equally efficient and safe as UFH, causing less complications (different types of hemorrhagic complications (ESSENCE, TIMI 11B (enoxaparin, FRAXIS - fraxiparin, whereas some studies show better efficacy and safety of enoxaparin in therapy of acute ST-elevated myocardial infarction (ASSENT 3, ASSENT 3 PLUS, HART II, AMI-SK. Material and methods. Inclusion criteria: acute anterior myocardial infarction with ST-elevation, first myocardial infarction, no other structural heart defects, no signs of cardiogenic shock. Our study included 30 patients receiving fibrinolytic therapy with streptokinase, antiplatelet therapy and LMWH during 6 days, and 30 patients receiving UFH instead of LMWH. The follow-up period lasted for 6 months. Results. Significantly more patients receiving unfractionated heparin presented with major adverse cardiac events (73.3% in regard to patients in the study group (44,2% nadroparin, 39.8% enoxaparin (p=0.025. In the group receiving UFH, 6.7% patients had hemorrhagic complications, while none of patients receiving LMWHs. An equal number of patients died. Conclusion. Patients who were treated with LMWHs experienced less major adverse cardiac events and lower mortality. None suffered from hemorrhagic complications. .

  2. Modified Heparin

    Institute of Scientific and Technical Information of China (English)

    XIONG; Jian

    2001-01-01

    Heparin, the naturally occurring blood anticoagulating agent, is a sulphated polysaccharide. In addition to famous anticoagulation, It also has other important pharmacological actions, such as preventing thrombosis, immunological accommodation, smooth muscle hyperplasia, antivirus etc.  ……

  3. Modified Heparin

    Institute of Scientific and Technical Information of China (English)

    XIONG Jian; YE Jun; GUAN Jialun; LI Lin

    2001-01-01

    @@ Heparin, the naturally occurring blood anticoagulating agent, is a sulphated polysaccharide. In addition to famous anticoagulation, It also has other important pharmacological actions, such as preventing thrombosis, immunological accommodation, smooth muscle hyperplasia, antivirus etc.

  4. Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization.

    Science.gov (United States)

    Chang, L C; Lee, H F; Yang, Z; Yang, V C

    2001-01-01

    Low molecular weight protamine (LMWP) appears to be a promising solution for heparin neutralization without the protamine-associated catastrophic toxic effects. The feasibility of this hypothesis was proven previously by using a peptide mixture produced from proteolytic digestion of protamine. To further examine the utility of this compound as an ultimate nontoxic protamine substitute, detailed studies on the purification and characterization of LMWP including the precise amino acid sequence, structure-function relationship, and possible mechanism were conducted. A number of LWMP fragments, composed of highly cationic peptides with molecular weights ranging from 700 to 1900 d, were prepared by digestion of native protamine with the protease thermolysin. These fragments were fractionated using a heparin affinity chromatography, and their relative binding strengths toward heparin were elucidated. Five distinct fractions were eluted at NaCl concentration ranging from 0.4 to 1.0 M and were denoted as TDSP1 to TDSP5, in increasing order of eluting ionic strength. Among these 5 fractions, TDSP4 and TDSP5 contained 3 LMWP peptide fragments, and they were found to retain the complete heparin-neutralizing function of protamine. By using a peptide mass spectrometry (MS) fingerprint mapping technique, the amino acid sequences of the microheterogeneous LMWP fragments in all these 5 elution fractions were readily identified. A typical structural scaffold made by arginine clusters in the middle and nonarginine residues at the N-terminal of the peptide sequence was observed for all these LMWP fragments. By aligning the sequences with the potency in heparin neutralization of these LMWP fragments, it was found that retention of potency similar to that of protamine required the presence of at least 2 arginine clusters in the LMWP fragments; such as the sequence of VSRRRRRRGGRRRR seen in the most potent LMWP fraction-TDSP5. The above finding was further validated by using a synthetic

  5. Heparin-mimetic polyurethane hydrogels with anticoagulant, tunable mechanical property and controllable drug releasing behavior.

    Science.gov (United States)

    Chen, Yuan; Wang, Rui; Wang, Yonghui; Zhao, Weifeng; Sun, Shudong; Zhao, Changsheng

    2017-05-01

    In the present study, novel heparin-mimetic polyurethane hydrogels were prepared by introducing chemical crosslinked sulfated konjac glucomannan (SKGM). Scanning electron microscopy (SEM) results indicated that the introduction of SKGM and the increase of the molecular weight of diol segments could enlarge the pore sizes of the hydrogels. The swelling behavior corresponded with the SEM results, and the hydrogels could absorb more water after the modification. The modification also led to an improvement in the mechanical property. Meanwhile, the SKGM and the modified polyurethane hydrogels showed excellent hemocompatibility. The thromboplastin time of SKGM could reach up to 182.9s. Gentamycin sulfate (GS) was used as a model drug to be loaded into the hydrogels, and the loading amount was increased ca. 50% after the introduction of SKGM, thus resulting in high bactericidal efficiency. The results indicated that the introduction of SKGM and the alternation in the diol's molecular weight bestowed polyurethane hydrogels with promising properties of integrated blood-compatibility, mechanical properties and drug loading-releasing behavior. Therefore, the heparin-mimetic multifunctional polyurethane hydrogels have great potential to be used in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xue [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Tao [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai’an (China); Chen, Yuan [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Zhang, Kun [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); School of Life Science, Zhengzhou University, Zhengzhou (China); Maitz, Manfred F. [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Hohe Str. 06, 01069 Dresden (Germany); Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai’an (China); Chen, Junying, E-mail: chenjy@263.net [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Huang, Nan [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China)

    2014-11-30

    Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment.

  7. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2013-01-01

    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  8. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-07-01

    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  9. The preparation and anticoagulant properties of heparin zinc potassium%肝素锌钾复盐的制备及抗凝血性能

    Institute of Scientific and Technical Information of China (English)

    尚小琴; 黄镇群; 赖雅平; 黄卫忠; 刘汝锋; 江洁萍; 高若璇

    2014-01-01

    The heparin zinc potassium was prepared by heparinized reaction with heparin sodium , potassium hy-droxide and zinc hydroxide as main raw material .The effect of pH on the zinc ion and potassium ion concentra-tion in products was investigated , and the relationship between anticoagulant concentration and the coagulation time was observed .And the anticoagulant properties of heparin sodium and heparin zinc potassium were com -pared.The results show the coagulation time of heparin zinc potassium was 17 min, and the anticoagulant prop-erties of heparin zinc potassium were better than heparin sodium .The influences of pH and anticoagulant con-centration on anticoagulant properties were predominant , and the optimum pH value was 3~4 .%以肝素钠、氢氧化钾和氢氧化锌为主要原料,通过肝素化反应,制备抗凝血剂肝素锌钾复盐,探讨反应过程中pH值对产物中锌、钾离子浓度的影响规律,考察抗凝剂用量与体外凝血时间的关系,并对原料肝素钠和肝素锌钾复盐的抗凝血性能进行对比.实验结果显示,制备的肝素锌钾复盐的体外抗凝血时间为17 min,优于肝素钠的抗凝血性能;反应过程中pH值和抗凝剂的浓度对产物抗凝血性能影响显著,最佳pH值为3~4.

  10. Unfractionated or Low-Molecular Weight Heparin for the Treatment of Cerebral Venous Thrombosis

    NARCIS (Netherlands)

    J.M. Coutinho; J.M. Ferro; P. Canhão; F. Barinagarrementeria; M.G. Bousser; J. Stam

    2010-01-01

    Background and Purpose-There is no consensus whether to use unfractionated heparin or low-molecular weight heparin for the treatment of cerebral venous thrombosis. We examined the effect on clinical outcome of each type of heparin. Methods-A nonrandomized comparison of a prospective cohort study (th

  11. Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature.

    LENUS (Irish Health Repository)

    Alkindi, Salam

    2011-08-01

    Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin-induced thrombocytopenia syndrome (HITS), which develops in about 3-5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7-14 days). Platelet counts decreased to a mean of 38.4 x 10(9) \\/l (12-82 x 10(9)\\/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis.

  12. Antithrombin Administration During Intravenous Heparin Anticoagulation in the Intensive Care Unit: A Single-Center Matched Retrospective Cohort Study.

    Science.gov (United States)

    Beyer, Jacob T; Schoeppler, Kelly E; Zanotti, Giorgio; Weiss, Gregory M; Mueller, Scott W; MacLaren, Robert; Fish, Douglas N; Kiser, Tyree H

    2016-09-13

    Unfractionated heparin (UFH) is a frequently utilized indirect anticoagulant that induces therapeutic effect by enhancing antithrombin (AT)-mediated procoagulant enzyme inhibition. In suspected heparin resistance (HR) during cardiopulmonary bypass, AT activity may be decreased and AT supplementation helps restore UFH responsiveness. The benefit of AT supplementation in HR over longer durations of UFH therapy is unclear. The objective of this study was to describe and evaluate the use of AT III concentrate in the intensive care units (ICUs) at our institution for improving UFH therapy response over 72 hours. A total of 44 critically ill patients were included in the analysis-22 patients received at least 1 dose of AT and 22 patients received no AT. Thirty (68.2%) of the 44 patients were receiving mechanical circulatory support. Baseline characteristics were similar between groups. The average AT activity prior to AT supplementation was 57.9% in the treatment group, and the median cumulative dose of AT was 786.5 U (9.26 U/kg) per patient. There were no significant differences observed in proportion of time spent in therapeutic range (31.9% vs 35.2%, P = .65), time to therapeutic goal (16.5 vs 15.5 hours, P = .97), or patients who experienced a bleeding event (5 vs 5, P = .99) between groups. In conclusion, AT supplementation had minimal impact on anticoagulant response in this cohort of ICU patients with mild to moderate HR receiving a prolonged UFH infusion. Additional research is needed to define AT activity targets and to standardize AT supplementation practices in patients receiving prolonged heparin infusion.

  13. Cancer-associated thrombosis, low-molecular- weight heparin, and the patient experience: a qualitative study

    Directory of Open Access Journals (Sweden)

    Seaman S

    2014-04-01

    Full Text Available Siwan Seaman,1 Annmarie Nelson,2 Simon Noble2 1Department of Palliative Medicine, Royal Gwent Hospital, Newport, Wales, UK; 2Marie Curie Palliative Care Research Unit, Cardiff University, Cardiff, Wales, UK Background: Venous thromboembolism is a common complication of cancer and its treatments. Treatment of cancer-associated thrombosis (CAT differs from treatment of thrombosis in noncancer patients, requiring a daily injection of low-molecular-weight heparin (LMWH for 6 months instead of an oral anticoagulant. Previous research suggested LMWH is an acceptable intervention in the treatment of CAT, yet clinical practice and therapeutic opportunities have changed in the decade since the study was conducted. Furthermore, in the previous study there was acknowledged selection bias in participant recruitment. There is increasing clinical use of the novel oral anticoagulants, although their efficacy and safety is yet to be demonstrated within the cancer population. The experience of patients receiving anticoagulation for CAT will inform future practice with respect to quality of life and adherence to anticoagulation therapy. Aim: To explore the acceptability of long-term LMWH for the treatment of CAT in the contexts of living with cancer and quality of life. Design: Qualitative study of cancer patients who had been receiving LMWH for at least 3 months for CAT was undertaken. Audiotaped semistructured interviews were conducted and transcribed. Thematic analysis was undertaken until theoretical saturation. Setting/participants: Fourteen patients attending a palliative care or CAT clinic were interviewed. Participants had been receiving LMWH for a median 6 months. Results: Participants reported distressing symptoms associated with symptomatic CAT, which they rated as worse than their cancer experiences. LMWH was considered an acceptable intervention despite challenges of long-term injections. Several adaptive techniques were reported to optimize ongoing

  14. Anticoagulation management in the ambulatory surgical setting.

    Science.gov (United States)

    Eisenstein, Diana Hill

    2012-04-01

    Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers.

  15. Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

    Institute of Scientific and Technical Information of China (English)

    Baiqiang Li; Kang Wang; Xin Zhao; Chao Lin; Haichen Sun

    2015-01-01

    Purpose:To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection.Methods:Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013.These patients were randomly divided into 2 groups.In group F (18 patients),the patients were treated with fondaparinux sodium,2.5 mg,1/d for 11 d.In group L (18 patients),the patients were treated with low molecular weight heparin,4100 U,1/12 h for 11 d.The incidence of deep vein thrombosis,bleeding events and multiple organ dysfunction syndrome (MODS) and mortality of two groups after anticoagulation therapy were analyzed.Fibrinogen,D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer.Results:The incidence of deep vein thrombosis,MODS incidence and mortality were not significantly different between the two groups.The rate of bleeding evens in group F was lower than group L (p < 0.05).Antithrombin Ⅲ got an upward trend after anticoagulant therapy,in which it was higher in group F than in group L on the 5th d and 11th d (p < 0.05).Fibrinogen levels were gradually increased,and there was no significant difference between two groups (p > 0.05).D-dimer was significantly decreased after anticoagulant therapy for 5 d (p < 0.01),and there were significant differences between two groups on the 5th d and 7th d (p < 0.05).It showed no significant difference on the 11th d (p > 0.05).Conclusion:Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection.Compared with low molecular weight heparin,fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.

  16. Intravitreal low molecular weight heparin in PVR surgery.

    Directory of Open Access Journals (Sweden)

    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  17. Arterial indications for the low molecular weight heparins

    Directory of Open Access Journals (Sweden)

    Ageno Walter

    2001-09-01

    Full Text Available Abstract Antithrombotic treatment is of proven importance in patients with acute coronary syndromes. There is now accumulating evidence from several clinical trials in patients with unstable angina pectoris that the low molecular weight heparins (LMWHs are at least as effective as unfractionated heparin. The LMWHs are easier to use, with the potential to facilitate long-term outpatient treatment. The results of the trials have actually failed to show any clear advantage, however, of the LMWHs over the standard antiplatelet treatment, despite the evidence of a sustained hypercoagulability. Potentially, the use of higher doses of LMWHs could improve the outcomes, but this is as yet unproven and could be associated with unacceptably increased risk of bleeding. During the acute phase of a stroke, aspirin is the first choice of antithrombotic drug because it reduces the risk of recurrent stroke. LMWH cannot be recommended as an antithrombotic agent for the acute treatment of stroke. Prophylactic use of low dose LMWH for the prevention of venous thromboembolism should be considered in every patient with a stroke.

  18. Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

    Science.gov (United States)

    Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

    2016-01-01

    Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Obstetric outcome with low molecular weight heparin therapy during pregnancy.

    LENUS (Irish Health Repository)

    Donnelly, J

    2012-01-01

    This was a prospective study of women attending a combined haematology\\/obstetric antenatal clinic in the National Maternity Hospital (2002-2008). Obstetric outcome in mothers treated with low molecular weight heparin (LMWH) was compared to the general obstetric population of 2006. There were 133 pregnancies in 105 women. 85 (63.9%) received prophylactic LMWH and 38 (28.6%) received therapeutic LMWH in pregnancy. 10 (7.5%) received postpartum prophylaxis only. The perinatal mortality rate was 7.6\\/1000 births. 14 (11.3%) women delivered preterm which is significantly higher than the hospital population rate (5.7%, p<0.05). Despite significantly higher labour induction rates (50% vs 29.2% p<0.01), there was no difference in CS rates compared to the general hospital population (15.4% vs 18.9%, NS). If carefully managed, these high-risk women can achieve similar vaginal delivery rates as the general obstetric population.

  20. Efficacy and safety of low molecular weight heparin compared to unfractionated heparin for chronic outpatient hemodialysis in end stage renal disease: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ghanshyam Palamaner Subash Shantha

    2015-03-01

    Full Text Available Background. Low molecular weight heparin (LMWH is an effective anti-coagulant for thrombotic events. However, due to its predominant renal clearance, there are concerns that it might be associated with increased bleeding in patients with renal disease.Objectives. We systematically evaluated the efficacy and safety of LMWH compared to unfractionated heparin (UH in end stage renal disease (ESRD patients.Search Methods. Pubmed, Embase and cochrane central were searched for eligible citations.Selection Criteria. Randomized controlled trials, comparing LMWH and UH, involving adult (age > 18 years, ESRD patients receiving outpatient, chronic, intermittent hemodialysis were included.Data Collection and Analysis. Two independent reviewers performed independent data abstraction. I2 statistic was used to assess heterogeneity. Random effects model was used for meta-analysis.Results. Nineteen studies were included for systematic review and 4 were included for meta-analysis. There were no significant differences between LMWH and UFH for extracorporeal circuit thrombosis [risk ratio: 1 (95% CI [0.62–1.62

  1. Interactions between nattokinase and heparin/GAGs.

    Science.gov (United States)

    Zhang, Fuming; Zhang, Jianhua; Linhardt, Robert J

    2015-12-01

    Nattokinase (NK) is a serine protease extracted from a traditional Japanese food called natto. Due to its strong fibrinolytic and thrombolytic activity, NK is regarded as a valuable dietary supplement or nutraceutical for the oral thrombolytic therapy. In addition, NK has been investigated for some other medical applications including treatment of hypertension, Alzheimer's disease, and vitreoretinal disorders. The most widely used clinical anticoagulants are heparin and low molecular weight heparins. The interactions between heparin and proteins modulate diverse patho-physiological processes and heparin modifies the activity of serine proteases. Indeed, heparin plays important roles in almost all of NK's potential therapeutically applications. The current report relies on surface plasmon resonance spectroscopy to examine NK interacting with heparin as well as other glycosaminoglycans (GAGs). These studies showed that NK is a heparin binding protein with an affinity of ~250 nM. Examination with differently sized heparin oligosaccharides indicated that the interaction between NK and heparin is chain-length dependent and the minimum size for heparin binding is a hexasaccharide. Studies using chemically modified heparin showed the 6-O-sulfo as well as the N-sulfo groups but not the 2-O-sulfo groups within heparin, are essential for heparin's interaction with NK. Other GAGs (including HS, DS, and CSE) displayed modest binding affinity to NK. NK also interfered with other heparin-protein interactions, including heparin's interaction with antithrombin and fibroblast growth factors.

  2. Earthworm extracts utilized in the green synthesis of gold nanoparticles capable of reinforcing the anticoagulant activities of heparin

    Science.gov (United States)

    Kim, Hee Kyeong; Choi, Myung-Jin; Cha, Song-Hyun; Koo, Yean Kyoung; Jun, Sang Hui; Cho, Seonho; Park, Youmie

    2013-12-01

    Gold nanoparticles were obtained using a green synthesis approach with aqueous earthworm extracts without any additional reducing or capping agents. The gold nanoparticles were characterized using UV-visible spectrophotometry, high-resolution transmission electron microscopy, atomic force microscopy, field emission scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and inductively coupled plasma mass spectrometry. The anticoagulant activity of the gold nanoparticles was assessed using the activated partial thromboplastin time and was mildly enhanced by combining the gold nanoparticles with heparin. In addition to the generation of spherical nanoparticles with an average diameter of 6.13 ± 2.13 nm, cubic and block-shaped nanoparticles with an average aspect ratio, defined as the length divided by width, of 1.47 were also observed.

  3. Anticoagulants

    Science.gov (United States)

    ... Receptor Blockers Angiotensin-Converting Enzyme (ACE) Inhibitors Antiarrhythmics Antiplatelet Therapy Aspirin Beta-Blockers Blood Thinners Calcium Channel Blockers Digitalis Medicines Diuretics Inotropic Agents Nitrates Statins, Cholesterol-Lowering Medicines Anticoagulants Related terms: ...

  4. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  5. Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar

    Directory of Open Access Journals (Sweden)

    Gerber Jonathan

    2005-04-01

    Full Text Available Abstract With the growing use of low-molecular-weight heparins (LMWH for the treatment and prevention of venous thromboembolism (VTE, it is important to provide an evidence-based comparison with unfractionated heparin (UFH concerning rates of heparin-induced thrombocytopenia (HIT. Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.

  6. Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin.

    Science.gov (United States)

    Gustafson, Elisabet; Asif, Sana; Kozarcanin, Huda; Elgue, Graciela; Meurling, Staffan; Ekdahl, Kristina N; Nilsson, Bo

    2017-01-24

    Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 μg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze-thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze-thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 μg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

  7. Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

    Directory of Open Access Journals (Sweden)

    Pratip Chakraborty

    Full Text Available The management of recurrent pregnancy loss (RPL still remains a great challenge, and women with polycystic ovarian syndrome (PCOS are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy, insulin resistance (IR and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

  8. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    DEFF Research Database (Denmark)

    Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

    1993-01-01

    to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent...

  9. Opposing effects of low molecular weight heparins on the release of inflammatory cytokines from peripheral blood mononuclear cells of asthmatics.

    Directory of Open Access Journals (Sweden)

    Madhur D Shastri

    Full Text Available T-cell-mediated inflammatory cytokines, such as interleukin (IL-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF-α, play an important role in the initiation and progression of inflammatory airways diseases. Low-molecular-weight heparins (LMWHs, widely used anticoagulants, possess anti-inflammatory properties making them potential treatment options for inflammatory diseases, including asthma. In the current study, we investigated the modulating effects of two LMWHs (enoxaparin and dalteparin on the release of cytokines from stimulated peripheral blood mononuclear cells (PBMCs of asthmatic subjects to identify the specific components responsible for the effects.PBMCs from asthmatic subjects (consist of ~75% of T-cells were isolated from blood taken from ten asthmatic subjects. The PBMCs were pre-treated in the presence or absence of different concentrations of LMWHs, and were then stimulated by phytohaemagglutinin for the release of IL-4, IL-5, IL-13 and TNF-α. LMWHs were completely or selectively desulfated and their anticoagulant effect, as well as the ability to modulate cytokine release, was determined. LMWHs were chromatographically fractionated and each fraction was tested for molecular weight determination along with an assessment of anticoagulant potency and effect on cytokine release.Enoxaparin inhibited cytokine release by more than 48%, whereas dalteparin increased their release by more than 25%. The observed anti-inflammatory effects of enoxaparin were independent of their anticoagulant activities. Smaller fractions, in particular dp4 (four saccharide units, were responsible for the inhibitory effect of enoxaparin. Whereas, the larger fractions, in particular dp22 (twenty two saccharide units, were associated with the stimulatory effect of dalteparin.Enoxaparin and dalteparin demonstrated opposing effects on inflammatory markers. These observed effects could be due to the presence of structurally different components in the two

  10. Low molecular weight heparin microcapsule coated occluder for atrial-septal defects

    Institute of Scientific and Technical Information of China (English)

    SUN Yong; WU Jian; ZHANG Ruo-xi; SHI Xiu-jie; LIU Hai-xia; ZHAO Yang; YU Bo

    2009-01-01

    Background Whether the low molecular weight heparin microcapsule coated occluder is helpful to endothelialization in atrial-septal defect models is uncertain. This study aimed to investigate the best conditions for low molecular weight heparin coated Nil-I alloy occluder and provide the evidence of the efficacy and safety of atrial-septal defect occluders in vivo.Methods Low molecular weight heparin microcapsules were investigated using gelatin as microcapsule material. The prepared low molecular weight heparin gelatin particles were subjected to nickel and titanium alloy occluder coating by sodium hyaluronate. A dog model of atrial septal defects was established after treatment with low molecular weight heparin microcapsule coated occluder (n=4) and uncoated occluder (n=4). Endotheliocytes and fibroblastic cells in occluders were observed. And the rate of endothelialization was detected.Results When the concentration of gelatin was 1%, the diameters of particles were mostly about 100 pm, and the particle size was uniform. The envelope efficiency of low molecular weight heparin microcapsule was about 80%. The endothelialization of occluder in the model was more obvious in the coated group than in the uncoated group (P <0.0001).Conclusions Low molecular weight heparin can be prepared into microcapsules with their particle size in nanometric grade. The antithrombotic properties are kept in the nickel and titanium alloy occluder successfully coated with sodium hyaluronate. The endothelialization after the interventional occlusion in the coated group is obvious, indicating that low molecular weight heparin is helpful to the growth of endothelial cells in the occlude and the healing after the interventional occlusion.

  11. Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism

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    Adiguzel Cafer

    2011-03-01

    Full Text Available Abstract Background The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. Methods MEDLINE and EMBASE databases were searched to identify relevant original articles. Results Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Conclusions Parenteral

  12. Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory.

    Science.gov (United States)

    Burnett, Allison E; Bowles, Harmony; Borrego, Matthew E; Montoya, Tiffany N; Garcia, David A; Mahan, Charles

    2016-11-01

    Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.

  13. Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma

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    Jin-Lian Chen; Jing Hong; Jin-Lai Lu; Ming-Xiang Chen; Wei-Xiong Chen; Jin-Shui Zhu; Ni-Wei Chen; Guo-Qiang Chen; Jian-Guo Geng

    2007-01-01

    AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice.METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SCID mice.The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group received i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences,10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100pL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SCID mice was detected by real time PCR.RESULTS: The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group(P < 0.05). MVD was 8.0±3.1 in normal saline group and 4.3±1.8 in N-desulfated heparin group (P < 0.05).VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated heparin treated group (90% VS 20%, P < 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.51±1.01 vs22.55±1.36, P < 0.05). N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group.CONCLUSION: N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious

  14. Comparison of aPTT and CT Parameter of the ROTEM Test to Monitor Heparin Anti-Coagulation Effect in ICU Patients: an Observational Study

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    Atabak Najafi

    2015-10-01

    Full Text Available Heparin is frequently used in different clinical settings to reduce the coagulating ability of the blood. Because of probable adverse effects owing to heparin therapy and regarding variability of patients’ responses to heparin, which make it very unreliable, it seems prudent to monitor meticulously its effects on the human body. There are a lot of laboratory tests to watch its effects on the body for example; aPTT and ROTEM are the most widely used tests that are performed today. We aimed to compare the aPTT test results against changes of CT parameter of the ROTEM test due to heparin administration. This study was conducted on 45 critically ill patients who needed to receive heparin according to their clinical status. All patients received 550 to 1500 unit heparin per hour (on average 17.5 unit heparin per kilogram weight. While the patients were under infusion of heparin, two blood samples (5 ml were taken from a newly established cubital vein, just five hours after commencement of heparin therapy. One sample was used for aPTT and the other one for ROTEM. The correlation between aPTT and the changes of CT parameter of the ROTEM with heparin dosage and infusion was the primary outcome. The correlation between heparin therapy and the changes of other parameters like MCF, CFT, and a number of platelets were the secondary outcome of the study. The only significant correlation was between changes of CT and aPTT (P=0.000. The other variables were not correlated. Changes of CT parameter of ROTEM test can be used for monitoring of reduced coagulability during heparin infusion instead of aPTT test.

  15. Gigantic retroperitoneal hematoma as a complication of anticoagulation therapy with heparin in therapeutic doses: a case report

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    Daliakopoulos Stavros I

    2008-05-01

    Full Text Available Abstract Introduction Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present as a rare life-threatening event characterized by sudden onset of bleeding into the retroperitoneal space, occurring in association with bleeding disorders, intratumoral bleeding, or ruptures of any retroperitoneal organ or aneurysm. The spontaneous form is the most infrequent retroperitoneal hemorrhage, causing significant morbidity and representing a diagnostic challenge. Case presentation We report the case of a patient with coronary artery disease who presented with transient ischemic attack, in whom anticoagulant therapy with heparin precipitated a massive spontaneous atraumatic retroperitoneal hemorrhage (with international normalized ratio 2.4, which was treated conservatively. Conclusion Delay in diagnosis is potentially fatal and high clinical suspicion remains crucial. Finally, it is a matter of controversy whether retroperitoneal hematomas should be surgically evacuated or conservatively treated and the final decision should be made after taking into consideration patient's general condition and the possibility of permanent femoral or sciatic neuropathy due to compression syndrome.

  16. Deep venous thrombosis and pulmonary embolism. Part 1. Initial treatment: usually a low-molecular-weight heparin.

    Science.gov (United States)

    2013-04-01

    Patients with deep venous thrombosis are at a short-term risk of symptomatic or even life-threatening pulmonary embolism, and a long-term risk of post-thrombotic syndrome, characterised by lower-limb pain, varicose veins, oedema, and sometimes skin ulcers. What is the best choice of initial antithrombotic therapy following deep venous thrombosis or pulmonary embolism, in terms of mortality and short-term and long-term complications? How do the harm-benefit balances of the different options compare? To answer these questions, we reviewed the available literature using the standard Prescrire methodology. Unfractionated heparin has documented efficacy in reducing mortality and recurrent thromboembolic events in patients with pulmonary embolism or symptomatic proximal (above-knee) deep venous thrombosis. The authors of a systematic review selected 23 trials of low-molecular-weight heparin (LMWH) versus adjusted-dose unfractionated heparin in a total of 9587 patients. Deaths, recurrences and major bleeds were less frequent with LMWH than with unfractionated heparin. The results of other meta-analyses are similar, but all are undermined by a probable publication bias and methodological flaws. Compared to unfractionated heparin, LMWHs have the advantage of fixed-dose administration, once or twice daily, by subcutaneous injection. All available LMWHs seem to have similar efficacy. Those with the longest experience of use are enoxaparin, dalteparin and nadroparin. The harm-benefit balances of fondaparinux and rivaroxaban do not appear more favourable than that of an LMWH followed by an adjusted-dose vitamin K antagonist. A meta-analysis included 12 trials comparing thrombolysis with anticoagulation alone in 700 patients with deep venous thrombosis. Adding a thrombolytic drug did not reduce mortality or the incidence of pulmonary embolism, whereas it increased the incidence of bleeding. A meta-analysis of 13 trials failed to show that adding a thrombolytic drug to initial

  17. Update on the clinical use of the low-molecular-weight heparin, parnaparin

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    Giuseppe Camporese

    2009-09-01

    Full Text Available Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

  18. Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.

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    van Zuuren, Esther J; Fedorowicz, Zbys

    2015-12-18

    Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect. This is an update of a previously published version of this review. To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 28 September 2015. Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease. Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors. Two studies comprising 287 participants were included. One study (with an overall unclear to high risk of bias) involved 253 participants and the quality of the evidence for most outcomes was very low. This study, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins

  19. Bottom-up low molecular weight heparin analysis using liquid chromatography-Fourier transform mass spectrometry for extensive characterization.

    Science.gov (United States)

    Li, Guoyun; Steppich, Julia; Wang, Zhenyu; Sun, Yi; Xue, Changhu; Linhardt, Robert J; Li, Lingyun

    2014-07-01

    Low molecular weight heparins (LMWHs) are heterogeneous, polydisperse, and highly negatively charged mixtures of glycosaminoglycan chains prescribed as anticoagulants. The detailed characterization of LMWH is important for the drug quality assurance and for new drug research and development. In this study, online hydrophilic interaction chromatography (HILIC) Fourier transform mass spectrometry (FTMS) was applied to analyze the oligosaccharide fragments of LMWHs generated by heparin lyase II digestion. More than 40 oligosaccharide fragments of LMWH were quantified and used to compare LMWHs prepared by three different manufacturers. The quantified fragment structures included unsaturated disaccharides/oligosaccharides arising from the prominent repeating units of these LMWHs, 3-O-sulfo containing tetrasaccharides arising from their antithrombin III binding sites, 1,6-anhydro ring-containing oligosaccharides formed during their manufacture, saturated uronic acid oligosaccharides coming from some chain nonreducing ends, and oxidized linkage region oligosaccharides coming from some chain reducing ends. This bottom-up approach provides rich detailed structural analysis and quantitative information with high accuracy and reproducibility. When combined with the top-down approach, HILIC LC-FTMS based analysis should be suitable for the advanced quality control and quality assurance in LMWH production.

  20. Surgical bleeding after pre-operative unfractionated heparin and low molecular weight heparin for coronary bypass surgery.

    Science.gov (United States)

    Renda, Giulia; Di Pillo, Raffaele; D'Alleva, Alberto; Sciartilli, Adolfo; Zimarino, Marco; De Candia, Erica; Landolfi, Raffaele; Di Giammarco, Gabriele; Calafiore, Antonio; De Caterina, Raffaele

    2007-03-01

    Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre-operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin. Forty-three patients with three-vessel coronary artery disease undergoing elective CABG surgery discontinued aspirin and were randomized to receive either UFH 180 UI/Kg x 2/day s.c. or enoxaparin 100 UI/Kg x 2/day s.c. until 12 h before surgery (median pre-operative treatment 8 days, range 6-12 days). Surgery was performed as usual with UFH. Neither UFH nor any low molecular weight heparin was given in the immediate post-operative period. The effects of UFH and enoxaparin were monitored by the activated partial thromboplastin time (aPTT) and the Enox-test (sensitive to factor Xa inhibition) using a Rapidpoint Coagulation Analyzer. aPTT and factor Xa activity were also measured by standard methods. Peri-operative bleeding and the nadirs of hemoglobin concentration, hematocrit and platelet count were monitored post-operatively. Patients in the two groups were similar for number of bypasses, on-pump time, total surgery time, and time from the last heparin administration. Coagulation parameters increased significantly and similarly at 30 min and 6 h with both treatments, but returned within the normal range at 12 h. Hemoglobin, hematocrit and platelet counts significantly decreased to the same extent after CABG and re-normalized at the same time. Transfusional requirements of blood and plasma units were similar in the two groups. From the kinetics of coagulation parameters and the evaluation of bleeding, enoxaparin is a safe alternative to UFH as a bridging therapy to CABG after discontinuation of aspirin.

  1. Heparina e K3EDTA como anticoagulantes para tambaqui (Colossoma macropomum Cuvier, 1816 Heparin and K3EDTA as anticoagulants for tambaqui (Colossoma macropomum Cuvier, 1816

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    Santiago Benites de Pádua

    2012-06-01

    Full Text Available Este estudo avaliou a eficácia da heparina sódica e do EDTA tripotássico como anticoagulantes e seus efeitos sobre os parâmetros hematológicos de tambaqui (Colossoma macropomum. Foram utilizados dez indivíduos de tambaqui com médias de 384,9 ± 85,71 g de peso e 27,90 ± 2,10 cm de comprimento total para avaliação da heparina 5.000 UI e 100 UI, bem como do K3EDTA 10%. Foram analisados a inibição da coagulação por 10 h, eritrograma e teste de fragilidade osmótica dos eritrócitos. Os resultados foram submetidos à análise de variância e as médias comparadas pelo teste de Tukey (P 0,05 na contagem de eritrócitos, hematócrito, taxa de hemoglobina e CHCM, no entanto, houve aumento do VCM (P The efficacy of sodium heparin and tripotassium EDTA as anticoagulant and their effect on the hematological parameters of tambaqui (Colossoma macropomum were evaluated in this study. Ten fish weighing 384.9 ± 85.71 g and measuring 27.90 ± 2.10 cm were used for heparin 5.000 IU, heparin 100 IU and K3EDTA 10% evaluation. Clotting inhibition after 10 h, erythrogram and osmotic fragility of erythrocytes were observed. The results were submitted to variance analysis and means compared by Tukey test (P 0.05 in erythrocyte count, hematocrit, hemoglobin and MCHC. On the other hand, an increase in MCV (P < 0.05 in samples kept with K3EDTA10% was observed. This anticoagulant provoked a significant increase (P < 0.01 in the osmotic fragility of erythrocytes when compared to pure heparin, diluted heparin and the control group. Heparin as an anticoagulant is more appropriate for tambaqui since it was effective in preventing coagulation for more than 10 h, without causing hemolysis, changes on hematological parameters or osmotic fragility of erythrocytes.

  2. Adverse outcomes of anticoagulant use among hospitalized patients with chronic kidney disease: a comparison of the rates of major bleeding events between unfractionated heparin and enoxaparin.

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    Fatemeh Saheb Sharif-Askari

    Full Text Available BACKGROUND: Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. OBJECTIVES: To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH and enoxaparin users. METHODS: One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10-59 ml/min/1.73 m(2 who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. RESULTS: Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05-10.35]. Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113] × 10(3/µL vs 205.56 [123] × 10(3/µL; P<0.001, and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85-12.36]. Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03-6.25]; longer length of hospitalization (HR, 1.04 [95% CI, 1.01-1.06]; and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10-2.91]. CONCLUSIONS: Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.

  3. Inactivation of Heparin by Cationically Modified Chitosan

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    Barbara Lorkowska-Zawicka

    2014-06-01

    Full Text Available This study was performed to evaluate the ability of N-(2-hydroxypropyl-3-tri methylammonium chitosan chloride (HTCC, the cationically modified chitosan, to form biologically inactive complexes with unfractionated heparin and thereby blocking its anticoagulant activity. Experiments were carried out in rats in vivo and in vitro using the activated partial thromboplastin time (APTT and prothrombin time (PT tests for evaluation of heparin anticoagulant activity. For the first time we have found that HTCC effectively neutralizes anticoagulant action of heparin in rat blood in vitro as well as in rats in vivo. The effect of HTCC on suppression of heparin activity is dose-dependent and its efficacy can be comparable to that of protamine-the only agent used in clinic for heparin neutralization. HTCC administered i.v. alone had no direct effect on any of the coagulation tests used. The potential adverse effects of HTCC were further explored using rat experimental model of acute toxicity. When administered i.p. at high doses (250 and 500 mg/kg body weight, HTCC induced some significant dose-dependent structural abnormalities in the liver. However, when HTCC was administered at low doses, comparable to those used for neutralization of anticoagulant effect of heparin, no histopathological abnormalities in liver were observed.

  4. Heparin and albumin as part of the priming solution limits exposure to anticoagulation during hemodialysis: in vitro studies.

    Science.gov (United States)

    Kyrk, Tobias; Bechara, Alex; Skagerlind, Malin; Stegmayr, Bernd

    2014-10-01

    Hemodialysis patients who are subject to increased risk of hemorrhage may need specific dialysis regimes to avoid bleeding. The aim of this study was to determine in vitro which of various anticoagulation options were most beneficial. 60 in vitro hemodialyses (HD) were performed in parallel using blood from healthy donors. The dialysis circuits were rinsed with either 1 L of 0.9% NaCl alone (n = 6), or with 1 L saline and the addition of either 5 mL 20% albumin (Alb, n = 6), 5,000 U of heparin (Hep, n = 6), Hep and Alb in combination (HA, n = 30), 20,000 U of Hep and Alb (4H-A, n = 6), and finally Hep and 20 mL 20% albumin (H-4A, n = 6). The blood was recirculated for a maximum of 192 min. Clotting was graded. A 192 min dialysis was completed with all series of HA, 4H-A, and H-4A, all with a slight grade of clotting. In contrast to the above settings (p = 0.002, Fisher's test), a total clotting of the dialysis circuit occurred for all series using the NaCl rinsing alone (median time to stop: 21, range:18-27 min, p = 0.026 compared to the HA setting) and for the Alb rinsing (median 26, range: 19-35 min, p = 0.028). Priming using HA, Hep, 4H-A, and H-4A reduced clotting and allowed 192 min of HD. Clinical studies need to confirm these data in vivo.

  5. Current management of heparin-induced thrombocytopenia.

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    Cosmi, Benilde

    2015-12-01

    Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients.

  6. 肝素、低分子肝素的抗肿瘤作用研究进展%Progress on anti-tumor effect of heparin,low molecular weight heparin

    Institute of Scientific and Technical Information of China (English)

    黄礼年; 陈余清; 肖伟

    2011-01-01

    Heparin and low molecular weight heparin are anticoagulant commonly used in clinic. Recently,researches have found that it also has a variety of biological activities and clinical applications,including anti-angiogenesis and anti-tumor role. Heparin and low molecular weight heparin can interfere with tumor by changing the cellular and molecular environment of tumor cells,for example,anti-tumor cell proliferation,inhibiting proliferation of vascular endothelial cell and angiogenesis,preventing degradation of extracellular matrix and basement membrane by inhibiting the activity and role of heparanase,matrix metalloproteinase,inhibiting adhesion,invasion,and migration of tumor cells and so on.%肝素、低分子肝素是临床常用的一种抗凝药物.近年来研究发现,其还具有多种生物活性和临床用途,包括抗血管生成及抗肿瘤作用等.肝素、低分子肝素可通过改变肿瘤细胞的细胞和分子学环境而干预肿瘤的发展,例如,肝素、低分子肝素具有抗肿瘤细胞增殖作用,抑制血管内皮细胞增殖和抑制血管形成,通过抑制乙酰肝素酶、基质金属蛋白酶等酶的活性及作用阻止细胞外基质及基底膜的降解,抑制肿瘤细胞黏附及其随后向组织的侵袭、迁移等.

  7. Perioperative Considerations and Management of Patients Receiving Anticoagulants

    Science.gov (United States)

    Shaikh, Safiya Imtiaz; Kumari, R. Vasantha; Hegade, Ganapati; Marutheesh, M.

    2017-01-01

    Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles. Increasingly, anesthesiologists are being requested to anesthetize patients who are on some form of anticoagulants and hence it is important to have sound understanding of pharmacology, dosing, monitoring, and toxicity of anticoagulants. We searched the online databases including PubMed Central, Cochrane, and Google Scholar using anticoagulants, perioperative management, anesthetic considerations, and LMWH as keywords for the articles published between 1994 and 2015 while writing this review. In this article, we will review the different classes of anticoagulants and how to manage them in the perioperative settings.

  8. New parenteral anticoagulants in development.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, Maria Luisa; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Vargas-Castrillón, Emilio

    2011-02-01

    The therapeutic armamentarium of parenteral anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and safe for prevention and/or treatment of thromboembolic diseases but they have some drawbacks. Among other inconveniences, UFH requires regular anticoagulant monitoring as a result of variability in the anticoagulant response and there is a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and recombinant hirudins are mainly cleared through the kidneys and their use in patients with severe renal insufficiency may be problematic. LMWH is only partially neutralized by protamine while fondaparinux and recombinant hirudins have no specific antidote. Novel anticoagulants in development for parenteral administration include new indirect activated factor Xa (FXa) inhibitors (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). These new compounds have the potential to complement established parenteral anticoagulants. In the present review, we discuss the pharmacology of new parenteral anticoagulants, the results of clinical studies, the newly planned or ongoing clinical trials with these compounds, and their potential advantages and drawbacks over existing therapies.

  9. Low molecular weight heparin (CY-216) versus unfractionated heparin in chronic hemodialysis.

    Science.gov (United States)

    Grau, E; Sigüenza, F; Maduell, F; Linares, M; Olaso, M A; Martinez, R; Caridad, A

    1992-01-01

    In 14 patients undergoing chronic hemodialysis, we investigated the safety and efficacy of the low molecular fragment (CY-216) in comparison to unfractionated heparin (UFH) in the prevention of clotting in the extracorporeal circuit (ECC). In this study, 168 hemodialysis sessions were undertaken with UFH in 2 bolus doses (5,437 +/- 1,477 SD IU) and 231 with CY-216 in a single bolus dose [initial dose 150 anti-Xa U Institut Choay (IC)/kg]. There were no clots in the bubble trap in any UFH sessions, and 14.8% had coagulated fibers in the dialyzer. Clotting in the bubble trap was observed in 2 CY-216 sessions (0.8%) and coagulated fibers in 22.6% of the sessions. At the end of the study, the mean dose of CY-216 was 250 anti-Xa UIC/kg but a dose of 350 anti-Xa UIC/kg was needed in the 2 patients treated by recombinant human erythropoietin. Anti-Xa levels at the end of the runs were higher (0.47 +/- 0.1 U/ml) in the CY-216 group than in the UFH group (0.28 +/- 0.1 U/ml). There was a correlation between anti-Xa levels and efficacy in the CY-216 group. An anti-Xa activity above 0.4 U/ml was needed in order to minimize thrombus formation. Antithrombin III-protease complexes (ATM) and D dimer fibrin derivatives (D dimer) were used as thrombotic markers but they were of little value for the detection of fibrin formation in the ECC. Our findings suggest that CY-216 administered as a single bolus dose seems to be of similar effectiveness to UFH.

  10. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism

    NARCIS (Netherlands)

    tenCate, JW; Buller, HR; Gent, M; Hirsh, J; Prins, MH; Baildon, R; Lensing, AWA; Anderson, DR; vanBeek, EJR; Fiesinger, JN; Tijssen, JGP; vanBarneveld, A; Eimers, LT; Graafsma, YP; Hettiarachchi, R; Hutten, B; Redekop, K; Haley, S; LIberale, L; Finch, T; Whittaker, S; Wilkinson, L; Prandoni, P; Villalta, S; Girolami, B; Bagatella, P; Rossi, L; Girolami, A; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Siragusa, S; Ascari, E; Kovacs, MJ; Morrow, B; Kovacs, J; Kuijer, PMM; Koopman, MMW; Jagt, H; Weitz, J; Kearon, C; Biagioni, L; Haas, S; Lossner, F; Spengel, FA; Berger, M; Demers, C; Poulin, J; vanderMeer, J; Que, GTH; Smid, WM; Robinson, KS; Boyle, E; Leclerc, [No Value; StJacques, B; Finkenbine, S; Gallus, AS; Cohlan, D; Rich, C; Brandjes, DPM; Hoefnagel, CA; deRijk, M; Turkstra, F; Desjardins, L; CoteDesjardins, J; Couture, L; Ruel, M; Villenueve, J; Geerts, WH; Jay, RM; Code, EKI; Turpie, AGG; Johnson, J; Nguyen, P; Cusson, [No Value; Roy, S; Wells, PS; Bormanis, J; Goudie, D; Cruickshank, M; vonLewinski, M; Monreal, M; Sahuquillo, JC; Lafoz, E; Simonneau, G; Parent, F; Jagot, J; Douketis, JD; Kinnon, K; Ginsberg, JS; BrillEdwards, P; Donovan, D; Ockelford, PA; Kassis, J; Bornais, S; Planchon, B; ElKouri, D; Pistorius, MA; Escribano, M; Garrido, G; Chesterman, CN; Chong, BH; Pritchard, S; Cade, JF; Bynon, T; Stanford, J; Brien, WM; Palmer, B; Faivre, R; Petiteau, B; Manucci, PM; Moia, M; Bucciarelli, P

    1997-01-01

    Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied. Methods We randomly assigned

  11. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara;

    2015-01-01

    BACKGROUND/AIM: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. PATIENTS: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comp...

  12. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism

    NARCIS (Netherlands)

    tenCate, JW; Buller, HR; Gent, M; Hirsh, J; Prins, MH; Baildon, R; Lensing, AWA; Anderson, DR; vanBeek, EJR; Fiesinger, JN; Tijssen, JGP; vanBarneveld, A; Eimers, LT; Graafsma, YP; Hettiarachchi, R; Hutten, B; Redekop, K; Haley, S; LIberale, L; Finch, T; Whittaker, S; Wilkinson, L; Prandoni, P; Villalta, S; Girolami, B; Bagatella, P; Rossi, L; Girolami, A; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Siragusa, S; Ascari, E; Kovacs, MJ; Morrow, B; Kovacs, J; Kuijer, PMM; Koopman, MMW; Jagt, H; Weitz, J; Kearon, C; Biagioni, L; Haas, S; Lossner, F; Spengel, FA; Berger, M; Demers, C; Poulin, J; vanderMeer, J; Que, GTH; Smid, WM; Robinson, KS; Boyle, E; Leclerc, [No Value; StJacques, B; Finkenbine, S; Gallus, AS; Cohlan, D; Rich, C; Brandjes, DPM; Hoefnagel, CA; deRijk, M; Turkstra, F; Desjardins, L; CoteDesjardins, J; Couture, L; Ruel, M; Villenueve, J; Geerts, WH; Jay, RM; Code, EKI; Turpie, AGG; Johnson, J; Nguyen, P; Cusson, [No Value; Roy, S; Wells, PS; Bormanis, J; Goudie, D; Cruickshank, M; vonLewinski, M; Monreal, M; Sahuquillo, JC; Lafoz, E; Simonneau, G; Parent, F; Jagot, J; Douketis, JD; Kinnon, K; Ginsberg, JS; BrillEdwards, P; Donovan, D; Ockelford, PA; Kassis, J; Bornais, S; Planchon, B; ElKouri, D; Pistorius, MA; Escribano, M; Garrido, G; Chesterman, CN; Chong, BH; Pritchard, S; Cade, JF; Bynon, T; Stanford, J; Brien, WM; Palmer, B; Faivre, R; Petiteau, B; Manucci, PM; Moia, M; Bucciarelli, P

    1997-01-01

    Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied. Methods We randomly assigned

  13. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G; Bergholt, Thomas

    2010-01-01

    OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød ...

  14. Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey

    Directory of Open Access Journals (Sweden)

    Sabrina Bertini

    2017-07-01

    Full Text Available In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP’s broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.

  15. 局部枸椽酸钠抗凝法与肝素抗凝法在CRRT中的应用比较%Comparative study on regional citrate anticoagulation and the heparin law used in the application of CRRT

    Institute of Scientific and Technical Information of China (English)

    刘锦全; 郑志忠; 罗文晓; 蔡洧丹

    2013-01-01

    目的 比较局部枸椽酸钠抗凝法与肝素抗凝法在CRRT中的应用效果.方法 将我院2011年11月至2012年12月行CRRT治疗的126例患者随机分为两组,肝素抗凝组患者采用常规肝素抗凝方式治疗,局部枸椽酸钠抗凝组患者采用局部枸椽酸钠抗凝方式治疗.结果 治疗后局部枸椽酸钠抗凝组患者未出现高钠血症和代谢性碱中毒情况;治疗后肝素抗凝组患者的体内钙离子浓度明显下降,局部枸椽酸钠抗凝组明显上升,两组比较差异有统计学意义(P<0.05).结论 在CRRT治疗中,局部枸椽酸钠抗凝比常规肝素抗凝更有效、更安全.%Objective To compare the clinical effects of regional citrate anticoagulation with heparin sodium anticoagulation method in the application of continuous renal replacement therapy (CRRT).Methods In our hospital from November 2011 to December 2012,126 cases of C RRT were randomly divided into 2 groups,namely regional citrate anticoagulation group and heparin group.Heparin group was treated with conventional heparin anticoagulation therapy,regional citrate anticoagulation group was treated by regional citrate anticoagulation treatment.Results After treatment of regional citrate anticoagulation group patients did not appear hypernatremia and metabolic alkalosis; after treatment with heparin patients with total body calcium concentration decreased significantly,regional citrate anticoagulation group increased obviously.With comparison of the two groups,the difference was statistically significant (P<0.05).Conclusion In the treatment of CRRT,regional citrate anticoagulation is more effective and safer than heparin anticoagulation

  16. Heparina de alto peso molecular. Uma alternativa nas operações com circulação extracorpórea: estudo experimental High molecular weight heparin. An alternative in extracorporeal circulation surgery: an experimental study

    Directory of Open Access Journals (Sweden)

    Roberto CATANI

    2001-06-01

    Full Text Available Introdução: As síndromes hemorrágicas no intra e pós-operatório de operações com circulação extracorpórea (CEC constituem motivo de preocupação e, parte delas, pode ser atribuída à heparina não fracionada (HNF, droga indispensável e, até hoje, insubstituível nesse tipo de procedimento. Alguns autores consideram a ação anticoagulante da HNF como o principal responsável pelo sangramento e investem em drogas antifibrinolíticas ou que alteram a atividade plaquetária para tentar substituí-la. Toda HNF contém frações de heparina de baixo peso molecular (HBPM, não neutralizáveis pela protamina, que, em doses elevadas, e/ou em pacientes heparino-sensíveis, podem causar vasoplegia e aumento no sangramento pós-operatório em operações com CEC. Material e Métodos: Isolamos uma heparina de alto peso molecular (HAPM - peso modal de 25.000 Daltons, com 11% de frações de HBPM (Introduction: In surgical procedures, with cardiopulmonary bypass, hemorrhagic syndromes during and after pump constitute a major concern and in a great number of cases they are heparin-related, a substance still without substitute. Most authors point out the anticoagulant action of heparin as the main problem in bleeding situations and research is developing on antifibrinolytic or platelet-like- drugs to try to substitute for usual heparin. Experience with low-molecular weight heparin, without anticoagulant properties, in cardiopulmonary bypass, was disastrous. High dosage was accompanied by high tube drainage suggesting that postoperative bleeding does not happen just because of the anticoagulant effect of heparin. Material and Methods: Believing in the vascular component of hemostasis and that low-molecular weight heparin non-neutralized by protamin is responsible for the paralysis of small vessels during and after cardiopulmonary bypass surgery, we isolated a high-molecular weight heparin ( modal weight of 25.000 Daltons to be tested "in vitro

  17. Anticoagulation in pregnant women with mechanical heart valves : the new ESC guidelines

    NARCIS (Netherlands)

    Pieper, P. G.

    2012-01-01

    In pregnant women with a mechanical valve prosthesis, anticoagulation therapy is challenging because of the risk of embryopathy with vitamin K antagonists (VKA's), while unfractioned heparin and low molecular weight heparin (LMWH) are associated with a higher risk of valve thrombosis [1]. The presen

  18. A review of the two major regulatory pathways for non-proprietary low-molecular-weight heparins.

    Science.gov (United States)

    Ofosu, Frederick A

    2012-02-01

    With the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable. The FDA views LMWHs as drugs and has approved two non-proprietary (generic) LMWHs, using the Abbreviated New Drug Application pathway. In contrast, the World Health Organization and the EMA view LMWHs as biological medicines. Therefore, the EMA and also the Scientific and Standardization Subcommittee on Anticoagulation of the International Society on Thrombosis and Haemostasis and the South Asian Society of Atherosclerosis and Thrombosis have all published specific guidelines for assessing non-proprietary (biosimilar) LMWHs. This manuscript reviews why there are two distinct pathways for approving non-proprietary LMWHs. Available literature on non-proprietary LMWHs approved in some jurisdictions is also reviewed in order to assess whether they satisfy the requirements for LMWHs in the three guidance documents. The review also highlights some of the significant difficulties the two pathways pose for manufacturers and an urgent need to develop a consensus governing the manufacture and regulation of non-proprietary LMWHs to make them more widely available.

  19. Discovery of anticoagulant drugs: a historical perspective.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Calvo-Rojas, Gonzalo; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio

    2012-06-01

    The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's activity may be identified by high-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, like unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e.: argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).

  20. An outpatient program to treat deep venous thrombosis with low-molecular-weight heparin.

    Science.gov (United States)

    Pearson, S D; Blair, R; Halpert, A; Eddy, E; Mckean, S

    1999-01-01

    Although recent trials have demonstrated the safety and efficacy of low-molecular-weight (LMW) heparin, clinicians may need help incorporating this drug into routine practice. To describe the development, implementation, and early results of an outpatient LMW heparin program for acute deep venous thrombosis (DVT). Before-after study. Eight health centers of Harvard Vanguard Medical Associates, a multispecialty group practice in Boston. Patients with confirmed acute, lower-extremity DVT before (40 patients given a diagnosis from January to August 1996) and after (67 patients given a diagnosis from September 1996 to April 1997) implementation of the LMW heparin program. A centrally coordinated outpatient LMW heparin program. Hospital and HMO financial databases; electronic patient medical records. Costs of care for 2-week episodes and short-term clinical outcomes. The proportion of patients with DVT treated in the hospital decreased from 90% to 46% after the introduction of the LMW heparin program. The mean cost of treatment for all patients with DVT decreased from $5465 to $3719 per patient. For the subset of patients actually treated in the outpatient program, the average cost was $1402 per patient. There were no deaths, no clinically recognized pulmonary emboli, and no cases of significant bleeding among patients treated in the program, although 3 patients were subsequently hospitalized for worsening leg pain. The cost of caring for patients with DVT decreased after introduction of the outpatient LMW heparin program. Given explicit selection criteria, short-term clinical outcomes after outpatient management have been excellent. This program may serve as a model for physicians and health plans interested in establishing a program for treating acute DVT in the outpatient setting.

  1. New Type of Oral Anticoagulants

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2012-01-01

    Since 1960,so far,has half a century,long-term oral vitamin K antagonists (VKA) for anticoagulation main plan,but the shortcomings of the VKA but not allow to ignore:( 1 ) the VKA effect to be slow,VKA after diagnosis should be immediate treatment,this plan have to start with unfractionated heparin (UFH),low molecular weight heparin (LMWH) and fondaparinux injection,use 5 ~ 10 d transition again after oral VKA,this plan for outpatient greatly inconvenience;(2) in the use of heparin drugs there is also monitoring problem during or the occurrence of heparin induction thrombocytopenic thrombosis disease (HITT) risk;(3) VKA treatment vulnerable to food,drugs,to VKA considerations of the interference of the individual differences are of great reaction;(4)VKA treatment window,need to narrow in close monitoring of adjusting dosage benefits under,but the present survey indicates that at least a third of patients with clinically failed to control the INR within the scope of the treatment.So send development new anticoagulants,especially oral anticoagulants listed was imminent

  2. New Insights in Thrombin Inhibition Structure–Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin

    Directory of Open Access Journals (Sweden)

    Pierre A. J. Mourier

    2017-03-01

    Full Text Available Low Molecular Weight Heparins (LMWH are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin. However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity.

  3. [Preparation and antithrombogenicity of oxidated low molecular weight heparin-antithrombin complex coated-polyvinyl chloride tubing].

    Science.gov (United States)

    Luo, Peng; Liu, Weiyong; Yang, Chun; Zhou, Hua; Cao, Ruijun; Yang, Jian

    2011-02-01

    Based on non-enzymatic protein glycated reaction, the sodium periodate-oxidated low molecular weight heparin-antithrombin covalent complex (SPLMWATH) was produced. By using polyethyleneimine-glutaraldehyde bonding technique, polyvinyl chloride (PVC) tubings were coated with SPLMWATH, heparin and low molecular weight heparin (LMWH). Spectrophotometry and dynamic clotting time experiment were used to determine the synthetic ratio of SPLMWATH, graft density, coating leaching ratio and to evaluate the antithrombogenicity of different coating on the PVC tubings. The results showed that the synthetic ratio of SPLMWATH was approximately 55%, and compared with heparin coating and LMWH coating, the graft density of SPLMWATH coating on the PVC tubing was smaller, but its coating stability and antithrombogenicity were significantly better than that of heparin coating and LMWH coating on the PVC tubings.

  4. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G.; Bergholt, Thomas

    2010-01-01

    were in good health at discharge. CONCLUSIONS: Individually dosed LMWH is well tolerated and safe for prophylaxis and treatment of thromboembolic complications during pregnancy, delivery and the postpartum periodOBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH...... December 2005. METHODS: Women treated with LMWH in pregnancy were identified and individual case records reviewed retrospectively. General data on the LMWH-treated women were compared to the 18,020 untreated pregnancies within the same period and with 306 matched controls as regards to postpartum......OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hiller...

  5. Low molecular weight heparin gels, based on nanoparticles, for topical delivery.

    Science.gov (United States)

    Loira-Pastoriza, C; Sapin-Minet, A; Diab, R; Grossiord, J L; Maincent, P

    2012-04-15

    A commercial suspension of nanoparticles (Eudragit RS 30D) was used to manufacture a gel for topical application. Gels were prepared by mixing a polycationic polymer (Eudragit(®) RS 30D) and a low molecular weight heparin (LMWH), an antithrombotic agent. Gels formed spontaneously at a ratio of 1:1 as a result of electrostatic interactions between the polyanionic drug and the polycationic polymer. Different types of heparin were used: Bemiparin, Enoxaparin (Lovenox), Nadroparin (Fraxiparin) and Tinzaparin (Innohep). Several LMWH concentrations were tested. Rheological measurements were performed to investigate the gel behavior. Gel formation was confirmed by dynamic rheological measurements as the elastic modulus (G') was higher than the viscous one (G″). The amount of heparin incorporated into the gel matrix was determined. A maximum of incorporation (100%) was reached using a heparin solution of 600 IU/mL. The release kinetics of LMWH from the gel were also studied. Regardless of the LMWH used in the formulation, a biphasic release profile was observed. Accordingly, a burst effect was observed. Afterwards, the release rate became steady. The penetration of the LMWH through the dermal barrier was also investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. [Contaminated heparins].

    Science.gov (United States)

    Monneret, C

    2008-08-01

    In January 2008, following the detection of severe allergic reaction, several batches of heparins were removed from the United-States market. Although less dramatic, comparable side effects were also reported in Germany but not in France despite the fact that low-weight heparins, obtained from contaminated batches of unfractionated heparins, were used to limit shortage. So far, tainted injectable heparin has been linked to over 80 deaths in the USA. Analyses demonstrated that such tainted heparins were contaminated by high levels of chondroïtin persulfate (5-20%), a cheaper hemi-synthetic product. All batches were furnished by several Chinese chemical industries, China representing 50% of all heparins produced worldwide. Thus, contamination of the heparin supply is a worldwide problem. Following this event, the efficiency of the quality insurance, particularly analytical controls before proceeding, remains questionable. The strict respect of the pharmaceutical chain is urgently required to avoid any kind of quality problem in the future.

  7. A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia.

    Science.gov (United States)

    Skeith, Leslie; Carrier, Marc; Kaaja, Risto; Martinelli, Ida; Petroff, David; Schleußner, Ekkehard; Laskin, Carl A; Rodger, Marc A

    2016-03-31

    We performed a meta-analysis of randomized controlled trials comparing low-molecular-weight heparin (LMWH) vs no LMWH in women with inherited thrombophilia and prior late (≥10 weeks) or recurrent early (thrombophilia.

  8. Novel Experimental and Clinical Therapeutic Uses of Low-Molecular-Weight Heparin/Protamine Microparticles

    Directory of Open Access Journals (Sweden)

    Shingo Nakamura

    2012-01-01

    Full Text Available Low-molecular-weight heparin/protamine microparticles (LMW-H/P MPs were produced as a carrier for heparin-binding growth factors (GFs and for various adhesive cells. A mixture of low-molecular-weight heparin (MW: approximately 5000 Da, 6.4 mg/mL and protamine (MW: approximately 3000 Da, 10 mg/mL at a ratio of 7:3 (vol:vol yields a dispersion of microparticles (0.5–3 µm in diameter. LMW-H/P MPs immobilize, control the release and protect the activity of GFs. LMW-H/P MPs can also bind to cell surfaces, causing these cells to interact with the LMW-H/P MPs, inducing cells/MPs-aggregate formation and substantially promoting cellular viability. Furthermore, LMW-H/P MPs can efficiently bind to tissue culture plates and retain the binding of important GFs, such as fibroblast growth factor (FGF-2. The LMW-H/P MPs-coated matrix with various GFs or cytokines may provide novel biomaterials that can control cellular activity such as growth and differentiation. Thus, LMW-H/P MPs are an excellent carrier for GFs and various cells and are an efficient coating matrix for cell cultures.

  9. A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change.

    Science.gov (United States)

    Honchel, R; Carraway, J; Gopee, N; Callicott, R; Chen, J; Patton, R; Xu, Q; Zalkkar, J; Laniyonu, A; Krefting, I; Cato, M; Robie-Suh, K; Rieves, R

    2011-08-01

    The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) was revised in October 2009. This revision was anticipated, based upon in vitro tests, to reduce UFH potency by approximately 10%. To study the potential in vivo consequences of the monograph change, we evaluated activated partial thromboplastin time (aPTT) and activated clotting time (ACT) responses in animals. Female mini-pigs and monkeys (n=8/species) were administered intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg "old" (pre-USP revision) UFH, respectively, in a Williams 4×4 crossover design. Blood samples for aPTT and ACT were collected at 15 min after dosing. The same study design was then repeated using "new" (post-USP revision) UFH. Mean "new" UFH aPTT and ACT values were generally lower than those for "old" UFH although individual animal responses varied considerably. The aPTT and ACT response was generally dose-proportional for both "old" and "new" UFH. These studies indicate that the USP monograph alteration for UFH may result in a modest reduction in the anticoagulant response across a population, but the variability in animal responses underscores the importance of individualization of clinical UFH dosing and the importance of anticoagulant test monitoring. Published by Elsevier Inc.

  10. Evaluation of heparin dosing based on adjusted body weight in obese patients.

    Science.gov (United States)

    Fan, Jingyang; John, Billee; Tesdal, Emily

    2016-10-01

    Results of a study to determine whether heparin dosing based on adjusted body weight (BWAdj) instead of actual body weight (ABW) can lead to faster achievement of therapeutic activated partial thromboplastin time (aPTT) values in obese patients are presented. A single-center retrospective cohort study was conducted to assess aPTT outcomes before and after implementation of a revised heparin protocol specifying BWAdj-based dosing for obese patients. The primary outcome was the percentage of first aPTT values within the target range after heparin initiation. Secondary outcomes included the median time to the first on-target aPTT and the rate of clinically significant bleeding. After protocol implementation, there was no significant difference between obese and nonobese patients in the primary outcome (17% and 21%, respectively, had first aPTT values in the target range) or in the median time to achieve the first on-target aPTT value. Among obese patients, on-target aPTT values were achieved significantly faster with BWAdj-versus ABW-based dosing (14 hours versus 24 hours, p = 0.002). Prior to implementation of BWAdj-based heparin dosing, obese patients had a higher rate of clinically significant bleeding than nonobese patients (11% versus 1%, p = 0.01); postimplementation bleeding rates did not differ significantly. The percentages of first aPTT values in the targeted range did not differ significantly in obese and nonobese patients before and after protocol implementation. The use of BWAdj for dose calculation in obese patients was associated with faster achievement of an aPTT value in the target range. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  11. A whole blood flow cytometric determination of platelet activation by unfractionated and low molecular weight heparin in vitro.

    Science.gov (United States)

    Klein, Bernd; Faridi, Andreé; von Tempelhoff, G F; Heilmann, Lothar; Mittermayer, Christian; Rath, Werner

    2002-12-15

    The influence of unfractionated (Heparin-Natrium) and low-molecular heparin (Fragmin(R)) on platelet activation in whole blood was investigated by FACS analysis in vitro using antibodies against glycoprotein (gp) IIb/IIIa (CD 41), GMP 140 (CD 62P), gp 53 (CD 63) and fibrinogen. Samples were also labeled with anti-gp Ib (CD 42b). Neither unfractionated heparin (UFH) nor low molecular weight heparin (LMWH) led to significant (i.e., p<0.05) changes in fluorescence intensities of platelets labeled with anti-gp IIb/IIIa or anti-gp 53. Significant platelet activation due to unfractionated heparin could be observed by labeling with anti-GMP 140 (UFH: p=0.009; LMWH: p=0.16). The proportion of platelets with surface-bound fibrinogen was significantly increased (UFH: p=0.00006; LMWH: p=0.008). After incubation with heparins, activation ability of platelets by adenosine diphosphate (ADP) was significantly increased. The potentiating action of unfractionated heparin was larger. Therefore, flow cytometric results of platelet activation in patients receiving heparin should be interpreted carefully.

  12. [Preparation of patients on anticoagulant treatment for invasive surgery].

    Science.gov (United States)

    Brejcha, M; Gumulec, J; Penka, M; Klodová, D; Wróbel, M; Bogoczová, E

    2009-03-01

    The management of warfarin therapy in patients undergoing surgery or other invasive procedures involves a balance between the risk of hemorrhage, and the risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of procedure and on pre-existing conditions. Procedures with low risk of hemorrhage (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need stop warfarin and start bridging anticoagulant therapy, such as unfractionated heparin or low molecular weight heparin, prior and after surgery. In patients requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh frozen plasma can be used to improve coagulation.

  13. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

    DEFF Research Database (Denmark)

    Rasmussen, Morten Schnack; Jørgensen, Lars Nannestad; Wille-Jørgensen, Peer

    2009-01-01

    AND ANALYSIS: The identification of studies and data extraction were performed by the authors. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcome were defined as bleeding complications and mortality within 3 months after surgery. MAIN RESULTS: The search exclusively detected trials...... significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery.......BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery...

  14. In vitro evaluation of heparinized cuprophan hemodialysis membranes

    NARCIS (Netherlands)

    Hinrichs, W.L.J.; Hinrichs, W.L.J.; ten Hoopen, Hermina W.M.; Engbers, G.H.M.; Feijen, Jan

    1997-01-01

    Cuprophan hemodialysis membranes can be heparinized using N,N-carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics of heparinized Cuprophan membranes have been evaluated. After immobilization, heparin partially retained its biologic activity. An anticoagulant activity of

  15. In vitro evaluation of heparinized Cuprophan hemodialysis membranes

    NARCIS (Netherlands)

    Hinrichs, W.L.J.; Hoopen, ten H.W.M.; Engbers, G.H.M.; Feijen, J.

    1996-01-01

    Cuprophan hemodialysis membranes can be heparinized using N,N-carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics of heparinized Cuprophan membranes have been evaluated. After immobilization, heparin partially retained its biologic activity. An anticoagulant activity of

  16. Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis.

    Directory of Open Access Journals (Sweden)

    Wilma Potze

    Full Text Available BACKGROUND: Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known. OBJECTIVES: We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis. PATIENTS/METHODS: Thirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs. RESULTS: Addition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001. The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma. CONCLUSIONS: The anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis.

  17. Heparin and Lovenox: What the Oral and Maxillofacial Surgeon Needs to Know.

    Science.gov (United States)

    Pasquale, LisaMarie Di; Ferneini, Elie M

    2016-11-01

    For the oral and maxillofacial surgeon, many patients will be on heparin products during surgery. So far, there is no standardized approach to treating anticoagulated patients during oral and maxillofacial surgical procedures. When a patient is on heparin therapy, heparin may be stopped 4 to 6 hours before surgery and resumed once hemostasis is achieved, usually within 24 hours. If low-molecular-weight heparin is administered, the treatment is generally stopped at least 12 hours before surgery and then resumed in a similar fashion. Local measures are generally enough to provide adequate hemostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Structural and binding studies of SAP-1 protein with heparin.

    Science.gov (United States)

    Yadav, Vikash K; Mandal, Rahul S; Puniya, Bhanwar L; Kumar, Rahul; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2015-03-01

    SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. © 2014 John Wiley & Sons A/S.

  19. 肝素杂化材料的制备及抗凝血性质的初步研究%Preparation and Preliminary Study of Anticoagulant Properties of Heparin Hybrid Materials

    Institute of Scientific and Technical Information of China (English)

    宋玉民; 缐萍; 李清萍; 张玉梅; 马新贤; 张强; 王怡云

    2011-01-01

    以甲苯二异氰酸酯(TDI)中的-NCO基与纳米金属氧化物表面的羟基发生反应,得到改性纳米金属氧化物,并使其与肝素钠(Heparin)进行接枝反应生成肝素杂化材料,结合红外、热重、扫描电镜(SEM)等表征方法,确定纳米金属氧化物确实接枝到了肝素钠的表面.通过对体外凝血时间和复钙时间的测定,来初步研究肝素杂化材料的抗凝血性质.结果表明:肝素杂化材料的抗凝血时间和复钙时间均比肝素钠的要短,表明它的抗凝血性比肝素钠的抗凝血性要弱一些;但比纳米金属氧化物和空白组的抗凝血时间和复钙时间要长,说明肝素杂化材料的抗凝血性与其相比则有明显的提高.%Heparin hybrid materials were obtained by the grafting reaction of heparin and modified metal oxide nanoparticles, which were synthsized by the reaction between the TDIs NCO group and the hydroxyl group on the surface of nano metal oxides, and characterized by infrared spectra, thermogravimetry, scanning electron microscopy (SEM). The anticoagulant effect of hybrid materials were studied by the measurements of coagulation time (CT) and recalcification time (RT). The results showed that nano metal oxides were indeed grafted on the heparin. Compared to heparin, the coagulation time and recalcification time of heparin hybrid materials is shorter, but longer than the corresponding nano metal oxides and control group. In conclusion, the heparin hybrid materials were successfully prepared, and can shorten anti-coagulation time of heparin, prolong anti-coagulation time of nano metal oxides.

  20. [Implementing ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity].

    Science.gov (United States)

    Kock, H J; Schmit-Neuerburg, K P; Hanke, J; Terwort, A; Rudofsky, G; Hirche, H

    1994-12-01

    Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively treated outpatients with plaster cast immobilisation of the leg (n = 163 control group without prophylaxis). By application of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n = 176) was reduced to 0% (p = 0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg.

  1. Low-molecular weight heparin versus vitamin K antagonists for the treatment of cancer-associated thrombosis: A cost-effectiveness analysis.

    Science.gov (United States)

    Connell, Nathan T; Abel, Gregory A; Connors, Jean M

    2017-02-01

    Cancer-associated venous thromboembolism (VTE) is primarily treated with low-molecular weight heparin (LMWH), a strategy based on studies showing it to be superior to the vitamin K antagonist (VKA) warfarin for preventing VTE recurrence. Subsequent analyses suggest that the magnitude of this benefit might be less than previously determined. Neither patient-focused measures of utility nor the costs of each strategy have been evaluated in the current treatment era. This is a cost-effectiveness analysis of VKA and LMWH for the treatment of cancer-associated thrombosis through use of a microsimulation model of outcomes for competing anticoagulation management strategies from a 2014 United States societal perspective. LMWH therapy added 0.27 QALYs relative to VKA treatment with an ICER of $217,007. One-way sensitivity analysis evaluating the utility of LMWH revealed that VKA was always the preferred strategy at a willingness to pay (WTP) threshold of $100,000 per QALY. Limitations include that the model incorporates a low VKA time in therapeutic range (TTR) and that the TTR in some centers may be higher thereby increasing the cost-effectiveness of the VKA strategy. Utilities for anticoagulation strategies were not derived from cancer patients, and preference is known to vary depending on how anticoagulation method is integrated with cancer treatment. Our findings suggest that compared to LMWH, warfarin is a more cost-effective strategy to treat cancer-associated VTE. Although LMWH is associated with a modest increase in life expectancy, this increase comes at significant cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Low-molecular-weight heparin biosimilars: potential implications for clinical practice. Australian Low-Molecular-Weight Heparin Biosimilar Working Group (ALBW).

    Science.gov (United States)

    Nandurkar, H; Chong, B; Salem, H; Gallus, A; Ferro, V; McKinnon, R

    2014-05-01

    A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme.

  3. Differentiating low-molecular-weight heparins based on chemical, biological, and pharmacologic properties: implications for the development of generic versions of low-molecular-weight heparins.

    Science.gov (United States)

    Jeske, Walter P; Walenga, Jeanine M; Hoppensteadt, Debra A; Vandenberg, Curtis; Brubaker, Aleah; Adiguzel, Cafer; Bakhos, Mamdouh; Fareed, Jawed

    2008-02-01

    Low-molecular-weight heparins (LMWHs) are polypharmacologic drugs used to treat thrombotic and cardiovascular disorders. These drugs are manufactured using different chemical and enzymatic methods, resulting in products with distinct chemical and pharmacologic profiles. Generic LMWHs have been introduced in Asia and South America, and several generic suppliers are seeking regulatory approval in the United States and the European Union. For simple small-molecule drugs, generic drugs have the same chemical structure, potency, and bioavailability as the innovator drug. Applying this definition to complex biological products such as the LMWHs has proved difficult. One major issue is defining appropriate criteria to demonstrate bioequivalence; pharmacopoeial specifications alone appear to be inadequate. Whereas available generic versions of LMWHs exhibit similar molecular and pharmacopoeial profiles, marked differences in their biological and pharmacologic behavior have been noted. Preliminary studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release after subcutaneous administration, as well as antiplatelet and profibrinolytic effects. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs with complex structures and activities and also underscore the importance of further pharmacologic studies involving animal models and human clinical trials. The U.S. Food and Drug Administration and the European Medicine Evaluation Agency are currently developing guidelines for the acceptance of biosimilar agents including LMWHs. Until such guidelines are complete, generic interchange may not be feasible.

  4. 21 CFR 864.7525 - Heparin assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Heparin assay. 864.7525 Section 864.7525 Food and... HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7525 Heparin assay. (a) Identification. A heparin assay is a device used to determine the level of the anticoagulant heparin in the...

  5. PHARMACOKINETIC PARAMETERS TO BE EVALUATED FOR SELECTED LOW MOLECULAR WEIGHT HEPARINs IN BIOEQUIVALENCE STUDIES

    Directory of Open Access Journals (Sweden)

    Chaitanya Gadiko*, Satyanarayana Thota and Sudhakar K. Tippabotla

    2012-11-01

    Full Text Available Bioequivalence needs to be established on healthy human volunteers for Low Molecular Weight Heparins (LMWHs such as Dalteparin, Enoxaparin, Tinzaparin and Fondaparinux using Pharmacodynamic marker(s for generic approval. Anti-Xa and anti-IIa activity are used to determine the activity of LMWHs (Dalteparin, Enoxaparin and Tinzaparin and anti-Xa activity for Fondaparinux in biological samples for the assessment of its bioavailability. These are selected based on the pharmacodynamic activities of LMWHs. LMWHs exhibit their antithrombotic activity preferentially by inhibiting clotting Factor Xa, and to a lesser extent Factor IIa. On the other hand Fondaparinux is a synthetic and specific inhibitor of Factor-Xa and hencebioequivalence needs to be established for only anti-Xa activity. The pharmacodynamic data of anti-IIa activity need to be submitted for regulatory agency as supportive data of comparable therapeutic outcome for all LMWHs except Fondaparinux. In addition to the above, pharmacokinetic data of Heptest (Heparin clotting assay and activated Partial Thromboplastin Time (aPTT may also serve as a supportive evidence for establishing bioequivalence of LMWH formulations as there were no clear recommendations available.

  6. Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives - An In Silico Approach.

    Science.gov (United States)

    Borkotoky, Subhomoi; Meena, Chetan Kumar; Murali, Ayaluru

    2016-01-01

    The single subunit T7 RNA polymerase (T7RNAP) is a model enzyme for studying the transcription process and for various biochemical and biophysical studies. Heparin is a commonly used inhibitor against T7RNAP and other RNA polymerases. However, exact interaction between heparin and T7RNAP is still not completely understood. In this work, we analyzed the binding pattern of heparin by docking heparin and few of its low molecular weight derivatives to T7RNAP, which helps in better understanding of T7RNAP inhibition mechanism. The efficiency of the compounds was calculated by docking the selected compounds and post-docking molecular mechanics/generalized Born surface area analysis. Evaluation of the simulation trajectories and binding free energies of the complexes after simulation showed enoxaparin to be the best among low molecular weight heparins. Binding free energy analysis revealed that van der Waals interactions and polar solvation energy provided the substantial driving force for the binding process. Furthermore, per-residue free energy decomposition analysis revealed that the residues Asp 471, Asp 506, Asp 537, Tyr 571, Met 635, Asp 653, Pro 780, and Asp 812 are important for heparin interaction. Apart from these residues, most favorable contribution in all the three complexes came from Asp 506, Tyr 571, Met 635, Glu 652, and Asp 653, which can be essential for binding of heparin-like structures with T7RNAP. The results obtained from this study will be valuable for the future rational design of novel and potent inhibitors against T7RNAP and related proteins.

  7. Use of anticoagulants in elderly patients: practical recommendations

    Directory of Open Access Journals (Sweden)

    Helia Robert-Ebadi

    2009-04-01

    Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa

  8. Feasibility Analysis of the Heparin Anticoagulant Blood Plasma Used for Emergency Biochemical Test%肝素抗凝血浆用于急诊生化检验的可行性分析

    Institute of Scientific and Technical Information of China (English)

    邓春凤

    2015-01-01

    目的:分析肝素抗凝血浆用于急诊生化检验的可行性。方法以医院130例受检者为研究对象,常规采集静脉血6 ml,均分分别注入普通干燥管(血清组)和肝素钠抗凝管(血浆组)中,观察两组患者生化检验结果。结果两组患者Na+、K+、GLU、GGT检验结果比较差异具有统计学意义(P<0.05);剩余生化检验指标结果比较差异无统计学意义(P>0.05)。结论肝素抗凝血浆具有分离血浆速度快、抗凝能力强的优点,在急诊生化检验中具有高的应用价值。%Objective To analyze heparin anticoagulant blood plasma used for biochemical test the feasibility of the emergency.Methods 130 cases of patients as the research objects,routine venous blood was colected 6 ml,half-and-half respectively devided into ordinary drying tube(serum) and heparin anticoagulant tube(plasma),biochemical test results were observed of two groups of patients.ResultsInspection results of Na+, K+,GLU,GGT in two groups of patients,the differences had statisticaly significant(P0.05).Conclusion The heparin anticoagulant blood plasma has fast separation of plasma,the advantages of the anticoagulant ability, in the emergency biochemical test has higher application value.

  9. Spontaneous Hemocholecyst in an End-Stage Renal Failure Patient on Low Molecular Weight Heparin Hemodialysis

    Directory of Open Access Journals (Sweden)

    Konstantinos Blouhos

    2012-01-01

    Full Text Available The present paper describes a case of spontaneous hemocholecyst in a patient with end-stage renal failure on low molecular weight heparin hemodialysis. The patient presented with acute right upper quadrant pain. An initial ultrasound scan demonstrated a distended gallbladder containing echogenic bile without stones. During hospitalization the patient became febrile, and jaundiced, developed leukocytosis, and had an elevation in serum bilirubin, transaminases, and alkaline phosphatase. A new ultrasound demonstrated a thick-walled gallbladder containing echogenic bile and pericholecystic fluid. MRI depicted a distended gallbladder containing material of mixed signal intensity and a normal biliary tract. Open cholecystectomy revealed a gallbladder filled with blood and clots, and transcystic common bile duct exploration flushed blood clots out of the bile duct. To our knowledge this is the second case of spontaneous hemocholecyst reported in the literature as a consequence of uremic bleeding and LMWH hemodialysis in the absence of other pathology.

  10. LOW MOLECULAR WEIGHT HEPARIN ENHANCES THE EFFECT OF aFGF IN ACCELERATING NEOVASCULA- RIZATION

    Institute of Scientific and Technical Information of China (English)

    陈书艳; 荣烨之; 吕宝经; 赵美华; 张建军

    2003-01-01

    Objective To explore the potential of low molecular weight heparin (LMWH) in combination cooperated with aFGF in accelerating neovascularization in vivo. Methods Ischemic model was set up in the right hindlimbs of 28 New Zealand white rabbits. Four groups of animals treated with saline, LMWH, aFGF and aFGF plus LMWH were allocated equally in group Ⅰ, group Ⅱ, group Ⅲ and group Ⅳ respectively. Vascular neovascularization and smooth muscular thickness of the ischemic hindlimb vessels of each animal in different groups were compared with each other on the 28th day postoperatively by angiography with DSA and the standard immunoperoxidase technique. Results No significant neovascularization was seen when aFGF adiministered in low dosage by venous infusion. But when the same dosage of aFGF plus LMWH were administered by venous infusion, a significant neovascularization was observed. Conclusion LMWH can potentiate aFGF in accelerating neovascularization.

  11. Unfractionated and low-molecular-weight heparin and the phosphodiesterase inhibitors, IBMX and cilostazol, block ex vivo Equid Herpesvirus type-1-induced platelet activation

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    2016-11-01

    Full Text Available Equid herpes virus type-1 (EHV-1 is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins or platelet inhibitors that impede post-receptor thrombin signaling (phosphodiesterase [PDE] antagonists would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque forming unit/cell in the presence or absence of unfractionated heparin (UFH, low-molecular-weight (LMWH heparin or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1 to 0.2 U/mL anti-Factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX or isoenzyme-3 selective (cilostazol PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  12. Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters.

    Science.gov (United States)

    Glusa, E; Barthel, W; Schenk, J; Radziwon, P; Butti, A; Markwardt, F; Breddin, K H

    1998-01-01

    In a phase I trial effects of a new supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters were investigated in healthy volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and anti-activated factor X (anti-FXa) activity, platelet adhesion, platelet count, platelet-induced thrombin generation time (PITT), bleeding time, antithrombin III, fibrinogen and several safety parameters. After single intravenous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest and PITT were strongly and dose-dependently prolonged. After ascending subcutaneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and PITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumulative effects were observed. Anti-FIIa and anti-FXa activity were not or only slightly increased. Bleeding time, thrombin time and platelet adhesion were not significantly changed after i.v. and s.c. injections of IK-SSH. However, tissue factor pathway inhibitor (TFPI) concentration was markedly increased after each injection of IK-SSH and returned to the preinjection value 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting thrombin time, FIIa and FXa activity. The release of TFPI may well be responsible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.

  13. Strategies for managing heparin therapy in patients with antiphospholipid antibody syndrome.

    Science.gov (United States)

    Mehta, Trupti P; Smythe, Maureen A; Mattson, Joan C

    2011-12-01

    Antiphospholipid antibody syndrome (APS) is a common acquired thrombophilia. The diagnosis of APS is based on both clinical and laboratory criteria. The clinical criteria include vascular thrombosis or pregnancy morbidity. The laboratory criteria include a positive test for lupus anticoagulant, anticardiolipin antibodies, or anti-β(2)-glycoprotein I (anti-β(2)GPI) antibodies on two or more occasions at least 12 weeks apart. Antiphospholipid antibodies with lupus anticoagulant activity may prolong phospholipid-dependent coagulation tests such as the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT). This prolongation adds a level of complexity to monitoring heparin therapy in patients with APS who have thrombosis. A literature search of the PubMed database was conducted for relevant articles published from 1995-April 2011. The usual management approach in nonsurgical patients with APS is to switch to low-molecular-weight heparin. In patients in whom heparin remains the agent of choice, management options include monitoring heparin antifactor Xa levels, determining an individualized therapeutic aPTT range, targeting an aPTT goal of 2 times the baseline aPTT, or using an aPTT reagent insensitive to lupus anticoagulant. An algorithm for anticoagulation management in nonsurgical patients with APS who require heparin is provided. The strategies to monitor intraoperative heparin in patients undergoing cardiac surgery include measuring heparin concentrations by an automated protamine titration device, targeting twice the baseline ACT, using preoperative in vitro heparin-ACT titration curves, and measuring heparin antifactor Xa levels. The available published case reports on the use of these strategies are reviewed. Each institution should determine an approach to managing heparin in patients with APS that best meets its needs and resources.

  14. Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature.

    Science.gov (United States)

    Myzienski, April E; Lutz, Mark F; Smythe, Maureen A

    2010-03-01

    Unfractionated heparin infusion therapy is often administered using a weight-based dosing strategy for the treatment of venous thromboembolism. In the last several decades, the prevalence of obesity in the United States has increased significantly. The applicability of weight-based heparin dosing recommendations in the obese and morbidly obese population is uncertain, as limited data are available. We describe a 388-kg man who was started on an intravenous infusion of heparin according to hospital protocol for suspected pulmonary embolism. The patient was given a 5000-unit heparin bolus followed by an initial heparin infusion rate of 1500 units/hour, the maximum initial rate specified in the protocol. After additional infusion rate adjustments, a therapeutic activated partial thromboplastin time (aPTT) was reached 55 hours later with a heparin infusion rate of 3650 units/hour. Due to concerns of heparin-induced thrombocytopenia, heparin therapy was discontinued, and fondaparinux 5 mg/day was started. However, heparin therapy was restarted 4 days later for persistent, refractory hypoxemia and recurrent concerns of possible pulmonary embolism. During this second course, a therapeutic aPTT was achieved with a heparin infusion rate of 3550 units/hour. The patient developed bloody pulmonary secretions (with a therapeutic aPTT), necessitating the discontinuation of the heparin infusion. The patient later died after developing pulseless electrical activity. Standard weight-based heparin dosing protocols that specify maximum doses for initial bolus and infusion rates can result in significant delays in time to achieve therapeutic anticoagulation in the obese and morbidly obese patient. Despite limited data on heparin dosing in obesity, we recommend the use of a dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients. It is reasonable to consider one of the following formulas: dosing weight = ideal body weight (IBW

  15. Effect of Low Molecular Weight Heparins (LMWHs on antiphospholipid Antibodies (aPL-mediated inhibition of endometrial angiogenesis.

    Directory of Open Access Journals (Sweden)

    Silvia D'Ippolito

    Full Text Available Antiphospholipid syndrome (APS is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL. Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with β2-glycoprotein I (β2GPI makes them adhere to trophoblast and human endometrial endothelial cell (HEEC membranes. β2GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH. Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind β2GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i in vitro HEEC angiogenesis through a Matrigel assay; (ii VEGF secretion by ELISA; (iii matrix metalloproteinase-2 (MMP-2 activity by gelatin zymography; (iv Nuclear Factor-κB (NF-κB DNA binding activity by colorimetric assay; (v STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-κB and/or STAT-3 activity, the VEGF secretion and the MMPs activity.The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis

  16. Microvesicles of pregnant women receiving low molecular weight heparin improve trophoblast function.

    Science.gov (United States)

    Shomer, Einat; Katzenell, Sarah; Zipori, Yaniv; Rebibo-Sabbah, Annie; Brenner, Benjamin; Aharon, Anat

    2016-01-01

    Microvesicles including exosomes and microparticles, participate in the placental-maternal crosstalk in normal pregnancies and gestational vascular complications (GVC). Low molecular weight heparin (LMWH) is known to reduce the risk of placenta-mediated pregnancy complications. This study was aimed to characterize microvesicles of pregnant women receiving LMWH and explore microvesicle involvement in trophoblast and endothelial cell function. Microvesicles were isolated from blood samples obtained from non-pregnant women, healthy pregnant women (HP) and pregnant woman treated with LMWH. Microvesicle protein contents were assessed by protein array and ELISA. Microvesicle effects on early stage trophoblasts, term trophoblasts and endothelial cell migration, angiogenesis and apoptosis were evaluated. Microvesicles derived from the group treated with LMWH contained higher levels of several proangiogenic proteins compared to those of HP women. Exposure of endothelial cells to circulating microvesicles derived from HP and LMWH treated groups induced significantly higher cell migration and branch tube formation compared to untreated cells. The effect of microvesicles from HP- and LMWH groups on early-stage trophoblast migration was similar. Microvesicles derived from these two study groups significantly decreased early-stage trophoblast apoptosis, while microvesicles derived from the HP-group (but not from the LMWH-group) significantly increased the term trophoblast apoptosis (TUNEL assay) compared to untreated cells. Therapy with LMWH affects patients' microvesicle content, leading to normalization of invasion, angiogenesis activity and survival of endothelial and trophoblast cells in vitro. The effects of LMWH on microvesicles may point to an additional mechanism of heparin action in high-risk pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Low molecular weight heparin alters porcine neutrophil responses to platelet-activating factor.

    Science.gov (United States)

    Kruse-Elliott, K T; Chaban, K; Grossman, J E; Tomasko, S; Kamke, C; Darien, B

    1998-09-01

    Because platelet-activating factor (PAF) is an important mediator of inflammation and heparin has anti-inflammatory effects, we hypothesized that low molecular weight heparin (LMWH) would inhibit PAF-induced activation and chemotaxis in porcine neutrophils. Citrated blood was obtained from pentobarbital-anesthetized pigs, and neutrophils were isolated over a 55%/65% Percoll gradient. The effect of LMWH on basal phorbol myristate acetate (PMA)-induced superoxide (SO) release, as well as its effect on PAF priming for PMA-induced SO release, were investigated. Additionally, the effect of LMWH on PAF-induced chemotaxis of neutrophils across transwell membranes was evaluated. Baseline SO release in response to PMA was .351+/-.046 nmol/10(6) cells/min, and this was decreased to .289+/-.034 nmol/10(6) cells/min by pretreatment with 50 U/mL LMWH. PMA-induced SO production was increased by .240+/-.042 nmol/10(6) cells/min when cells were primed with 10 microM PAF. This priming effect of PAF was reduced significantly by pretreatment of neutrophils with LMWH at 10 and 50 U/mL. Chemotaxis of neutrophils in response to 100 microM PAF was significantly decreased to 70.02+/-6.4% (n = 8) of the control response by pretreatment of cells with 50 U/mL LMWH. We conclude that LMWH has anti-inflammatory effects on porcine neutrophils, which includes attenuation of cell activation and chemotaxis in response to the lipid-derived inflammatory mediator, PAF.

  18. Perioperative management of the chronically anticoagulated patient.

    Science.gov (United States)

    Heit, J A

    2001-09-01

    Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.

  19. [Bridging: Perioperative management of chronic anticoagulation or antiplatelet therapy].

    Science.gov (United States)

    Nowak-Göttl, U; Langer, F; Limperger, V; Mesters, R; Trappe, R U

    2014-06-01

    Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective in preventing thromboembolic diseases. In case of interventional of surgical procedures patients with indications for chronic anticoagulation [atrial fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet agents [cerebrovascular events, cardiovascular events] will require interruption of antithrombotic/antiplatelet therapy with the need of replacement with a short-acting agent. Due to limited data available from randomized studies and meta-analyses the evidence level is low in the majority of recommendations. Therefore for each patient the bleeding and thrombosis risk depending on the individual patient constitution and the planned intervention must be weighted. In patients with an intermediate risk for thrombosis the bleeding risk of the scheduled intervention will influence the bridging recommendation: In patients with a low bleeding risk oral anticoagulation/antiplatelet therapy can be continued or reduced in intensity. In patients with an intermediate or high bleeding risk along with a low thrombosis risk a temporary interruption of the anticoagulation/antiplatelet therapy is feasible. In patients with a high thrombosis and bleeding risk anticoagulation should be bridged with unfractionated heparin [renal insufficiency] or low molecular weight heparin. In the latter risk situation, inhibition of platelet function can be achieved with short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to intervention patients treated with the new oral anticoagulants [Dabigatran; Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation depending on the individual drug half-life and their renal function. Bridging therapy with heparin prior to intervention is not necessary with the new oral anticoagulants.

  20. Solute clearance effect of citrate anticoagulation hemodialysate for hemodialysis in patients with high risk of bleeding

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To study the solute clearance effect of the new concentrated anticoagulation hemodialysate of citrate for hemodialysis in patients with high risk of bleeding. Methods Forty-two kidney failure patients with high risk of bleeding were divided into two groups (Group A and Group B) according to their hemodialysis manners. Patients in Group A were hemodialyzed with bicarbonate hemodialysate with low-molecular-weight heparin (dalteparin) anticoagulation and those in Group B with the new citrate anticoag...

  1. Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yizhao Li; Guixiang Cui; Qingde Wang; Hongxia Liu; Xiaoxia Zhang; Fengshan Wang; Keqin Xie

    2009-01-01

    BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect.OBJECTIVE: To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 (IL-6) overexpressing mice following local cerebral ischemia.DESIGN, TIME AND SETTING: Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005.MATERIALS: Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups: sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice.Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University.METHODS: Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxicle dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment.MAIN OUTCOME MEASURES: The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy (x200).RESULTS: In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger

  2. Extraction of Anticoagulant Compound from Persian Gulf sea anemone Stichodactyla haddoni

    Directory of Open Access Journals (Sweden)

    Mahdeah Tahmasebi

    2015-07-01

    Full Text Available Background: The marine environment is anexceptional reservoir of bioactive natural products, many of them exhibit structural/chemical features that not found in terrestrial natural products.Glycosaminoglycans are one of this various bioactive compounds. Heparin, as a well known glycosaminoglycan, is a sulfated glycosaminoglycan that has natural anticoagulant properties. Heparin and heparin-like compounds are used as anticoagulants in many aspects of medicine. However, for two main reasons: 1. Contamination in heparin samples obtained from pig intestine or bovine lung pathogens and other pathogens, 2 .resource for use of heparin is limited and there are a lot of requirements for new compounds from natural resources. According to GAGs importance and widespread using of heparin in medicine, in the present study, GAGs compounds extracted from sea anemones and anticoagulant properties of the human blood is investigated. Materials and Methods: GAGs compound was extracted by using cetylpyridinium chloride. Anticoagulation activity of extracted GAGs (the extracted tentacle was tested in human blood plasma, using manual procedures, and assay system, prothrombin time (PT and activated partial thromboplastin time (APTT. Results: In this study the amount of the crude GAGs was 24 mg per gram of tentacle dry weight. The results ofanticoagulant activity extracted on human blood plasma showed that these compounds prolonged clotting time compared to the control. In APTT and PT assay of the extracted GAGs from the sea anemone also clotting time prolonged in compared to the control. Conclusion: The results demonstrated that anticoagulant compounds existed in the tentacle of the sea anemone, and although their effects is weaker than the heparin, but they can be substituted for heparin, at least in laboratory conditions.

  3. New anticoagulant strategies in ST elevation myocardial infarction: Trials and clinical implications

    Directory of Open Access Journals (Sweden)

    Conor J McCann

    2008-04-01

    Full Text Available Conor J McCann, Ian BA MenownCraigavon Cardiac Centre, Craigavon Area Hospital, Craigavon, Northern Ireland, UKAbstract: New data have re-established the importance of anticoagulation of patients with ST segment elevation myocardial infarction (STEMI, both as an adjuvant to reperfusion therapy or in patients ineligible for reperfusion. Recent randomized trials have found newer agents to be superior to conventional unfractionated heparin. This article summarizes current understanding of the underlying pathophysiology of STEMI and provides a comprehensive review of emerging trial data for low molecular weight heparins, anti-factor Xa agents and direct thrombin inhibitors in this setting.Keywords: myocardial infarction, treatment, anticoagulants

  4. Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo.

    Science.gov (United States)

    Mellor, P; Harvey, J R; Murphy, K J; Pye, D; O'Boyle, G; Lennard, T W J; Kirby, J A; Ali, S

    2007-09-17

    Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; PLMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases.

  5. A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

    Science.gov (United States)

    Kaiser, B; Glusa, E; Hoppensteadt, D A; Breddin, H K; Amiral, J; Fareed, J

    1998-09-01

    Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

  6. Antibody profile of pregnant women with antiphospholipid syndrome and pregnancy outcome after treatment with low dose aspirin and low-weight-molecular heparin.

    Science.gov (United States)

    Glasnović, Marija; Bosnjak, Ivica; Vcev, Aleksandar; Soldo, Ivan; Kosuta, Maja; Lenz, Bahrija; Glasnović-Horvatić, Elizabeta; Soldo-Butković, Silva; Mićunović, Nikola

    2007-03-01

    The aim of the research was to show our diagnostic and therapeutic experience with antiphospholipid syndrome (APS) in pregnant women. 36 pregnant women suspect on APS were included in the study: 32 with primary antiphospholipd syndrome (PAPS) and 4 with secondary antiphospholipid syndrome (SAPS). All pregnant women received low-molecular-weight-heparin (LMWH) and low dose aspirin (LDA) therapy. Control group represented 26 women with SAPS and previous bad reproductive anamnesis. Average pregnancy lasted 37.06 +/- 0.707 weeks. LMWH and LDA therapy was successful in 97.22%. Lupus anticoagulant (LA) was found to be more frequent in PAPS group (71.87%). Anticardiolipin antibodies (aCL) were found to be more frequent in SAPS (26.66%). For three patients (3.37%), PAPS was diagnosed due to a fact that they had positive antibeta2-glycoproteinl (antibeta-GP1). To make APS diagnosis, it is of great importance to search for all antiphospholipid antibodies. LMWH and low dose of acetylsalicylic acid should be the first choice therapy.

  7. Angiogenic efficacy of Heparin on chick chorioallantoic membrane

    Directory of Open Access Journals (Sweden)

    Rema Reji

    2012-04-01

    Full Text Available Abstract Heparin is an anticoagulant agent known to have diverse effects on angiogenesis with some reports suggesting that it can induce angiogenesis while a few have indicated of its inhibitory property. Cancer patients treated for venous thromboembolism with low molecular heparin had a better survival than the unfractionated heparin (UFH. Heparin is known to interact with various angiogenic growth factors based on its sulfation modifications within the glycosaminoglycan chains. Therefore it is important to study the mechanism of action of heparin of different molecular weight to understand its angiogenic property. In this concern, we examined the angiogenic response of higher molecular weight Heparin (15 kDa of different concentrations using late CAM assay. Growth of blood vessels in terms of their length and size was measured and thickness of the CAM was calculated morphometrically. The observed increase in the thickness of the CAM is suggestive of the formation of capillary like structures at the treated region. Analysis of the diffusion pattern showed internalized action of heparin that could affect gene expression leading to proliferation of endothelial cells. Angiogenesis refers to formation of new blood vessels from the existing ones and occurrence of new blood vessels at the treated area strongly confirms that heparin of 15 kDa molecular weight has the ability to induce angiogenesis on CAM vascular bed in a dose dependent manner. The results demonstrate the affinity of heparin to induce angiogenesis and provide a novel mechanism by which heparin could be used in therapeutics such as in wound healing process.

  8. LUPUS ANTICOAGULANTS: PATHOPHYSIOLOGY, CLINICAL AND ...

    African Journals Online (AJOL)

    2003-11-02

    Nov 2, 2003 ... clinical, laboratory, pathophysiology and management. Only data relevant to the ... pulmonary hypertension, heparin related ... anticoagulant effect of beta 2 factor Xa. .... with severe valvular heart disease in patients with and.

  9. Efficacy and Safety of Low Molecular Weight Heparin Prophylaxis for Venous Thromboembolism Following Lumbar Decompression Surgery

    Institute of Scientific and Technical Information of China (English)

    Zhi-jian Sun; Xiang Li; Yu Zhao; Giu-xing Qiu; Yi-peng Wang; Xi-sheng Weng; Hong Zhao; Jian-xiong Shen; Yu Jiang; Ye Li

    2011-01-01

    Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaris for venous thromboembolism (VTE) after lumbar decompression surgery.Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study.All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge.We recorded incidences of deep venous thrombosis (DVT),pulmonary embolism (PE),bleeding complications,and medication side effects.Results Seventy-eight consecutive patients were eligible and enrolled in this study.The mean hospital stat was 8.5+4.5 days.No symptomatic DVT,PE,or major bleeding events were observed.One patient developed wound ecchymosis,another developed wound bleeding,four had mild hepatic aminotransferase level elevation,and one developed a suspicious allergic reaction.Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression surgery.

  10. Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia.

    Science.gov (United States)

    Selmeczi, Anna; Roach, Rachel E J; Móré, Csaba; Batta, Zoltán; Hársfalvi, Jolán; van der Bom, Johanna G; Boda, Zoltán; Oláh, Zsolt

    2015-02-01

    Pregnancy is associated with increased risk of venous thromboembolism, especially in the presence of thrombophilia. However, there is no consensus on the optimal approach for thromboprophylaxis in this population. Recent evidence suggests that thrombin generation correlates with the overall procoagulant state of the plasma. Our aim was to evaluate thrombin generation in a prospective cohort of thrombophilic pregnant women, and investigate the effectiveness of low-molecular-weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies. Thrombin generation was evaluated in each trimester as well as five days and eight weeks postpartum (as a reference category). In women undergoing LMWH prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration (peak effect). Thrombin generation was determined using Technothrombin TGA assay system. For the analysis, median peak thrombin and endogenous thrombin potential were used. Peak thrombin and endogenous thrombin potential were increased during pregnancy compared to the non-pregnant state with the highest results in the severe thrombophilia group. In women receiving LMWH prophylaxis a decrease was observed in thrombin generation at peak effect but over the progression of pregnancy the extent of this decrease reduced in a stepwise fashion. Our results show that thrombin generation demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition, we found the effect of LMWH prophylaxis to progressively decrease with advancing stages of pregnancy.

  11. Low molecular weight heparin (enoxaparin) reverses pregangrene in a preterm neonate.

    Science.gov (United States)

    Gohil, Jayendra R; Solanki, Dhaval I; Vaghjiyani, Lalji

    2009-01-01

    A 34-week-old, 1.6 kg preterm boy was admitted for management of mild respiratory distress syndrome. On the third day of life 1 min after an intravenous cannulation attempt at the right cubital fossa, he developed pregangrene bluish discoloration of all fingertips up to the distal interphalangial joint and pallor of right palm. Pulsations on right forearm were reduced. There was no evidence of sepsis.Enoxaparin, a low molecular weight heparin (1.5 mg/kg (standard dose)) was injected subcutaneously in the abdomen in two doses 12 h apart within 2 h of the event. At 6 h after the first dose, brachial artery pulsation was bilaterally symmetrical. After the second dose, bilateral radial artery pulsation became symmetrical. The pregangrene changes returned to normal within 20 h as the distal phalanges became pink and warm. He was discharged on the eighth day of life. Enoxaparin was safe and effective in this preterm infant for reversal of pregangrene.

  12. Absolute and comparative subcutaneous bioavailability of ardeparin sodium, a low molecular weight heparin.

    Science.gov (United States)

    Troy, S; Fruncillo, R; Ozawa, T; Mammen, E; Holloway, S; Chiang, S

    1997-08-01

    Ardeparin sodium (Normiflo, Wyeth-Ayerst) is a low molecular weight heparin undergoing clinical evaluation as an antithrombotic agent. The objective of this study was to evaluate the absolute and comparative bioavailability of ardeparin following subcutaneous administration of three different formulations [two formulations of ardeparin at 10,000 anti-factor Xa (aXa) U/ml, but with different preservatives, and a 20,000 aXa U/ml formulation]. The study was conducted using a randomized 4-period crossover design (three subcutaneous treatments and one intravenous treatment) in 24 healthy subjects, and the pharmacokinetics of ardeparin were characterized by plasma anti-factor IIa (aIIa) and anti-factor Xa (aXa) activities. The mean absolute bioavailability of ardeparin based on aIIa activity ranged from 62% to 64% and the mean absolute bioavailability based on aXa activity ranged from 88% to 97%. Based on bioequivalence testing criteria, the three ardeparin formulations were bioequivalent.

  13. Proteomics analysis of human umbilical vein endothelial cells (HUVEC) after treatment with low molecular weight heparin

    Institute of Scientific and Technical Information of China (English)

    YanPAN; Jun-huaWANG; He-mingYU; Xue-junLI

    2004-01-01

    AIM: The endothelium is involved in the generation and the regulation of multiple physiological and pathological processes of blood vessels. Previously we confirmed low molecular weight heparin (LMWH) could inhibit tumor metastasis by protecting human umbilical vein endothelial cells (HUVEC). To understand the effects of LMWH on the protein expression of HUVEC, we performed a comprehensive proteomics to survey global changes in proteins after LMWH treatment in HUVEC cells. METHODS:

  14. Effect of low molecular weight heparin in combined with Shuxuetong in preventing the post-traumatic deep venous thrombosis

    Institute of Scientific and Technical Information of China (English)

    Li-Mian Xu

    2016-01-01

    Objective:To observe the effect of low molecular weight heparin in combined with Shuxuetong in preventing the post-traumatic deep venous thrombosis (DVT).Methods:A total of 120 patients with post-traumatic DVT who were admitted in our hospital from February, 2014 to February, 2015 were included in the study and divided into the treatment group and the control group with 60 cases in each group according to different treatment protocols. The patients in the treatment group were given subcutaneous injection of low molecular weight heparin calcium and intravenous drip of Shuxuetong, while the patients in the control group were only given subcutaneous injection of low molecular weight heparin calcium. The changes of swelling degrees and coagulation indicators of the affected limb before and after treatment, and the clinical efficacy in the two groups were compared.Results:The total effective rate in the treatment group was significantly higher than that in the control group. The mean range of the perimeter 15cm above and below the bilateral knee joints after treatment in the treatment group was significantly lower than that in the control group. The shrinking rate of the mean range of the perimeter of the bilateral limbs in the treatment group was significantly higher than that in the control group. The comparison of PT, APTT, FIB, and INR before treatment between the two groups was not statistically significant. PT, APTT, and INR after treatment in the treatment group were significantly higher than those in the control group, while FIB was significantly lower than that in the control group.Conclusions:The low molecular weight heparin in combined with Shuxuetong can effectively prevent the post-traumatic DVT, with no requirement of monitoring of the bleeding tendency and safety.

  15. 肝素诱导的血小板减少症患者体外循环抗凝管理%Anticoagulation Management in Patients with Heparin-induced Thrombocytopenia Undergoing Extracorporeal Circulation

    Institute of Scientific and Technical Information of China (English)

    周伯颐

    2012-01-01

    Patients with heparin-induced thrombocytopenia have a poor prognosis and high mortality, thus surgical risk under extracorporeal circulation increased. Early diagnosis, safe and effective alternative anticoagulation strategy are crucial for these patients to receive extracorporeal circulation surgery. This review focuses on the pathophysiology, laboratory examination, diagnosis and alternative anticoagulation strategy of extracorporeal circulation for patients with heparin-induced thrombocytopenia.%肝素诱导的血小板减少症患者预后差,病死率高,大大增加了体外循环手术的风险.对其早期诊断和选择一种安全有效的药物替代肝素抗凝是这类患者接受体外循环手术的关键.我们对肝素诱导的血小板减少症发病机制、实验室检查、诊断以及体外循环抗凝管理进行综述.

  16. Anticoagulation for Prosthetic Valves

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Kaneko

    2013-01-01

    Full Text Available Implantation of prosthetic valve requires consideration for anticoagulation. The current guideline recommends warfarin on all mechanical valves. Dabigatran is the new generation anticoagulation medication which is taken orally and does not require frequent monitoring. This drug is approved for treatment for atrial fibrillation and venous thromboembolism, but the latest large trial showed that this drug increases adverse events when used for mechanical valve anticoagulation. On-X valve is the new generation mechanical valve which is considered to require less anticoagulation due to its flow dynamics. The latest study showed that lower anticoagulation level lowers the incidence of bleeding, while the risk of thromboembolism and thrombosis remained the same. Anticoagulation poses dilemma in cases such as pregnancy and major bleeding event. During pregnancy, warfarin can be continued throughout pregnancy and switched to heparin derivative during 6–12 weeks and >36 weeks of gestation. Warfarin can be safely started after 1-2 weeks of discontinuation following major bleeding episode.

  17. 采用肝素钠抗凝血浆测定电解质可行性分析%The Feasibility Analysis Concerning Using Heparin Sodium Anticoagulation Plasma To Assay Electrolyte

    Institute of Scientific and Technical Information of China (English)

    许祖林; 易彩响; 鲁海平; 陈桃丽; 谭琼

    2012-01-01

    Objective: To Probe into the feasibility of using the heparin sodium anticoagnlation plasma instead of serum by comparing with direct electrode method to assay the difference of electrolyte concentration between in the serum and in the heparin sodium anticoagulation plasma. Methods : Using the 9886 type electrolyte analyzer made by Shenzhen Hangchuang to assay the electrolyte concentration of the patient' s serum and heparin sodium anticoagulation plasma, and doing statistic analysis. Result: The result differences of testing Potassium, Sodium between in serum and in plasma is statistically significant; and the result differences of testing Chlorine between in serum and in plasma is not statistically significant. But the results of testing Potassium, Sodium and Chlorine between in both has good correlation, and all of the coefficient of this correlation is over or equal to 0. 975, and the biases of measured value about Potassium, Sodium and Chlorine between both of the specimens are not beyond the allowable error based on 1/2 CLIA' 88. Conclusion: It is feasible to assay Potassium, Sodium, Chlorine with the heparin sodium anticoagulation plasma instead of the serum, but should establish a corresponding conversion system.%目的:比较用电极直接法测定血清和肝素钠抗凝血浆电解质浓度的差异,探讨肝素钠抗凝血浆代替血清检测电解质的可行性。方法:用深圳航创9886型电解质分析仪测定患者血清和肝素钠抗凝血浆的电解质浓度并进行统计分析。结果:血浆与血清钾、钠测定结果差异具有统计学意义,血浆与血清氯测定结果差异无统计学意义,但血浆与血清钾、钠、氯的测定结果具的很好的相关性,相关性系数(r)均〉10.975,且两种标本钾、钠、氯测定值平均偏倚均没有超出1/2CLIA’88允许误差。结论:行肝素钠抗凝血浆代替血清测定钾、钠、氯是可行的,但应建立相应的换算体系。

  18. Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism

    Institute of Scientific and Technical Information of China (English)

    WU Jun-ping; SUN Xin; WU Qi; DU Zhong-zhen; LI Li; WU Qian; SUN Hong-fen

    2013-01-01

    Background Pulmonary embolism (PE) is a common and often fatal disease.Early after pulmonary thromboembolism,inflammation and associated intimal hyperplasia occur within the pulmonary arteries,similar to what is observed with chronic thromboembolic pulmonary hypertension.This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.Methods Seventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group).Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography,and other 18 rabbits underwent sham operations.Fifty-four rabbits in the PE group were randomly divided into three groups:a control group (treated with normal saline),a low-molecularweight heparin (LMWH) group (treated with LMWH),and a urokinase (UK) group (treated with UK).Arterial blood gas was analyzed at 2,7,and 28 days (n=6 per time point by random group division),then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines,and were stained for intimal hyperplasia.Results The overall survival of rabbits undergoing PE was 100%.PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs).The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group.Compared with controls,the UK group had a decreased level of PA-aO2 on day 2 (P <0.05),however,there was no significant difference in the LMWH group.Compared with controls,the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P <0.05),and the UK group had

  19. Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

    Science.gov (United States)

    McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

    2017-01-01

    Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

  20. The effect of low molecular weight heparin thromboprophylaxis on bleeding complications after gastric cancer surgery.

    Science.gov (United States)

    Jeong, Oh; Ryu, Seong Yeop; Park, Young Kyu; Kim, Young Jin

    2010-09-01

    Low molecular weight heparin (LMWH) has been widely used to prevent venous thromboembolism in cancer surgical patients. However, relatively few studies have examined the safety aspects related to the use of LMWH after abdominal cancer surgery. This study was designed to investigate the relationship between bleeding complications and LMWH thromboprophylaxis after gastric cancer surgery. From March to July in 2009, 179 consecutive patients who underwent gastric cancer surgery at our institution were administered LMWH (3200 U once daily from 2 to 6 h before surgery until discharge) perioperatively. A total of 182 patients consecutively treated before the introduction of LMWH prophylaxis were selected as controls. There were 234 men and 127 women (mean age, 60 +/- 12 years). No significant intergroup differences were observed with respect to clinicopathological features and operative procedures. No patient in the LMWH or control group developed symptomatic venous thromboembolism postoperatively. However, the LMWH group had a significantly higher surgical complication rate (27.4 versus 15.4%, P = 0.005). Among the surgical complications, postoperative bleeding and wound complications were significantly higher in the LMWH group, whereas other complications were similar in the two study groups. Multivariate analysis showed that LMWH administration was an independent risk factor (odds ratio, 2.83; 95% confidence interval, 1.28-6.23, P = 0.009) of postoperative bleeding. LMWH thromboprophylaxis was found to increase significantly the risk of bleeding complications after gastric cancer surgery. Optimal LMWH prophylaxis regimens, including the dosage and timing of treatment commencement, for gastric cancer surgery should be determined in further clinical trials.

  1. Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action

    Directory of Open Access Journals (Sweden)

    Qudsia Rashid

    2015-01-01

    Full Text Available Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants have been approved, including various forms of heparin. However, the polyanionic nature and multispecificity of heparin pose several complications. Generally, the polysulfated compounds with antithrombotic potential are thought to have feasible synthetic procedures with much less bleeding, thus having favourable safety profiles. Here we report the synthesis of a novel compound, trehalose octasulfate and the assessment of its anticoagulation potential. Molecular docking of trehalose and trehalose octasulfate with antithrombin showed a specificity switch in binding affinity on sulfation, where trehalose octasulfate interacts with critical residues of AT that are either directly involved in heparin binding or in the conformational rearrangement of AT on heparin binding. An in vitro analysis of trehalose octasulfate demonstrated prolonged clotting time. Lead compound when intravenously injected in occlusion induced thrombotic rats showed remarkable reduction in the size and weight of the clot at a low dose. Delay in coagulation time was observed by analysing blood plasma isolated from rats preinjected with trehalose octasulfate. A decrease in Adenosine 5′-Diphosphate (ADP induced platelet aggregation indicated a probable dual anticoagulant and antiplatelet mechanism of action. To summarize, this study presents trehalose octasulfate as a novel, effective, dual acting antithrombotic agent.

  2. Value Analysis of Heparin Anticoagulant Plasma in the Emergency Biochemical Test%肝素抗凝血浆用于急诊生化检验的价值分析

    Institute of Scientific and Technical Information of China (English)

    柳宝忠

    2015-01-01

    Objective To explore the feasibility of heparin anticoagulant plasma in the emergency biochemical test. Methods We select 40 cases of patients in our hospital from January to July in 2014 who need emergency biochemical test and collect from them 40 copies of blood specimens,each of which is divided evenly into routine plasma group and heparin anticoagulant plasma group.The two groups of specimens are tested under routine examination and theresults are compared. Results According to the results,it is of significant difference in testing K+、Na+、Clu but not in Cl-、Ca2+、Mg2+、Bun、ALT、Cr、AST between the two groups. Conclusion Heparin anticoagulant plasma is of more efficency in the emergency biochemical test and can be a substitute for routine plasma.%目的:探究肝素抗凝血浆用于急诊生化检验的可行性。方法选择我院于2014年1月~2014年7月期间收治的40例需急诊生化检验的患者,采集血液标本40份,每份标本分成两份,分别为常规血清组和肝素抗凝剂血浆组。按常规检测方法检测,并比较检验结果。结果检测结果显示,在K+、Na+、Clu等方面,组间差异显著;在Cl-、Ca2+、Mg2+、Bun、ALT、Cr、AST等方面,组间差异不显著。结论肝素抗凝血浆检测速度快,可代替常规血清进行生化检验项目检测。

  3. Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases

    Directory of Open Access Journals (Sweden)

    Giulio Illuminati, MD

    2016-01-01

    Conclusions: These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions.

  4. Vein wall remodeling after deep vein thrombosis: differential effects of low molecular weight heparin and doxycycline.

    Science.gov (United States)

    Sood, Vikram; Luke, Cathy; Miller, Erin; Mitsuya, Mayo; Upchurch, Gilbert R; Wakefield, Thomas W; Myers, Dan D; Henke, Peter K

    2010-02-01

    Venous thrombus resolution sets up an early intense inflammatory reaction, from which vein wall damage results. Tissue response to injury includes matrix metalloproteinase (MMP) activation and extracellular matrix protein turnover. This study sought to determine the effect of exogenous MMP inhibition and its potential attenuation of early vein wall injury. Rats received treatment beginning 24 hr after a stasis venous thrombosis by near occlusive ligation and until harvest at day 7. Three groups were evaluated: (1) vehicle saline controls (NaCl), (2) low molecular weight heparin (LMWH; Lovenox, 3 mg/kg daily SQ), and (3) doxycycline (DOXY, 30 mg/kg daily PO). Thrombus size (mg/mm), levels of tumor necrosis factor alpha (TNF alpha) and D-dimer by colorimetric assay, and monocytes counts by immunohistochemistry were assessed. Vein wall assessment included stiffness by tensiometry, interleukin 1beta (IL-1 beta protein levels by enzyme-linked immunosorbent assay, MMP2 and -9 by zymography, and histological analysis of intimal thickness (IT). Comparisons were by t-test to control. p DOXY-treated groups (NaCl = 1.0 +/- 0.8, LWMH = 9 +/- 3, DOXY = 27 +/- 5 pg/mg protein, n = 6-8, p DOXY group (NaCl = 3.0 +/- 2.5, DOXY = 23 +/- 4.2 pg/mg protein, n = 5, p DOXY, compared to controls (NaCl = 0.33 +/- 0.05, LMWH = 0.17 +/- 0.03, DOXY = 0.43 +/- 0.09 N/mm, n = 5-7, p DOXY group at 7 days (NaCl = 26 +/- 3, LMWH = 38 +/- 17, DOXY = 6 +/- 3 pg/mg protein, n = 4-6, p DOXY = 0.8 +/- 0.20, n = 4-6, p DOXY groups (NaCl = 85 +/- 24, LMWH = 23 +/- 7( *), DOXY = 13 +/- 5 U/mg protein, n = 6-8, p DOXY did not alter the size of deep vein thrombosis, mildly altered thrombus composition, and differentially affected vein wall injury, despite similar reductions in early MMP9 activity. Whether exogenous MMP inhibition affects long-term vein wall fibrosis will require further study. Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  5. Prevention and treatment of venous thromboembolism with low-molecular-weight heparins: Clinical implications of the recent European guidelines

    Directory of Open Access Journals (Sweden)

    Prandoni Paolo

    2008-09-01

    Full Text Available Abstract Venous thromboembolism (VTE is an important cause of avoidable morbidity and mortality. However, routine prophylaxis for at-risk patients is underused. Recent guidelines issued by an international consensus group, including the International Union of Angiology (IUA, recommend use of low-molecular-weight heparins (LMWHs for the treatment of acute VTE and prevention of recurrence, and for prophylaxis in surgical and medical patients. This review highlights current inadequacies in the provision of thromboprophylaxis, and considers the clinical implications of the European guidelines on the prevention and treatment of VTE.

  6. pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fan, Bo; Xing, Yang; Zheng, Ying; Sun, Chuan; Liang, Guixian

    2016-01-01

    The aim of present study was to investigate a pH-responsive and mucoadhesive nanoparticle system for oral bioavailability enhancement of low-molecular weight heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to chitosan (CS) with 396.97 ± 54.54 μmol thiol groups per gram of polymer and then the nanoparticles were prepared with thiolated chitosan (TCS) and pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross-linking method. The obtained nanoparticles were characterized for the shape, particle size, zeta potential, drug entrapment efficiency and loading capacity. In vitro results revealed the acid stability of pH-responsive nanoparticles, which had a significant control over LMWH release and could effectively protect entrapped drugs in simulated gastric conditions. By the attachment of the thiol ligand, an improvement of permeation-enhancing effect on freshly excised carp intestine (1.86-fold improvement) could be found. The mucoadhesive properties were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared with the controls, a significant improvement of mucoadhesion on rat intestinal mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning microscopy. The activated partial thromboplastin time (APTT) was significantly prolonged and an increase in the oral bioavailability of LMWH was turned out to be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats, which suggested enhanced anticoagulant effects and improved absorption of LMWH. In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral delivery of LMWH.

  7. Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells.

    Science.gov (United States)

    Takeuchi, Akihiko; Yamamoto, Yasuhiko; Munesue, Seiichi; Harashima, Ai; Watanabe, Takuo; Yonekura, Hideto; Yamamoto, Hiroshi; Tsuchiya, Hiroyuki

    2013-06-01

    The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and its engagement by ligands such as high mobility group box 1 (HMGB1) is implicated in tumor growth and metastasis. Low molecular weight heparin (LMWH) has an antagonistic effect on the RAGE axis and is also reported to exert an antitumor effect beyond the known activity of anticoagulation. However, the link between the anti-RAGE and antitumor activities of LMWH has not yet to be fully elucidated. In this study, we investigated whether LMWH could inhibit tumor cell proliferation, invasion, and metastasis by blocking the RAGE axis using in vitro and in vivo assay systems. Stably transformed HT1080 human fibrosarcoma cell lines were obtained, including human full-length RAGE-overexpressing (HT1080(RAGE)), RAGE dominant-negative, intracellular tail-deleted RAGE-overexpressing (HT1080(dnRAGE)), and mock-transfected control (HT1080(mock)) cells. Confocal microscopy showed the expression of HMGB1 and RAGE in HT1080 cells. The LMWH significantly inhibited HMGB1-induced NFκB activation through RAGE using an NFκB-dependent luciferase reporter assay and the HT1080 cell lines. Overexpression of RAGE significantly accelerated, but dnRAGE expression attenuated HT1080 cell proliferation and invasion in vitro, along with similar effects on local tumor mass growth and lung metastasis in vivo. Treatment with LMWH significantly inhibited the migration, invasion, tumor formation, and lung metastasis of HT1080(RAGE) cells, but not of HT1080(mock) or HT1080(dnRAGE) cells. In conclusion, this study revealed that RAGE exacerbated the malignant phenotype of human fibrosarcoma cells, and that this exacerbation could be ameliorated by LMWH. It is suggested that LMWH has therapeutic potential in patients with certain types of malignant tumors. © 2013 Japanese Cancer Association.

  8. Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.

    Science.gov (United States)

    Burr, Nick; Lummis, Katie; Sood, Ruchit; Kane, John Samuel; Corp, Aaron; Subramanian, Venkataraman

    2017-02-01

    Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with

  9. The platelet proaggregating and potentiating effects of unfractionated heparin, low molecular weight heparin and heparinoid in intensive care patients and healthy controls

    NARCIS (Netherlands)

    Burgess, J K; Chong, B H

    1997-01-01

    Heparin binds to platelets and can cause platelet proaggregating and potentiating effects, possibly causing thrombocytopenia, particularly in patients in intensive care with hyperaggregable platelets. In this study we compared the platelet proaggregating and potentiating effects of unfractionated he

  10. [Ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity].

    Science.gov (United States)

    Kock, H J; Schmit-Neuerburg, K P; Hanke, J; Hakmann, A; Althoff, M; Rudofsky, G; Hirche, H

    1993-06-01

    Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study on patients with minor injuries incidence of DVT in conservatively treated out-patients with plaster cast immobilisation of the leg was 3.9% in the control group (n = 126) without prophylaxis. By s.c. self-application of LMV heparin once daily the number of DVT in the prophylaxis group (n = 115) was reduced to 0. No severe side effects of NMH were observed. We conclude that thromboprophylaxis with LMW heparin once daily up to now conspiciously reduced the risk of DVT in outpatients with plaster cast immobilisation of the leg.

  11. [The role of new oral anticoagulants].

    Science.gov (United States)

    Pierard, Luc; Sprynger, Muriel

    2014-08-27

    New oral anticoagulants (NOACs) are going to deeply modify the treatment of non valvular atrial fibrillation and thromboembolic disease. They are non-inferior to warfarin and trials show a similar bleeding rate (even lower for some NOACs). Nevertheless one must be cautious when dealing with patients at risk (elderly patients, frail ones, renal or liver impairment...) and practicians must be well aware of doses and contraindications. NOACs' long- term tolerance is not yet well-known. In cancer, their benefit-risk ratio compared to low molecular weight heparin remains to be determined.

  12. Heparin pharmacovigilance in Brazil.

    Science.gov (United States)

    Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

    2011-01-01

    To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

  13. Development of a recombinant antithrombin variant as a potent antidote to fondaparinux and other heparin derivatives.

    Science.gov (United States)

    Bianchini, Elsa P; Fazavana, Judicael; Picard, Veronique; Borgel, Delphine

    2011-02-10

    Heparin derivative-based therapy has evolved from unfractionated heparin (UFH) to low-molecular-weight heparins (LMWHs) and now fondaparinux, a synthetic pentasaccharide. Contrary to UFH or LMWHs, fondaparinux is not neutralized by protamine sulfate, and no antidote is available to counteract bleeding disorders associated with overdosing. To make the use of fondaparinux safer, we developed an antithrombin (AT) variant as a potent antidote to heparin derivatives. This variant (AT-N135Q-Pro394) combines 2 mutations: substitution of Asn135 by a Gln to remove a glycosylation site and increase affinity for heparins, and the insertion of a Pro between Arg393 and Ser394 to abolish its anticoagulant activity. As expected, AT-N135Q-Pro394 anticoagulant activity was almost abolished, and it exhibited a 3-fold increase in fondaparinux affinity. AT-N135Q-Pro394 was shown to reverse fondaparinux overdosing in vitro in a dose-dependent manner through a competitive process with plasma AT for fondaparinux binding. This antidote effect was also observed in vivo: administration of AT-N135Q-Pro394 in 2.5-fold molar excess versus plasma AT neutralized 86% of the anti-Xa activity within 5 minutes in mice treated with fondaparinux. These results clearly demonstrate that AT-N135Q-Pro394 can reverse the anticoagulant activity of fondaparinux and thus could be used as an antidote for this drug.

  14. Current Trends in Heparin Use During Arterial Vascular Interventional Radiology

    Energy Technology Data Exchange (ETDEWEB)

    Durran, Alexandra C., E-mail: durranjobs@hotmail.com [Peninsula Radiology Academy, Plymouth International Business Park (United Kingdom); Watts, Christopher, E-mail: Christopher.watts@salisbury.nhs.uk [Salisbury District Hospital (United Kingdom)

    2012-12-15

    Purpose: This study was designed to assess the current use of heparinized saline and bolus doses of heparin in non-neurological interventional radiology and to determine whether consensus could be reached to produce guidance for heparin use during arterial vascular intervention. Methods: An interactive electronic questionnaire was distributed to members of the British Society of Interventional Radiology regarding their current practice in the use, dosage, and timing of heparin boluses and heparinized flushing solutions.ResultsA total of 108 completed questionnaires were received. More than 80% of respondents used heparinized saline with varying concentrations; the most prevalent was 1,000 IU/l (international units of heparin per liter) and 5,000 IU/l. Fifty-one percent of interventionalists use 3,000 IU as their standard bolus dose; however, the respondents were split regarding the timing of bolus dose with {approx}60% administering it after arterial access is obtained and 40% after crossing the lesion. There was no consensus on altering dose according to body weight, and only 4% monitored clotting parameters. Conclusions: There seems to be some coherence among practicing interventionalists regarding heparin administration. We hypothesize that heparinized saline should be used at a recognized standard concentration of 1,000 IU/l as a flushing concentration in all arterial vascular interventions and that 3,000 IU bolus is considered the standard dose for straightforward therapeutic procedures and 5000 IU for complex, crural, and endovascular aneurysm repair work. The bolus should be given after arterial access is obtained to allow time for optimal anticoagulation to be achieved by the time of active intervention and stenting. Further research into clotting abnormalities following such interventional procedures would be an interesting quantifiable follow-up to this initial survey of opinions and practice.

  15. SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

    Directory of Open Access Journals (Sweden)

    E.A. Nemets

    2012-01-01

    Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

  16. Antitumor properties of a new non-anticoagulant heparin analog from the mollusk Nodipecten nodosus: Effect on P-selectin, heparanase, metastasis and cellular recruitment.

    Science.gov (United States)

    Gomes, Angélica Maciel; Kozlowski, Eliene Oliveira; Borsig, Lubor; Teixeira, Felipe C O B; Vlodavsky, Israel; Pavão, Mauro S G

    2015-04-01

    Inflammation and cancer are related pathologies acting synergistically to promote tumor progression. In both, hematogenous metastasis and inflammation, P-selectin participates in interactions involving tumor cells, platelets, leukocytes and endothelium. Heparin has been shown to inhibit P-selectin and as a consequence it blunts metastasis and inflammation. Some heparin analogs obtained from marine invertebrates are P-selectin inhibitors and do not induce bleeding effects. The present work focuses on the P-selectin blocking activity of a unique heparan sulfate (HS) from the bivalve mollusk Nodipecten nodosus. Initially, we showed that the mollusk HS inhibited LS180 colon carcinoma cell adhesion to immobilized P-selectin in a dose-dependent manner. In addition, we demonstrated that this glycan attenuates leukocyte rolling on activated endothelium and inflammatory cell recruitment in thioglycollate-induced peritonitis in mice. Biochemical analysis indicated that the invertebrate glycan also inhibits heparanase, a key player in cell invasion and metastasis. Experimental metastasis of Lewis lung carcinoma cells was drastically attenuated by the mollusk HS through a mechanism involving inhibition of platelet-tumor-cell complex formation in blood vessels. These data suggest that the mollusk HS is a potential alternative to heparin for inhibiting P-selectin-mediated events such as metastasis and inflammatory cell recruitment.

  17. [Antiplatelet agents and anticoagulants: management of the anticoagulated surgical patient].

    Science.gov (United States)

    Llau, Juan V; Ferrandis, Raquel; López Forte, Cristina

    2009-06-01

    Among the drugs most widely consumed by patients are both antiplatelet agents (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin, low molecular weight heparin, fondaparinux). The use of these drugs in the perioperative period is an essential concern in patient care due to the need to balance the risk of bleeding against thrombotic risk (arterial or venous), which is increased in surgical patients. The present review highlights three main aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week and 10 days before surgery to minimize perioperative bleeding. However, this practice has been questioned because patients without the required antiplatelet coverage may be at greater risk of developing cardiac, cerebral or peripheral vascular complications. Therefore, the recommendation of systematic antiplatelet withdrawal for a specific period should be rejected. Currently, risks should be evaluated on an individual basis to minimize the time during which the patient remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is required in most surgical patients due to the high prevalence of venous thromboembolic disease. This implies the use of anticoagulants and the practice of regional anesthesia has been questioned in these patients. However, with the safety recommendations established by the various scientific societies, this practice has been demonstrated to be safe. Finally, "bridge therapy" in patients anticoagulated with acenocoumarol should be performed on an individual basis rather than systematically without taking into account the thrombotic risks of each patient. The perioperative period involves high arterial and venous thrombotic risk and the optimal use of antiplatelet agents and anticoagulants should be a priority to minimize this risk without increasing hemorrhagic risk. Multidisciplinary consensus is essential on this matter.

  18. Diffuse Alveolar Hemorrhage Associated With Low Molecular Weight Heparin and Dual Anti-platelet Therapy After Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yildirim, Fatma; Kara, İskender; Okuyan, Hızır; Abaci, Adnan; Turkoglu, Melda; Aygencel, Gülbin

    2016-01-19

    A 54-year-old man had undergone to percutaneous coronary intervention (PCI) and two stents were placed to left anterior coronary artery and circumflex artery. Low molecular weight heparin (LMWH) together with ticagrelor 90 mg twice a day and acetylsalicylic acid (Aspirin) were started after PCI due to high risk of stent trombosis. On the fourth day of patient's follow-up in the intensive care unit (ICU), bloody secretion was started from endotracheal tube. Hemoglobin dropping, bilateral infiltration on the chest X-ray and bleeding from lung were diagnosed as diffuse alveolar hemorrhage (DAH). Apart from LMWH and antiplatelet therapies with aspirin and ticagrelor, there were no other identified risk factors for DAH. As far as we know, our report is the first case of DAH caused by LMWH and dual anti-platelet therapy including ticagrelor. This article is protected by copyright. All rights reserved.

  19. Sterilization of heparinized cuprophan hemodialysis membranes

    NARCIS (Netherlands)

    ten Hoopen, Hermina W.M.; Hinrichs, W.L.J.; Hinrichs, W.L.J.; Engbers, G.H.M.; Feijen, Jan

    1996-01-01

    The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated.

  20. Heparin sensing: Blue-chip binding

    Science.gov (United States)

    Shriver, Zachary; Sasisekharan, Ram

    2013-08-01

    Heparin is an anionic polysaccharide that has tremendous clinical importance as an anticoagulant. Several dyes have been developed that can detect heparin, and the latest example -- named Mallard Blue -- has now been shown to have excellent sensing properties under biologically relevant conditions.

  1. A photoacoustic tool for therapeutic drug monitoring of heparin (Conference Presentation)

    Science.gov (United States)

    Wang, Junxin; Hartanto, James; Jokerst, Jesse V.

    2017-03-01

    Heparin is used broadly in cardiac, pulmonary, surgical, and vascular medicine to treat thrombotic disorders with over 500 million doses per year globally. Despite this widespread use, it has a narrow therapeutic window and is one of the top three medication errors. The active partial thromboplastin time (PTT) monitors heparin, but this blood test suffers from long turnaround times, a variable reference range, and limited utility with low molecular weight heparin. Here, we describe an imaging technique that can monitor heparin concentration and activity in real time using photoacoustic spectroscopy via methylene blue as a simple and Federal Drug Agency-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood (R2>0.90). Clinically relevant concentrations were detected in blood with a heparin detection limit of 0.28 U/mL and a low molecular weight heparin (enoxaparin) detection limit of 72 μg/mL. We validated this imaging approach by correlation to the PTT (Pearson's r = 0.86; p<0.05) as well as with protamine sulfate treatment. To the best of our knowledge, this is the first report to use imaging data to monitor anticoagulation.

  2. Preparation, Properties and Preclinical Pharmacokinetics of Low Molecular Weight Heparin-modified Isoliquiritigenin-loaded Solid Lipid Nanoparticle

    Science.gov (United States)

    Zhang, Xiaoyun; Qiao, Hua; Chen, Ying; Li, Lin; Xia, Huxiong; Shi, Yanbin

    2016-01-01

    Low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle (LMWH-ISL-SLN) was developed for injective application. The morphological observation, particle diameter and zeta potential of LMWH-ISL-SLN were characterized using transmission electron microscopy (TEM) and a Malvern Zetasizer. Its entrapment efficiency (EE) and drug loading (DL) were determined by ultracentrifuge. The in-vitro release experiments were performed by dialysis technique. The cytotoxic effects of LMWH-ISL-SLN on Hep-G2 cell lines were determined using an MTT assay. Pharmacokinetic and tissue distribution studies were conducted in kunming mice after intravenous administration of LMWH-ISL-SLN. The average drug entrapment efficiency for LMWH-ISL-SLN was (99.80 ± 3.27)%, drug loading was (18.68 ± 1.51)%, mean particle size was (217.53 ± 4.86) nm and zeta potential was (–18.24 ± 2.47) mV. The in-vitro release experiments demonstrated isoliquiritigenin release from LMWH-ISL-SLN was in line with Weibull’s distribution law. Hemolysis test and dose-related toxic effects proved that LMWH-ISL-SLN was a safe and non toxic product when given by intravenous injection. The pharmacokinetics results of LMWH-ISL-SLN showed that the area under the concentration-time curve (AUC0→∞)of LMWH-ISL-SLN was greater than that for the isoliquiritigenin solution in plasma. Tissue distribution study indicated that ISL were mainly distributed in the liver and lung. In conclusion, low molecular weight heparin-modified SLN system is a promising carrier for the intravenous delivery of ISL. PMID:27980562

  3. Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate

    Directory of Open Access Journals (Sweden)

    L Bellamy

    2009-07-01

    Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran

  4. Bridging of oral anticoagulation therapy for invasive procedures.

    Science.gov (United States)

    Spyropoulos, Alex C

    2005-09-01

    The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.

  5. Hematology of Nile tilapia (Oreochromis niloticus subjected to anesthesia and anticoagulation protocols

    Directory of Open Access Journals (Sweden)

    Nadia Cristine Weinert

    2015-12-01

    Full Text Available Clinical hematology facilitates the diagnosis of disease and can act as a prognostic indicator of pathological conditions in fish. The aim of the present study was to evaluate hematological parameters of Nile tilapia (Oreochromis niloticus subjected to different anesthetics and anticoagulants. Thirty apparently healthy fishes (average weight of 473 ± 35. 50 g and mean total length of 29. 33 ± 0. 37 cm, were selected from the local commercial fish farm in the Lages municipality (Santa Catarina, Brazil. The animals were randomly divided into three groups of 10. In two groups, anesthesia was induced with eugenol (70 mg·L- 1 (EG and Benzocaine hydrochloride (100 mg·L-1 (BG, respectively. Anesthesia was not administered to fish of the third group (CG/control group. Blood samples were obtained by venipuncture of the caudal vessels and placed into microtubes containing sodium heparin or Na2EDTA for further analysis. The results were analyzed by Sigma Stat for Windows, the paired t-test for significant differences between anticoagulants of the same group, and analysis of variance followed by the Tukey test for comparison of means between groups (p ? 0. 05. Most of the observed changes in the erythrogram were significantly higher for the anticoagulant heparin and benzocaine group in comparison to the control group. However, the values obtained for the leukogram were significantly higher for all groups subjected to the Na2EDTA anticoagulant, suggesting that heparin may cause cell clumping. The results suggest that the anesthetics under investigation effectively minimizes the effects of stress caused by handling and invasive procedures, and that the anticoagulant heparin causes less hemolysis in comparison to Na2EDTA for Nile tilapia. Thus, the hematological variations attributed to different anesthetic protocols and/or different anticoagulants should be considered for the species Oreochromis niloticus.

  6. Efficacy Observation of Low Molecular Weight Heparin in Severe and Above AECOPD%低分子肝素钠在重度及极重度AECOPD疗效观察

    Institute of Scientific and Technical Information of China (English)

    周曦; 张柏膺; 严峻海

    2012-01-01

    目的 探讨重度及以上AECOPD应用抗凝治疗的临床意义.方法 选取60例入住病房的重度及以上AECOPD患者,随机分为实验组(抗凝)30例,对照组30例,均给予常规氧疗、抗感染、解痉平喘、化痰等治疗,实验组同时给予低分子肝素治疗1周.治疗前后分别检查动脉血气分析中PaO2、PaCO2,同时取静脉血测C-反应蛋白浓度(C-RP).结果抗凝治疗结束后,实验组中动脉血气分析中PaO2、PaCO2较对照组有明显改善,实验组的CRP浓度较对照组下降.两组比较差异均有统计学意义.结论 抗凝治疗可以改善重度及以上AECOPD患者的动脉血气分析中PaCO2、PaCO2,同时减轻患者体内炎症反应.%Objective To investigate the clinical significance of anticoagulant therapy on severe chronic obstructive pulmonary disease ( CORD ) with acute exacerbation. Methods 60 cases of severe level or above CORD patients with acute exacerbations were randomly divided into experimental groups ( anticoagulant ) having 30 cases, 30 cases in the control group undergone conventional oxygen therapy, antibiotics, antispasmodic asthma, phlegm and other treatment, and the experimental group at the same time were given low molecular weight heparin for 1 week. Blood oxygen pressure ( PaO2 ) in arterial blood, carbon dioxide partial pressure ( PaCO2 ) and C-reac-tive protein concentration ( CRP ) before and after treatment were measured. Results After the end of the anticoagulant therapy, PaO2 , PaGO-, in the experimental group had a more significant improvement than those in the control group; CRP in the experimental group decreased more significantly than that in the control group; and there were significant differences in PaO-, , PaGO-, and CRP between two groups. Conclusions The anticoagulant therapy can improve PaO-, , PaGO-, in severe and above AECOPD, and reduce the inflammatory response.

  7. Does intrauterine injection of low-molecular-weight heparin improve the clinical pregnancy rate in intracytoplasmic sperm injection?

    Science.gov (United States)

    Kamel, Ahmed Mohamed; El-Faissal, Yahia; Aboulghar, Mona; Mansour, Ragaa; Serour, Gamal I; Aboulghar, Mohamed

    2016-12-01

    Heparin can modulate proteins, and influence processes involved in implantation and trophoblastic development. This study aimed to assess the improvement of clinical pregnancy and implantation rates after local intrauterine injection of low-molecular-weight heparin (LMWH) in patients undergoing intracytoplasmic sperm injection (ICSI). A randomised case/control design was followed in women scheduled for ICSI. The study arm was injected with intrauterine LMWH during mock embryo transfer immediately following the ovum pickup procedure, while the control arm was given an intrauterine injection with a similar volume of tissue culture media. Side effects, the clinical pregnancy rate, and the implantation rate were recorded. The pregnancy rate was acceptable (33.9%) in the LMWH arm with no significant reported side effects, confirming the safety of the intervention. No statistically significant differences were found in the clinical pregnancy and implantation rates between both groups (p=0.182 and p=0.096, respectively). The odds ratio of being pregnant after intrauterine injection with LMWH compared to the control group was 0.572 (95% confidence interval [CI], 0.27-1.22), while the risk ratio was 0.717 (95% CI, 0.46-1.13; p=0.146). No statistical significance was found between the two groups in other factors affecting implantation, such as day of transfer (p=0.726), number of embryos transferred (p=0.362), or embryo quality. Intrauterine injection of LMWH is a safe intervention, but the dose used in this study failed to improve the outcome of ICSI. Based on its safety, further research involving modification of the dosage and/or the timing of administration could result in improved ICSI success rates.

  8. Comparative study on efficacy and influence on blood coagulation between low molecular weight heparin and unfractionated heparin in the treatment of elderly patients with severe pneumonia%低分子肝素与普通肝素佐治老年重症肺炎中疗效及对凝血功能的研究

    Institute of Scientific and Technical Information of China (English)

    梁玉荣

    2015-01-01

    Objective To compare the clinical efficacy and influence on blood coagulation between low mo-lecular weight heparin (LMWH) and unfractionated heparin (UFH) in the adjuvant treatment of elderly patients with severe pneumonia (SP). Methods 105 elderly SP cases were randomly divided into the LMWH group and the UFH group. All patients were treated with comprehensive treatment, such as anti-infection, anti-inflammation, spasm re-lieving, oxygen therapy, anti-coagulation and preventing complications, etc. Anticoagulation of the LMWH group was adopted with LMWH subcutaneous injection, 5000IU per time, twice a day for 7 days. The UFH group was used FUH subcutaneous injection, 6250IU per time, twice a day for 7 days. Their oxygenation indexes, APACHE Ⅱscore, clinical efficacy, blood coagulation indexes and bleeding were compared between the two groups. Results Af-ter the treatment, the levels of PaO2 and SpO2 were significantly higher, and the levels of PaCO2 and APACHE Ⅱscore were significantly lower in the LMWH group than in the UFH group (P 0. 05). After the treatment, the level of TXB2 decreased significantly in both groups, and 6-keto-PGF1α increased significantly, but there was no significant difference between the two groups (P > 0. 05). The level of CD62p was significantly lower in the LMWH group than in the UFH group (P 0.05);两组治疗后 TXB2明显下降,6-keto-PGF1α明显上升,治疗后差异无统计学意义(P >0.05);LMWH 组治疗后 CD62p 水平明显低于 UFH组(P <0.05)。结论老年重症肺炎患者在常规治疗基础上联合使用低分子肝素较普通肝素在改善肺部氧合与降低 APACHE Ⅱ评分方面具有显著优势,在抗凝效果与出血发生率方面具有比较优势。

  9. Does anticoagulant therapy improve pregnancy outcome equally, regardless of specific thrombophilia type?

    Science.gov (United States)

    Kovac, Mirjana; Mikovic, Zeljko; Mitic, Gorana; Djordjevic, Valentina; Mandic, Vesna; Rakicevic, Ljiljana; Radojkovic, Dragica

    2014-03-01

    The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.

  10. Oral heparin: status review

    Directory of Open Access Journals (Sweden)

    Gomez-Orellana Isabel

    2006-05-01

    Full Text Available Abstract Unfractionated heparin and low molecular weight heparin are the most commonly used antithrombotic and thromboprophylactic agents in hospital practice. Extended out-of-hospital treatment is inconvenient in that these agents must be administered parenterally. Current research is directed at development of a safe and effective oral antithrombotic agent as an alternative for the effective, yet difficult to use vitamin K antagonists. A novel drug delivery technology that facilitates transport of drugs across the gastrointestinal epithelium has been harnessed to develop an oral dosage form of unfractionated heparin. Combining unfractionated heparin with the carrier molecule, sodium N-(8 [2-hydroxybenzoyl]amino caprylate, or SNAC has markedly increased the gastrointestinal absorption of this drug. Preclinical and clinical studies to-date suggests that oral heparin-SNAC can confer a clinical efficacious effect; further confirmation is sought in planned clinical trials.

  11. Bioengineered heparin

    Science.gov (United States)

    Lord, Megan S; Whitelock, John M

    2014-01-01

    Heparin is a widely used drug for the control of blood coagulation. The majority of heparin that is produced commercially is derived from animal sources, is poly-disperse in nature and therefore ill-defined in structure. This makes regulation of heparin challenging with respect to identifying its absolute structural identity, purity, and efficacy. This raises the question as to whether there might be alternative methods of producing commercial grade heparin. The commentary highlights ways that we might manufacture heparin using bioengineering approaches to yield a successful therapeutic replacement for animal-derived heparin in the future. PMID:24902029

  12. Perioperative anticoagulation management in antiphospholipid syndrome.

    Science.gov (United States)

    Ishida, Keiichi; Masuda, Masahisa; Kohno, Hiroki; Tamura, Yusaku; Matsumiya, Goro

    2015-09-01

    Patients with antiphospholipid syndrome are at increased risk of developing thrombotic and hemorrhagic complications after cardiac surgery, and may have abnormal coagulation tests and develop thrombocytopenia after invasive procedures, which can complicate the perioperative management of anticoagulant therapy. We describe a patient with chronic thromboembolic pulmonary hypertension and antiphospholipid syndrome, who presented with prolonged activated partial thromboplastin and activated clotting times, and developed thrombocytopenia after the catheterization workup. We performed pulmonary endarterectomy and successfully managed anticoagulation by restricting heparin use at the time of surgery and monitoring the heparin effect by measuring heparin concentrations during cardiopulmonary bypass.

  13. A Case of “Refractory” Neuropsychiatric Lupus Responsive to Anticoagulation

    OpenAIRE

    Rui Wu; Sun Hu

    2017-01-01

    Neuropsychiatric disorder is a severe complication in 14% to 75% of systemic lupus erythematosus (SLE) patients, which can result in significant morbidity. A 15-year-old female SLE patient with coexistence of dural sinus thrombosis and intracerebral hemorrhage resistant to two pulses of high dose of glucocorticoid was treated with anticoagulation of the low-molecular-weight [LMW] heparin subcutaneously followed by warfarin. The patient demonstrated a remarkable clinical response.

  14. Recent progress and applications in glycosaminoglycan and heparin research

    OpenAIRE

    Laremore, Tatiana N.; Zhang, Fuming; Dordick, Jonathan S.; LIU, Jian; Linhardt, Robert J.

    2009-01-01

    Heparin, the focus of this review, is a critically important anticoagulant drug produced from animal sources, which was contaminated last year leading to a number of adverse side effects, some resulting in death. Heparin is a highly acidic polysaccharide and a member of a family of biopolymers called glycosaminoglycans. The structure and activities of heparin are detailed along with recent advances in heparin structural analysis and biological evaluation. Current state-of-the-art chemical and...

  15. Postoperative start compared to preoperative start of low-molecular-weight heparin increases mortality in patients with femoral neck fractures

    Science.gov (United States)

    Leer-Salvesen, Sunniva; Dybvik, Eva; Dahl, Ola E; Gjertsen, Jan-Erik; EngesæTer, Lars B

    2017-01-01

    Background and purpose — Controversies exist regarding thromboprophylaxis in orthopedic surgery. Using data in the nationwide Norwegian Hip Fracture Register (NHFR) with postoperative death and reoperation in the first 6 months after surgery as endpoints in the analyses, we determined whether the thromboprophylaxis in patients who undergo hemiarthroplasty for femoral neck fracture should start preoperatively or postoperatively. Patients and methods — After each operation for hip fracture in Norway, the surgeon reports information on the patient, the fracture, and the operation to the NHFR. Cox regression analyses were performed with adjustments for age, ASA score, gender, type of implant, length of surgery, and year of surgery. Results — During the period 2005–2014, 25,019 hemiarthroplasties as treatment for femoral neck fractures were reported to the registry. Antithrombotic medication was given to 99% of the patients. Low-molecular-weight heparin predominated with dalteparin in 57% of the operations and enoxaparin in 41%. Only operations with these 2 drugs and with known information on preoperative or postoperative start of the prophylaxis were included in the analyses (n = 20,241). Compared to preoperative start of thromboprophylaxis, postoperative start of thromboprophylaxis gave a higher risk of death (risk ratio (RR) = 1.13, 95% CI: 1.06–1.21; p < 0.001) and a higher risk of reoperation for any reason (RR =1.19, 95% CI: 1.01–1.40; p = 0.04), whereas we found no effect on reported intraoperative bleeding complication or on the risk of postoperative reoperation due to hematoma. The results did not depend on whether the initial dose of prophylaxis was the full dosage or half of the standard dosage. Interpretation — Postoperative start of thromboprophylaxis increased the mortality and risk of reoperation compared to preoperative start in femoral neck fracture patients operated with hemiprosthesis. The risks of bleeding and of reoperation due to

  16. Bioengineered heparins and heparan sulfates.

    Science.gov (United States)

    Fu, Li; Suflita, Matthew; Linhardt, Robert J

    2016-02-01

    Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan sulfate is a widely distributed membrane and extracellular glycosaminoglycan, heparin is found primarily intracellularly in the granules of mast cells. While heparin has historically received most of the scientific attention for its anticoagulant activity, interest has steadily grown in the multi-faceted role heparan sulfate plays in normal and pathophysiology. The chemical synthesis of these glycosaminoglycans is largely precluded by their structural complexity. Today, we depend on livestock animal tissues for the isolation and the annual commercial production of hundred ton quantities of heparin used in the manufacture of anticoagulant drugs and medical device coatings. The variability of animal-sourced heparin and heparan sulfates, their inherent impurities, the limited availability of source tissues, the poor control of these source materials and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans, driven by both therapeutic applications and as probes to study their natural functions. This review focuses on the complex biology of these glycosaminoglycans in human health and disease, and the use of recombinant technology in the chemoenzymatic synthesis and metabolic engineering of heparin and heparan sulfates. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. [Thrombocytopenia induced by heparin. Diagnosis, treatment, physiopathology: current concepts].

    Science.gov (United States)

    Gruel, Y; Drouet, L

    1986-01-01

    Iatrogenic thrombocytopenia is a rare, but severe complication of treatments with heparin and heparinoids. Mean temporary thrombocytopenia failing to show any complications are usually diagnosed as quite different from acute and delayed thrombocytopenia of which severity depends mainly on thrombotic symptoms demonstrated in 65 p. 100 of cases; the initial evolution of an average thrombocytopenia is not easy to diagnose; it may as well exist a connection between the two diseases, from a physiopathogenic point of view. The diagnosis of severe thrombocytopenia depends:--clinically, on the initial data, delayed as compared with the heparin treatment beginning and existence of arterial and/or venous thrombosis;--biologically, by demonstrating an aggregating activity for platelets in presence of heparin, in the patient plasma. Such an activity requires the suppression of standard heparinotherapy as well as the choice of substitutive anticoagulant treatment in case of evolutive thrombosis. Low molecular weight heparins are prescribed only if in vitro tests of platelet aggregation with the patient's plasma are negative. Antivitamins K are to be used as soon as possible alone or combined with heparin fractions. Antiaggregants are prescribed alone, above all in case of isolated thrombocytopenia and combined with AVK. Treatment of thrombotic complications depends on surgical disobstruction if arterial thrombosis, and use of fibrinolytics if pulmonary embolisms. The acute reaction of some thrombocytopenia to heparin as well as therapeutic difficulties demonstrate the efficiency of an early diagnosis performed thanks to systematic platelet numerations during the first 15 days of a treatment with heparin, as well as to the prevention along with systematic association with aspirin, especially if replaced with AVK.

  18. Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.

    Science.gov (United States)

    Zhang, Hailong; Mi, Jie; Huo, Yayu; Huang, Xiaoyan; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2014-05-15

    Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.

  19. Patient Adherence and Experience with Extended Use of Prophylactic Low-Molecular-Weight Heparin Following Pancreas and Liver Resection.

    Science.gov (United States)

    Lemke, Madeline; Beyfuss, Kaitlyn; Hallet, Julie; Coburn, Natalie G; Law, Calvin H L; Karanicolas, Paul J

    2016-12-01

    Guidelines recommend 28 days venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) following major abdominal surgery for cancer. Overall adherence with these recommendations is poor, but little is known about feasibility and tolerability from a patient perspective. An institution-wide policy for routine administration of 28 days of post-operative LMWH following major hepatic or pancreatic resection for cancer was implemented in April 2013. Patients having surgery from July 2013 to June 2015 were approached to participate in an interview examining adherence and experience with extended duration LMWH. There were 100 patients included, with 81.4 % reporting perfect adherence with the regimen. The most frequent reasons for non-adherence were that a healthcare provider stopped the regimen or because of poor experience with injections. Most patients were able to correctly recall the reason for being prescribed LMWH (82.6 %), and 78.4 % of patients performed all injections themselves. Over half the patients (55.7 %) did not find the injections bothersome. Patients reported high adherence and a manageable experience with post-operative extended-duration LMWH in an ambulatory setting following liver or pancreas resection. These findings suggest that patient adherence is not a major contributor to poor compliance with VTE prophylaxis guidelines.

  20. The effect of subcutaneous injection duration on patients receiving low-molecular-weight heparin: Evidence from a systematic review

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    Li-juan Yi

    2016-03-01

    Full Text Available To assess the effect of the injection duration of subcutaneous low-molecular-weight heparin (LMWH on pain and bruising in patients. Randomized controlled trials and quasi-experimental studies were searched for in four electronic databases. The pooled effect size was expressed as relative risk (RR and mean difference (MD with 95% confidence intervals (CI for dichotomous and continuous data. Cochrane Q and p value were used to assess heterogeneity and the I2 statistic was adopted to quantify the level. Finally, eight studies involving a total of 532 participants met our inclusion criteria. The slow (30 second injection was associated with a reduction in pain intensity and duration, and lower bruising occurrence at 48–72 hours and 48 hours post injection. The bruising area was also smaller at 48 hours and 60 hours post injection. No differences were identified between the slow and fast (10 second injection in bruising area and bruising occurrence at 24 hours and 60 hours post injection. With present evidences, slow injection of LMWH is beneficial to the patient's well being, but further studies to identify the feasibility and standardization of the technique is recommended.

  1. Transdermal delivery of low molecular weight heparin loaded in flexible liposomes with bioavailability enhancement: comparison with ethosomes.

    Science.gov (United States)

    Song, Yun-Kyoung; Hyun, Seo Yeon; Kim, Hyung-Tae; Kim, Chong-Kook; Oh, Jung-Mi

    2011-01-01

    Low molecular weight heparin (LMWH)-loaded flexible liposomes (flexosomes) were formulated for transdermal delivery, and their physicochemical and pharmacokinetic parameters were compared with LMWH-loaded ethosomes. Flexosomes had similar particle size compared with ethosomes, but their deformability was higher than that of ethosomes (76.7% vs. 46.8%). In vitro, flexosomes demonstrated 2.6-fold higher permeability coefficient than ethosomes. In comparison to LMWH aqueous solution, skin deposition of flexosome increased 3.2-fold, while that of ethosome increased only 2.0-fold. In vivo, after the topical application of flexosome to hairless mouse, [anti-Xa](max) was 1.11 IU/mL, while ethosomes showed only 0.32 IU/mL. Moreover, AUC(0-24 h) of flexosomes was 2.5-fold higher than ethosomes. In conclusion, the enhanced skin permeation and bioavailability of LMWH can be achieved with flexosomes in comparison with ethosomes. The LMWH transdermal delivery via flexosomes has the potential to replace the parenteral dosage forms for the treatment of venous thromboembolism, pulmonary embolism and cardiovascular events.

  2. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

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    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  3. Bowel obstruction from intramural hematoma in two children treated with low molecular weight heparin: Case report and review of the literature

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    Richard M. Schroeder

    2014-10-01

    Full Text Available Low molecular weight heparin (LMWH is frequently employed in children to prevent extension of intravascular thrombosis. However, this therapy can result in pathologic bleeding, including spontaneous intramural hematoma of the intestinal wall. In this report, we describe two cases of intestinal obstruction resulting from intramural hematomas during therapeutic LMWH therapy in children. The diagnostic studies and management of spontaneous intramural hematoma in children are discussed.

  4. Heparin Characterization: Challenges and Solutions

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    Jones, Christopher J.; Beni, Szabolcs; Limtiaco, John F. K.; Langeslay, Derek J.; Larive, Cynthia K.

    2011-07-01

    Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.

  5. Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3.

    Science.gov (United States)

    Gerotziafas, Grigoris T; Galea, Vassiliki; Mbemba, Elisabeth; Sassi, Mouna; Roman, Marie-Paule; Khaterchi, Amir; van Dreden, Patrick; Japcowitz, Max; Lotz, Jean Pierre; Bernaudin, Jean Francois; Fareed, Jawed; Hatmi, Mohamed; Elalamy, Ismail

    2014-01-01

    Low molecular weight heparins (LMWHs) and fondaparinux are widely used for prophylaxis and treatment of venous thromboembolic disease in cancer patients. However, the optimization of the antithrombotic treatment especially in patients with adenocarcinoma of the pancreas is a challenging issue. The understanding of the mechanism of action of the LMWHs and fondaparinux in cancer-induced hypercoagulability might help to optimize antithrombotic treatment. To this aim, we investigated the influence of BXPC3 pancreas adenocarcinoma cells on the antithrombotic activity of LMWHs and fondaparinux. Thrombin generation (TG) in normal platelet poor (PPP) and platelet rich plasma (PRP) spiked with clinically relevant concentrations of dalteparin, enoxaparin, nadroparin tinzaparin and fondaparinux was assessed with the Calibrated Automated Thrombogram assay. BXPC3 (5 cells/μl) were added to plasma. The mean rate index (MRI) of the propagation phase of TG and the endogenous thrombin potential (ETP) were analyzed. The IC50 of the studied compounds were determined and compared on the basis of anti-Xa and anti-IIa equivalent units. We demonstrate that the specific antithrombin (AT)-dependent anti-Xa activity of LMWHs and fondaparinux almost selectively inhibits the propagation phase of TG. The synergy between the anti-Xa and anti-IIa activities of LMWHs rather than the selective inhibition of FXa warrants abrogation of TG. The mean molecular weight and anti-Xa/anti-IIa ratio of the AT-dependent agents cannot predict the alteration of their capacity to inhibit TG. Tinzaparin was the most potent inhibitor of TG than the other LMWHs. Enoxaparin was more potent than nadroparin and dalteparin.

  6. Pharmacology of Heparin and Related Drugs.

    Science.gov (United States)

    Mulloy, Barbara; Hogwood, John; Gray, Elaine; Lever, Rebecca; Page, Clive P

    2016-01-01

    Heparin has been recognized as a valuable anticoagulant and antithrombotic for several decades and is still widely used in clinical practice for a variety of indications. The anticoagulant activity of heparin is mainly attributable to the action of a specific pentasaccharide sequence that acts in concert with antithrombin, a plasma coagulation factor inhibitor. This observation has led to the development of synthetic heparin mimetics for clinical use. However, it is increasingly recognized that heparin has many other pharmacological properties, including but not limited to antiviral, anti-inflammatory, and antimetastatic actions. Many of these activities are independent of its anticoagulant activity, although the mechanisms of these other activities are currently less well defined. Nonetheless, heparin is being exploited for clinical uses beyond anticoagulation and developed for a wide range of clinical disorders. This article provides a "state of the art" review of our current understanding of the pharmacology of heparin and related drugs and an overview of the status of development of such drugs.

  7. Does ′heparin-induced thrombocytopenia′ hit our minds?

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    Arun R Thangavel

    2016-01-01

    Full Text Available Unfractionated heparin is a widely used drug to prevent deep vein thrombosis and pulmonary emboli in patients at risk. With the advent of newer anticoagulants having lesser side effects, its use has diminished but not out of service. Here, we report a case of deep venous thrombosis, in a patient on prophylactic dose of heparin, which was later found to be a manifestation of heparin-induced thrombocytopenia (HIT. Thrombosis in the presence of heparin prophylaxis should be considered as HIT rather than a failure of anticoagulation.

  8. Clinical application of disposable heparin sensors. Blood heparin measurements during open heart surgery.

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    Yun, J H; Lee, L M; Wahr, J A; Fu, B; Meyerhoff, M E; Yang, V C

    1995-01-01

    The authors previously reported the development of an ion selective electrode type heparin sensor consisting of a specially formulated polymer membrane doped with tridodecylmethylammonium chloride as the heparin complexing agent. They also demonstrated the feasibility of measuring blood heparin levels by protamine titration, using a disposable copper wire sensor coated with the heparin sensing membrane to probe the titration end point. In this article, the results of further titration studies conducted on 44 clinical whole blood specimens obtained from 8 patients undergoing open heart surgery were reviewed. Samples were taken from patients at four different stages during the bypass surgery: 1) before heparin administration; 2) immediately after heparin administration; 3) within 30 min to 3 hr after heparin administration; and 4) within 30 min after protamine administration. Heparin anticoagulant activity in these samples was monitored by the activated clotting time assay, whereas heparin concentrations were measured by protamine titration using either the Hepcon HMS Titrator (Medtronic HemoTec Inc., Englewood, CO) or the coated wire heparin sensor to determine titration end points. Results indicate that heparin levels determined by the sensor method were in good agreement with those determined by the Hepcon HMS Titrator. When the heparin concentrations estimated by the two methods show significant discrepancy (> 1.0 unit/ml), the sensor method seems to provide more precise values, as verified by an additional chromogenic heparin assay. The overall time required to complete the titration process and heparin measurement with a pre made heparin sensor was less than 3 min. Clinically, the heparin sensor could be used as a safeguard to precisely monitor heparin levels during surgical procedures. Alternatively, the sensor could be used to assess the accurate protamine dose required for full heparin reversal.

  9. Heparin-induced thrombocytopenia type II: Innovations in diagnostics and treatment

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    Antonijević Nebojša

    2003-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT Management of heparin-induced thrombocytopenia (HIT and treatment options have significantly changed recently. Heparin may induce two types of thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%, is characterized by mild thrombocytopenia without significant clinical manifestations. Type II is less frequent (0.5-2%, life threatening immune type, develops following a period of minimum 5-7 days upon introduction of heparin therapy (patients earlier treated with heparin are excluded. Type II heparin-induced thrombocytopenia with severely reduced platelet count may be clinically manifested by thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable Sensitivity of a highly specific platelet aggregation assay is only 36% sensitivity and specificity of 14C-serotonin release assays amounts to 95% while ELISA using a heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and antigen assays. Furthermore, new classes of antigen assays, like antibody detection tests of complexes between heparin and neutrophil-activating peptide-2 as well as those between heparin and interleukin-8, have been used. Current therapy options Current therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80–100%. Danaparoid sodium exhibits in vitro cross-reactivity of 10–61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment: lepirudin, especially in patients without renal failure and argatroban, particularly in patients with renal failure. The following procedures and agents are also efficient: asmapheresis

  10. Heparina de baixo peso molecular no tratamento da tromboembolia pulmonar Low-molecular-weight heparin in the treatment of pulmonary embolism

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    RENATO MACIEL

    2002-06-01

    Full Text Available Este artigo de revisão analisa as propriedades farmacocinéticas das heparinas de baixo peso molecular, compara os resultados do seu uso com heparina não fracionada no tratamento da tromboembolia pulmonar, mostrando que são uma alternativa segura e efetiva. Sugere que as heparinas de baixo peso molecular administradas por via subcutânea uma ou duas vezes ao dia e sem necessidade de monitorização laboratorial freqüente permitem o manejo ambulatorial ou com internação hospitalar breve de alguns casos de tromboembolia pulmonar, resultando em redução de custos e maior satisfação do paciente.This article reviews the pharmacokinetic properties of low-molecular weight heparins, compares the results of their use to that of unfractioned heparin in a pulmonary embolism treatment, showing they are a safe an effective alternative. The authors suggest that low-molecular-weight heparins administered subcutaneously once or twice-daily and without frequent laboratory monitoring have permitted out-of-hospital or short hospitalization management in some cases of pulmonary embolism, resulting in cost savings and increased patient satisfaction.

  11. Direct oral anticoagulants and venous thromboembolism

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    Massimo Franchini

    2016-09-01

    Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

  12. Strategies and outcomes of periprocedural bridging therapy with low-molecular-weight heparin in patients with mechanical heart valves.

    Science.gov (United States)

    Schulman, Jacqueline M; Majeed, Ammar; Mattsson, Eva; Schulman, Sam; Holmström, Margareta; Ågren, Anna

    2015-11-01

    Patients with mechanical heart valves (MHV) undergoing invasive procedures often receive periprocedural bridging with low-molecular-weight heparin (LMWH). The bridging strategies used in real-life and the predictors for bleeding and thrombosis are not well studied. We retrospectively assessed patients with MHV that underwent invasive procedures requiring vitamin K antagonist interruption and LMWH bridging. Thromboembolic and bleeding events occurring up to 30 days after the procedures were recorded. Predictors of major bleeding events (MBEs) were analyzed with logistic regression. We evaluated 547 patients with MHV who underwent 275 procedures during a 6.5-year period. Bridging with LMWH was used in 185 procedures in a total of 117 patients. Combined pre- and post-operative bridging was the most frequently employed (63 %). Doses of LMWH were prophylactic in 96 (52 %) of the procedures and therapeutic in 89 (48 %). The procedure-related bleeding risk was evaluated as high in 70 (38 %) and low in 115 (62 %) of the procedures. There was a trend to more frequent use of prophylactic doses (61 %) in high-risk surgery, and more therapeutic doses (53 %) in low-risk ones. There were 36 bleeding episodes, 21 (11 % of procedures) of which were classified as MBEs, but there were no thromboembolic events. Most MBEs (n = 14; 67 %) occurred in surgeries with high bleeding risk. In the multivariate analysis, the bleeding risk of the surgery itself was the only independent predictor for MBEs. For patients with MHV receiving perioperative bridging with LMWH, the major predictor for MBE is the bleeding risk of the surgery.

  13. Preparation and optimization of N-trimethyl-O-carboxymethyl chitosan nanoparticles for delivery of low-molecular-weight heparin.

    Science.gov (United States)

    Mahjub, Reza; Heidari Shayesteh, Tavakol; Radmehr, Moojan; Vafaei, Seyed Yaser; Amini, Mohsen; Dinarvand, Rasoul; Dorkoosh, Farid Abedin

    2016-01-01

    The aim of this study was preparation, optimization and in vitro characterization of nanoparticles composed of 6-[O-carboxymethyl]-[N,N,N-trimethyl] (TMCMC) for oral delivery of low-molecular-weight heparin. The chitosan derivative was synthesized. Nanoparticles were prepared using the polyelectrolyte complexation method. Box-Behnken response surface experimental design methodology was used for optimization of nanoparticles. The morphology of nanoparticles was studied using transmission electron microscopy. In vitro release of enoxaparin from nanoparticles was determined under simulated intestinal fluid. The cytotoxicity of nanoparticles on a Caco-2 cell line was determined, and finally the transport of prepared nanoparticles across Caco-2 cell monolayer was defined. Optimized nanoparticles with proper physico-chemical properties were obtained. The size, zeta potential, poly-dispersity index, entrapment efficiency and loading efficiency of nanoparticles were reported as 235 ± 24.3 nm, +18.6 ± 2.57 mV, 0.230 ± 0.03, 76.4 ± 5.43% and 12.6 ± 1.37%, respectively. Morphological studies revealed spherical nanoparticles with no sign of aggregation. In vitro release studies demonstrated that 93.6 ± 1.17% of enoxaparin released from nanoparticles after 600 min of incubation. MTT cell cytotoxicity studies showed no cytotoxicity at 3 h post-incubation, while the study demonstrated concentration-dependent cytotoxicity after 24 h of exposure. The obtained data had shown that the nanoparticles prepared from trimethylcarboxymethyl chitosan may be considered as a good candidate for oral delivery of enoxaparin.

  14. Hand-held personal digital assistant program for the HEMOCHRON RxDx heparin and protamine dosing system.

    Science.gov (United States)

    El Rouby, Soumaya; Rinehart, Kristin; Zucker, Marcia L; LaDuca, Frank M

    2003-09-01

    The use of in vitro dosing assays for heparin and protamine during cardiac surgery has significantly improved overall postoperative patient outcome. The HEMOCHRON RxDx system (International Technidyne Corp, Edison, NJ) is widely used for anticoagulation management. Based on a series of consecutive in vitro tests, the RxDx system is used to quantify the patient's heparin requirement (heparin response test, HRT), measure the activated clotting time (ACT), calculate the blood heparin concentration and the required protamine dose (protamine response test, PRT), as well as determine the efficacy of heparin reversal (protamine dose assay, PDA-O). A hand-held personal digital assistant (PDA) program has been developed that performs the RxDx calculations used for anticoagulation management during cardiac surgery. The Palm m505 hand-held device (Palm, Inc., Santa Clara, CA) is used in concert with any standard Hemochron blood coagulation system. The Palm m505 device has been programmed to perform all the calculations required for the RxDx test system. Patient's body weight, height, and gender are entered into the program using the onscreen keypad and the template provided in the Hemochron program. The calculator automatically provides the patient's blood volume and the recommended heparin dose upon entering the baseline ACT and HRT values and a target ACT. At the end of the case, the optimal protamine dose is determined, and the total heparin level is calculated and displayed upon entry of ACT and PRT clotting times. Following protamine administration, the program calculates any additional protamine required to neutralize residual heparin using the data from a PDA-O test. The RxDx hand-held PDA is accurate, quick, simple, and easy to use, patient data are saved and can be retrieved. The inclusion of this rapid computing technology into the Hemochron RxDx system serves to expand the applications of the Hemochron RxDx system during cardiac interventions.

  15. [Heparin-induced thrombocytopenia. New therapeutical options].

    Science.gov (United States)

    Seculini Patiño, Carina E; Tabares, Aldo H

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

  16. Management of the anticoagulated dental patient.

    Science.gov (United States)

    Ball, J H

    1996-11-01

    An understanding of the primary mechanisms of hemostasis, including the coagulation pathways and the intrinsic, extrinsic, and common systems, is the basis for treating the anticoagulated patient. Two major anticoagulants are used for treating those who may be at risk for thromboembolic crisis. These drugs include Coumadin, which is an oral anticoagulant, and heparin, a parenteral anticoagulant, which is often used for acute thromboembolic episodes or for hospitalization protocols that include significant surgical procedures. The practitioner should be familiar with common dental drugs that can interact with anticoagulants and should consult with the patient's physician before administering any such drugs. By placing the patient into one of three dental treatment categories, appropriate anticoagulation therapy can be rendered to each patient according to his or her needs. Low-risk procedures require no change in anticoagulation medication. For moderate-risk procedures, withdrawal of anticoagulation medication 2 days before the procedure and verified with the PT the day of the procedure is indicated. For high-risk dental procedures, using a heparin protocol should be strongly considered. In all instances of dental treatment, the oral tissues should be treated atraumatically using local hemostatic measures for control of hemorrhage. Treating medically compromised patients who are on a variety of medications is becoming more common in dentistry today. Understanding the underlying disease and the appropriate protocol for treatment of anticoagulated patients reduces the risk of thromboembolism and hemorrhagic complications.

  17. Increased accuracy in heparin and protamine administration decreases bleeding: a pilot study.

    Science.gov (United States)

    Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

    2009-03-01

    Three to 5 percent of the patients undergoing cardiac surgery are reoperated because of bleeding. When a surgical cause can be excluded, heparin/protamine mismatch may be considered. Insufficient reversal of heparin and overdosing of protamine may cause postoperative bleeding. The purpose of the study was to evaluate whether a heparin-protamine titration system, Hemochron RxDx, could reduce postoperative bleeding and blood transfusion. Fifty-three patients were included prospectively over a 6-month period. The test group (RxDx group; 28 patients) received heparin and protamine doses calculated using the Hemochron RxDx system, which performs a baseline activated clotting time (ACT) value together with a heparin response test. An accurate heparin dose was calculated based on the Bull dose/response curve. Protamine doses were calculated by the same method. In the control group (25 patients), heparin was administered based on weight (3.5 mg/kg) and monitored by ACT. Heparin was reversed with protamine (1 mg/l mg of total heparin). Postoperative bleeding was significantly lower in the RxDx group (375 mL; range, 125-700 mL) compared with the control group (600 mL; range, 250-1920 mL; p = .018). A reduced number of patients needed blood transfusions in the RxDx group, although this was not statistically significant (19% vs. 38%, respectively; p = .13). Initial heparin dose was significantly reduced in the RxDx group (250 mg; range, 100-375 mg) compared with the control group (300 mg; range, 200-350 mg; p = .04). The additional heparin during cardiopulmonary bypass (CPB) was significantly lower as well 62 (range, 0-185) vs. 100 mg (range, 0-350 mg); p = .04. Initial protamine dose was reduced in the RxDx group 200 (range, 75-340) vs. 350 mg (range, 200-500 mg); p = .0001. Satisfactory end ACT values were obtained in both groups. Using the Hemochron RxDx, we observed a significant reduction in postoperative blood loss, as well as the amount of heparin and initial doses of

  18. A heparin-like glycosaminoglycan from shrimp containing high levels of 3-O-sulfated D-glucosamine groups in an unusual trisaccharide sequence.

    Science.gov (United States)

    Chavante, Suely F; Brito, Adriana S; Lima, Marcelo; Yates, Edwin; Nader, Helena; Guerrini, Marco; Torri, Giangiacomo; Bisio, Antonella

    2014-05-22

    The detailed characterization of a novel heparin-like glycosaminoglycan purified from the viscera (heads) of the shrimp Litopenaeus vannamei is reported. Structural analysis performed by mono- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed it to be rich in both glucuronic acid and N,6-sulfated glucosamine residues. The key peculiarities were its high 3-O-sulfated glucosamine content compared to mammalian heparins; a residue which is usually associated with the antithrombin (AT) binding site, and the location of these residues within 2-O-sulfated iduronate and glucuronate-containing sequences (I2S-A(∗)-G), a situation not found in mammalian heparin. It also exhibited higher molecular weight (∼36kDa) than conventional heparin (∼16kDa) but, negligible anticoagulant activity (∼5IU/mg compared to heparin ∼190IU/mg) and stabilization of AT, which has been linked directly to anticoagulation activity. A high affinity fraction, eluting at a similar salt concentration (0.75-1.5M NaCl) from an antithrombin affinity column, to the high affinity fraction of heparin, also showed only weak thermal stabilization of AT (+∼2°C). These structural peculiarities may help elucidate more clearly the relationship between structure and function of sulfated polysaccharides, and provide useful model compounds with which to better understand interactions of biological significance.

  19. Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review.

    Science.gov (United States)

    Stutzmann, Jean-Marie; Mary, Veronique; Wahl, Florence; Grosjean-Piot, Odile; Uzan, André; Pratt, Jeremy

    2002-01-01

    The development of treatments for acute neurodegenerative diseases (stroke and brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke therapy) and (ii) on protecting neurons from cytotoxic events (i.e. neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents for stroke and neurotrauma therapies). This paper reviews the preclinical data for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24 h after lesion when the treatment was started up to 18 h after insult. Enoxaparin was also tested after an ischemic insult using the transient middle cerebral artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v., significantly reduced the lesion size and improved the neuroscore when the treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h after insult, reduced cortical lesion size in a dose-dependent manner. In permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion size and improved neuroscore. A slight and reversible elevation of activated partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by secondary ischemia due in part to edema-induced compression of blood vessels. When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later than 30 h after TBI, it significantly reduced edema in hippocampus and parietal cortex. At one week after TBI the lesion size was significantly reduced and the neurological deficit significantly improved in enoxaparin treated animals. Finally, the cognitive impairment was significantly improved by enoxaparin at 48 h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin and specifically enoxaparin can explain

  20. Heterofucans from Dictyota menstrualis have anticoagulant activity.

    Science.gov (United States)

    Albuquerque, I R L; Queiroz, K C S; Alves, L G; Santos, E A; Leite, E L; Rocha, H A O

    2004-02-01

    Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT) using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 g/ml) was only 4.88-fold higher than that of the low molecular weight heparin Clexane (4.1 g/ml), whereas 80 g/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.

  1. Heterofucans from Dictyota menstrualis have anticoagulant activity

    Directory of Open Access Journals (Sweden)

    I.R.L. Albuquerque

    2004-02-01

    Full Text Available Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml, whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.

  2. Heparin interaction with protein-adsorbed surfaces

    NARCIS (Netherlands)

    Winterton, Lynn C.; Andrade, Joseph D.; Feijen, Jan; Kim, Sung Wan

    1986-01-01

    Albumin and fibrinogen show no binding affinity to varied molecular weights of heparin at physiological pH. Human plasma fibronectin was shown to bind heparins in both the solution and adsorbed states. Fibronectin was shown to have six active binding sites for heparins which may be sterically blocke

  3. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.

    Science.gov (United States)

    Schleussner, Ekkehard; Kamin, Gabriele; Seliger, Gregor; Rogenhofer, Nina; Ebner, Susanne; Toth, Bettina; Schenk, Michael; Henes, Melanie; Bohlmann, Michael K; Fischer, Thorsten; Brosteanu, Oana; Bauersachs, Rupert; Petroff, David

    2015-05-05

    A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable. To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL. Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387). 14 university hospitals and perinatal care centers in Germany and Austria. 449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography. Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation. Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications. At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH). Placebo injections were not used, and neither trial staff nor patients were blinded. Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not

  4. Incidence of pocket hematoma after electrophysiological device placement:dual antiplatelet therapy versus low-molecular-weight heparin regimen

    Institute of Scientific and Technical Information of China (English)

    Yan CHEN; Xin-Cun YANG; Kang MENG; Yun-Tao LI; Ming-Dong GAO; Ze-Chun ZENG; Jin-Rong ZHANG; Hong-Liang CONG; Yin LIU; Ru ZHAO; Le-Feng WANG

    2014-01-01

    Background Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49%vs. 16.47%, respectively;X2 = 6.66,P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012-0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket

  5. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Sarah Mousavi

    2015-01-01

    Full Text Available Background. Heparin, used clinically as an anticoagulant, also has anti-inflammatory properties. The purpose of this systematic review was to provide a comprehensive review regarding the efficacy and safety of heparin and its derivatives as anti-inflammatory agents. Methods. We searched the following databases up to March 2012: Pub Med, Scopus, Web of Science, Ovid, Elsevier, and Google Scholar using combination of Mesh terms. Randomized Clinical Trials (RCTs and trials with quasi-experimental design in clinical setting published in English were included. Quality assessments of RCTs were performed using Jadad score and Consolidated Standards of Reporting Trials (CONSORT checklist. Results. A total of 280 relevant studies were reviewed and 57 studies met the inclusion criteria. Among them 48 studies were RCTs. About 65% of articles had score of 3 and higher according to Jadad score. Twelve studies had a quality score > 40% according to CONSORT items. Asthma (n=7, inflammatory bowel disease (n=5, cardiopulmonary bypass (n=8, and cataract surgery (n=6 were the most studied disease condition. Forty studies use unfractionated heparin (UFH for intervention; the remaining studies use low molecular weight heparin (LMWH. Conclusion. Despite the conflicting results, heparin seems to be a safe and effective anti-inflammatory agent; although it is shown that heparin can decrease the level of inflammatory biomarkers and improves patient conditions, still more data from larger rigorously designed studies are needed to support use of heparin as an anti-inflammatory agent in clinical setting. However, because of the association between inflammation, atherogenesis, thrombogenesis, and cell proliferation, heparin and related compounds with pleiotropic effects may have greater therapeutic efficacy than compounds acting against a single target.

  6. Detection of heparin in the salivary gland and midgut of Aedes togoi.

    Science.gov (United States)

    Ha, Young-Ran; Oh, So-Ra; Seo, Eun-Seok; Kim, Bo-Heum; Lee, Dong-Kyu; Lee, Sang-Joon

    2014-04-01

    Mosquitoes secrete saliva that contains biological substances, including anticoagulants that counteract a host's hemostatic response and prevent blood clotting during blood feeding. This study aimed to detect heparin, an anticoagulant in Aedes togoi using an immunohistochemical detection method, in the salivary canal, salivary gland, and midgut of male and female mosquitoes. Comparisons showed that female mosquitoes contained higher concentrations of heparin than male mosquitoes. On average, the level of heparin was higher in blood-fed female mosquitoes than in non-blood-fed female mosquitoes. Heparin concentrations were higher in the midgut than in the salivary gland. This indicates presence of heparin in tissues of A. togoi.

  7. Use of recombinant factor VIIa for emergency reversal of anticoagulation

    Directory of Open Access Journals (Sweden)

    Ingerslev J

    2007-01-01

    Full Text Available Context: There is limited data regarding the use of activated recombinant factor VII (rFVIIa in anticoagulated patients requiring reversal. Aims: To identify and describe characteristics of subjects who received rFVIIa as part of emergency treatment aimed at improving hemostasis. Settings and Design: Data was obtained from an international peer-reviewed registry haemostasis.com. This registry contains data reported by physicians, who had elected to use rFVIIa to control bleeding in an emergency clinical situation. The contributors′ approval for inclusion in the study was obtained and they were requested to validate and update information. Materials and Methods: Database review of cases receiving rFVIIa to manage bleeding coherent with the use of anticoagulant therapy. Statistical Analysis: The Wilcoxon signed rank test was used to compare requirements for blood products and crystalloids/colloids during the 24h preceding and following rFVIIa administration, as well as changes in the levels of clotting factors during that period. Results: Eighteen patients were treated with rFVIIa (median dose: 87.35 µg/kg; range: 20.0-106.0 µg/kg for bleeding. Anticoagulants requiring reversal included low-molecular-weight heparin (n = 6, unfractionated heparin (n =8, coumarin (n =3 and warfarin (n=1. All patients had failed to respond to traditional antidotes and blood products. Following administration, bleeding stopped in 10, markedly decreased in five and slowed in the remaining three. Amongst 12/16 patients, a response was observed within 2.0 h of first administration. The requirement for blood products and crystalloids/colloids decreased ( P < 0.05 after rFVIIa administration. rFVIIa was well tolerated. Conclusions: rFVIIa may play a role in control of untoward bleeding in subjects receiving anticoagulation therapy.

  8. Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

    DEFF Research Database (Denmark)

    Bendstrup, K.E.; Newhouse, M.T.; Pedersen, Ole Finn

    1999-01-01

    Inhaled heparin has been used for asthma treatment, but results have been inconsistent, probably due to highly varying lung doses. We determined the output per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations in ...

  9. 低分子肝素应用于膝关节镜术后的临床观察%Clinical effects observation on the application of loW molecular Weight heparin after Knee arthroscopic surgery

    Institute of Scientific and Technical Information of China (English)

    刘金辉; 聂喜增; 李锋; 王华军

    2015-01-01

    Objective To discuss the clinical effects of low molecular weight heparin after arthroscopic surgery of the knee, Methods A analysis of 337 cases of arthroscopic surgery of the knee were done from January 2012 to January 2013, To_tally 337 patients were randomly divided into treatment group(n = 180 cases)and control group(n = 157 cases), The treat_ment group was given routine preventive application of low molecular heparin calcium;while the control group was not applied low molecule heparin and other anticoagulant and assisted thrombolytic drug, The occurrence of hemarthrosis,deep venous thrombosis( DVT)and pulmonary embolism were observed after surgery, Results Hemorrhage were founded 16 cases (8, 8% )in treatment group and 2 cases(1, 3% )in control group, DVT were founded 1 case in treatment group and 5 cases in control group by sonogram, Symptomatic DVT was not be founded in 2 groups, Symptomatic pulmonary embolism was founded 1 case in control group, Conclusion The antithrombotic drugs could cause the hemarthrosis after arthroscopic surgery of the knee,the application of which is not necessary for patients without risk factors, The functional rehabilitation exercises can pre_vent DVT and pulmonary embolism.%目的:探讨膝关节镜术后低分子肝素的应用价值。方法分析2012年1月_2013年1月337例膝关节镜手术,术后分为治疗组180例和对照组157例,治疗组予常规预防应用低分子肝素钙,对照组不应用低分子肝素及其它抗凝血药物和辅助溶血栓药物。观察术后关节积血、下肢深静脉血栓栓塞和肺栓塞的发生率。结果关节积血:治疗组16例(8,8%);对照组2例(1,3%)。术后30d 内经超声确诊发生患肢深静脉血栓栓塞:治疗组1例;对照组5例。2组均未发现具有临床症状的深静脉血栓栓塞,治疗组也未发现具有明显临床症状肺栓塞,但对照组发生1例。结论应用抗凝血药物是膝关节镜术后关节积

  10. A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital.

    Science.gov (United States)

    Ahmad, Akram; Patel, Isha; Asani, Himani; Jagadeesan, M; Parimalakrishnan, S; Selvamuthukumaran, S

    2015-01-01

    Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs. The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease. This was a noninvasive prospective observational descriptive study carried out at a multi-specialty tertiary care teaching hospital situated in rural Tamil Nadu, India. Male and female coronary heart disease (CHD) patients aged 35-75 years newly diagnosed or those having a history of CHD were included. The intervention group received enoxaparin for 5 days. A series of resting the electrocardiogram, prothrombin time and ADRs were measured in all patients during days 1 and 21 respectively. Compared to unfractionated heparin group of patients, the average prothrombin time was significantly higher (P < 0.0001) whereas hypokalemia was significantly lower (P < 0.02) in enoxaparin group of patients. Even though recurrence of angina and ADRs such as bleeding, nausea, headache and sudden cough occurred less frequently in the enoxaparin group of patients compared to unfractionated heparin group of patients, the differences were not significant. Antithrombotic therapy with enoxaparin plus aspirin was safer and more effective than unfractionated heparin plus aspirin, in reducing the incidence of ischemic events in patients with unstable angina or myocardial infarction in the early phase.

  11. Heparinization during percutaneous cardiac catheterization in children.

    Science.gov (United States)

    Netz, H; Madu, B; Röhner, G

    1987-01-01

    The effect of heparin on blood clotting was studied by measuring the activated clotting time (ACT) in 120 infants and children with congenital heart disease after a single intravenous bolus of 100 IU heparin/kg body weight. Before heparinization, infants and children with cyanotic heart disease showed signs of hypocoagulation. Heparin bolus led to a threefold increase of ACT after 15 min. After 1 h, the ACT was still two times the normal value. Any further administration of heparin may be based on ACT monitoring.

  12. Heparin platelet factor 4 antibody positivity in pseudothrombocytopenia.

    Science.gov (United States)

    Balcik, Ozlem Sahin; Akdeniz, Derya; Cipil, Handan; Uysal, Sema; Isik, Ayse; Kosar, Ali

    2012-01-01

    Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.

  13. Stepwise inhibition of T cell recruitment at post-capillary venules by orally active desulfated heparins in inflammatory arthritis

    Science.gov (United States)

    Al Faruque, Hasan; Kang, Jin Hee; Hwang, Seung Rim; Sung, Shijin; Alam, Md. Mahmudul; Sa, Keum Hee; Nam, Eon Jeong; Byun, Young Ro; Kang, Young Mo

    2017-01-01

    Identification of the structure-function relationship of heparin, particularly between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory activities, is critical in order to evaluate the biological effects of heparin, especially in conjunction with modifications for oral formulation. In this study, we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic modifications have differential effects on the blocking of interactions between sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH to interfere with T cell adhesion via selectin-sLeX interactions. Furthermore, 6DSHbD coated on the apical surface of inflamed endothelium directly blocked the adhesive interactions of circulating T cells, which was confirmed in vivo by suppressing T cell adhesion at post-capillary venular endothelium. Thus, in series with our previous study demonstrating inhibition of transendothelial migration, oral delivery of low anticoagulant LMWH to venular endothelium of inflamed joint tissues ameliorated arthritis by the stepwise inhibition of T cell recruitment and provides a rationale for the development of modified oral heparins as innovative agents for the treatment of chronic inflammatory arthritis. PMID:28419144

  14. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo

    2013-01-01

    Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.

  15. Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide, glutathione peroxidase, and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Qingde Wang; Guixiang Cui; Hongxia Liu; Yizhao Li; Fengshan Wang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that low molecular weight heparin-superoxide dismutase (LMWH-SOD) conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE: To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide (NO), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING: A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS: A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation (sham-operated group). Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS: Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups: physiological saline, LMWH-SOD, SOD, LMWH + SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD (20 000 U/kg) and LMWH (LMWH dose calculated according to weight ratio, LMWH: SOD = 23.6:51), and LMWH (dose as in the LMWH + SOD group) were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES: Serum levels of NO, MPO, and GSH-Px. RESULTS: Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum

  16. Determination of heparin sodium anticoagulation plasma concentration of the electrolyte and the study on the normal reference value%肝素钠抗凝血浆测定电解质浓度及正常参考值研究

    Institute of Scientific and Technical Information of China (English)

    蒲泽晏; 丁波; 李祥坤; 范婵

    2012-01-01

    目的 比较用间接电极法测定血清和肝素钠抗凝血浆电解质浓度的差别,探讨肝素钠抗凝血浆电解质浓度的正常参考值.方法 采用罗氏MUDULAR ISE900模块式电解质分析仪检测70例体检者血清和肝素钠抗凝血浆的电解质浓度.结果 血清与肝素抗凝血浆的K+、Na+、Cl-的测定结果差异有统计学意义(P<0.01),平均差值分别为0.24、1.42、0.94 mmol/L,相对偏差分别为5.60%、0.99%和0.89%.Na+和Cl-差别小,相对偏差小于1%,在临床上无实际意义;K+的差异已超过5%,且相对恒定.统计1 739例健康体检者肝素钠抗凝血浆电解质浓度,以x±2s为正常参考质范围,则K+:3.27~4.67 mmol/L,Na+:137.9~147.5 mmol/L,Cl-:99.2~110.8 mmol/L.结论 肝素钠是一种较理想的电解质抗凝剂,适合于电解质的测定,但是肝素钠抗凝血浆K+明显低于血清,不能沿用血清的正常参考值,建议各实验室建立自已的正常参考范围.%Objective To compare the; difference of serum and heparin sodium anticoagulation plasma electrolyte concentration by indirect electrode method,and to explore the normal reference values of heparin sodium anticoagulation plasma electrolyte con -cent ration .Methods Using the Roche MUDULAR ISE900 modular electrolyte analyzer to test 70 healthy persons electrolyte in serum and heparin sodium anticoagulant plasma . Results The difference of K,Na and Cl lenels were statistically significant (P< 0 .01),The average difference of the serum and plasma K,Na and Cl were 0 .24 mmol/L,1 .42 mmol/L and 0 .94 mmol/L respectively,and the relative deviation were 5 .6%,0 .99% and 0 .89%.The difference of Na and Cl was small and the relative deviation were less than l%,which no practical significance was in clinic ;while the difference of the K in serum and plasma has exceeded 5/o and constant relatively .We analyzed the concentration of plasma electrolyte in 1 739 healthy examination adults .The normal reference value was le±2s

  17. Anticoagulant Resistance

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte

    Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...

  18. The use of long-term low-molecular weight heparin for the treatment of venous thromboembolism in palliative care patients with advanced cancer : a case series of sixty two patients

    NARCIS (Netherlands)

    Noble, Sir; Hood, K.; Finlay, I. G.

    2007-01-01

    The advantages of low-molecular weight heparin (LMVVH) over warfarin, in the treatment of cancer associated venous thromboembolism (VTE) are well reported. However the studies supporting LMWH include few patients representative of the palliative care population. Although LMWH has advantages over war

  19. POSSIBILITIES OF USING LOW-MOLECULAR-WEIGHT HEPARIN IN THE COMPLEX TREATMENT OF WOMEN WITH TUMORS OF THE REPRODUCTIVE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. G. Kedrova

    2017-01-01

    Full Text Available Benign and malignant tumors of the organs of the female reproductive system are the most common diseases requiring medical and surgical treatment. They are rarely the cause of acute complications. However, the thromboembolic disease is a serious illness, sometimes causing death due to acute the pulmonary embolism. Venous thromboembolism secondary to Benign and malignant tumors of the organs of the female reproductive system should be considered in a female presenting with abdominal mass and pelvic pressure. Thromboembolic disease secondary to large tumors should be treated with anticoagulation then hysterectomy. The article presents an analysis of modern literature on optimal prevention of the pulmonary thromboembolism in patients with tumors of the female reproductive system. There are analysis data of 17 (0.7 % cases of the pulmonary thromboembolism that occurred of 2358 gynecological and oncogynecologic patients.

  20. Anticoagulant Therapy In Ischemic Stroke Or TIA

    Directory of Open Access Journals (Sweden)

    Kaveh Mehrvar

    2017-02-01

    Full Text Available Stroke is the leading cause of disability and the third leading cause of death  . Anticoagulants   have been used to treat patients with acute ischemic stroke for many years. Despite their widespread use, the usefulness of emergency anticoagulation is a subject of debate. Disagreements exist about the best agent to administer, the route of administration, the use of a bolus dose to start treatment, the level of anticoagulation required, and the duration of treatment. There are 2 types of anticoagulants: Parenteral and oral. Heparin is an anticoagulant that used parenteral. Oral anticoagulants are including Warfarin and new anticoagulants such as Dabigatrn,Rivaroxaban ,Apixaban and other newer drugs. In patients with noncardioembolic  ischemic stroke or TIA antiplatelet agents are treatment of choice and preferred to anticoagulants. In cardioembolic  ischemic stroke or TIA with high risk of reembolization  anticoagulants  are considered as preferred treatment.  Warfarin, apixaban10mg/d ,Rivaroxaban20mg/d, and dabigatran 150 mg/d are all indicated for the prevention of recurrent stroke in patients with nonvalvular AF, whether paroxysmal or permanent.Also anticoagulant therapy is recommended for ischemic stroke or TIA patients in the setting of acute MI, atrial or ventricular thrombosis or dilated and restricted cardiomyopathy. Some valvular heart diseases are other indication for anticoagulant therapy in ischemic stroke or TIA patients. Ischemic  Stroke or TIA in patients with Cerebral vein thrombosis and  known hypercoagulable state specially anti phospholipid antibody syndrome are other indications for anticoagulant treatment.

  1. Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies.

    Science.gov (United States)

    Lecumberri, Ramón; Páramo, José A; Rocha, Eduardo

    2005-09-01

    The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens.

  2. Stabilisation of SWNTs by alkyl-sulfate chitosan derivatives of different molecular weight: towards the preparation of hybrids with anticoagulant properties

    Science.gov (United States)

    Fatouros, Dimitrios G.; Power, Kieron; Kadir, Omar; Dékány, Imre; Yannopoulos, Spyros N.; Bouropoulos, Nikolaos; Bakandritsos, Aristides; Antonijevic, Milan D.; Zouganelis, George D.; Roldo, Marta

    2011-03-01

    We have previously demonstrated that chitosan derivative N-octyl-O-sulfate chitosan (NOSC), which presents important pharmacological properties, can suspend single walled carbon nanotubes (SWNTs) up to 20 times more effectively than other chitosan derivatives in an aqueous environment. In an attempt to further investigate the impact of different molecular weights of chitosan to the solubilization and anticoagulant properties of these hybrids an array of NOSC derivatives varying their molecular weight (low, medium and high respectively) was synthesised and characterised by means of FT-IR spectroscopy, NMR spectroscopy and thermal gravimetric analysis (TGA). Microwave and nitric acid purified SWNTs, characterised by FT-IR spectroscopy, transmission electron microscopy (TEM) and Raman spectroscopy, were colloidally stabilised by these polymers and their anticoagulant activity was assessed. The results revealed that the low molecular weight NOSC coated SWNTs exhibit the highest activity when 0.5 mg mL-1 NOSC solutions are used, activity which is similar to that of the free polymer. Preliminary studies by exposure of these hybrids to Brine Shrimp (Artemia) cysts revealed no effect on the viability of sub-adult Artemia. Our findings suggest the possibility of tailoring these nanomaterials to bear the required properties for application as biocompatible building blocks for nanodevices including biosensors and biomaterials.We have previously demonstrated that chitosan derivative N-octyl-O-sulfate chitosan (NOSC), which presents important pharmacological properties, can suspend single walled carbon nanotubes (SWNTs) up to 20 times more effectively than other chitosan derivatives in an aqueous environment. In an attempt to further investigate the impact of different molecular weights of chitosan to the solubilization and anticoagulant properties of these hybrids an array of NOSC derivatives varying their molecular weight (low, medium and high respectively) was synthesised

  3. Biomedical application of low molecular weight heparin/protamine nano/micro particles as cell- and growth factor-carriers and coating matrix.

    Science.gov (United States)

    Ishihara, Masayuki; Kishimoto, Satoko; Takikawa, Makoto; Hattori, Hidemi; Nakamura, Shingo; Shimizu, Masafumi

    2015-05-22

    Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm-3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.

  4. Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization

    Institute of Scientific and Technical Information of China (English)

    Wei Lai; Shi-Chun Lu; Guan-Yin Li; Chuan-Yun Li; Ju-Shan Wu; Qing-Liang Guo; Meng-Long Wang; Ning Li

    2012-01-01

    AIM:To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion alter splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly.Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63patients in group A (63/153,41.17%) and 31 patients in group B (31/148,20.94%).There were 50 (32.67%)patients in group A and 27 (18.24%) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50 (79.37%) in group A and 26 (83.87%) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.

  5. The application of low molecular weight heparin and sodium citrate in continuous renal replacement therapy%枸橼酸钠对比低分子肝素抗凝在持续肾脏替代治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    赵飞; 刘培俊; 何先弟

    2014-01-01

    Objective To compare the application of sodium citrate and heparin in the treatment of CRRT through a retrospective analysis .Methods A total of 53 patients were randomly divided into two groups , patients in the two groups were treated with sodium citrate and low molecular weight heparin for CRRT pre -wash. We comparred the coagulation ,electrolyte, acid-base balance and the life of the filter pipeline of the two groups . Results The life of filter of citrate hemodialysis group was significantly longer than low molecular weight heparin group.The differences of APTT and TT between the two groups was statistically significant (P<0.05).Sodium citrate was precede heparin in anticoagulant effect for it's stable electrolyte and acid -base balance .Conclusions Anticoagulation of sodium citrate is safe and effective , suitable for promotion .Closely observe during dialysis and adjust the dose of sodium citrate according to arterial blood gas and electrolyte can ensure the successful treatment.%目的:通过回顾性分析比较枸橼酸钠与肝素抗凝在CRRT 治疗中的应用。方法纳入54例患者,随机分为两组,分别接受枸橼酸钠,低分子肝素预冲CRRT,同步抗凝,比较凝血指标、电解质和酸碱平衡以及滤器管路寿命。结果枸橼酸盐组血液透析器使用时间明显长于低分子肝素组。枸橼酸盐组在血液透析中APTT、PT与低分子肝素组比较,差异均有统计学意义( P<0.05),应用枸橼酸钠局部抗凝后血滤管道内血液的凝血指标(APTT、PT)延长,经过滤器后凝血指标变化不大(P>0.05),体内静脉血凝血指标恢复正常范围内;低分子肝素组滤器前后管道中凝血指标变化不大(P>0.05),与枸橼酸钠组比较,低分子肝素组在体内的( APTT、PT)均延长。结论枸橼酸钠抗凝方式安全有效,适于推广。在透析过程中密切观察,依据动脉血气,电解质结果调整枸橼酸

  6. Safety of anticoagulation after hemorrhagic infarction.

    Science.gov (United States)

    Pessin, M S; Estol, C J; Lafranchise, F; Caplan, L R

    1993-07-01

    Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke in an anticoagulated individual, is usually associated with clinically stable or improving neurologic signs; fear of transforming the hemorrhagic infarction into a hematoma, however, usually prompts cessation of anticoagulation until the blood has cleared on CT, despite the recognized risk of recurrent embolism during this non-anticoagulated period. We now report our experience with 12 patients with hemorrhagic infarction who remained anticoagulated. Eleven men and one woman, ages 33 to 77, developed hemorrhagic infarction while on heparin, warfarin, or both, for prevention of recurrent embolism. Patients were either continued on uninterrupted anticoagulation from stroke onset (n = 6), or anticoagulation was withheld for several days and then resumed (n = 4), or it was withheld for 5 and 14 days (n = 2) after stroke onset and then continued uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven patients had a definite cardioembolic source for stroke (atrial fibrillation, seven; ventricular thrombus, two; and ventricular dyskinesia, two). One patient had carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied in size and were located in the middle cerebral artery territory in 11 patients and posterior cerebral artery territory in one. All patients remained clinically stable or improved on anticoagulation. Serial CTs showed fading hemorrhagic areas. When the risk of recurrent embolism is high, anticoagulation may be safely used in some patients with hemorrhagic infarction.

  7. Observation of the effect of urokinase thrombolysis combined the guide wire fragmentation and low molecular heparin anticoagulation for the treatment of arteriovenous fistula embolization%尿激酶溶栓联合导丝碎栓及低分子肝素抗凝治疗血液透析患者动静脉内瘘栓塞的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张雷; 柯斯奇

    2015-01-01

    Objective To analyze the curative effect used the common urokinase thrombolysis combined with topo-guide-wire fragmentation and low molecular heparin in the treatment of hemodialysis patients with arteriove-nous fistula embolization and explore the prospects of its application.Methods 30 hemodialysis patients with arterio-venous fistula embolization were divided into 15 cases of thrombolysis group and 15 cases of thrombectomy group ac-cording to the voluntary.The thrombolysis group was given simple urokinase thrombolysis,and the thrombectomy group was given thrombectomy combined with anticoagulant therapy.The curative effect and the difference in complication were compared.Results In curative effect,the recanalization rate,using time after recanalization,and dosage of uro-kinase of the thrombectomy group were better than those of the thrombolysis group[13cases vs.7cases,(22.13 ± 17.51)months vs.(11.05 ±10.55)months,(40.48 ±22.26)ten thousands IU vs.(60.29 ±15.81)ten thousands IU,χ2 =5.40,t=2.10,all P0.05).For the thrombectomy group,there were fewer cases of re -embolization after recanalization (2 cases/13 cases vs.4 cases/7 cases,χ2 =3.85,P <0.05),but more cases of organ embolism(4 cases vs.0 cases,χ2 =4.62,P<0.05).Conclusion Compared with the traditional urokinase thrombolytic therapy,the guide wire fragmentation combined with low molecular weight hepa-rin anticoagulant therapy has a higher fistula recanalization rate and a lower re-embolization rate.It does not increase the incidence of bleeding complications.Besides,it can extend the use of internal fistula.However,it may cause the serious organ embolism,so it is necessary to strictly grasp the indications,applying only to the patients who are in the poor efficiency of thrombolytic and unable to have another operation.%目的:分析常规尿激酶溶栓联合局部导丝碎栓和低分子肝素抗凝治疗血液透析患者动静脉内瘘栓塞的疗效,探讨其应用前景。方法30例血液透

  8. Application of different concentrations of heparin anticoagulant autologous blood recovery technology in ab-dominal trauma operation%自体血液回收技术中不同浓度肝素抗凝剂在腹部外伤手术中的应用

    Institute of Scientific and Technical Information of China (English)

    王开秀; 李晓玲; 刘辉梅

    2014-01-01

    目的:探讨自体血液回收技术应用不同浓度肝素抗凝剂在腹部外伤手术中的效果,为临床自体血液回收选择最适宜的肝素浓度,增加患者自体输血的安全系数。方法将40例腹部外伤手术使用自体血液回收技术的患者随机分为A、B两组,各20例。 A组抗凝剂为0.9%生理盐水500 mL加肝素钠12500 U;B组抗凝剂为0.9%生理盐水500 mL加肝素钠25000 U,比较两组患者失血量、自体血回输量、手术前后红细胞压积、血小板、凝血酶原时间( PT)、活化凝血酶原时间(APTT)、血红蛋白(Hb)的变化。结果两组患者术中平均失血量A组为(2605.15±29.68)mL,B组为(2611.59±21.58) mL;A组回输量为(1524.86±26.15)mL,B组(1511.24±25.75)mL,差异均无统计学意义(均P>0.05)。而两组组内回输自体血前与回输自体血后比较Hb、红细胞压积(HCT)差异均有统计学意义(均P<0.05),PT、APTT的差异则无统计学意义(均P>0.05)。结论通过分析自体血液回收不同浓度肝素抗凝剂在腹部外伤手术中的应用效果,认为12500 U肝素浓度作为抗凝剂可用于自体血液回收,安全可靠。%Objective To study the effect of autologous blood recovery with different concentrations of heparin in anticoagu-lant application in abdominal trauma surgery.To choose a most suitable concentration of heparin for clinical autologous blood recovery amd to increase the safety factor of autologous blood transfusion in patients.Methods 40 cases of patients with abdominal trauma using autologous blood recovery operation were randomly divided into A and B group.A group included 20 cases,B group included 20 cases. In group A,anticoagulant was used with 500 mL of 0.9%saline water and heparin sodium 12500 U.Anticoagulant was used with 0.9%saline water 500 mL and heparin sodium 25000 U in group B.The blood loss,autologous blood

  9. Effects of topical application of 10,000 IU heparin on patients with perineal dermatitis and second-degree burns treated in a public pediatric hospital.

    Science.gov (United States)

    Ferreira Chacon, Julieta Maria; Mello de Andrea, Maria Lydia; Blanes, Leila; Ferreira, Lydia Masako

    2010-11-01

    High-molecular-weight sodium heparin (10,000 IU) has been developed based on studies conducted on burn patients; it has anti-inflammatory, antigenic and anticoagulant properties. The aim of this paper was to evaluate the effects of topical application of sodium heparin spray on two immunosuppressed patients (a child and a young person) with perineal dermatitis and an immunosuppressed child with second-degree burns. This is a report of three clinical cases treated in a pediatric hospital. Sodium heparin spray (10,000 IU) was applied at a dose of 4200 IU per percentage of body surface area affected over the hyperemic region. Heparin spray treatment was discontinued after crust formation and wound reepithelialization; essential fatty acid was applied until spontaneous separation of the crust or total wound reepithelialization. Heparin spray had analgesic, angiogenic and anti-inflammatory effects, and did not require secondary wound closure. Pain control was of fundamental importance to the patients; in the three cases, improvement in analgesia was achieved within 24 h of treatment. The topical application of heparin spray in patients with perineal dermatitis or superficial second-degree burns demonstrated good tolerability, resulted in good aesthetic outcomes, and reduced pain. Copyright © 2010 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  10. [Set up of a protocol for heparin use in special patients].

    Science.gov (United States)

    Manresa Ramón, N; Nájera Pérez, Ma D; Page del Pozo, Ma Ángeles; Sánchez Martínez, I; Sánchez Catalicio, Ma del M; Roldán Schilling, V

    2014-04-01

    Low-molecular weight (LMW) heparins bring a series of advantages as compared to non-fractionated heparin (NFH), such as safety, efficacy, bioavailability, fewer monitoring, and persistent anti-coagulant response. There exist, however, a concern about their use in particular patients that may require a special control, such as those with renal failure, age over 75 years, obesity, and pregnancy. The aim of this study was the set up between the department of Pharmacy, Hematology, and Internal Medicine of a consensus protocol for the follow-up ad monitoring of LMWH in patients requiring a special control. For this purpose, we carried out a bibliographical review of the different heparins used under de above mentioned conditions. Based on the evidence available and the consensus among the members of the working group, we established a protocol that contained recommendations on prophylaxis, management and monitoring by means of the determination of anti-Xa factor. Besides, we included some clues on the therapeutic figures of anti-Xa and administration schedules for obtaining anti-Xa values within the range. Enoxaparin was the selected heparin given the evidence and its availability at our center.

  11. Simultaneous immobilization of heparin and gentamicin on polypropylene textiles: a dual therapeutic activity.

    Science.gov (United States)

    Degoutin, Stéphanie; Jimenez, Maude; Chai, Feng; Pinalie, Thibaut; Bellayer, Severine; Vandenbossche, Marianne; Neut, Christel; Blanchemain, Nicolas; Martel, Bernard

    2014-11-01

    The aim of this work was to prepare a nonwoven polypropylene (PP) textile functionalized with bioactive molecules in order to improve simultaneously anticoagulation and antibacterial properties. The immobilization of either heparin (anticoagulation agent) or gentamicin (aminoglycoside class antibiotic) alone has already been proven to be effective on PP nonwoven textiles. In this work, we managed to go further, by immobilizing both heparin and gentamicin at the same time on one unique textile. A successive immersion in different heparin and gentamicin bathes successfully led to a dual drug coated textile, as confirmed by several characterization techniques (Fourier transform infrared-attenuated total reflectance, X-ray photoelectron spectroscopy, and scanning electron microscopy). The immobilization times were varied in order to determine the best compromise between cytocompatibility, anticoagulant effect, and antimicrobial activity. Short immersion times in gentamicin solutions confer very good antimicrobial activity to the textile and avoid cytotoxicity, whereas long immersion times in heparin solution were necessary to observe a significant anticoagulant effect.

  12. Sulfated polysaccharide heparin used as carrier to load hydrophobic lappaconitine.

    Science.gov (United States)

    Sun, Wenxiu; Saldaña, Marleny D A; Fan, Liyan; Zhao, Yujia; Dong, Tungalag; Jin, Ye; Zhang, Ji

    2016-03-01

    One-step self-assembly was used to prepare pH-sensitive lappaconitine-loaded low-molecular-weight heparin (LMWH-LA) and to demonstrate that the sulfur group promotes dissolution and has synergistic effect on the analgesic property of lappaconitine (LA). The LMWH-LA was characterized in terms of releasing behavior, pH-sensitivity, analgesic activity and anticoagulation property. The drug loading level of LA in low-molecular-weight heparin (LMWH) reached 24.3% (w/w). The LA, self-assembled in LMWH, released faster in an acidic environment than that in neutral or alkaline environments. Analgesic experiments showed that the LMWH-LA had earlier onset time and longer duration than the LA. Compared with LMWH, the LMWH-LA can reduce clotting time more effectively. These results suggest that the LMWH is a good template and has great potential to achieve synergistic effect of LA. In addition, similar macromolecular structure can be used as a new natural polymeric carrier for loading hydrophobic alkaloids.

  13. Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements

    NARCIS (Netherlands)

    Nielen, J.T.; Dagnelie, P.C.; Emans, P.J.; Veldhorst-Janssen, N.; Lalmohamed, A.; Staa, T.P. van; Boonen, A.E.; Bemt, B.J. van den; Vries, F de

    2016-01-01

    BACKGROUND: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery. OBJECTIVE: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral

  14. Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements

    NARCIS (Netherlands)

    Nielen, Johannes T H; Dagnelie, Pieter C; Emans, Pieter J; Veldhorst-Janssen, Nicole; Lalmohamed, Arief; van Staa, Tjeerd-Pieter; Boonen, Annelies E R C H; van den Bemt, Bart J F; de Vries, Frank

    2016-01-01

    BACKGROUND: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery. OBJECTIVE: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagu

  15. Delayed-onset heparin-induced thrombocytopenia presenting with multiple arteriovenous thromboses: case report

    Directory of Open Access Journals (Sweden)

    Omran Abbas

    2007-11-01

    Full Text Available Abstract Background Delayed-onset heparin-induced thrombocytopenia with thrombosis, albeit rare, is a severe side effect of heparin exposure. It can occur within one month after coronary artery bypass grafting (CABG with manifestation of different thrombotic events. Case presentation A 59-year-old man presented with weakness, malaise, bilateral lower limb pitting edema and a suspected diagnosis of deep vein thrombosis 18 days after CABG. Heparin infusion was administered as an anticoagulant. Clinical and paraclinical work-up revealed multiple thrombotic events (stroke, renal failure, deep vein thrombosis, large clots in heart chambers and 48 ×103/μl platelet count, whereupon heparin-induced thrombocytopenia was suspected. Heparin was discontinued immediately and an alternative anticoagulant agent was administered, as a result of which platelet count recovered. Heparin-induced thrombocytopenia, which causes thrombosis, is a serious side effect of heparin therapy. It is worthy of note that no case of delayed-onset heparin-induced thrombocytopenia with thrombosis associated with cardiopulmonary bypass surgery has thus far been reported in Iran. Conclusion Delayed-onset heparin-induced thrombocytopenia should be suspected in any patient presenting with arterial or venous thromboembolic disorders after recent heparin therapy, even though the heparin exposure dates back to more than a week prior to presentation; and it should be ruled-out before the initiation of heparin therapy.

  16. Sulfation patterns determine cellular internalization of heparin-like polysaccharides

    OpenAIRE

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R.; Kuberan, Balagurunathan

    2013-01-01

    Heparin is a highly sulfated polysaccharide which serves biologically relevant roles as an anticoagulant and anti-cancer agent. While it is well known that modification of heparin’s sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently-labeled ...

  17. Inhibition of allergic airway responses by heparin derived oligosaccharides: identification of a tetrasaccharide sequence

    Directory of Open Access Journals (Sweden)

    Ahmed Tahir

    2012-01-01

    Full Text Available Abstract Background Previous studies showed that heparin's anti-allergic activity is molecular weight dependent and resides in oligosaccharide fractions of Objective To investigate the structural sequence of heparin's anti-allergic domain, we used nitrous acid depolymerization of porcine heparin to prepare an oligosaccharide, and then fractionated it into disaccharide, tetrasaccharide, hexasaccharide, and octasaccharide fractions. The anti-allergic activity of each oligosaccharide fraction was tested in allergic sheep. Methods Allergic sheep without (acute responder and with late airway responses (LAR; dual responder were challenged with Ascaris suum antigen with and without inhaled oligosaccharide pretreatment and the effects on specific lung resistance and airway hyperresponsiveness (AHR to carbachol determined. Additional inflammatory cell recruitment studies were performed in immunized ovalbumin-challenged BALB/C mice with and without treatment. Results The inhaled tetrasaccharide fraction was the minimal effective chain length to show anti-allergic activity. This fraction showed activity in both groups of sheep; it was also effective in inhibiting LAR and AHR, when administered after the antigen challenge. Tetrasaccharide failed to modify the bronchoconstrictor responses to airway smooth muscle agonists (histamine, carbachol and LTD4, and had no effect on antigen-induced histamine release in bronchoalveolar lavage fluid in sheep. In mice, inhaled tetrasaccharide also attenuated the ovalbumin-induced peribronchial inflammatory response and eosinophil influx in the bronchoalveolar lavage fluid. Chemical analysis identified the active structure to be a pentasulfated tetrasaccharide ([IdoU2S (1→4GlcNS6S (1→4 IdoU2S (1→4 AMan-6S] which lacked anti-coagulant activity. Conclusions These results demonstrate that heparin tetrasaccharide possesses potent anti-allergic and anti-inflammatory properties, and that the domains responsible for anti

  18. Pseudothrombocytopenia with multiple anticoagulant sample collection tubes

    Science.gov (United States)

    Kovacs, Ferenc; Varga, Marina; Pataki, Zsolt; Rigo, Erzsebet

    2016-01-01

    The knowledge of pseudothrombocytopenia (PTCP) is important for the accuracy of a clinical assessment and for avoiding unnecessary treatment. An elderly patient was hospitalized with left lung pneumonia. Severe thrombocytopenia [platelet (PLT) number: 18 × 109/L] without any clinical bleeding was found in ethylenediaminetetraacetic acid blood collection tube. PLT measurement was repeated in various anticoagulant [sodium citrate, lithium heparin, disodium oxalate, hirudin, and magnesium sulfate (Mg-sulfate)] sample collection tubes and all of them showed thrombocytopenia except with Mg-sulfate. To the best of our knowledge, PTCP with five anticoagulant sample collection tubes has not been reported earlier.

  19. Safety Assessment of Anticoagulation therapy in Patients with Hemorrhagic Cerebral Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Kavian Ghandehari

    2013-07-01

    hemisphere had a significant influence on the distribution of clinical courses (X2 = 5.867, df = 2, P = 0.044. Difference in distribution of clinical course among the two groups of our hemorrhagic CVT patients was not significant (X2 = 8.14, df = 1, P = 0.87.Conclusion: Patients with hemorrhagic CVT without other contraindication for anticoagulation should be treated either with dose-adjusted intravenous heparin or body-weight-adjusted subcutaneous low molecular-weight heparin.

  20. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis

    Directory of Open Access Journals (Sweden)

    Arno M. Wiersema

    2016-01-01

    Full Text Available A large variety exists for many aspects of the use of heparin as periprocedural prophylactic antithrombotics (PPAT during peripheral arterial interventions (PAI. This variation is present, not only within countries, but also between them. Due to a lack of (robust data, no systematic review on the use of heparin during PAI could be justified. A synopsis of all available literature on heparin during PAI describes that heparin is used on technical equipment to reduce the thrombogenicity and in the flushing solution with saline. Heparin could have a cumulative anticoagulant effect when used in combination with ionic contrast medium. No level-1 evidence exists on the use of heparin. A measurement of actual anticoagulation status by means of an activated clotting time should be mandatory.

  1. Determination of the Molecular Weight of Low-Molecular-Weight Heparins by Using High-Pressure Size Exclusion Chromatography on Line with a Triple Detector Array and Conventional Methods

    Directory of Open Access Journals (Sweden)

    Antonella Bisio

    2015-03-01

    Full Text Available The evaluation of weight average molecular weight (Mw and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs. As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC, the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn by HP-SEC combined with a triple detector array (TDA was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS; refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of

  2. A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. MethodsEighty-five severe-type patients (severe group) and 71 critical-type patients (critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. ResultsThe frequency of CRRT in the critical group was higher than thatin the severe group (P<0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was signiifcantly higher than that of the severe group (P=0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

  3. Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava.

    Science.gov (United States)

    Li, Na; Liu, Xue; He, Xiaoxi; Wang, Shuyao; Cao, Sujian; Xia, Zheng; Xian, Huali; Qin, Ling; Mao, Wenjun

    2017-03-01

    An anticoagulant-active polysaccharide PF2 was extracted with boiling water from the green seaweed Monostroma angicava, further purified by anion-exchange and size-exclusion chromatography. PF2 was a rhamnan-type sulfated polysaccharide with molecular weight of about 88.1kDa. Results of chemical and spectroscopic analyses demonstrated that PF2 consisted of→3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→residues, with partially branches at C-2 of→3)-α-l-Rhap-(1→residues. Sulfate groups were substituted at C-3 of →2)-α-l-Rhap-(1→ residues. The sulfated polysaccharide PF2 had a high anticoagulant action, and the mechanism of anticoagulant activity mediated by PF2 was mainly attributed to strong potentiation thrombin by heparin cofactor II. PF2 also exhibited weak effect on antithrombin-dependent thrombin or factor Xa inhibition. The fibrin(ogen)olytic activity and thrombolytic activity of PF2 were also evaluated. The investigation revealed that PF2 was a novel sulfated rhamnan differing from previously described sulfated polysaccharides from green seaweed and could be a potential anticoagulant polysaccharide.

  4. Heparin-resistant Thrombosis Due to Homozygous Antithrombin Deficiency Treated With Rivaroxaban : A Case Report

    NARCIS (Netherlands)

    Van Bruwaene, Lore; Huisman, Albert; Urbanus, Rolf T; Versluys, Birgitta

    BACKGROUND: Heparin fulfills its anticoagulant action through activation of antithrombin (AT), and thus thrombosis secondary to AT deficiency can be associated with heparin resistance. OBSERVATION: A 12-year-old girl with severe venous thrombosis was referred to us because of undetectable anti-Xa

  5. Production methods for heparosan, a precursor of heparin and heparan sulfate

    NARCIS (Netherlands)

    Chavaroche, A.A.E.; Broek, van den L.A.M.; Eggink, G.

    2013-01-01

    Heparin and heparan sulfate belong to the glycosaminoglycan family. Heparin which is known as a powerful anticoagulant has been also described to have potential in therapeutic applications such as in the treatment against cancer and prevention of virus infections. Heparan sulfate, an analog of hepar

  6. Effect of fibronectin on the binding of antithrombin III to immobilized heparin

    NARCIS (Netherlands)

    Byun, Youngro; Jacobs, Harvey A.; Feijen, Jan; Kim, Sung Wan

    1996-01-01

    An objective of this research is to verify the mechanism of anticoagulant activity of surface-immobilized heparin in the presence of plasma proteins. The competition and binding interaction between immobilized heparin and antithrombin III (ATIII)/thrombin have been described in vitro. However, the s

  7. Low-molecular-weight heparins for managing vasoocclusive crises in people with sickle cell disease: a summary of a cochrane systematic review.

    Science.gov (United States)

    van Zuuren, Esther J; Fedorowicz, Zbys

    2014-01-01

    We summarize a Cochrane systematic review that was conducted to assess the effects of low-molecular-weight heparins (LMWH) for managing vasoocclusive crises (VOC) in people with sickle cell disease. Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be divided into three broadly distinct clinical phenotypes characterized by either hemolysis, pain syndromes or organ damage. Pain is the most prominent symptom of vasoocclusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Searches included the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, abstract books of conference proceedings and several online trials registries (December 2012). One study (with an overall unclear to high risk of bias) comprising 253 participants was included. This study provided limited data, but concluded that tinzaparin resulted in a more rapid resolution of pain, and in a statistically significant lower number of hospitalization days compared to a placebo. Two minor bleeding events were reported as adverse events in the tinzaparin group. Based on the results from this single study, there is incomplete evidence to either support or refute the effectiveness of LMWH in people with sickle cell disease.

  8. Insight into the role of dual-ligand modification in low molecular weight heparin based nanocarrier for targeted delivery of doxorubicin.

    Science.gov (United States)

    Du, Hongliang; Liu, Mengrui; Yu, Aihua; Ji, Jianbo; Zhai, Guangxi

    2017-05-15

    Low molecular weight heparin nanoparticles (LMWH) modified by glycyrrhetinic acid (GA) (LMWH-GA) and further decorated by lactobionic acid (LA) (LA-LMWH-GA) were reported as novel hepatocellular carcinoma (HPC)-targeted carriers to overcome multidrug resistance (MDR) of doxorubicin (DOX). The drug-loaded nanoparticles had negative charge of around -25mV and average size range of 70-170nm. These nanoparticles performed sustained drug release in vitro and prolonged DOX residence time in blood circulation in vivo. Compared to free DOX, DOX-loaded nanoparticles demonstrated increased DOX accumulation in drug-resistance HepG2/ADR cells and enhanced in vitro therapeutic efficacy. However, DOX/LA-LMWH-GA with dual ligands didn't show higher cellular uptake and cytotoxicity than single GA modified DOX/LMWH-GA, although both GA-mediated and LA-mediated endocytosis were involved in their cell internalization. Uptake pathway inhibition study revealed the less efficacy of DOX/LA-LMWH-GA in cellular level could be attributed to the reduced effect of micropinocytosis and caveolae-mediated endocytosis in cellular uptake. Interestingly, the DOX-loaded nanoparticles developed from lower drug/carrier feeding ratio possessed higher performance in cell internalization and in vitro efficacy compared to those developed from higher drug/carrier feeding ratio, which could highlight the role of carrier in drug delivery process. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

    Science.gov (United States)

    Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

    2015-08-01

    The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered

  10. Heparinase Digestion-based Disaccharide Analysis of Clinical Heparin and Heparinoids Drug%临床肝素类药物酶解分析二糖组成

    Institute of Scientific and Technical Information of China (English)

    韩章润; 邢新会; 于广利; 曾洋洋; 张丽娟

    2015-01-01

    Heparin and low molecular weight heparin have been widely used in clinical therapy as anticoagulants in cardiovascular disease and in hemodialysis. Crude heparin is usually prepared from porcine intestinal mucosa. Purified heparin is a mixture of polysaccharides consisting mainly of repeating GlcNS(6S)-IdoA2S disaccharides and other disaccharides with different GlcNAc/GlcNS±3S±6S-GlcA/IdoA±2S residues. Heparin injections are drugs prepared from heparin active pharmaceutical ingredient ( API ) that is prepared from crude heparin. Low molecular weight heparins are dominant heparin-based drugs used clinically, which are prepared by degrading heparin into smaller sizes. As a result, low molecular weight heparins are sharing the same major disaccharides but have different reducing and non-reducing ends. In current study, we focused on the disaccharide compositional analysis of clinically used heparin and heparin-based drugs. HeparinaseⅠ,II, and Ⅲ were used to degrade all heparin and heparin-based drugs including heparin sodium injection, Enoxaparin sodium injection, Nadroparin calcium injection, Dalteparin sodium injection, Fondaparinux sodium into disaccharides. All the degraded products were analyzed by strong anion high perforance liquid chromatography ( SAX-HPLC) coupled with an UV-detector. Commercially available unsaturated disaccharide standards were then used for structral identification. Furthermore, unusual disaccharides present in Nadroparin, Dalteparin, and Fondaparinux were confirmed by reversed-phase ion pair HPLC coupled with mass spectrometry. The developed method produced detailed structural information, which should be useful for quality control of heparin and heparin-based drugs.%肝素是一类结构复杂的高分子糖类,以N-硫酸、6-O硫酸氨基葡萄糖和2-O硫酸艾杜糖醛酸为主要成分组成二糖。常见的肝素注射液是以未分级肝素为原料纯化灭菌制备而来,在临床上使用更为广泛的是将肝素降

  11. Cost analysis of bivalirudin versus reference anticoagulants without GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention for acute coronary syndrome in routine clinical practice. Pompidou registry.

    Science.gov (United States)

    Puymirat, E; Cohen, S; Védrenne, G; Caruba, T; Sabatier, B; Danchin, N; Durand, E

    2013-04-01

    Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to other anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study analyzed the cost/efficacy profile of bivalirudin-based anticoagulation strategy versus non bivalirudin-based anticoagulant strategy without use of GP IIb/IIIa inhibitors in routine clinical practice. From January 2009 to December 2010, 216 patients who underwent PCI for ACS at hospital Georges-Pompidou without GP IIb/IIIa inhibitors were studied. Of these patients, 24 (11%) received bivalirudin and 192 (88%) received others anticoagulants (mainly unfractionated heparin or low molecular weight heparin). Ischemic events and bleeding or transfusion were slightly lower in bivalirudin group (0 vs. 4.2%, P=0.60 and 4.2 vs. 8.9%, P=0.70, respectively). In spite of a higher cost of the medication, the overall cost of the bivalirudin strategy was slightly lower (9167±3688 € vs. 14,016±14,749 €, P=0.23), in relation with a shorter average duration of the hospital stay. In conclusion, in this limited, single-center, population of patients with ACS, the clinical efficacy and safety of bivalirudin appeared at least as good as that of reference anticoagulants in real world clinical practice, with no increase in overall costs.

  12. Increased accuracy in heparin and protamine administration decreases bleeding

    DEFF Research Database (Denmark)

    Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

    2009-01-01

    using the Hemochron RxDx system, which performs a baseline activated clotting time (ACT) value together with a heparin response test. An accurate heparin dose was calculated based on the Bull dose/response curve. Protamine doses were calculated by the same method. In the control group (25 patients...... values were obtained in both groups. Using the Hemochron RxDx, we observed a significant reduction in postoperative blood loss, as well as the amount of heparin and initial doses of protamine used during CPB. Individual patient managed anticoagulation during cardiac surgery using dose/response curve...

  13. A systematic review of contemporary trials of anticoagulants in orthopaedic thromboprophylaxis: suggestions for a radical reappraisal.

    Science.gov (United States)

    Chan, Noel C; Siegal, Deborah; Lauw, Mandy N; Ginsberg, Jeffrey S; Eikelboom, John W; Guyatt, Gordon H; Hirsh, Jack

    2015-08-01

    In the last decade, major advances in venous thromboembolism (VTE) prophylaxis in orthopaedic surgery have included the development of new anticoagulants that are poised to replace low molecular weight heparins (LMWHs) and improvements in operative and perioperative care that have likely led to a decline in the rates of symptomatic VTE and mortality independent of anticoagulant use. A systematic review of the literature was performed to identify phase III randomized controlled trials of VTE prevention that compared new anticoagulants (fondaparinux, rivaroxaban, dabigatran, apixaban) with LMWH (enoxaparin) in major elective orthopaedic surgery. Our aims were to obtain best estimates of the rates of patient important events (symptomatic VTE, mortality, and bleeding) in contemporary trials of VTE prevention, and to consider the implications of these contemporary rates for clinical practice and future research. Fourteen studies, which enrolled 40,285 patients, were included in the analyses. The combined median rates (ranges) for all five anticoagulants for symptomatic VTE and mortality to the end of follow-up were 0.99 % (0.15-2.58 %) and 0.26 % (0-0.92 %) respectively, whereas the median rate (range) of clinically important bleeding was 3.44 % (2.25-7.74 %). In contemporary trials of anticoagulants, the rates of symptomatic VTE and mortality are low, but the rates of clinically important post-operative bleeding remain relatively high. Based on these results, we propose that approaches that minimize bleeding without substantially reducing efficacy merit investigation, particularly if improvement in surgical and perioperative care have also resulted in falling baseline patient important VTE rates independent of anticoagulant use.

  14. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2016-08-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0: 1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC 50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  15. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2017-07-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  16. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Gómez-Outes A

    2013-05-01

    Full Text Available Antonio Gómez-Outes,1 M Luisa Suárez-Gea,1 Ramón Lecumberri,2 Ana Isabel Terleira-Fernández,3,4 Emilio Vargas-Castrillón,3,4 Eduardo Rocha51Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices, Madrid, 2Department of Hematology, University Clinic of Navarra, Pamplona, 3Department of Clinical Pharmacology, Hospital Clínico, Madrid, 4Department of Pharmacology, Universidad Complutense, Madrid, 5Department of Hematology, School of Medicine, University of Navarra, Pamplona, SpainAbstract: Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs, supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents, and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number. New anticoagulants in development for prophylaxis

  17. Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

    DEFF Research Database (Denmark)

    Bendstrup, K.E.; Newhouse, M.T.; Pedersen, Ole Finn;

    1999-01-01

    Inhaled heparin has been used for asthma treatment, but results have been inconsistent, probably due to highly varying lung doses. We determined the output per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations...... depended upon the viscosity and temperature of the solution. MMD was independent of formulation, temperature, or concentration and ranged from 5.61 to 7.03 /urn. Sodium heparin/calcium heparin in a concentration of 20,000 IU/mL in the jet nebulizer driven at 10 L/min produced the highest dose of heparin...... capable of reaching the lower respiratory tract. Mass balance was determined for these combinations with the jet nebulizer run until visible aerosol generation ceased. Of a loading dose of 80,000 IU of heparin, 45,000 IU remained in the dead space of the nebulizer, 20,000 IU was deposited...

  18. Heparin stability by determining unsubstituted amino groups using hydrophilic interaction chromatography mass spectrometry.

    Science.gov (United States)

    Fu, Li; Li, Lingyun; Cai, Chao; Li, Guoyun; Zhang, Fuming; Linhardt, Robert J

    2014-09-15

    The thermal instability of the anticoagulant heparin is associated, in part, with the solvolytic loss of N-sulfo groups. This study describes a new method to assess the increased content of unsubstituted amino groups present in thermally stressed and autoclave-sterilized heparin formulations. N-Acetylation of heparin samples with acetic anhydride-d6 is followed by exhaustive heparinase treatment and disaccharide analysis by hydrophilic interaction chromatography mass spectrometry (HILIC-MS). The introduction of a stable isotopic label provides a sensitive probe for the detection and localization of the lost N-sulfo groups, potentially providing valuable insights into the degradation mechanism and the reasons for anticoagulant potency loss.

  19. Low molecular weight heparin for the prevention of deep venous thrombosis: a suitable monitoring in elderly patients?

    Science.gov (United States)

    Mahé, Isabelle; Drouet, Ludovic; Chassany, Oliver; Grenard, Anne-Sophie; Caulin, Charles; Bergmann, Jean-François

    2002-01-01

    Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.5 +/- 10.7 years) hospitalized in a medical department receiving 4000 IU enoxaparin daily subcutaneously for the prevention of venous thromboembolic disease were studied. After the first injection of enoxaparin, the aXa of 57.4% patients was superior to 0.5 IU/ml while 69.4% had an aXa higher than 0.5 after 8.4 +/- 1.2 days. A negative relationship between aXa and body weight and a trend towards a positive correlation between aXa and age but not with creatinine clearance were noted. Our findings question the opportunity to monitor aXa in elderly patients receiving 4000 IU enoxaparin as antithrombotic prophylaxis.

  20. Effects of low molecular weight heparin on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Bing Xia; Hong Han; Ke-Jian Zhang; Jin Li; Guang-Song Guo; Ling-Ling Gong; Xian-Chang Zeng; Jun-Yan Liu

    2004-01-01

    AIM: To observe the effects of Iow molecular weight heparin (LMWH) on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.METHODS: Colitis was induced in female Sprauge-Dawley rats by colonic administration of 2, 4, 6-TNBS. LMWH, a dalteparin (150 U/kg, 300 U/kg) was subcutaneously administrated one hour before induction of colitis and went on once a day for 6 days. Then a half dose was given for the normal saline once a day for 14 days after treated by TNBS.Animals were sacrificed at 24 h, days 7 and 14 after induction of colitis. The colon was excised for the evaluation of macroscopic and histological findings and TNF-a immunohistochemical assay. Platelet surface P-selectin expression was determined by radioimmunoassay and serum IL-8 production was assayed by ELISA method.RESULTS: LMWH treatment in a dose of 300 U/kg for 14 days significantly improved colonic inflammation by histological examination. Serum IL-8 production in the 300 U/kg treatment group was more significantly decreased at day 14 than that at 24 h (P<0.05). However, platelet surface P-selectin expression and TNF-a staining in colonic tissue were not significantly different among the three groups.CONCLUSION: LMWH has an anti-inflammatory effect on TNBS induced colitis in rats. The effect is possibly related to inhibition of proinfiammatory cytokine IL-8, but not involved platelet surface P-selectin expression.

  1. A retrospective study on the use of a low-molecular-weight heparin for thromboembolism prophylaxis in large-volume liposuction and body contouring procedures.

    Science.gov (United States)

    Newall, Germán; Ruiz-Razura, Amado; Mentz, Henry A; Patronella, Christopher K; Ibarra, Francis R; Zarak, Alberto

    2006-01-01

    This retrospective study was designed to evaluate the efficacy of low-molecular-weight heparin (enoxeparin) as a prophylaxis for venous thromboembolism and deep venous thrombosis (DVT) in the management of large-volume liposuction, added body-contouring procedures, or both. The author present an 18-month experience with the use of this therapy for 291 consecutive patients. All the patients fell into the categories of high risk and highest risk for the development of deep vein thrombosis, embolism, or both. Three patients experienced transient DVT-like symptoms and underwent a thorough workup by an independent highly specialized critical care medical team. The results were found ultimately to be inconclusive for DVT and pulmonary embolism. However, all the patients experienced a complete recovery. The results show a 0% incidence of DVT and pulmonary embolism among patients who received enoxeparin as prophylaxis. The medication did not precipitate major bleeding when administered 1 h after surgery. This study offers the first report that describes the use of enoxeparin in aesthetic surgery for high-risk patients. The authors feel the need to inform their colleagues of the benefits obtained over the past 18 months by incorporating this therapy in large-volume liposuction and extensive body-contouring procedures performed during the same operative session. This study was conducted by a highly experienced surgical team in a fully accredited outpatient facility with established protocols for handling these types of procedures on a daily basis. The authors are optimistic about the results, and the use of enoxeparin is now part of their postoperative regimen in high-risk aesthetic surgery cases.

  2. Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1β and inhibiting syndecan-1 shedding in the intestinal mucosa.

    Directory of Open Access Journals (Sweden)

    Xian-fei Wang

    Full Text Available Low molecular weight heparin (LMWH exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18. Disease activity was scored by a disease activity index (DAI. Histological changes were evaluated by hematoxylin and eosin (HE staining. The mRNA levels of syndecan-1, interleukin (IL-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group. In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group. LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

  3. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    Science.gov (United States)

    Zhang, Ting; Xiong, Hui; Zohra Dahmani, Fatima; Sun, Li; Li, Yuanke; Yao, Li; Zhou, Jianping; Yao, Jing

    2015-04-01

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects.

  4. Heparin inhibits human coronary artery smooth muscle cell migration.

    Science.gov (United States)

    Kohno, M; Yokokawa, K; Yasunari, K; Minami, M; Kano, H; Mandal, A K; Yoshikawa, J

    1998-09-01

    Heparin, an anticoagulant, has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies, but the clinical trials of heparin in coronary balloon angioplasty have been negative. The current study, therefore, examined the effect of heparin on basal or stimulated migration by serum and platelet-derived growth factor (PDGF)-BB in cultured human coronary artery smooth muscle cells (SMCs) by Boyden's chamber method. In addition, the reversibility of the heparin effect on human coronary artery SMC migration was examined. Fetal calf serum (FCS) and PDGF-BB stimulated SMC migration in a concentration-dependent manner. Heparin in moderate to high concentration (10 to 100 U/mL) exhibited concentration-related inhibition of FCS- and PDGF-BB-stimulated SMC migration; however, a low concentration (1 U/mL) of heparin had no inhibitory effects. Heparin also had weak inhibitory effects on nonstimulated SMC migration. The SMCs that were exposed to a high concentration (100 U/mL) of heparin for 6 hours were capable of migrating after a short lag period of removal of heparin from the culture medium. These SMCs also showed recovery of responses to FCS and PDGF-BB by migrating significantly greater than the nonstimulated level. Furthermore, heparin-containing medium did not contain detached cells. These results indicate that heparin inhibits human coronary artery SMC migration, especially when stimulated by FCS or PDGF-BB, and that this inhibitory effect of heparin is reversible and not simply a function of killing cells.

  5. Peri-operative management of anticoagulation and antiplatelet therapy in gastrointestinal surgery.

    Science.gov (United States)

    Degirmenci, S-E; Steib, A

    2014-04-01

    Peri-operative management of the risks of hemorrhage and thrombosis related to gastrointestinal surgery tailored to patient characteristics are part of daily multidisciplinary practice tasks. The goal of this update is to discuss current practices concerning antithrombosis prophylaxis and the management of recently developed anticoagulants and antiplatelet agents. The duration of prophylaxis is 1 month for oncological surgery. The recommended doses in bariatric surgery are twice daily injections of low-molecular weight heparin without exceeding a total dose of 10,000 IU/day. Dual antiplatelet therapy is necessary for 6 weeks after placement of bare-metal stents, from 6-12 months for drug-eluting stents, and 12 months after an acute coronary artery syndrome. Abrupt discontinuation of antiplatelet therapy exposes the patient to an increased risk of thrombosis. Data are insufficient to make specific recommendations for antiplatelet therapy in gastrointestinal surgery. For major digestive surgery, prescription of daily aspirin should be discussed case by case. If discontinuation of treatment is absolutely necessary, this should be as short as possible (aspirin: 3 days, ticagrelor and clopidogrel: 5 days, prasugrel: 7 days). The modalities for elective management of new oral anticoagulants are similar to those for classical vitamin K antagonists (VKA) therapy, except that any overlapping with heparin administration must be avoided. In the emergency setting, an algorithm can be proposed depending on the drug, the available coagulation tests and the interval before performing surgery.

  6. Use of antiplatelet agents and anticoagulants for cardiovascular disease: current standards and best practices.

    Science.gov (United States)

    Faxon, David P

    2005-01-01

    Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding.

  7. Segurança da ablação de fibrilação atrial com RNI terapêutico: comparação com a transição com heparina de baixo peso Safety of ablation for atrial fibrillation with therapeutic INR: comparison with transition to low-molecular-weight heparin

    Directory of Open Access Journals (Sweden)

    Eduardo B. Saad

    2011-10-01

    Full Text Available FUNDAMENTO: O manejo ideal da anticoagulação oral (ACO no período pré- e pós-ablação de fibrilação atrial (FA ainda é motivo de controvérsia. OBJETIVO: Comparar duas estratégias de anticoagulação: suspensão da warfarina com a utilização de heparina de baixo peso molecular (HBPM e a realização da ablação sem a suspensão da warfarina, mantendo o RNI terapêutico (entre 2,0 e 3,0. MÉTODOS: 140 pacientes (pt portadores de FA persistente/ permanente submetidos à ablação por cateter de FA foram divididos em dois grupos: no grupo I (70 pt, a warfarina foi suspensa cinco dias antes do procedimento e utilizada terapia de transição com HBPM (enoxaparina 1 mg/kg 2x/dia pré-ablação e 0,5 mg/kg 2x/dia após o procedimento; no grupo II (70 pt, a warfarina não foi suspensa e o procedimento foi realizado com RNI terapêutico. Ambos os grupos receberam heparina intravenosa (TCA > 350 seg durante o procedimento. RESULTADOS: No Grupo I, observou-se complicação hemorrágica maior (1,4% e 4 pt (5,7% com complicações hemorrágicas menores. No Grupo II, 2 pt (2,8% apresentaram complicações hemorrágicas menores e 1 pt apresentou sangramento maior; porém, este ocorreu após uso de HBPM por RNI BACKGROUND: The ideal management of oral anticoagulation (OAC before and after catheter ablation for atrial fibrillation (AF is still controversial. OBJECTIVE: To compare two anticoagulation strategies for catheter ablation for AF: warfarin withholding and use of low-molecular-weight heparin (LMWH; and maintenance of warfarin and therapeutic INR (between 2.0 and 3.0. METHODS: 140 patients (pt with persistent/permanent AF undergoing catheter ablation for AF were divided into two groups: Group I (70 pt, in which warfarin was withheld five days prior to the procedure and transition to LMWH was used (enoxaparin: 1 mg/kg 2x/day before ablation, and 0.5 mg/kg 2x/day after ablation; Group II (70 pt, in which warfarin was not withheld and the

  8. 生脉注射液联合低分子肝素钠改善围生期心肌病患者心功能及血栓形成临床研究%Clinical Research on Low Molecular Weight Heparin Sodium with Shengmai Injection Combined for Improving Heart Function and Thrombogenesis in Patients with Peripartum Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    韩宇

    2014-01-01

    Objective To observe the anticoagulation effects of low molecular weight heparin sodium combined with Shengmai Injection in treating patients with peripartum cardiomyopathy(PPCM). Methods 80 patients with PPCM were randomly divided into the observa-tion group and the control group,40 cases in each group. The control group was treated with the conventional anti-heart failure therapy and the anticoagulation treatment of aspirin,while on this basis the observation group was added with low molecular weight heparin sodium and Shengmai Injection. The two groups were followed up after treatment for 3-6 months. Results The various cardiac function indexes after treatment in the two groups were significantly improved compared with those before treatment( P < 0. 05),and the im-provement degree of observation group was significantly higher than that of the control group( P < 0. 05);the plasma D-D levels in the two groups were significantly decreased compared with those before treatment( P < 0. 05),and the decrease degree of the observa-tion was significantly greater than that of the control group( P < 0. 05);the incidence rates of pulmonary embolism and deep venous thrombosis(DVT) in the observation group were significantly lower than those in the control group( P < 0. 05);the incidence rate of hemorrhage had no statistical difference between the two groups. The hemorrhage symptoms were disappeared after reducing anticoagulant agents. Conclusion The application of low molecular weight heparin sodium combined with Shengmai Injection in the anticoagulation treatment for PPCM patients can significantly improve the cardiac function,effectively rectify the plasma hypercoagulable state and pre-vent the thrombus formation without increasing the hemorrhage tendency and with higher security.%目的:观察低分子肝素钠和生脉注射液对围生期心肌病(PPCM)患者的抗凝治疗效果。方法将80例围生期心肌病患者随机分为观察组和对照组,各40例

  9. Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats Comparação dos efeitos da heparina não fracionada e heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

    Directory of Open Access Journals (Sweden)

    Can Engin Durmaz

    2012-09-01

    Full Text Available PURPOSE: To compare the effects of unfractionated heparin (UH and a low molecular weight heparin (LMWH on skin wound healing of rats. METHODS: Forty eight male Sprague-Dawley rats underwent 8mm full thickness dorsal skin wounds and were randomly assigned to three equal groups. In experimental group A, heparin sodium was injected at a concentration of 1000U/kg. In experimental group B, enoxaparin was injected at a concentration of 1mg/kg. Physiologic saline (0.5ml was administered to the control group. Injections were made subcutaneously, once daily, for seven days. At 7th and 10th days tissue samples were taken from all rats. Histologic examination of these tissues was made under light microscope and scored. RESULTS: Histological examination showed a significant difference between the 7th and 10th day groups in wound healing. It was observed that wound healing of LMWH injected group is better. This difference is statistically significant at 10th day. CONCLUSIONS: Daily administration of single doses of unfractionated heparin and a low molecular weight heparin improves wound healing positively. Low molecular weight heparin induces wound healing more than unfractionated heparin.OBJETIVO: Comparar os efeitos da heparina não fracionada (HNF e da heparina de baixo peso molecular (HBPM na cicatrização de feridas cutâneas de ratos. MÉTODOS: Quarenta e oito ratos machos Sprague-Dawley foram submetidos à ferida na pele dorsal com espessura total de 8mm e foram distribuídos aleatoriamente em três grupos iguais. No grupo experimental A, a heparina sódica foi injetada a uma concentração de 1000U/kg. No grupo experimental B, a enoxaparina foi injetada a uma concentração de 1mg/kg. Solução salina fisiológica (0,5ml foi administrada para o grupo controle. As injeções foram feitas por via subcutânea, uma vez por dia, durante sete dias. Nos dias 7º e 10º amostras de tecido foram obtidas de todos os ratos. O exame histológico destes tecidos

  10. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X).

    Science.gov (United States)

    Nieuwenhuizen, W; Gravesen, M

    1981-03-27

    Early plasmin degradation products (X fragments) of human fibrinogen were prepared in the presence of calcium-ions or EGTA, and purified on Sepharose 6B-CL. X fragments were characterized with respect to amino-terminal amino acids, polypeptide-chain composition, anticlotting properties and calcium-binding. Amino-terminal amino acids were alanine and tyrosine. The molecular weights of the chains were about 26 000, 58 000 and 48 000 for A alpha-, B beta- and gamma-chains, respectively. X fragments were about 6-times as potent in anticlotting behaviour as D fragments prepared in the presence of calcium ions. Calcium-binding properties were essentially identical to those of fibrinogen. No differences were observed between X fragments prepared in the presence of calcium ions and those prepared in the presence of EGTA. This indicates that the carboxy-terminal parts of the A alpha-chains of fibrinogen are not involved in calcium-binding and that differences in chain-remnants as observed in late plasmic degradation products (which depend on the presence of calcium ions or EGTA [23] in the incubation medium) are introduced beyond the stage of fragment X formation.

  11. Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay.

    Science.gov (United States)

    Bhakuni, Teena; Ali, Mohammad Farhan; Ahmad, Irshad; Bano, Shadabi; Ansari, Shoyab; Jairajpuri, Mohamad Aman

    2016-08-15

    Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression. Serpins; a superfamily of protease inhibitors, play a key role in regulating both angiogenesis and coagulation. They are characterized by the presence of highly conserved secondary structure comprising of 3 β-sheets and 7-9 α-helices. Inhibitory role of serpins is modulated by binding to cofactors, specially heparin and heparan sulfate proteoglycans (HSPGs) present on cell surfaces and extracellular matrix. Heparin and HSPGs are the mainstay of anti-coagulant therapy and also have therapeutic potential as anti-angiogenic inhibitors. Many of the heparin binding serpins that regulate coagulation cascade are also potent inhibitors of angiogenesis. Understanding the molecular mechanism of the switch between their specific anti-coagulant and anti-angiogenic role during inflammation, stress and regular hemostasis is important. In this review, we have tried to integrate the role of different serpins, their interaction with cofactors and their interplay in regulating coagulation and angiogenesis.

  12. Heparin-derived heparan sulfate mimics that modulate inflammation and cancer

    OpenAIRE

    Casu, Benito; Naggi, Annamaria; Torri, Giangiacomo

    2010-01-01

    The heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPG) are “ubiquitous” components of the cell surface and the extracellular matrix (EC) and play important roles in the physiopathology of developmental and homeostatic processes. Most biological properties of HS are mediated by interactions with “heparin-binding proteins” and can be modulated by exogenous heparin species (unmodified heparin, low molecular weight heparins, shorter heparin oligosaccharides and various non-antico...

  13. Heparin-Mimicking Polymers: Synthesis and Biological Applications.

    Science.gov (United States)

    Paluck, Samantha J; Nguyen, Thi H; Maynard, Heather D

    2016-11-14

    Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed.

  14. Heparin-Mimicking Polymers: Synthesis and Biological Applications

    Science.gov (United States)

    2016-01-01

    Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed. PMID:27739666

  15. Anticoagulant-induced pseudothrombocytopenia and pseudoleucocytosis.

    Science.gov (United States)

    Schrezenmeier, H; Müller, H; Gunsilius, E; Heimpel, H; Seifried, E

    1995-03-01

    Pseudothrombocytopenia (PTP) is the phenomenon of falsely low platelet counts due to in vitro platelet clumping in the presence of platelet autoantibodies and anticoagulants. We assessed anticoagulant-dependence, time course of platelet counts and impact of different counter devices on the phenomenon. Blood of 10 persons with previously recognized pronounced EDTA-dependent PTP was collected into 7 different anticoagulants and counted after different intervals in parallel in a Coulter T540 and a Coulter STKS counter and by phase contrast microscopy. With the Coulter T540 model PTP was most pronounced in blood samples anticoagulated with EDTA, Na-oxalate or Na-citrate. In the STKS counter EDTA, heparin and oxalate presented as the worst anticoagulants. The time course of platelet counts was significantly different between the two counters. Our results demonstrate that PTP is not restricted to EDTA, but is also present with other anticoagulants. In contrast, pseudoleucocytosis was observed only in EDTA-anticoagulated blood in the Coulter T540 device. We investigated the expression of platelet integrins and activation antigens on platelets of persons with anticoagulant-dependent PTP and in healthy controls without PTP. In the presence of EDTA the expression of GpIIb/IIIa was significantly reduced in the PTP subjects compared to control. Activation antigens CD62, CD63 and thrombospondin-antigen were upregulated in the presence of EDTA. These alterations in the expression of platelet antigens could also be induced on platelets of normal donors by incubation with sera of PTP subjects and EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Heparin Leakage in Central Venous Catheters by Hemodynamic Transport

    Science.gov (United States)

    Barbour, Michael; McGah, Patrick; Gow, Kenneth; Aliseda, Alberto

    2014-11-01

    Central venous catheters (CVCs), placed in the superior vena cava for hemodialysis, are routinely filled with heparin, an anticoagulant, while not in use to maintain patency and prevent thrombus formation at the catheter tip. However, the heparin-lock procedure places the patient at risk for systemic bleeding incidences, as heparin is known to leak into the blood stream. We propose that the driving mechanism behind heparin leakage is advective-diffusive transport due to the pulsatile blood flow surrounding the catheter tip. This novel hypothesis is based on Planar Laser Induced Fluorescence (PLIF) measurements of heparin transport from a CVC placed inside an in vitro pulsatile flow loop and validated with CFD simulations. The results show an initial, fast (catheter lumen, where concentration is still high, that is insufficient at replenishing the lost heparin at the tip. These results, which estimate leakage rates consistent with published in vivo data, predict that the concentration of heparin at the catheter tip is effectively zero for the majority of the interdialytic phase, rendering the heparin lock ineffective.

  17. Sulfation patterns determine cellular internalization of heparin-like polysaccharides.

    Science.gov (United States)

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R; Kuberan, Balagurunathan

    2013-04-01

    Heparin is a highly sulfated polysaccharide that serves biologically relevant roles as an anticoagulant and anticancer agent. While it is well-known that modification of heparin's sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently labeled heparins consisting of a variety of sulfation patterns. These polysaccharides were thoroughly characterized using anion exchange chromatography and size exclusion chromatography. Subsequently, we utilized flow cytometry and confocal imaging to show that sulfation patterns differentially affect the amount of heparin uptake in multiple cell types. This study provides the first comprehensive analysis of the effect of sulfation pattern on the cellular internalization of heparin or heparan sulfate like polysaccharides. The results of this study expand current knowledge regarding heparin internalization and provide insights into developing more effective heparin-based drug conjugates for applications in intracellular drug delivery.

  18. The development and introduction of biosimilar anticoagulants – focus on enoxaparin

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    Ginsberg JS

    2012-09-01

    Full Text Available Jeffrey S GinsbergDepartment of Medicine, McMaster University, Hamilton, Ontario, CanadaAbstract: The aims of this paper are to discuss the: (1 pharmacology of low-molecular-weight heparins (LMWHs emphasizing their synthesis, mechanism of action, and comparison with the parent compound, unfractionated heparin (UFH; and (2 recent controversial approval by the Food and Drug Administration (FDA of a generic enoxaparin. Enoxaparin is one of several LMWHs that are currently available worldwide for clinical use. LMWHs are derived by chemical or enzymatic depolymerization of the “parent” molecule, UFH. Both UFH and LMWHs exert their primary antithrombotic effect by binding to and catalyzing the naturally-occurring anticoagulant, antithrombin. LMWHs are more effective at inhibiting factor Xa than factor IIa (thrombin. They also produce less heparin-induced thrombocytopenia and osteoporosis than UFH and are at least as effective and safe as UFH for each approved indication. They are safe and effective when given subcutaneously once or twice daily, without the need for anticoagulant monitoring, and are suitable for out-of-hospital treatment. The FDA first approved enoxaparin (Lovenox® in March 1993. Despite its cost effectiveness, individual patients without drug insurance are often left paying for the cost of the drug. Uninsured pregnant subjects are particularly disadvantaged because they often require several months of therapy, costing several thousand dollars. To evaluate a less expensive, generic enoxaparin, the FDA chose to use the “abbreviated new drug application” because it considered enoxaparin to be a drug rather than a biologic medicine. This requires that the generic enoxaparin meets the following five criteria for “sameness”: equivalence of (1 UFH source material and method of depolymerization; (2 physicochemical properties; (3 disaccharide building blocks, fragment mapping, and sequence of oligosaccharide species; (4 biological

  19. No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy

    NARCIS (Netherlands)

    Myrup, B.; Jensen, T.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1997-01-01

    OBJECTIVE - The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DES

  20. Massive retroperitoneal hematoma as a complication of anticoagulation therapy in a patient treated in a pulmonary intensive care unit

    Directory of Open Access Journals (Sweden)

    Stjepanović Mihailo

    2015-01-01

    Full Text Available Introduction. Retroperitoneal hematoma may occur as a result of trauma, but also from rupture of arterial aneurysms (aortic or iliac, surgical complications, tumors or anticoagulation therapy. Case report. We presented a patient on permanent anticoagulation therapy. On the day of admission to our institution, the patient had the value of his INR 5.57 which required immediate suspension of the therapy. The main symptom in this patient was pain in the right inguinal canal with propagation along the right leg, which was indicated in clinical picture of spontaneous retroperitoneal haematoma. After three days the fall of hemoglobin occurred, so the additonal diagnostics was done. A computed tomography of the abdomen was performed showing well limited, large retroperitoneal hematoma (213 x 79 x 91 mm. Transfusion of concentrated red blood cells was performed twice with satisfactory correction of hemoglobin level, and four units of fresh frozen plasma. The patient was hemodynamically stabilized and discharged after a two-month long intensive care unit treatment, with the advice to use low-molecular weight heparin 2 x 0.4 mg subcutaneusly, due to persistent arrhythmia. Conclusion. In patients on anti-coagulation therapy regular monitoring of the anticoagulant status is extremely important, because of the possibility of fatal complications development, such as retroperitoneal hematoma.

  1. Massive retroperitoneal hematoma as a complication of anticoagulation therapy in a patient treated in a pulmonary intensive care unit.

    Science.gov (United States)

    Stjepanović, Mihailo; Buha, Ivana; Raljević, Snezana; Babić, Uroš; Savić, Milan; Mašković, Jovana; Roksandić, Marina; Marić, Dragana

    2015-06-01

    Retroperitoneal hematoma may occur as a result of trauma, but also from rapture of arterial aneurysms (aortic or iliac), surgical complications, tumors or anticoagulation therapy. We presented a patient on permanent anticoagulation therapy. On the day of admission to our institudon, the patient had the value of his INR 5.57 which required immediate suspension of the therapy. The main symptom in this patient was pain in the right inguinal canal with propagation along the right leg, which was indicated in clinical picture of spontaneous retroperitoneal haematoma. After three days the fall of hemoglobin occurred, so the additonal diagnostics was done. A computed tomography of the abdomen was performed showing well limited, large retroperitoneal hematoma (213 x 79 x 91 mm). Transfusion of concentrated red blood cells was performed twice with satisfactory correction of hemoglobin level, and four units of fresh frozen plasma. The patient was hemodynamically stabilized and discharged after a two-month long intensive care unit treatment, with the advice to use low-molecular weight heparin 2 x 0.4 mg subcutaneusly, due to persistent arrhythmia. In patients on anticoagulation therapy regular monitoring of the anticoagulant status is extremely important, because of the possibility of fatal complications development, such as retroperitoneal hematoma.

  2. Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholate-tetrameric deoxycholate).

    Science.gov (United States)

    Alam, Farzana; Al-Hilal, Taslim A; Park, Jooho; Choi, Jeong Uk; Mahmud, Foyez; Jeong, Jee-Heon; Kim, In-San; Kim, Sang Yoon; Hwang, Seung Rim; Byun, Youngro

    2016-04-01

    Targeting multiple stages in metastatic breast cancer is one of the effective ways to inhibit metastatic progression. To target human metastatic breast cancer as well as improving patient compliance, we developed an orally active low molecular weight heparin (LMWH)-taurocholate conjugated with tetrameric deoxycholic acid, namely LHTD4, which followed by physical complexation with a synthetic bile acid enhancer, DCK. In breast cancer, both transforming growth factor-β1 (TGF-β1) and CXCL12 exhibit enhanced metastatic activity during the initiation and progression stages of breast cancer, thus we direct the focus on investigating the antimetastatic effect of LHTD4/DCK complex by targeting TGF-β1 and CXCL12. Computer simulation study and SPR analysis were performed for the binding confirmation of LHTD4 with TGF-β1 and CXCL12. We carried out in vitro phosphorylation assays of the consecutive receptors of TGF-β1 and CXCL12 (TGF-β1R1 and CXCR4, respectively). Effects of LHTD4 on in vitro cell migration (induced by TGF-β1) and chemotaxis (mediated by CXCL12) were investigated. The in vivo anti-metastatic effect of LHTD4 was evaluated in an accelerated metastasis model and an orthotopic MDA-MB-231 breast cancer model. The obtained KD values of TGF-β1 and CXCL12 with LHTD4 were 0.85 and 0.019 μM respectively. The simulation study showed that binding affinities of LHTD4 fragment with either TGF-β1 or CXCL12 through additional electrostatic interaction was more stable than that of LMWH fragment. In vitro phosphorylation assays of TGF-β1R1 and CXCR4 showed that the effective inhibition of receptor phosphorylation was observed with the treatment of LHTD4. The expressions of epithelial to mesenchymal transition (EMT) marker proteins such as vimentin and Snail were prevented by LTHD4 treatment in in vitro studies with TGF-β1 treated MDA-MB-231 cells. Moreover, we observed that LHTD4 negatively regulated the functions of TGF-β1 and CXCL12 on migration and

  3. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    Directory of Open Access Journals (Sweden)

    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  4. The Hemochron Response RxDx heparin and protamine dosing system.

    Science.gov (United States)

    Jaryno, Stacy A; Zucker, Marcia L; LaDuca, Frank M

    2004-09-01

    The use of dosing assays to calculate heparin and protamine dose requirements during cardiac surgery has been shown to significantly improve overall postoperative patient outcome. When patients are managed with an individualized dosing system, intraoperative and postoperative transfusion requirements and bleeding are reduced. The Hemochron RxDx system is widely used as a complement to traditional activated clotting time testing to optimize anticoagulation management. The system consists of the heparin response test, the protamine response test, and the protamine dose assay. All are modifications of the activated clotting time using either Celite (Celite Corporation, Santa Barbara, CA) or kaolin as the activator. Dosing is calculated manually using earlier version Hemochron instruments (model 801) or automatically with the Hemochron 8000 or with the early versions of the Hemochron Response and the personal digital assistant (PDA) RxDx calculator. Missing from available user options is an automated RxDx system for the Response. A study was conducted at four clinical sites to compare recently developed Response RxDx software, which eliminates the need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the Response-PDA RxDx systems. Similar to the current system, the operator inputs the patient's height, weight, and gender, and the software automatically calculates the blood volume. Using the clotting times determined on the Response, bolus heparin and protamine doses and any additional heparin and protamine requirements are calculated automatically. Data were collected from 76 patients, of which, 64 patients were on pump, 11 patients were off pump, and 1 patient was converted from off to on pump. The Response estimated blood volume calculations showed a correlation coefficient of 0.989 when compared with available systems. A good correlation was also observed for the bolus heparin (r = 0.925) and protamine doses (r = 0.900) with equivalence

  5. 低分子肝素与肝素钠在维持性血液透析患者对血脂影响的比较%THE COMPARISON OF THE INFLUENCE OF LOW MOLECULAR WEIGHT HEPARIN AND HEPARIN SODIUM FOR THE BLOOD LIPID OF MAINTENANCE HEMODIALYSIS PATIENTS

    Institute of Scientific and Technical Information of China (English)

    刘凌汐

    2011-01-01

    [目的]探讨低分子肝素与肝素钠在维持性血液透析患者治疗中血脂变化情况的比较.[方法]选取某院2008年7月~2010年6月透析患者60例作为研究对象,全部患者随机分为对照组(肝素组)30例和观察组30例(低分子肝素组),观察比较两组透析前后血脂变化,包括血清总胆固醉(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C )、低密度脂蛋白胆固醇(LDL-C).[结果]两组患者透析后血脂水平较透析前均有所改善,且观察组患者透析后血清总胆固醇(TG)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、改善较对照组更明显(P<0.05).两组患者在透析器及管路方面凝血、透析后出血倾向方面有明显差异(P<0.05).B组复用次数明显增多.[结论]低分子肝素在维持性血液透析患者中血脂变化较肝素明显.%[Objective] To study the comparison of the influence of low molecular weight heparin and heparin sodium for the blood lipid of maintenance hemodialysis patients. [Methods] 60 patients treated with hemodialysis in our hospital from July 2008 to June 2010 were selected as research subjects, and all the patients were randomly divided into control group (heparin group) 30 cases and observation group (low molecular weight heparin group) 30 cases, then the blood lipid including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) of the two groups were observed and compared. [Results] The levels of blood lipid in the two groups after the hemodialysis were better than those before the hemodialysis, and the levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) of observation group after the hemodialysis were more improved than those of control group (P < 0.05). And there were obvious differences

  6. Heparin based polyurethanes: A state-of-the-art review.

    Science.gov (United States)

    Zia, Fatima; Zia, Khalid Mahmood; Zuber, Mohammad; Tabasum, Shazia; Rehman, Saima

    2016-03-01

    Polyurethanes (PUs) are considered currently as one of the established bio compatible and blood compatible biomaterials offering tremendous structure-property relationship. But few limitations such as low resistance to micro-emboli and thrombi are still associated with these biomaterials that restricted their applications and hence need to be modified. Heparin, a highly sulfonated and negatively charged member of glycosaminoglycan family is well established for their anti-thrombin, anticoagulant and many biological activities that make it a highly attractive candidate capable of modifying or tailoring polymer properties. Incorporation of heparin for the improvement of biocompatibility of PUs is an interesting approach and enabling emerging technology. This review focuses on the methods used for modification of PUs via heparin with their pros and cons. The major PU-heparin systems with the recent developments and their possible biomedical applications are discussed.

  7. Heparin coatings for improving blood compatibility of medical devices.

    Science.gov (United States)

    Biran, Roy; Pond, Daniel

    2016-12-29

    Blood contact with biomaterials triggers activation of multiple reactive mechanisms that can impair the performance of implantable medical devices and potentially cause serious adverse clinical events. This includes thrombosis and thromboembolic complications due to activation of platelets and the coagulation cascade, activation of the complement system, and inflammation. Numerous surface coatings have been developed to improve blood compatibility of biomaterials. For more than thirty years, the anticoagulant drug heparin has been employed as a covalently immobilized surface coating on a variety of medical devices. This review describes the fundamental principles of non-eluting heparin coatings, mechanisms of action, and clinical applications with focus on those technologies which have been commercialized. Because of its extensive publication history, there is emphasis on the CARMEDA(®) BioActive Surface (CBAS(®) Heparin Surface), a widely used commercialized technology for the covalent bonding of heparin.

  8. Heparin-coated Palmaz-Schatz Stents in Human Coronary Arteries. .: Early Outcome of the Benestent-II Pilot Study

    OpenAIRE

    Serruys, Patrick; Emanuelsson, Hakan; Lunn, A.C.; Kiemeneij, Ferdinand; Miguel, Carlos; Rutsch, Wolfgang; Heyndrickx, Guy; Suryapranata, Harry; Legrand, Victor; Goy, Jean-Jacques; Materne, Phillipe; Bonnier, Hans; Morice, Marie-Claude; Fajadet, Jean; Belardi, Jorge

    1996-01-01

    textabstractBackground The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. Methods and Results The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 10...

  9. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art

    Science.gov (United States)

    Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

    2015-01-01

    Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed. PMID:26664901

  10. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art.

    Science.gov (United States)

    Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

    2015-01-01

    Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

  11. Anticoagulation therapy in intra-aortic balloon counterpulsation:Does IABP really need anti-coagulation?

    Institute of Scientific and Technical Information of China (English)

    JIANG Chen-yang(蒋晨阳); ZHAO Li-li(赵莉莉); WANG Jian-an(王建安); SAN Jiang(单江); MOHAMMOD Balgaith

    2003-01-01

    Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoagulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were randomly assigned into two groups. Anticoagulation group(Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50-70 seconds. Non-anticoagulation group(Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1(PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded. Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups (P0.05). Three patients in Group A and 2 patients in Group B developed minor limb ischemia(P>0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B(P<0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.

  12. Anticoagulation therapy in intra-aortic balloon counterpulsation: Does IABP really need anti-coagulation

    Institute of Scientific and Technical Information of China (English)

    蒋晨阳; 赵莉莉; 王建安; 单江; MOHAMMODBalgaith

    2003-01-01

    Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoag-ulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were random-ly assigned into two groups. Anticoagulation group( Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50 - 70 seconds. Non-anticoagulation group( Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded.Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups ( P 0.05) . Three patients in Group A and 2 patients in Group B developed minor limb ischemia( P > 0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B ( P <0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.

  13. Technetium-99m labelled heparin: potential value as a tracer of heparin activity in pharmacokinetic and biodistribution studies

    Energy Technology Data Exchange (ETDEWEB)

    Perdrisot, R.; Barbu, M.; Bok, B.; Berthelot, J.L.; Mazoyer, B.; Colas-Linhart, N. (Laboratoire de Biophysique des Traceurs, Faculte 10-Bichat, 75 - Paris (France))

    1984-01-01

    Pharmacokinetics and biodistribution of 99m Technetium (sup(99m)Tc) labelled heparin were studied to assess its value as a tracer of heparin kinetics in comparison with unlabelled heparin. In vitro, the stability and labelling efficiency (98%) of the labelled drug were excellent and elution was minimal. In vivo, after I.V. infusion of the drug, there was no difference in the same animal between anticoagulant activity measurements and radioactive countings, both displaying a plasmatic biexponential pattern (T/sub 1/=2.9 minutes, T/sub 2/=76 minutes). Biodistribution studies showed primarily liver, spleen and kidney accumulation, with no thyroid uptake. The advantages of this technetium labelling may therefore be used for the heparin drug in various experimental and pathological situations even in humans.

  14. 低分子肝素钠联用丹红治疗不稳定型心绞痛的临床疗效分析%Clinical observation on low molecular weight heparin sodium combined with Danhong injection in the treatment of unstable angina

    Institute of Scientific and Technical Information of China (English)

    樊晓洋

    2014-01-01

    Objective To analyze the clinical efficacy of low molecular weight heparin combined with Danhong injection in the treatment of unstable angina. Methods The study group were treated with low molecular weight heparin combined with Danhong treated control group were given low molecular weight heparin. Results The total effective rate was significantly higher, the difference was statistically significant (P<0.05). Conclusion The effect of low molecular weight heparin combined with Danhong injection in the treatment of unstable angina was significantly better than with low molecular weight heparin with less adverse reaction, so it is worthy of clinical application.%目的:分析研究低分子肝素钠联用丹红治疗不稳定型心绞痛的临床疗效。方法观察组患者给予低分子肝素钠联用丹红治疗,对照组仅给予低分子肝素钠治疗。结果观察组总有效率显著高于对照组,两组比较差异有统计学意义(P<0.05)。结论低分子肝素钠联用丹红治疗不稳定型心绞痛的疗效明显优于单用低分子肝素钠,且不良反应少,值得临床应用。

  15. Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality.

    Science.gov (United States)

    Becker, R C; Corrao, J M; Bovill, E G; Gore, J M; Baker, S P; Miller, M L; Lucas, F V; Alpert, J A

    1990-06-01

    An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.

  16. Role of heparin during endovascular therapy for acute ischemic stroke.

    Science.gov (United States)

    Farook, Naureen; Haussen, Diogo; Sur, Samir; Snelling, Brian; Gersey, Zachary; Yavagal, Dileep; Peterson, Eric

    2016-06-01

    Systemic heparinization has become the mainstay anticoagulant in neurointerventional procedures to prevent thromboembolic complications. Its benefit during endovascular therapy for acute stroke however has not been established. The purpose of this study is to retrospectively evaluate the impact of heparin during endovascular therapy for acute ischemic stroke (AIS). We performed a retrospective review of our interventional stroke database from February 2009 to September 2012 for patients with anterior circulation AIS with ICA-T or MCA M1 occlusions. 76 patients were categorized into 2 groups: intraprocedural vs. no intraprocedural heparin use. Outcomes measured included reperfusion (modified TICI scale), cerebral hemorrhages (ECASS criteria), and 90-day outcomes (modified Rankin scale). Baseline characteristics were similar between heparin and non-heparin treated patients, except for presence of CAD (6% vs. 30%, p=0.01), Coumadin (0% vs. 11%, p=0.04), and NIHSS (15.6±5.0 vs. 18.1±4.6, p=0.03). There was a nonsignificantly higher reperfusion rate achieved in heparin-treated patients compared to non heparin-treated patients (63% vs. 50%, p=0.35). Patients who received heparin had significantly lower rates of hemorrhage (p=0.02). Multivariate logistic regression for good outcome revealed only age (OR 0.86; 95% CI 0.78-0.95; p<0.01), ASPECTS (OR 2.14; 95% CI 1.01-4.50; p=0.04), and successful reperfusion (OR 19.25; 95% CI 2.37-155.95; p<0.01) independently associated with mRS 0-2 at 90 days. The use of intraprocedural heparin in patients with AIS from MCA M1 or ICA-T occlusion was found safe. The impact of heparinization is unclear and warrants further evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Comparison of the antiangiogenic effects of heparin sodium, enoxaparin sodium, and tinzaparin sodium by using chorioallantoic membrane assay.

    Science.gov (United States)

    Katrancioglu, Nurkay; Karahan, Oguz; Kilic, Ahmet Turhan; Altun, Ahmet; Katrancioglu, Ozgur; Polat, Zubeyde Akin

    2012-04-01

    Unfractionated heparin (UFH) and low molecular weight heparins have been used as anticoagulation agents in cardiovascular clinics for decades. However, these molecules also have potent antiangiogenic effects. Whereas, angiogenesis may be the most crucial determinant of the prognosis of cardiovascular diseases, and except some special situation, antiangiogenic effect is not desirable in the most of the cardiovascular disease. In this study, we aimed to compare the antiangiogenic potency of UFH, enoxaparin, and tinzaparin. The antiangiogenic efficacies of UFH, enoxaparin, and tinzaparin were examined in vivo by using the chick chorioallantoic membrane (CAM) model. Twenty fertilized eggs were used for each studied drug. Drug solutions were prepared in 10 and 1 IU/10 μl concentrations. Decreases in the density of the capillaries were assessed and scored. All three drugs showed antiangiogenic effects on the chick CAM at the 10 IU/10 μl concentration. However, the antiangiogenic score of the UFH was significantly higher than that of enoxaparin and tinzaparin at 1 and 10 IU/10 μl concentrations. UFH had stronger and antiangiogenic potential than enoxaparin and tinzaparin. However, tinzaparin showed dose-dependent antiangiogenic effects. We think that an anticoagulant molecule with a less and dose-dependent antiangiogenic effect, as in the case of tinzaparin, may be more desirable in case of cardiovascular disease related with insufficient angiogenesis.

  18. Clinical Application of Low Molecular Weight Heparin in Patients with Recurrent Spontaneous Abortion%低分子肝素在复发性流产患者中的临床应用研究

    Institute of Scientific and Technical Information of China (English)

    王岚; 任小青; 苏胜红; 吴坚

    2016-01-01

    ObjectiveTo analyze the efficacy and safety of low molecular weight heparin in the treatment of recurrent abortion. MethodsFrom January 2010 - June 2014 in our hospital to prevent abortion 78 cases of recurrent abortion, randomly divided into treatment group and control group, the control group received routine tocolysis medicine progesterone and chorionic gonadotropin and vitamin E, the treatment group in medicine based on the use of low molecular weight heparin calcium 0.4-0.8mg/d,for 13 weeks. Comparing the two groups of tocolysis success rate and efficacy of low molecular weight heparin drug side effects .ResultsThe living rate of the treatment group was 95.00%, the control group was 76.32%, the difference was statistically significant (P 0.05). ConclusionLow molecular weight heparin can be effective in the treatment of RSA,improve the pregnancy success rate of RSA women. Low molecular weight heparin is less adverse reactions during pregnancy, do a good job in monitoring, can be used in pregnancy safety. Some patients use process will produce slight side effects, should strengthen the monitoring of drug use.%目的:分析探讨低分子肝素对复发性流产的治疗效果及安全性。方法选取2010年1月至2014年6月在本院安胎的复发性流产患者78例,随机分为治疗组和对照组,给予对照组常规安胎药黄体酮、绒毛膜促性腺激素及维生素E,治疗组在上药基础上加用低分子肝素钙0.4-0.8mg/日,用至13周。对比两组的安胎成功率及观察低分子肝素药物副作用。结果治疗组的活胎率95.00%,对照组为76.32%,差异有统计学意义(P<0.05);安胎成功38例治疗前与治疗后1月D2聚体数值差异有统计学意义(P<0.05);治疗组治疗前后APTT、PLT数值差异无统计学意义(P>0.05)。结论低分子肝素可以有效治疗RSA,提高RSA妇女妊娠成功率。低分子肝素在妊娠期应用不良反应少,做好监测,可于孕期

  19. Maternal and fetal sequelae of anticoagulation during pregnancy.

    Science.gov (United States)

    Hall, J G; Pauli, R M; Wilson, K M

    1980-01-01

    Review of published cases of pregnancies in which coumarin derivatives or heparin were administered demonstrates that use of either class of anticoagulant carries substantial risks. Of 418 reported pregnancies in which coumarin derivatives were used, one-sixth resulted in abnormal liveborn infants, one-sixth in abortion or stillbirth and, at most, two-thirds in apparently normal infants. In addition to the expected hemorrhagic complications, fetal effects of coumarin derivative administration include a specific embryopathy and central nervous system abnormalities. All available cases (including unpublished ones) of warfarin embryopathy and central nervous system abnormalities following gestational exposure to coumarin derivatives are reviewed, various complications are tabulated, critical periods of teratogenesis are discussed and possible mechanisms proposed. The use of heparin during gestation does not result in a significantly better outcome of pregnancy. In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and, again at most, in two-thirds apparently normal. Because of the substantial risks of both clases of anticoagulants, and the inherent risks of pregnancy complicated by the indications for anticoagulation, prevention of pregnancy is usually indicated. If pregnancy occurs, a relatively normal outcome can be anticipated in about two-thirds of the pregnancies regardless of the anticoagulant used. Heparin does not appear to be a clearly superior alternative to coumarin derivatives.

  20. Hemodialysis without systemic anticoagulation: a prospective randomized trial to evaluate 3 strategies in patients at risk of bleeding.

    Directory of Open Access Journals (Sweden)

    Bruno Guéry

    Full Text Available OBJECTIVE: In this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization. METHODS: This open-label monocentric randomized « n-of-one » trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i a complete coagulation of the circuit; (ii a partial coagulation of the circuit; (iii a>50% rise over baseline in the venous pressure. RESULTS: At the end of the inclusion period (May, 2007 to December, 2008, the number of patients to include (n=75 was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events. CONCLUSION: Heparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur. TRIAL REGISTRATION: ClinicalTrials.gov NCT

  1. New anticoagulants for the prevention and treatment of venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Simon J McRae

    2005-04-01

    Full Text Available Simon J McRae, Jeffrey S GinsbergDepartment of Medicine, McMaster University, Hamilton, ON, CanadaAbstract: Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety, ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.Keywords: venous thromboembolism, anticoagulants, antithrombotic

  2. Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors

    Directory of Open Access Journals (Sweden)

    Ha Na Kim

    2017-05-01

    Full Text Available Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity.

  3. Low thrombogenicity of polyethylene glycol-grafted cellulose membranes does not influence heparin requirements in hemodialysis.

    Science.gov (United States)

    Wright, M J; Woodrow, G; Umpleby, S; Hull, S; Brownjohn, A M; Turney, J H

    1999-07-01

    Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.

  4. Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Nagarik Amit

    2010-01-01

    Full Text Available Systemic heparinization during continuous renal replacement therapy (CRRT is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 pa-tients including 42 males. Co-morbidities were comparable in both groups. HMARF was signifi-cantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 ± 6.4 hours while it was 24.5 ± 6.36 hours in heparin free group ( P=NS. Patients receiving heparin had 16 bleeding episodes (0.45/patient while only four bleeding episodes occurred in heparin free group (0.13/patient, P< 0.05. Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

  5. Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review.

    Science.gov (United States)

    Salter, Benjamin S; Weiner, Menachem M; Trinh, Muoi A; Heller, Joshua; Evans, Adam S; Adams, David H; Fischer, Gregory W

    2016-05-31

    Heparin-induced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. In this comprehensive review, the authors highlight heparin-induced thrombocytopenia's risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment. The authors place special emphasis on the management of patients requiring procedures using cardiopulmonary bypass or interventions in the catheterization laboratory. Clinical vigilance of this disease process is important to ensure its recognition, diagnosis, and treatment. Misdiagnosis of the syndrome, as well as misunderstanding of the disease process, continues to contribute to its morbidity and mortality.

  6. Variability in heparin sensitivity of appt reagents in heparinized plasma in vitro and patients receiving heparin

    National Research Council Canada - National Science Library

    Fernanda Daniela Serralvo; Jacinta Ludovico Zamboti; Maria Emilia Favero; José Wander Bregano

    2015-01-01

    ... used for its determination. Objective: To evaluate the sensibility to heparin in the different reagents used to determine APPT in samples of heparinized plasma in vitro and in patients using non-fractioned heparin (NFH...

  7. Electrophoresis for the analysis of heparin purity and quality.

    Science.gov (United States)

    Volpi, Nicola; Maccari, Francesca; Suwan, Jiraporn; Linhardt, Robert J

    2012-06-01

    The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007-2008 produced a global crisis resulting in extensive revisions to the pharmacopeia monographs and prompting the FDA to recommend the development of additional methods for the analysis of heparin purity. As a consequence, a wide variety of innovative analytical approaches have been developed for the quality assurance and purity of unfractionated and low-molecular-weight heparins. This review discusses recent developments in electrophoresis techniques available for the sensitive separation, detection, and partial structural characterization of heparin contaminants. In particular, this review summarizes recent publications on heparin quality and related impurity analysis using electrophoretic separations such as capillary electrophoresis (CE) of intact polysaccharides and hexosamines derived from their acidic hydrolysis, and polyacrylamide gel electrophoresis (PAGE) for the separation of heparin samples without and in the presence of its relatively specific depolymerization process with nitrous acid treatment.

  8. Contribution of novel anticoagulants fondaparinux and dabigatran to venous thromboembolism prevention

    Directory of Open Access Journals (Sweden)

    Antonijević Nebojša

    2015-01-01

    Full Text Available The data that episodes and sequels of venous thromboembolism (VTE are recorded in a significant percentage of patients receiving standard anticoagulants as VTE prophylaxis (unfractionated, low-molecular-weight heparin and vitamin K inhibitors as well as the fact that these drugs have significant limitations and that they may cause serious side-effects in some patients indicate the need for the introduction of new anticoagulant drugs. Fondaparinux, a selective inhibitor of Factor Xa, administered following major orthopedic surgeries having a high risk for the development of VTE, is more efficient than enoxaparin sodium used in European and North-American approved doses. The increased incidence of major bleeding (excluding fatal due to fondaparinux could be perhaps lowered by dosage reduction in patients with a mildly decreased creatinine clearance. Dabigatran, a peroral direct thrombin inhibitor, administered for VTE prophylaxis in elective hip and knee surgery, showed in to date studies the efficacy comparable (if dabigatran is given in both dosage regimes of 150 mg and 220 mg daily or superior (if dabigatran is given at a dose of 220 mg daily to enoxaparin administered in European-approved doses, while North American-approved doses of enoxaparin were superior than dabigatran in VTE reduction. No significant differences in bleeding rates were determined in any of the study groups. We consider that the introduction of new anticoagulants, including fondaparinux and dabigatran, will contribute to the establishment of a better safety profile and efficacy, and will also enable adequate therapy individualization for each patient depending on his/hers clinical characteristics. The introduction of novel peroral anticoagulants will, inter alia, significantly contribute to improvement in the quality of life, release the patient from numerous limitations in nutrition, interreaction, frequent laboratory monitoring, and also significantly improve therapeutic

  9. An effective analysis of treating progressive cerebral infarction with low molecular weight heparin sodium%低分子量肝素钠治疗进展型脑梗塞的临床疗效分析

    Institute of Scientific and Technical Information of China (English)

    项素娥

    2015-01-01

    Objective: To investigate clinical effects of low molecular weight heparin sodium on progressive cerebral infarction. Methods: 76 patients with progressive cerebral infarction were selected and divided into the test group (received low molecular weight heparin sodium) and the control group (received conventional treatment), 38 cases for each. Results: After the treatment, neurological deficit in the test group was improved, better than that in the control group. The difference was statistically significant (P<0.05). The total efficiency in the test group was 86.85%, much higher than that in the control group (68.42%). Conclusion: The low molecular weight heparin sodium was significantly effective on progressive cerebral infarction, could improve the quality of life of patients, and was worthy of promotion.%目的:探讨采用低分子量肝素钠治疗进展型脑梗塞患者的临床效果。方法:选取76例进展型脑梗塞患者的临床资料,根据治疗方法将其分为试验组(低分子量肝素钠治疗)与对照组(常规治疗),各38例。结果:治疗后,试验组的神经功能缺损改善情况明显优于对照组,差异有统计学意义(P<0.05);试验组的治疗总有效率为86.85%,显著高于对照组的68.42%,差异有统计学意义(P<0.05)。结论:对进展性脑梗塞患者采用低分子量肝素钠治疗,能有效改善患者的临床症状,疗效显著,有利于提高患者的生活质量,值得推广。

  10. Anticoagulants influence the in vitro activity and composition of shock lymph but not its in vivo activity.

    Science.gov (United States)

    Deitch, Edwin A; Qin, Xiaofa; Sheth, Sharvil U; Tiesi, Gregory; Palange, David; Dong, Wei; Lu, Qi; Xu, Dazhong; Feketeova, Eleonora; Feinman, Rena

    2011-08-01

    Many models of trauma-hemorrhagic shock (T/HS) involve the reinfusion of anticoagulated shed blood. Our recent observation that the anticoagulant heparin induces increased mesenteric lymph lipase activity and consequent in vitro endothelial cell cytotoxicity prompted us to investigate the effect of heparin-induced lipase activity on organ injury in vivo as well as the effects of other anticoagulants on mesenteric lymph bioactivity in vitro and in vivo. To investigate this issue, rats subjected to trauma-hemorrhage had their shed blood anticoagulated with heparin, the synthetic anticoagulant arixtra (fondaparinux sodium), or citrate. Arixtra, in contrast to heparin, did not increase lymph lipase activity or result in high levels of endothelial cytotoxicity. Yet, the arixtra-treated rats subjected to T/HS still manifested lung injury, neutrophil priming, and red blood cell dysfunction, which was totally abrogated by lymph duct ligation. Furthermore, the injection of T/HS mesenteric lymph, but not sham-shock lymph, collected from the arixtra rats into control mice recreated the pattern of lung injury, polymorphonucleocyte (PMN) priming, and red blood cell dysfunction observed after actual shock. Consistent with these observations, citrate-anticoagulated rats subjected to T/HS developed lung injury, and the injection of mesenteric lymph from the citrate-anticoagulated T/HS rats into control mice also resulted in lung injury. Based on these results, several conclusions can be drawn. First, heparin-induced increased mesenteric lymph lipase activity is not responsible for the in vivo effects of T/HS mesenteric lymph. Second, heparin should be avoided as an anticoagulant when studying the biology or composition of mesenteric lymph because of its ability to cause increases in lymph lipase activity that increase the in vitro cytotoxicity of these lymph samples.

  11. Mast cell-derived heparin proteoglycans as a model for a local antithrombotic.

    Science.gov (United States)

    Lassila, Riitta; Jouppila, Annukka

    2014-11-01

    Mast cell-derived heparin proteoglycans (HEP-PG) reside in vascular tissue and serve as a local antithrombotic. Heparin, as used clinically, is isolated from its protein backbone from porcine and bovine gut mucosa. The isolated heparin is an anticoagulant; however, when bound to a protein carrier the heparin conjugates will become antiplatelet agents by inhibiting collagen-induced platelet aggregation and procoagulant activity, as distinct from soluble heparin. HEP-PG, whether soluble or immobilized to a surface, inhibit platelet deposition on the collagen surface in flowing blood. Mimics of HEP-PG, can be tailored to molecules carrying both antiplatelet and anticoagulant (APAC) properties. These molecules can target the vascular injury site and take residence there. Inhibition of thrombus growth using these APACs under these conditions has been demonstrated in several animal models. Although efficacious for antiplatelet and anticoagulant effects, the bleeding time is shorter with APACs than with unfractionated heparin, suggestive of beneficial efficacy/safety ratio. These strategies may be utilized in drug development, where many vascular injury-related problems can be tackled locally.

  12. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program.

    Science.gov (United States)

    McGowan, Kelly E; Makari, Joy; Diamantouros, Artemis; Bucci, Claudia; Rempel, Peter; Selby, Rita; Geerts, William

    2016-04-21

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% of patients exposed to unfractionated heparin (UFH). We examined the impact of a hospital-wide strategy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs. The Avoid-Heparin Initiative, implemented at a tertiary care hospital in Toronto, Ontario, Canada, since 2006, involved replacing UFH with low-molecular-weight heparin (LMWH) for prophylactic and therapeutic indications. Consecutive cases with suspected HIT from 2003 through 2012 were reviewed. Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-intervention (2003-2005) and the avoid-heparin (2007-2012) phases. The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in the pre-intervention phase to 49.0 per 10 000 admissions in the avoid-heparin phase ( ITALIC! Pheparin phase. To the best of our knowledge, this is the first study demonstrating the success and feasibility of a hospital-wide HIT prevention strategy.

  13. Heparin bridge therapy and post-polypectomy bleeding

    OpenAIRE

    Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

    2016-01-01

    AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonosc...

  14. Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber.

    Science.gov (United States)

    Wu, Mingyi; Xu, Li; Zhao, Longyan; Xiao, Chuang; Gao, Na; Luo, Lan; Yang, Lian; Li, Zi; Chen, Lingyun; Zhao, Jinhua

    2015-04-13

    Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.

  15. Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber

    Directory of Open Access Journals (Sweden)

    Mingyi Wu

    2015-04-01

    Full Text Available Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2 and (1→3-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.

  16. A non-anticoagulant heterofucan has antithrombotic activity in vivo.

    Science.gov (United States)

    Barroso, Edjane M A; Costa, Leandro S; Medeiros, Valquíria P; Cordeiro, Sara L; Costa, Mariana S S P; Franco, Célia R C; Nader, Helena B; Leite, Edda L; Rocha, Hugo A O

    2008-06-01

    Fucan is a term used to denominate a family of sulfated L-fucose-rich polysaccharides. The brown alga Spatoglossum schröederi (Dictyotaceae) has three heterofucans namely fucan A, B and C. The 21 kDa fucan A is composed of a core of a beta (1-3) glucuronic acid-containing oligosaccharide of 4.5 kDa with branches at C4 of the fucose chains alpha (1-3) linked. The fucose is mostly substituted at C4 with a sulfate group and at C2 with chains of beta (1-4) xylose. This fucan has neither anticoagulant (from from 0.1 to 100 microg) nor hemorrhagic activities (from 50 to 800 microg/mL). The antithrombotic test in vivo showed that fucan A has no activity in any of the concentrations (from 0.2 to 20 microg/g/day) tested 1 h after polysaccharide administration. However, when fucan A was injected endovenously 24 h before the ligature of the venae cavae, we observed a dose-dependent effect, reaching saturation at around 20 microg/g of rat weight. In addition, this effect is also time-dependent, reaching saturation around 16 h after fucan administration. In addition, regardless of the administration route, fucan A displayed antithrombotic activity. The exception was the oral pathway. Of particular importance was the finding that fucan A stimulates the synthesis of an antithrombotic heparan sulfate from endothelial cells like heparin. The hypothesis has been raised that the in vivo antithrombotic activity of fucan A is related to the increased production of this heparan. Taken together with the fact that the compound is practically devoid of anticoagulant and hemorrhagic activity, the data suggest that it may be an ideal antithrombotic agent in vivo.

  17. The Anticoagulation Effects of Glycosaminoglycan from Mactra veneriformis

    Directory of Open Access Journals (Sweden)

    Yue Wang

    2015-07-01

    Full Text Available In this study, the anticoagulation effect of glycosaminoglycan from Mactra veneriformis was studied. The results showed that glycosaminoglycan mainly exerted anticoagulation via antithrombin III. Glycosaminoglycan could passivate the function of heparin cofactor II inhibiting thrombin activity. Glycosaminoglycan significantly reduced the activities of coagulation factor II, V, VII, X, VIII, IX, XI, XII as well as fibrinogen content in the plasma (p<0.05, p<0.01. Besides, glycosaminoglycan could extend blood recalcification time in rats by shielding Ca2+ in plasma and significantly reduced Ca2+ concentration in rats and mice serum (p<0.05, p<0.01. Glycosaminoglycan reduced the Ca2+ concentration in serum in a more intensive way than that of heparin sodium (p<0.05, p<0.01.

  18. Increased accuracy in heparin and protamine administration decreases bleeding: a pilot study

    DEFF Research Database (Denmark)

    Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

    2009-01-01

    using the Hemochron RxDx system, which performs a baseline activated clotting time (ACT) value together with a heparin response test. An accurate heparin dose was calculated based on the Bull dose/response curve. Protamine doses were calculated by the same method. In the control group (25 patients...... values were obtained in both groups. Using the Hemochron RxDx, we observed a significant reduction in postoperative blood loss, as well as the amount of heparin and initial doses of protamine used during CPB. Individual patient managed anticoagulation during cardiac surgery using dose/response curve...

  19. Binding Potency of Heparin Immobilized on Activated Charcoal for DNA Antibodies.

    Science.gov (United States)

    Snezhkova, E A; Tridon, A; Evrard, B; Nikolaev, V G; Uvarov, V Yu; Tsimbalyuk, R S; Ivanuk, A A; Komov, V V; Sakhno, L A

    2016-02-01

    In vitro experiments showed that heparin adsorbed on activated charcoal can bind antibodies raised against native and single-stranded DNA in a diluted sera pool with a high level of these DNA. Thus, heparin used as anticoagulant during hemosorption procedure can demonstrate supplementary therapeutic activity resulting from its interaction with various agents involved in acute and chronic inflammatory reactions such as DNA- and RNA-binding substances, proinflammatory cytokines, complement components, growth factors, etc. Research and development of heparin-containing carbonic adsorbents for the therapy of numerous inflammatory and autoimmune diseases seems to be a promising avenue in hematology.

  20. Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments

    Science.gov (United States)

    Li, Jun-hui; Li, Shan; Zhi, Zi-jian; Yan, Lu-feng; Ye, Xing-qian; Ding, Tian; Yan, Lei; Linhardt, Robert John; Chen, Shi-guo

    2016-01-01

    Fucosylated chondroitin sulfate (fCS) from sea cucumber Isostichopus badionotus (fCS-Ib) with a chondroitin sulfate type E (CSE) backbone and 2,4-O-sulfo fucose branches has shown excellent anticoagulant activity although has also show severe adverse effects. Depolymerization represents an effective method to diminish this polysaccharide’s side effects. The present study reports a modified controlled Fenton system for degradation of fCS-Ib and the anticoagulant activity of the resulting fragments. Monosaccharides and nuclear magnetic resonance (NMR) analysis of the resulting fragments indicate that no significant chemical changes in the backbone of fCS-Ib and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-Ib should result in a dramatic decrease in prolonging activated partial thromboplastin time and thrombin time. A decrease in the inhibition of thrombin (FIIa) by antithromin III (AT III) and heparin cofactor II (HCII), and the slight decrease of the inhibition of factor X activity, results in a significant increase of anti-factor Xa (FXa)/anti-FIIa activity ratio. The modified free-radical depolymerization method enables preparation of glycosaminoglycan (GAG) oligosaccharides suitable for investigation of clinical anticoagulant application. PMID:27657094

  1. Anticoagulation in the Elderly

    Directory of Open Access Journals (Sweden)

    Helia Robert-Ebadi

    2010-12-01

    Full Text Available Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future.

  2. Monitoring of heparin concentration in serum by Raman spectroscopy within hollow core photonic crystal fiber

    Science.gov (United States)

    Khetani, Altaf; Tiwari, Vidhu S.; Harb, Alaa; Anis, Hanan

    2011-08-01

    The feasibility of using hollow core photonic crystal fiber (HC-PCF) in conjunction with Raman spectroscopy has been explored for real time monitoring of heparin concentration in serum. Heparin is an important blood anti-coagulant whose precise monitoring and controlling in patients undergoing cardiac surgery and dialysis is of utmost importance. Our method of heparin monitoring offers a novel alternative to existing clinical procedures in terms of accuracy, response time and sample volume. The optical design configuration simply involves a 785-nm laser diode whose light is coupled into HC-PCF filled with heparin-serum mixtures. By non-selectively filling HC-PCF, a strong modal field overlap is obtained. Consequently, an enhanced Raman signal (>90 times) is obtained from various heparin-serum mixtures filled HC-PCFs compared to its bulk counterpart (cuvette). The present scheme has the potential to serve as a `generic biosensing tool' for diagnosing a wide range of biological samples.

  3. The US regulatory and pharmacopeia response to the global heparin contamination crisis.

    Science.gov (United States)

    Szajek, Anita Y; Chess, Edward; Johansen, Kristian; Gratzl, Gyöngyi; Gray, Elaine; Keire, David; Linhardt, Robert J; Liu, Jian; Morris, Tina; Mulloy, Barbara; Nasr, Moheb; Shriver, Zachary; Torralba, Pearle; Viskov, Christian; Williams, Roger; Woodcock, Janet; Workman, Wesley; Al-Hakim, Ali

    2016-06-09

    The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.

  4. Heparin-Induced Cardiac Tamponade and Life-Threatening Hyperkalemia in a Patient with Chronic Hemodialysis

    Directory of Open Access Journals (Sweden)

    Ho-Ming Su

    2005-03-01

    Full Text Available Heparin, a commonly used anticoagulant agent, is frequently used in patients undergoing hemodialysis. As with most medications, heparin has a significant side effect profile. Two of its most important side effects, major bleeding and hyperkalemia, may be devastating without immediate diagnosis and treatment. Major bleeding such as gastrointestinal, genitourinary or intracranial bleeding is occasionally encountered and rarely neglected. However, heparin-induced cardiac tamponade is rarely encountered and may be easily overlooked. Another side effect, heparin-induced hyperkalemia, an unusual but well-described side effect, is frequently forgotten until life-threatening arrhythmia has occurred. We report a case involving a 40-year-old male patient with uremia, who had received heparin for 10 days for deep vein thrombosis in the left lower extremity. Hemopericardium with cardiac tamponade and life-threatening hyperkalemia were both noted in this patient.

  5. The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

    Directory of Open Access Journals (Sweden)

    Kyle M. Ware

    2017-01-01

    Full Text Available Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor. Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

  6. Selection of an aptamer antidote to the anticoagulant drug bivalirudin.

    Science.gov (United States)

    Martin, Jennifer A; Parekh, Parag; Kim, Youngmi; Morey, Timothy E; Sefah, Kwame; Gravenstein, Nikolaus; Dennis, Donn M; Tan, Weihong

    2013-01-01

    Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT). Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug), and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction) and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.

  7. Selection of an aptamer antidote to the anticoagulant drug bivalirudin.

    Directory of Open Access Journals (Sweden)

    Jennifer A Martin

    Full Text Available Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT. Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug, and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.

  8. Facile Conjugation of Heparin onto Titanium Surfaces via Dopamine Inspired Coatings for Improving Blood Compatibility

    Institute of Scientific and Technical Information of China (English)

    LI Guicai; XIE Bing; PAN Changjiang; YANG Ping; DING Hongyan; HUANG Nan

    2014-01-01

    Immobilization of heparin on biomaterials surface has been proven to be an effective strategy for preventing thrombus formation. However, the procedures of most immobilization methods (physical adsorption, covalent linkage, electrostatic interaction) are complicated and time-consuming. In the present study, heparin with various concentrations immobilized on a titanium (Ti) substrate via polydopamine layer for improving blood compatibility was investigated. Water contact angle measurement showed that the immobilization of heparin resulted in an increase of the hydrophilicity. X-ray photoelectron spectroscopy (XPS) and Toluidine Blue O (TBO) tests displayed that the heparin molecules were successfully immobilized on Ti surface. The evaluations of blood compatibility (hemolysis rate, APTT, platelet adhesion and activation, fibrinogen conformational change) showed that the immobilization of heparin decreased hemolysis rate, prolonged blood coagulation time, reduced platelets adhesion and activation, and induced less fibrinogen conformational change. Moreover, a significant inhibition of blood coagulation and platelet adhesion was obtained when the heparin concentration was higher than 5 mg/mL, indicating that only with a certain surface densities could heparin perform its anticoagulant properties well. The results suggest that the immobilization of heparin via polydopamine layer can confer excellent antithrombotic properties, and the heparin immobilization method via polydopamine layer provides an alternative approach for other biomolecules immobilization on biomaterials surface. Thus it is envisaged that this method will be potentially useful for the surface modification of blood-contacting biomaterials.

  9. Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells.

    Science.gov (United States)

    Ling, Ling; Camilleri, Emily T; Helledie, Torben; Samsonraj, Rebekah M; Titmarsh, Drew M; Chua, Ren Jie; Dreesen, Oliver; Dombrowski, Christian; Rider, David A; Galindo, Mario; Lee, Ian; Hong, Wanjin; Hui, James H; Nurcombe, Victor; van Wijnen, Andre J; Cool, Simon M

    2016-01-15

    Chronic use of heparin as an anti-coagulant for the treatment of thrombosis or embolism invokes many adverse systemic events including thrombocytopenia, vascular reactions and osteoporosis. Here, we addressed whether adverse effects might also be directed to mesenchymal stem cells that reside in the bone marrow compartment. Harvested human bone marrow-derived mesenchymal stem cells (hMSCs) were exposed to varying doses of heparin and their responses profiled. At low doses (heparin exerted a variable effect on hMSC proliferation and multipotentiality across multiple donors, while at higher doses (≥ 100 μg/ml), heparin supplementation inhibited cell growth and increased both senescence and cell size. Gene expression profiling using cDNA arrays and RNA-seq analysis revealed pleiotropic effects of low-dose heparin on signaling pathways essential to hMSC growth and differentiation (including the TGFβ/BMP superfamily, FGFs, and Wnts). Cells serially passaged in low-dose heparin possess a donor-dependent gene signature that reflects their altered phenotype. Our data indicate that heparin supplementation during the culturing of hMSCs can alter their biological properties, even at low doses. This warrants caution in the application of heparin as a culture supplement for the ex vivo expansion of hMSCs. It also highlights the need for careful evaluation of the bone marrow compartment in patients receiving chronic heparin treatment.

  10. Characterization of anticoagulant heparinoids by immunoprofiling.

    Science.gov (United States)

    Wijnhoven, Tessa J; van de Westerlo, Els M; Smits, Nicole C; Lensen, Joost F; Rops, Angelique L; van der Vlag, Johan; Berden, Jo H; van den Heuvel, Lambert P; van Kuppevelt, Toin H

    2008-02-01

    Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III, resulting in inactivation of factor Xa and-when additional saccharides are present-inactivation of factor IIa. Structural and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs (extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics, such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural and biological characteristics.

  11. Low molecular weight heparins prevent thrombin-induced thrombo-embolism in mice despite low anti-thrombin activity. Evidence that the inhibition of feed-back activation of thrombin generation confers safety advantages over direct thrombin inhibition.

    Science.gov (United States)

    Momi, S; Nasimi, M; Colucci, M; Nenci, G G; Gresele, P

    2001-03-01

    Thrombin-induced thromboembolism in mice is a model in which the feed-back clotting activation produced by the injected enzyme greatly contributes to fibrin accumulation in lungs and to mortality. Using this model we have previously shown that activated human protein C (aPC), by interrupting endogenous clotting activation at a high level (factors Va and VIIIa), prevents mortality inducing only a minor hemostatic impairment. With the same model we have now compared the antithrombotic and prohemorrhagic effects of two low molecular weight heparins (LMWHs), reviparin and tinzaparin, which are expected to inhibit preferentially the positive feed-back triggered by thrombin (anti Xa activity), with those of unfractionated heparin (UFH) and PEG-hirudin, which inhibit mainly or exclusively thrombin activity (anti IIa activity). Pulmonary thromboembolism was induced in mice by i.v. injection of bovine thrombin (1,000U/kg). Drugs (from 0.12 to 1.2 mg/kg) were given as bolus injection 2 min prior to thrombin challenge and mortality was assessed within 15 min. The bleeding time was assessed by a tail tip transection model. Activated partial thromboplastin time (aPTT), thrombin clotting time (TcT), fibrinogen assay and anti Xa activity determination were performed in citrated plasma from saline- or drug-treated animals. All drugs protected mice from thrombin-induced mortality in a dose-dependent way. At comparable antithrombotic dosages, the anti IIa activity generated in plasma (assessed by TcT) was highest with UFH, intermediate with tinzaparin and very low with reviparin. Accordingly, the fibrinogen drop, which is caused mainly by the injected thrombin, was prevented by the heparins to an extent that was fairly well related to their anti IIa activity. aPTT and bleeding time, used as measures of hemorrhagic risk, were markedly more prolonged by UFH than by reviparin. Tinzaparin, instead, had an intermediate effect. Interestingly, PEG-hirudin, at equipotent antithrombotic

  12. Anticoagulation Strategies in Venovenous Hemodialysis in Critically Ill Patients: A Five-Year Evaluation in a Surgical Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Christoph Sponholz

    2014-01-01

    Full Text Available Renal failure is a common complication among critically ill patients. Timing, dosage, and mode of renal replacement (RRT are under debate, but also anticoagulation strategies and vascular access interfere with dialysis success. We present a retrospective, five-year evaluation of patients requiring RRT on a multidisciplinary 50-bed surgical intensive care unit of a university hospital with special regard to anticoagulation strategies and vascular access. Anticoagulation was preferably performed with unfractionated heparin or regional citrate application (RAC. Bleeding and suspected HIT-II were most common causes for RAC. In CVVHD mode filter life span was significantly longer under RAC compared to heparin or other anticoagulation strategies (P=0.001. Femoral vascular access was associated with reduced filter life span (P=0.012, especially under heparin anticoagulation (P=0.015. Patients on RAC had higher rates of metabolic alkalosis (P=0.001, required more transfusions (P=0.045, and showed higher illness severity measured by SOFA scores (P=0.001. RRT with unfractionated heparin represented the most common anticoagulation strategy in this study population. However, patients with bleeding risk and severe organ dysfunction were more likely placed on RAC. Citrate provided longer filter life spans regardless of vascular access site. Attention has to be paid to metabolic disturbances.

  13. Estudo experimental dos efeitos da heparina de baixo peso molecular (Enoxaparina na formação de calo ósseo em fêmures de ratos The effects of low-molecular-weight heparin (Enoxaparin on bony callus formation in rats' femurs - an experimental study

    Directory of Open Access Journals (Sweden)

    Salim Mussi Filho

    2006-01-01

    Full Text Available O tromboembolismo venoso é uma complicação grave que pode ocorrer após fraturas. O tratamento anticoagulante mais utilizado é com a heparina de baixo peso molecular (HBPM. Existem estudos que mostram que essa droga pode interferir no metabolismo ósseo. Com o objetivo de avaliar a influência da HBPM no processo de formação de calo ósseo, realizamos um estudo experimental em ratos. A amostra constituiu-se de 22 ratos de linhagem Wistar, machos, que foram submetidos à fratura diafisária de seus fêmures direitos. Foram divididos em dois grupos de 11. No grupo controle, os animais recebiam soro fisiológico e no grupo de estudo, recebiam HBPM, enoxaparina, diariamente, por 28 dias. Após este período os ratos foram submetidos à eutanásia e os fêmures foram avaliados. No estudo macroscópico foi constatada consolidação em 11 animais (100% que não receberam enoxaparina, e, em dez animais (90,9% que receberam a droga em estudo. No estudo histológico foi constatada a formação de calo ósseo em todos os fêmures. Concluiu-se neste experimento que a enoxaparina não altera o processo de consolidação óssea em fêmures de ratos Wistar.Venous thromboembolism is a serious complication that may follow fractures. The most commonly used anticoagulant treatment is low-molecular-weight heparin (LMWH. There are some studies showing that this drug may interfere on bone metabolism. With the objective of evaluating the LMWH influence on the process of bony callus formation, we conducted an experimental study on rats. Sample was constituted of 22 Wistar male rats, which were submitted to diaphyseal fracture on their right femurs. They were divided into two groups of 11 subjects each. In the control group, the animals received saline solution and in the study group, they received LMWH - enoxaparin - in a daily basis, during 28 days. After that period, the rats were submitted to euthanasia for femur assessment purposes. At the macroscopic study

  14. A simplified screening procedure for determination of total N-NO groups (TNG) and nitrite (NO2-) in commercial low-molecular-weight heparins (LMWH) by selective chemical denitrosation followed by high-sensitivity chemiluminescence detection (NO-analyzer, NOA).

    Science.gov (United States)

    Beretta, Giangiacomo; Gelmini, Fabrizio; Merlino, Mario; Furlanetto, Sandra; Facino, Roberto Maffei

    2009-07-12

    Aim of this work was to set up a method for the sensitive and selective determination of nitrite (NO(2)(-)) and total N-nitroso groups (TNG) in dalteparin and nadroparin, commercial low- molecular-weight heparins (LMWH), prepared by deaminative depolymerization of heparin with nitrous acid. The European Pharmacopoeia VI ed. indicates respectively 5 ppm as the maximum content for contaminant NO(2)(-) in the former and 0.25 ppm for TNG in the latter and no clear indication is given for N-NO groups in dalteparin, i.e. TNG must be absent because of the specific manufacturing process. The proposed technique is based on the development of a pre-analytical device, coupled to a chemiluminometer, constituted by three sequentially connected and commercially available purge vessels, where selective reagents are employed for the conversion of NO(2)(-) and N-NO to nitric oxide (NO). In detail, NO(2)(-) was determined in the first chamber and non-volatile and volatile TNG in the second and third. This method was validated for selectivity, sensitivity, linearity, accuracy and precision. The method was shown to be selective, with a quantitative linear range of 1-1000 ppb). The bias, intra- and inter-day percent relative error was lower than 1%. The contamination of NO(2)(-) and TNG in nadreparin was below the limits; for dalteparin NO(2)(-) fell within the limit, but there was a huge amount of TNG (15.80+/-0.05 ppm-6.69+/-0.02 ppm). Preliminary investigation on the solvent-extractable material from dalteparin showed the majority of chemiluminescence retained in the aqueous residue to indicate that this N-NO groups may belong to solvent unextractable material or be tightly bound to the dalteparin backbone.

  15. Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin.

    Science.gov (United States)

    Saccullo, Giorgia; Malato, Alessandra; Raso, Simona; Santoro, Marco; Zammit, Valentina; Casuccio, Alessandra; Siragusa, Sergio

    2012-04-01

    No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc(3) and VKA after a stable platelet count ≥ 50,000 mmc(3) . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four belonging to the high-risk and one to the low-risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long-term VKA.

  16. Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history.

    Science.gov (United States)

    Mutlu, Ilknur; Mutlu, Mehmet Firat; Biri, Aydan; Bulut, Berk; Erdem, Mehmet; Erdem, Ahmet

    2015-04-01

    This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.

  17. Partial characterization and anticoagulant activity of a heterofucan from the brown seaweed Padina gymnospora.

    Science.gov (United States)

    Silva, T M A; Alves, L G; de Queiroz, K C S; Santos, M G L; Marques, C T; Chavante, S F; Rocha, H A O; Leite, E L

    2005-04-01

    The brown algae Padina gymnospora contain different fucans. Powdered algae were submitted to proteolysis with the proteolytic enzyme maxataze. The first extract of the algae was constituted of polysaccharides contaminated with lipids, phenols, etc. Fractionation of the fucans with increasing concentrations of acetone produced fractions with different proportions of fucose, xylose, uronic acid, galactose, and sulfate. One of the fractions, precipitated with 50% acetone (v/v), contained an 18-kDa heterofucan (PF1), which was further purified by gel-permeation chromatography on Sephadex G-75 using 0.2 M acetic acid as eluent and characterized by agarose gel electrophoresis in 0.05 M 1,3 diaminopropane/acetate buffer at pH 9.0, methylation and nuclear magnetic resonance spectroscopy. Structural analysis indicates that this fucan has a central core consisting mainly of 3-beta-D-glucuronic acid 1-> or 4-beta-D-glucuronic acid 1 ->, substituted at C-2 with alpha-L-fucose or beta-D-xylose. Sulfate groups were only detected at C-3 of 4-alpha-L-fucose 1-> units. The anticoagulant activity of the PF1 (only 2.5-fold lesser than low molecular weight heparin) estimated by activated partial thromboplastin time was completely abolished upon desulfation by solvolysis in dimethyl sulfoxide, indicating that 3-O-sulfation at C-3 of 4-alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the polymer.

  18. Partial characterization and anticoagulant activity of a heterofucan from the brown seaweed Padina gymnospora

    Directory of Open Access Journals (Sweden)

    Silva T.M.A.

    2005-01-01

    Full Text Available The brown algae Padina gymnospora contain different fucans. Powdered algae were submitted to proteolysis with the proteolytic enzyme maxataze. The first extract of the algae was constituted of polysaccharides contaminated with lipids, phenols, etc. Fractionation of the fucans with increasing concentrations of acetone produced fractions with different proportions of fucose, xylose, uronic acid, galactose, and sulfate. One of the fractions, precipitated with 50% acetone (v/v, contained an 18-kDa heterofucan (PF1, which was further purified by gel-permeation chromatography on Sephadex G-75 using 0.2 M acetic acid as eluent and characterized by agarose gel electrophoresis in 0.05 M 1,3 diaminopropane/acetate buffer at pH 9.0, methylation and nuclear magnetic resonance spectroscopy. Structural analysis indicates that this fucan has a central core consisting mainly of 3-ß-D-glucuronic acid 1-> or 4-ß-D-glucuronic acid 1 ->, substituted at C-2 with alpha-L-fucose or ß-D-xylose. Sulfate groups were only detected at C-3 of 4-alpha-L-fucose 1-> units. The anticoagulant activity of the PF1 (only 2.5-fold lesser than low molecular weight heparin estimated by activated partial thromboplastin time was completely abolished upon desulfation by solvolysis in dimethyl sulfoxide, indicating that 3-O-sulfation at C-3 of 4-alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the polymer.

  19. Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies.

    Science.gov (United States)

    Galland, Joris; Mohamed, Shirine; Revuz, Sabine; de Maistre, Emmanuel; de Laat, Bas; Marie, Pierre-Yves; Zuily, Stéphane; Lévy, Bruno; Regnault, Véronique; Wahl, Denis

    2016-07-01

    Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins.

  20. Assessment of HIT Antibody Complex in Hip Fracture Patients Receiving Enoxaparin or Unfractionated Heparin

    DEFF Research Database (Denmark)

    Griffin, Justin W; Hopkinson, William J; Rud-Lassen, Michael

    2011-01-01

    Thromboembolic disease is a common complication of hip fracture in the elderly. Anticoagulants represent a standard of care in preventing postoperative thrombotic complications following surgical fixation. We asked whether levels of antibody to heparin-platelet factor 4 (PF4) complex were differe...

  1. Human single chain antibodies against heparin: selection, characterization, and effect on coagulation.

    NARCIS (Netherlands)

    Westerlo, E.M.A. van de; Smetsers, T.F.; Dennissen, M.A.B.A.; Linhardt, R.J.; Veerkamp, J.H.; Muijen, G.N.P. van; Kuppevelt, A.H.M.S.M. van

    2002-01-01

    Heparin, located in mast cells and basophilic granulocytes, is widely used as an anticoagulant. It belongs to a class of linear polysaccharides called glycosaminoglycans (GAGs). Using phage display technology, we have selected 19 unique human antiheparin antibodies. Some antibodies react almost excl

  2. Characterization of PF4-Heparin Complexes by Photon Correlation Spectroscopy and Zeta Potential.

    Science.gov (United States)

    Bertini, Sabrina; Fareed, Jawed; Madaschi, Laura; Risi, Giulia; Torri, Giangiacomo; Naggi, Annamaria

    2017-01-01

    Heparin-induced thrombocytopenia (HIT) is associated with antibodies to complexes between heparin and platelet factor 4 (PF4), a basic protein usually found in platelet alpha granules. Heparin-induced thrombocytopenia antibodies preferentially recognize macromolecular complexes formed between positively charged PF4 and polyanionic heparins over a narrow range of molar ratios. The aim of this work was to study the complexes that human PF4 forms with heparins from various species, such as porcine, bovine, and ovine; heparins from various organs, such as mucosa and lung; and different low-molecular-weight heparins (LMWHs) at several stoichiometric ratios to evaluate their sizes and charges by photo correlation spectroscopy and zeta potential measurements. The resulting data of the PF4 complexes with unfractionated heparins (UFHs), LMWHs and their fractions, and oligosaccharide components suggest that the size of aggregates is not only a simple function of average molecular weight but also of the molecular weight distribution of the sample. Moreover, it was found that lower concentrations of the tested ovine-derived mucosal heparin are required to form the large PF4/heparin complexes as compared to mucosal porcine and bovine heparin.

  3. Clinical study of low molecular weight heparin in early intervention and therapy of FGR%低分子肝素钠早期干预治疗FGR的临床研究

    Institute of Scientific and Technical Information of China (English)

    杨鹃; 李聪; 杨永华

    2014-01-01

    Objective To study the clinical effect of low molecular weight heparin in early intervention and therapy of fetal growth restriction (FGR) and the effect of perinatal fetus outcome. Methods 200 pregnant women who were diagnosed as FGR prenatal examination in our hospital from January 2009 to January 2014 were divided into treatment group and control group, with 100 cases in each group. Based on the treatment of maternal basic diseases of the two groups, treatment group was early treated by low molecular weight heparin, while control group was simply strengthened with diet nutrition. To observe weekly the uterine height, the abdominal circumference, the fetal biparietal diameter, the head circumference, and the femur length of the two groups. Results The treatment group was was significantly higher than the control group, the difference had statistical significance(P 0.05), while which were higher after treatment in treatment group than in control group, the difference was significant between the two groups(P < 0.05). The fetal age, the body weight, and the situation of asphyxia of newborns between the two groups had significant difference (P<0.05). Conclusion The clinical effect of low molecular weight heparin in the improvement of placental circulation and the promotion of the fetal growth is affirmative, and the safety of which in mothers and fetus is better.%目的:探讨低分子肝素钠早期干预治疗胎儿生长受限的临床效果及对围生儿结局的影响。方法选取我院2009年1月~2014年1月收治的经产前检查诊断为胎儿生长受限的孕妇200例,分为观察组和对照组,每组100例。两组患者在治疗母体基础性疾病基础上,观察组早期进行低分子肝素钠治疗,对照组单纯为加强饮食营养。观察两组孕妇每周宫高和腹围、胎儿双顶径、头围、股骨长。结果观察组明显优于对照组,差异具有统计学意义(P<0.05);两组患者胎儿治疗前的羊

  4. Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant.

    Science.gov (United States)

    Soule, Erin E; Bompiani, Kristin M; Woodruff, Rebecca S; Sullenger, Bruce A

    2016-02-01

    Potent and rapid-onset anticoagulation is required for several clinical settings, including cardiopulmonary bypass surgery. In addition, because anticoagulation is associated with increased bleeding following surgery, the ability to rapidly reverse such robust anticoagulation is also important. Previously, we observed that no single aptamer was as potent as heparin for anticoagulating blood. However, we discovered that combinations of two aptamers were as potent as heparin. Herein, we sought to combine two individual anticoagulant aptamers into a single bivalent RNA molecule in an effort to generate a single molecule that retained the potent anticoagulant activity of the combination of individual aptamers. We created four bivalent aptamers that can inhibit Factor X/Xa and prothrombin/thrombin and anticoagulate plasma, as well as the combination of individual aptamers. Detailed characterization of the shortest bivalent aptamer indicates that each aptamer retains full binding and functional activity when presented in the bivalent context. Finally, reversal of this bivalent aptamer with a single antidote was explored, and anticoagulant activity could be rapidly turned off in a dose-dependent manner. These studies demonstrate that bivalent anticoagulant aptamers represent a novel and potent approach to actively and reversibly control coagulation.

  5. Anticoagulação em terapias contínuas de substituição renal Anticoagulation in continuous renal replacement therapies (CRRT

    Directory of Open Access Journals (Sweden)

    Erwin Otero Garcés

    2007-10-01

    circuit unclotted, with minimal complications such as bleeding due to excessive anticoagulation. Several features can contribute to dialysis circuit thrombosis, such as the speed of pump blood flow, dialysis catheter, type of dialyzer membrane and also, the type of technique prescribed. Unfractioned heparin (UFH is the anticoagulant most used in CRRT. Recently, low-molecular weight heparins (LMWH have been shown to be safe and effective drugs for this purpose. In critically ill patients, who frequently have contraindications to systemic anticoagulation, regional anticoagulation with trisodium citrate is an increasingly accepted method due to its safety and efficiency if applied under strict metabolic control. Regional anticoagulation with UFH/protamin now has limited use because of side effects related to protamin. If the patient has contraindication to systemic anticoagulation or if regional anticoagulation with citrate is not available, continuous flushing of circuit dialysis with saline is the only applicable alternative. In patients with contraindication to heparinization, new drugs not yet available in Brazil, such as prostaglandins, recombinant hirudin, argatroban and nafamostat can be used.

  6. 低分子肝素联用地塞米松抑制家兔导管相关血栓形成%Inhibition Effect of Low Molecular Weight Heparin Combined with Dexamethasone on Catheter-related Thrombosis in Rabbit

    Institute of Scientific and Technical Information of China (English)

    艾熙; 陈劲; 冯丽娟; 官艳; 范亚维; 阳军; 张志伟

    2015-01-01

    目的:建立稳定的家兔颈静脉导管相关血栓模型,并探讨低分子肝素与地塞米松对其形成的影响。方法将60只日本大耳白兔分为对照组、低分子肝素组、地塞米松组和合用组。将中心静脉导管(CVC )插入右侧颈静脉制造导管相关血栓动物模型。术后分别给予低分子肝素钠/地塞米松。术后第7天观察颈静脉导管相关血栓形成情况及血浆内D‐D二聚体水平。结果成功建立简便有效的日本大耳白兔导管相关血栓模型。低分子肝素组及合用组实验兔导管相关血栓形成较对照组显著降低,D‐D二聚体水平明显下降( P<0.01)。结论应用低分子肝素能有效预防导管相关血栓。糖皮质激素抗炎治疗可能对预防导管相关血栓形成有一定作用。%Objective To investigate the therapeutic effect of low molecular weight heparin sodium and dexamethasone so‐dium phosphate on catheter‐related thrombosis.Methods Sixty Japanese big ear white rabbits were divided into four groups (n=15 each):control group ,low molecular weight heparin group ,dexamethasone sodium phosphate group ,low molecular weight heparin combined with dexamethasone group.A central venous catheter was inserted into right jugular vein to induce catheter‐related thrombosis.After the surgery ,control group was treated with normal saline ;molecular weight heparin group and dexam‐ethasone sodium phosphate group were subcutaneously injected with low molecular weight heparin and dexamethasone ,respec‐tively ;low molecular weight heparin combined with dexamethasone group received injection of both.Catheter‐related thrombosis in jugular vein and D‐Dimer concentration in serum were observed 7 days after the surgery.Results Catheter‐related thrombo‐sis model was successfully established in Japanese big ear white rabbits.Compared with control group ,the formation rates of catheter‐related thrombosis in low molecular

  7. Control of anticoagulant and antiplatelet therapy. Managing patients with acute thrombotic disorders.

    OpenAIRE

    Anderson, D. R.; Fernandez, L. A.

    1993-01-01

    Indications for using standard anticoagulants, heparin and warfarin; the dosage and route of administration; the importance of monitoring therapy with reliable laboratory indices; and complications of therapy are discussed. Acetylsalicylic acid and ticlopidine can be used as antiplatelet agents. Because their effect on platelet function is not monitored clinically, their clinical indications are emphasized.

  8. Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation.

    Science.gov (United States)

    de Oliveira Barddal, Helyn Priscila; Gracher, Ana Helena Pereira; Simas-Tosin, Fernanda Fogagnoli; Iacomini, Marcello; Cipriani, Thales Ricardo

    2015-09-01

    Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit α-thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents.

  9. Self-titrating anticoagulant nanocomplexes that restore homeostatic regulation of the coagulation cascade.

    Science.gov (United States)

    Lin, Kevin Y; Lo, Justin H; Consul, Nikita; Kwong, Gabriel A; Bhatia, Sangeeta N

    2014-09-23

    Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide-polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants.

  10. Na2EDTA anticoagulant impaired blood samples from the teleost Piaractus mesopotamicus

    Directory of Open Access Journals (Sweden)

    Thaís Heloisa Vaz Farias

    2016-05-01

    Full Text Available Abstract: The present study aimed to evaluate the effects of Na heparin and Na2EDTA on blood of Piaractus mesopotamicus (360.7±42.4g, 26.4±1.0cm. Twenty fishes were sampled in two experiment trials, ten for erythrocyte fragility analysis and ten for hematologic and plasma biochemical study. The blood collected by venous-caudal puncture was fractioned and stored in anticoagulants solution: Na2EDTA 10%, Na2EDTA 3%, Na heparin 5000 IU and Na heparin 100 IU. Plasmatic levels of calcium presented in the Na2EDTA stored samples were about 80% lower than both heparin groups. Blood samples of P. mesopotamicus stored with Na2EDTA demonstrated increase in the hematocrit and MCV, and decrease in MCHC. The dose-response effect was observed in this study. The results are reinforced by the higher levels of plasmatic protein and hemolysis presented in the Na2EDTA 10% stored blood, confirming the deleterious effect of this anticoagulant treatment on the quality of blood samples. Na2EDTA is not indicated to store P. mesopotamicus blood samples, but sodium heparin at 100 IU is the most recommended anticoagulant, since this treatment presented the lower rate of alterations in the stored blood.

  11. Non-Anticoagulant Fractions of Enoxaparin Suppress Inflammatory Cytokine Release from Peripheral Blood Mononuclear Cells of Allergic Asthmatic Individuals.

    Directory of Open Access Journals (Sweden)

    Madhur D Shastri

    Full Text Available Enoxaparin, a low-molecular-weight heparin, is known to possess anti-inflammatory properties. However, its clinical exploitation as an anti-inflammatory agent is hampered by its anticoagulant effect and the associated risk of bleeding.The aim of the current study was to examine the ability of non-anticoagulant fractions of enoxaparin to inhibit the release of key inflammatory cytokines in primed peripheral blood mononuclear cells derived from allergic mild asthmatics.Peripheral blood mononuclear cells from allergic asthmatics were activated with phytohaemag glutinin (PHA, concanavalin-A (ConA or phorbol 12-myristate 13-acetate (PMA in the presence or absence of enoxaparin fractions before cytokine levels were quantified using specific cytokine bead arrays. Together with nuclear magnetic resonance analysis,time-dependent and target-specific effects of enoxaparin fractions were used to elucidate structural determinants for their anti-inflammatory effect and gain mechanistic insights into their anti-inflammatory activity.Two non-anticoagulant fractions of enoxaparin were identified that significantly inhibited T-cell activation. A disaccharide fraction of enoxaparin inhibited the release of IL-4, IL-5, IL-13 and TNF-α by more than 57% while a tetrasaccharide fraction was found to inhibit the release of tested cytokines by more than 68%. Our data suggest that the observed response is likely to be due to an interaction of 6-O-sulfated tetrasaccharide with cellular receptor(s.The two identified anti-inflammatory fractions lacked anticoagulant activity and are therefore not associated with risk of bleeding. The findings highlight the potential therapeutic use of enoxaparin-derived fractions, in particular tetrasaccharide, in patients with chronic inflammatory disorders.

  12. Safety and efficacy of catheter-based left atrial appendage closure in patients with contraindications for long-term anticoagulation.

    Science.gov (United States)

    Seidel, Adrian; Parwani, Abdul S; Krackhardt, Florian; Huemer, Martin; Attanasio, Philipp; Haverkamp, Wilhelm; Pieske, Burkert; Boldt, Leif-Hendrik

    2017-05-31

    Percutaneous left atrial appendage closure (LAAC) and the role of post interventional anticoagulation often evokes controversy in daily practice. This study aimed to evaluate LAAC in patients with non-rheumatic atrial fibrillation, high thromboembolic risk and contraindications for long-term anticoagulation in a clinical scenario. Between 2010-2015, LAAC was attempted in 118 patients (47 women). Devices were successfully implanted in 95% (Watchman™ device n=97, St. Amplatzer™ Cardiac Plug/Amulet n=14, Amplatzer PFO Occluder n=1). Mean age, HAS-BLED and CHA2DS2VASc score were 75 years (SD 8.35yrs), 4.3 and 4.9, respectively. Median followup was 447 days (P25=183d, P75=789d). The primary safety endpoint was defined as major bleeding according to the International Society on Thrombosis and Haemostasis. The combined efficacy endpoint included ischemic strokes, transitory ischemic attacks (TIA) and systemic embolisms. Procedural complication rate was 3.4%. After successful intervention, either a therapy with anticoagulants (n=62) or dual antiplatelet therapy (DAPT, n=50) was prescribed temporarily. Medication was reduced if implantation proved satisfying in a 6-week follow-up transesophageal echocardiography, which was the case in 79% of these patients. During follow-up, one patient suffered a TIA (0.6%/year). No other efficacy event was observed. 11 major bleedings occurred (6.6%/year): one each under DAPT plus phenprocoumon, DAPT plus rivaroxaban, acetylsalicylic acid (ASA) plus rivaroxaban, two under DAPT, two under ASA plus low molecular weight heparin, and four under ASA only. In our analysis, catheter-based LAA occlusion prevented thromboembolisms with high efficacy. Major bleedings were however common in patients with, but also without anticoagulation, independent from time course.

  13. A model ternary heparin conjugate by direct covalent bond strategy applied to drug delivery system.

    Science.gov (United States)

    Wang, Ying; Xin, Dingcheng; Hu, Jiawen; Liu, Kaijian; Pan, Jiangao; Xiang, Jiannan

    2009-01-01

    A model ternary heparin conjugate by direct covalent bond strategy has been developed, in which modified heparin using active mix anhydride as intermediate conjugates with model drug molecule and model specific ligand, respectively. Designed ester bonds between model drug and heparin facilitate hydrolysis kinetics research. The strategy can be extended to design and synthesize a targeted drug delivery system. The key point is to use mixed anhydride groups as activating intermediates to mediate the synthesis of the ternary heparin conjugate. Formation of mixed anhydride is detected by the conductimetry experiment. The ternary heparin conjugate is characterized by (13)C NMR, FT-IR and GPC, respectively. The decreased trend on degree of substitution (DS) is consistent with that of introduced anticancer drug and specific ligand in drug delivery system. Moreover, their anticoagulant activity is evaluated by measuring activated partial thromboplastin time (APTT) and anti-factor Xa activity. The results show that model ternary heparin conjugate with reduced anticoagulant activity may avoid the risk of severe hemorrhagic complication during the administration and is potential to develop a safe and effective drug delivery system on anticancer research.

  14. Efficacy of low molecular weight heparin on severe pneumonia in elderly patients with high level of D-dimer%低分子肝素钠辅助治疗D二聚体升高的老年重症肺炎疗效观察

    Institute of Scientific and Technical Information of China (English)

    倪军; 林宏; 孙嵘; 刘伟春; 郑海燕; 王倩

    2013-01-01

    Objective To evaluate the clinical effect and safety of low molecular weight heparin in the treatment of severe pneumonia in elderly patients with high D-dimer.Methods Eighty-nine cases of severe pneumonia with high level of D-dimer were randomly divided into two groups.The experiment group was given subcutaneous injection of low molecular weight heparin 5000 IU/d for 5 to 7 days.The control group was given conventional therapy.Artery Blood oxygen pressure(PaO2) in arterial blood and C-reactive protein concentration (CRP),D-dimer before and after treatment were measured.The fatality rate and adverse drug reactions were observed.Results After anticoagulant therapy,PaO2 in the experimental group had a more significant improvement than that in the control group [(77.4 ± 12.9) mmHg vs (62.8 ±12.3) mmHg,P <0.05].The level of D-dimer in the experiment group had a more significant decrease than that in the control group[(0.66 ±0.38) mg/L vs (1.19 ±0.55) mg/L,P <0.01].The experiment group had shorter hospital stay (days) and lower cost of hospitalization than the control group.There was no statistical difference in the fatality rate between two groups (9.09 % vs 20.45%,P > 0.05).The adverse drug reactions were few and mild in both groups.Conclusions Low molecular weight heparin is effective and safe to severe pneumonia in elderly patients.%目的 观察低分子肝素在老年重症肺炎患者中的治疗作用及不良反应. 方法 将2009年1月自2012年12月闸北区中心医院住院的D二聚体(D-D)升高的老年重症肺炎患者随机分为抗凝组和对照组.抗凝组予低分子肝素钠(法安明5000 IU/d,皮下注射)治疗;对照组仅给予常规治疗.观察2组治疗前后D-D、静脉血C反应蛋白浓度、动脉血氧分压(PaO2).比较2组平均住院天数及住院费用,观察2组病死率及不良反应. 结果 抗凝组治疗后D-D较对照组显著降低(P<0.01),为(0.66±0.38) mg/L和(1.19±0.55) mg/L.抗凝组治疗后PaO2

  15. Severe heparin osteoporosis in pregnancy.

    OpenAIRE

    Griffiths, H. T.; Liu, D T

    1984-01-01

    A case of severe osteoporosis following administration of low dose subcutaneous heparin in pregnancy is reported. Possible reasons for the condition are suggested which caution against the indiscriminate use of subcutaneous heparin in pregnancy.

  16. The rapeutic value of low-molecular-weight heparin in early preeclampsia%低分子肝素在早发型子痫前期期待治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    汪丽兰; 陈宏霞; 曹伍兰

    2012-01-01

    Objective To investigate the effect of the low-molecular-weight heparin on the coagulation function and pregnancy outcome of early preeclampsia, and to explore the manegement methods to prolong the gestation weeks of early preeclampsia. Methods From January 2009 to march 2012, 80 early preeclampsia patients in our hospital were chosen in this study. The patients were divided into two groups named 1 and II respectively based on the gestation weeks when they were admitted. Group I was in the weeks of 28-31+6, while group II was in the weeks of 32-33+6. The two groups were divided into two subgroups named A and B by treatment. Group I (Ⅱ) A was the study group which was treated by low-molecular-weight heparin plus the routine therapy, while I (Ⅱ) B was only by routine therapy that served as con-trolls. The blood pressure, coagulation function, complications of the prenant women, prolonged days and the outcome of perinate of all the patients were recorded. Results The genaral clinical data in group I (Ⅱ) A and B was without any sig-nifcant difference (P > 0.05). The finbrinogen and D-dimer in I (Ⅱ) A is lower than that in I (Ⅱ) B (P 0.05). The prevalence of neonatal asphyxia in group I A was lower than that in I B (P 0.05).经治疗,加用低分子肝素组即研究组纤维蛋白原(Fbg)及D二聚体(D-D)显著降低(P 0.05),Ⅰ组A新生儿窒息率较Ⅰ组B低,差异有统计学意义(P 0.05).结论 低分子肝素有助于提高早发型子痫前期孕妇期待治疗效果,可以明显改善围生儿结局,提高母儿安全性.

  17. Arterial and venous complications of heparin-induced thrombocytopenia in burn patients.

    Science.gov (United States)

    Scott, Jeffrey R; Klein, Matthew B; Gernsheimer, Terri; Honari, Shari; Gibbons, Janet; Gibran, Nicole S

    2007-01-01

    Heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin treatment that can result in a number of devastating thrombotic complications. Given the common use of heparin for deep venous thrombosis prophylaxis in patients with burns, we reviewed the incidence and complications of HIT in our burn center. We performed a retrospective review of all patients treated with heparin at our burn center who underwent testing for HIT from 2001 to 2005. Screening for HIT was performed by platelet factor 4 enzyme-linked immunoassay. Records were reviewed with particular attention to indications for HIT testing, duration of heparin therapy, type of heparin used (fractionated vs unfractionated), indication for heparin use (prophylactic vs therapeutic), treatment of HIT, and complications of HIT. During the 4-year study period, 625 patients received heparin therapy at some point during their hospital course. Of these patients, 43 (6.9%) underwent testing for HIT and 10 of the 43 screened patients (23%) were positive; the incidence among all heparinized burn patients was 1.6%. Thrombotic complications of HIT included arterial thrombosis requiring limb amputation (two patients), deep venous thrombosis (three patients), and pulmonary embolism (two patients). One patient died, presumably secondary to a pulmonary embolism. All patients were anticoagulated after HIT diagnosis, and four patients developed bleeding complications. HIT is a potentially devastating complication of heparin administration. Whereas our overall incidence of HIT was low, HIT+ patients developed significant complications, including arterial and venous thrombosis, pulmonary embolus, limb loss, and death. Treatment for such HIT-related thromboses usually resulted in bleeding complications requiring transfusions. The routine use of heparin for deep venous thrombosis prophylaxis needs to be carefully considered in light of these potential complications.

  18. Best practices for use of the HEMOX analyzer in the clinical laboratory: quality control determination and choice of anticoagulant.

    Science.gov (United States)

    Vanhille, Derek L; Nussenzveig, Roberto H; Glezos, Christopher; Perkins, Sherrie; Agarwal, Archana M

    2012-09-01

    The HEMOX Analyzer (TCS Scientific) has been used to measure the full oxygen-dissociation curve (ODC) and to calculate P(50) and the Hill coefficient. The effects of different anticoagulants on sample stability and P(50) values have not been evaluated extensively for this instrument. We characterized an artificial hemoglobin (Equil QC463) for quality control (QC) and compared P(50) values for blood samples drawn into 3 different anticoagulants (acid citrate dextrose [ACD], heparin, and EDTA). P(50) values were not stable in ACD but were stable in heparin and EDTA anticoagulants for up to 4 days. Tests with Equil QC463 showed that P(50) values were quite sensitive to small variations in buffer pH. Use of the correct anticoagulant and strict control of buffer pH are 2 parameters that need to be accounted for in best-practices use of this hemoximeter and before determining P(50).

  19. 低分子肝素仿制药一致性研究法规现状%Current Regulatory Situation of Quality Consistency Evaluation for Generic Low Molecular Weight Heparin

    Institute of Scientific and Technical Information of China (English)

    柳晓芳; 崔慧斐

    2013-01-01

    Quality consistency evaluation is required for generic low molecular weight heparin (LMWH) because it is a multi-component biochemical medicine. The patents for LMWH have expired or will expire shortly, thus guidelines for quality consistency evaluation of generics have been issued in many countries or regions. In this paper, these guidelines or statements were summarized to provide reference for development of such generics.%低分子肝素(LMWH)是一类多组分生化药,其复杂的结构特点决定了其仿制药与原研药一致性研究的必要性。随着LMWH,如依诺肝素钠等原研药专利的到期,各国均发布了针对此类产品仿制药与原研药一致性研究的指导原则。本文综述了各国或各组织发布的指导原则或声明,为LMWH仿制药的研究提供借鉴。

  20. Delayed intra-abdominal bleeding following trans-vaginal ultrasonography guided oocyte retrieval for in vitro fertilization in patients at risk for thrombo-embolic events under anticoagulant therapy [v1; ref status: indexed, http://f1000r.es/1uf

    Directory of Open Access Journals (Sweden)

    Roy Mashiach

    2013-09-01

    Full Text Available We report herein, two cases of massive delayed (2 and 4 days intra abdominal hemorrhage following ovum pick-up (OPU, in patients at risk for thrombo-embolic events, who concomitantly used therapeutic doses of low molecular weight heparin (LMWH. We discuss the possible mechanisms involved in causing the aforementioned delayed bleeding, and call for re-evaluation of the presently accepted anticoagulant co-treatment regimen. These case reports should direct physicians' attention and keep them alert, while conducting IVF treatment to this subgroup of high risk patients.

  1. Delayed intra-abdominal bleeding following trans-vaginal ultrasonography guided oocyte retrieval for in vitro fertilization in patients at risk for thrombo-embolic events under anticoagulant therapy [v2; ref status: indexed, http://f1000r.es/24f

    Directory of Open Access Journals (Sweden)

    Roy Mashiach

    2013-10-01

    Full Text Available We report herein, two cases of massive delayed (2 and 4 days intra abdominal hemorrhage following ovum pick-up (OPU, in patients at risk for thrombo-embolic events, who concomitantly used therapeutic doses of low molecular weight heparin (LMWH. We discuss the possible mechanisms involved in causing the aforementioned delayed bleeding, and call for re-evaluation of the presently accepted anticoagulant co-treatment regimen. These case reports should direct physicians' attention and keep them alert, while conducting IVF treatment to this subgroup of high risk patients.

  2. The Efficacy of Low Molecular Weight Heparin in Prevention Deep of Vein Thrombosis after the Operation of Great Saphenous Varicose Vein%低分子肝素在预防大隐静脉曲张术后患肢深静脉血栓形成中的作用

    Institute of Scientific and Technical Information of China (English)

    董春锋; 王苏杭

    2012-01-01

    目的 探讨低分子肝素在预防大隐静脉曲张术后患肢深静脉血栓形成中的作用.方法 分析200例大隐静脉曲张术后应用低分子肝素抗凝患者(观察组)及200例术后未应用低分子肝素抗凝患者(对照组)下肢深静脉血栓形成发生情况及术后患肢皮下血肿的发生情况.结果 两组患者术后患肢深静脉血栓形成的发生率比较差异有统计学意义(P0.05).结论 大隐静脉曲张术后应用低分子肝素抗凝治疗,可显著降低下肢深静脉血栓形成的发生,同时不增加患肢术后出血的风险.%Objective To investigate the efficacy of low molecular weight heparin in prevention deep vein thrombosis( DVT )after the operation of great saphenous varicose vein. Methods The DVT incidence of 200 case of great saphenous varicose vein who were given low molecular weight heparin after operation( observation group )and 200 case of great saphenous varicose vein who were not given low molecular weight heparin after operation( control group )were analyzed, and the incidence of subcutaneous hematoma of the two groups were observed. Results There was significant difference between the two groups in DVT incidence ( P 0.05 ). Conclusion The therapy of the low molecular weight heparin after the operation of great saphenous varicose vein can reduce the incidence of DVT,without increasing the incidence of subcutaneous hematoma.

  3. Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management.

    Science.gov (United States)

    Levi, M M; Eerenberg, E; Löwenberg, E; Kamphuisen, P W

    2010-02-01

    The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. Heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralised by administration of vitamin K or prothrombin complex concentrates. The antihaemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are currently being evaluated in clinical studies, showing promising results. The new-generation anticoagulants include specific inhibitors of factor IIa or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives. A limitation of the new class of anti-IIa and anti-Xa agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option.

  4. Underutilization of Anticoagulant for Venous Thromboembolism Prophylaxis in Three Hospitals in Jakarta

    Directory of Open Access Journals (Sweden)

    T. Djumhana Atmakusuma

    2016-05-01

    Full Text Available Aim: to assess the current use of anticoagulants and implementation of International Guidelines in venous thromboembolism (VTE prophylaxis in hospitalized patients with acute medical illnesses in Jakarta, Indonesia. Methods: a multicenter, prospective, disease registry, recruiting patients diagnosed as acutely ill medical diseases and other medical conditions at risk of VTE, with in-hospital immobilization for at least 3 days. Results: of 401 patients, 46.9% received anticoagulants which included unfractionated heparin (64.4%, fondaparinux (11.7%, enoxaparin (9.6%, warfarin (3.7%, and combination of anticoagulants (10.6%. VTE prophylaxis using physical and mechanical method was used in 81.3% of patients, either as a single modality or in combination with anticoagulants. During hospitalization, VTE were found in 3.2% patients; 10 patients (2.5% had lower limb events and 3 patients (0.75% had a suspected pulmonary embolism. The main reference international guidelines used were AHA/ASA 2007 (47.4%, followed by ACCP 2008 (21.7%. Conclusion: the study showed underutilization of prophylaxis anticoagulants in which mechanical thromboprophylaxis either alone or combination with anticoagulants was the most commonly used. Unfractionated heparin was the preferable choice. The most commonly used guideline was AHA/ASA 2007. VTE thromboprophylaxis in medically ill patients needs to be encouraged. Key words: venous thromboembolism (VTE, prophylaxis, registry, non-surgery hospitalization.

  5. Slow versus fast subcutaneous heparin injections for prevention of bruising and site-pain intensity.

    Science.gov (United States)

    Akbari Sari, Ali; Janani, Leila; Mohammady, Mina; Nedjat, Saharnaz

    2014-07-18

    Heparin is an anticoagulant medication that is normally injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma and pain at the injection site. One of the factors that may affect pain, haematoma and bruising is injection speed. To assess the effects of the duration (speed) of subcutaneous heparin injection on pain, haematoma and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin or low molecular weight heparin. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 7). We searched MEDLINE, EMBASE, CINAHL and two Persian databases Iranmedex and SID (August 2013). We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injections of heparin on pain, bruising and haematoma at the injection site. Two review authors, working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by the Cochrane Handbook to assess the quality of included studies. The study outcomes were summarised using quantitative and qualitative methods. One RCT was identified which met the inclusion criteria, involving 50 participants with a mean age of 55.25 (± 12.37) years. In this trial it was not possible to blind the participants and care givers. The method of sequence generation and allocation concealment was not described. The overall quality of the evidence was moderate due to the single small included study. Each participant had two injections, one in the left side and one in right side of the abdomen. One of these was injected slowly (intervention) and the other was injected fast (control). The second injection was 12 hours after the first injection. The duration of fast injection was 10 seconds and the duration of slow injection was 30

  6. Assessing Bleeding Risk in Patients Taking Anticoagulants

    Science.gov (United States)

    Shoeb, Marwa; Fang, Margaret C.

    2013-01-01

    Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

  7. Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy.

    Directory of Open Access Journals (Sweden)

    John W Avery

    Full Text Available Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM, characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.

  8. Trombocitopenia induzida por heparina Heparin-induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Fernanda Longhi

    2001-08-01

    Full Text Available O objetivo deste relato é fazer uma revisão a fim de obter informações atualizadas sobre trombocitopenia induzida por heparina, suas manifestações clínicas, seu diagnóstico e seu manejo terapêutico. Após, concluímos que a trombocitopenia induzida por heparina é uma complicação comum em pacientes submetidos a tratamento com heparina, indiferentemente da doença de base. Complicações trombóticas potencialmente fatais têm sido descritas. Por essa razão, se houver suspeita de trombocitopenia induzida por heparina, uma abordagem adequada incluindo suspensão precoce da heparina é mandatória. Produtos que substituem a heparina incluem hirudina e danaparóide sódico. Heparina de baixo peso molecular é contra-indicada.The aim of this paper is to review current information about the clinical manifestations, diagnosis and management of heparin-induced thrombocytopenia. This was achieved by a bibliographic review using Public Medline and consulting Hematology textbooks. From this study we concluded that heparin-induced thrombocytopenia is a common complication of patients exposed to heparin therapy regardless of underlying conditions. Potentially fatal thrombotic complications have been reported. Therefore, if heparin-induced thrombocytopenia is suspected, an adequate approach including early heparin discontinuation is mandatory. Alternative products for heparin include hirudin and danaparoid sodium. Low-molecular-weight heparin is contraindicated.

  9. Anticoagulant effect of marine algae.

    Science.gov (United States)

    Kim, Se-Kwon; Wijesekara, Isuru

    2011-01-01

    Recently, a great deal of interest has been developed in the nutraceutical and pharmaceutical industries to isolate natural anticoagulant compounds from marine resources. Among marine resources, marine algae are valuable sources of novel bioactive compounds with anticoagulant effect. Phlorotannins and sulfated polysaccharides such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae have been recognized as potential anticoagulant agents. Therefore, marine algae-derived phlorotannins and SPs have great potential for developing as anticoagulant drugs in nutraceutical and pharmaceutical areas. This chapter focuses on the potential anticoagulant agents in marine algae and presents an overview of their anticoagulant effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. 持续性肾脏替代治疗抗凝技术的应用%The current state and prospect of continuous renal replacement treatment anticoagulation technique

    Institute of Scientific and Technical Information of China (English)

    管向东; 孙冠青; 陈娟

    2012-01-01

    Continuous renal replacement treatment (CRRT) is a common organ function support ive technique in the field of Critical Care Medicine. Since sepsis patients are always combined with hemodynamic instability and coagulation dysfunction , anticoagulation therapy has been an indispensable component part in CRRT for sepsis patients. Anticoagulation therapy enables to slow or reduce the clottings in pipeline and/or filter so as to prolong its life,improve the efficacy of CRRT treatment, and reduce the loss of blood components and thrombosis under pathological state. So far,the common CRRT anticoagulation drugs include heparin,antithrombin,low molecular weight heparin (LMWH) and/or hyparinoids from animal organs, II factor antagonists, nafamostat, sodium citrate and antiplatelet agents. Coagulation function should be regularly monitored in the process of CRRT anticoagulation treatment. Under the circumstance of anticoagulation taboo, heparin-saline priming, predilution and hydrophilic filter can be used to reduce the clottings in pipeline and/or filter.%持续性肾脏替代治疗(CRRT)是重症医学领域常用的器官功能支持技术.由于脓毒症患者常合并血流动力学不稳定及凝血功能障碍,抗凝技术已成为脓毒症患者CRRT过程中必不可少的组成部分.抗凝技术能延缓或减少管路和(或)滤器的凝血,延长其寿命,提高CRRT治疗效率,减少血液成分的丢失及病理状态下的血栓形成.目前常用的CRRT抗凝药物包括肝素、抗凝酶、低分子肝素和(或)肝素类似物、Ⅱ因子拮抗剂、萘莫斯他、枸橼酸钠及抗血小板药物.CRRT抗凝治疗过程中需动态监测凝血功能等指标.在抗凝禁忌的情况下,可用肝素盐水浸泡、前稀释及选择高亲水性滤器等方法减少管路和(或)滤器凝血.

  11. Clinical study in acupressure time after abdominal injection of low-molecular-weight heparin calcium%腹壁注射低分子肝素钙按压时间的临床研究

    Institute of Scientific and Technical Information of China (English)

    韩利民

    2008-01-01

    目的 探讨腹壁注射低分子肝素钙的患者,注射后按压时间的长短与皮下出血发生率及出血面积的关系,同时找出适当的按压时间,以减少皮下出血的发生,减小出血面积.方法 选择2005年10月-2006年8月腹壁注射低分子肝素钙的患者60例,将每例患者的16次腹壁注射按局部按压时间的长短分为8组,每组按压时间分别为3,4,5,6,7,8,9,10 min.观察皮下出血的发生例次及出血面积的大小.结果 腹壁注射低分子肝素钙后,局部不同按压时间与皮下出血的发生率及出血面积的大小之间存在关联,P<0.01,且6min组与7min组出血率及出血面积比较差异有统计学意义.P<0.01,其他相邻组间差异无统计学意义.结论 腹壁注射低分子肝素钙后局部按压7 min可以有效降低皮下出血的发生率并缩小出血面积.%Objective To investigate the relation of acupressure time and incidence rate of sub-cutaneous hemorrhage after abdominal injection of low-molecular-weight beparin calcium.At the same time to seek the most appropriate acupressure time to reduce incidence rate and area of subcutaneous hemor-rhage. Methods Patients(60 cases)undergoing abdominal injection of low-molecular-weight heparin cal-cium from October 2005 to August 2006 were selected.Each patient received 16 times of injection.They were divided into 8 groups according to acupressure time,the acupressure time for each group was 3,4,5,6,7,8,9,10 minutes. Incidence rate and area of subcutaneous hemorrhage was observed. Results Lo-cal acupressure time was related to the incidence rate and area of subcutaneous hemorrhage,P<0.01. The incidence rate and area of subcutaneous hemorrhage was statistically different between acupressure time of 6 minutes and 7 minutes,P<0.01,while other adjacent groups had no statistical difference. Conclusions Local acupressure time of 7 minutes can effectively reduce incidence rate and area of subcutaneous hemor-rhage after abdominal

  12. Immobilization of NaIO4-treated heparin on PEG-modified 316L SS surface for high anti-thrombin-III binding.

    Science.gov (United States)

    Chuang, Tzu-Wen; Lin, Dong-Tsamn; Lin, Feng-Huei

    2008-09-01

    Poor compatibility between blood and metallic coronary artery stents is one reason for arterial restenosis; however, the immobilization of anticoagulant agents on the surface of the stent is a feasible method of improving stent compatibility. Heparin, a well-known anticoagulant, has been frequently used to coat the surfaces of certain biomaterials to attain blood compatibility. The compound 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide has often been utilized for the immobilization of heparin, but the critical carboxyl groups of heparin (with regards to heparin's anticoagulant activity) will be reduced by this method. This study examined possible methods of heparin immobilization without consuming these carboxyl groups. The 316L stainless steel surface was first activated with hexamethylene diisocyanate and then coupled with bis-amine-terminated poly (ethylene glycol) (BA-PEG) so as to create active amine groups. Sodium periodate (NaIO(4); SP) was then used to oxidize heparin to form aldehyde groups. The treated heparin could then be grafted onto the activated surface of the test material without losing its carboxyl groups. Effective surface modification of the hexamethylene diisocyanate-activated and BA-PEG-grafted 316L SS surface was confirmed using Fourier Transform Infrared Spectroscopy, electron spectroscopy for chemical analysis and a water contact angle test. After the heparin was immobilized on the BA-PEG-grafted 316L SS surface by SP, the surface showed an improvement in antithrombrin III (AT III) binding ability, its anticoagulant property, and hemocompatibility in comparison with heparin grafted by 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide.

  13. How much heparin do we really need to go on pump? A rethink of current practices.

    LENUS (Irish Health Repository)

    Shuhaibar, M N

    2012-02-03

    OBJECTIVES: Patients undergoing myocardial revascularisation using extracorporeal circulation require heparin anticoagulation. We aimed to evaluate the effect of reducing heparin dosage on target activated clotting time (ACT) and postoperative blood loss. METHODS: In a prospective randomised trial, 195 patients undergoing isolated primary CABG were randomised into four groups A, B, C, and D receiving an initial heparin dosage of 100, 200, 250 and 300 iu\\/kg, respectively. Extra incremental heparin (50 iu\\/kg) was added if required to achieve a target ACT of 480 s before initiating cardiopulmonary bypass. Postoperative blood loss was measured from the time of heparin reversal to drain removal 24h later. RESULTS: Target ACT was achieved in 0, 63, 68.3 and 82.4% of patients in groups A, B, C and D, respectively, after the initial dose of heparin. In group B, of those not achieving target act a single increment of heparin was sufficient to achieve target ACT in further 18.6%. The mean ACT after the initial dose in groups B, C and D was 482.9, 519 and 588 s, respectively (P<0.05). Postoperative blood loss in millilitre per kilogram was directly proportional to preoperative heparin dose. CONCLUSIONS: Patients receiving lower dose of heparin has lower postoperative blood loss. Of those achieving the target ACT, group B was significantly the closest to the target ACT. A starting dose of 200 iu\\/kg of heparin and if necessary one 50 iu\\/kg increment achieved target ACT in 81.5% of patients. The added benefit of significant drop in postoperative blood loss is evident.

  14. Anticoagulant therapy in patients undergoing dental interventions: a critical review of the literature and current perspectives.

    Science.gov (United States)

    Isola, G; Matarese, G; Cordasco, G; Rotondo, F; Crupi, A; Ramaglia, L

    2015-02-01

    Patients treated with oral anticoagulant therapy (OAT) represent an issue to the dentist, as an increasing number of people are using anticoagulant drugs for cardiovascular disease. The choice of an eventual suspension or continuation of anticoagulant therapy is important when considering an efficient management of the patient. Patients in anticoagulant therapy and requiring dental procedures sometimes represent therapeutic concerns especially concerning the suspension of the anticoagulant treatment. At the moment there is no consensus among international experts of a possible discontinuation of therapy before invasive dental procedures. In this paper, the authors try to focus on this topic through a critical review of the literature. Most of the studies suggest the continuation of the anticoagulant treatment with heparin before invasive oral surgical interventions. Based on the data of the literature, two rules must be adopted in clinical practice: 1) maintenance of anticoagulation related to the international normalized ratio (INR); 2) local application of antifibrinolytic agents to ensure a proper hemostatic process. Given the widespread use of anticoagulant drugs in cardiovascular disease, dentists must often face the problem of the therapy and, since there is no consensus on the management of these patients, the authors propose, after a thorough critical review of the literature, the implementation of a multiphase protocol of surgical approach to be implemented with safety in daily clinical practice.

  15. Improvement in physical and biological properties of chitosan/soy protein films by surface grafted heparin.

    Science.gov (United States)

    Wang, Xiaomei; Hu, Ling; Li, Chen; Gan, Li; He, Meng; He, Xiaohua; Tian, Weiqun; Li, Mingming; Xu, Li; Li, Yinping; Chen, Yun

    2016-02-01

    A series of chitosan/soy protein isolate (SPI) composite films (CS-n, n=0, 10 and 30, corresponding to SPI content in the composites) were prepared. Heparin was grafted onto the surface of CS-n to fabricate a series of heparinized films (HCS-n). CS-n and HCS-n were characterized by ATR-Fourier transform infrared spectroscopy and water contact angle. The surface heparin density was measured by toluidine blue assay. The results showed that heparin has been successfully grafted onto the surface of CS-n. Heparin evenly distributed on the surface of the films and the heparin content increased with the increase of SPI content, and the hydrophilicity of the films was enhanced due to the grafted heparin. The cytocompatibility and hemocompatibility of CS-n and HCS-n were evaluated by cell culture (MTT assay, live/dead assay, cell morphology and cell density observation), platelet adhesion test, plasma recalcification time (PRT) measurement, hemolysis assay and thrombus formation test. HCS-n showed higher cell adhesion rate and improved cytocompatibility compared to the corresponding CS-n. HCS-n also exhibited lower platelet adhesion, longer PRT, higher blood anticoagulant indexes (BCI) and lower hemolysis rate than the corresponding CS-n. The improved cytocompatibility and hemocompatibility of HCS-n would shed light on the potential applications of chitosan/soy protein-based biomaterials that may come into contact with blood.

  16. RO-heparin Inhibits L-Selectin-mediated Neutrophils Adhesion to Vascular Endothelium Under Flow Conditions

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin's anti-inflammatory effects are mainly mediated by blocking L- or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin (RO-heparin) can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte rolling on thioglycollate-induced rat mesenteric venules and L-selectin-metadiated neutrophil rolling on TNF-α-induced human umbilical vein endothelial cells(HUVECs) under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.

  17. 低分子肝素钙围术期应用预防老年髋部骨折术后深静脉血栓疗效观察%The efficacy of low molecular weight heparin to prevent postoperative deep vein thrombosis of elderly hip fracture patients

    Institute of Scientific and Technical Information of China (English)

    汪阳; 蒋林; 陈丰; 杜非

    2012-01-01

    目的:为观察低分子肝素钙(low molecular weight heparins calcium injection,LMWH)围术期应用预防老年髋部骨折术后深静脉血栓(deep venous thrombosis,DVT)的疗效和安全性.方法:将50例接受手术的患者随机分为2组,每组25例.A组应用低分子肝素钙预防,B组运用普通血管活性药物,术后14~20 d患侧下肢行彩超检查了解深静脉血栓发生情况.结果:A组0例(0%)发生深静脉血栓,B组为6例(24%),两组比较差异有统计学意义(P<0.05);A组出血量(295±80) ml,B组(272±80) ml,两组比较差别无统计学意义(P>0.05),两组均未发生明显大出血.结论:表明低分子肝素钙围术期应用可安全有效预防下肢骨折术后深静脉血栓形成.%Objective:To observe the efficacy and safety of the low molecular weight heparin (low molecular weight heparins calcium injection, LMWH) to prevent postoperative deep vein thrombosis (deep venous thrombosis. DVT) in elderly hip fracture patients. Method; Fifty patients undergoing surgery were randomly divided into two groups. A group use low molecular weight heparin. And B group use common vasoactive drugs. The incidence of deep vein thrombosis were detected by lower limb ultrasonography after 14 ~ 20 days of operation. Result: There were no cases of patients with deep venous thrombosis in group A, and there were 6 cases of deep venous thrombosis occurred in group B(24%). The difference between the two groups was significant (P0. 05). Conclusion: The perioperative application of low molecular weight heparin can be safe and effective in prevention of the lower extremity deep vein thrombosis in elderly hip fracture patients.

  18. Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

    Science.gov (United States)

    Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

    2016-08-01

    Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

  19. New perspectives and recommendations for anticoagulant therapy post orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Marcelo Kropf

    2011-12-01

    Full Text Available Anticoagulant therapy is essential for the prevention of risks associated with the formation of thrombus in patients after surgery, especially in orthopedics. Recently, new oral anticoagulants were introduced in the therapeutic arsenal. This fact is important, because the current drug of choice in clinical practice is enoxaparin, a low molecular weight heparin. As all injecting drugs, enoxaparin may reduce patients' adherence to treatment by dissatisfaction with and resistance to the administration. This article reviews the available literature on the overall utility of these innovative medicines, approaching the pharmacology, the compared efficacy in relation to current agents, and the potential targets for new agents, as well as points to new trends in research and development. The article also contributes with a practical guide for use and recommendations to health professionals, especially focusing on the reversibility of hemorrhagic events, and discusses the importance of convenience/satisfaction of use, the cost of treatment, and the risk-benefit profile for patients.A terapia anticoagulante é fundamental para a prevenção de riscos associados à formação de trombos em pacientes pós-cirúrgicos, principalmente em ortopedia. Recentemente, novos anticoagulantes orais foram introduzidos no arsenal terapêutico. Tal fato é importantíssimo, visto que o atual medicamento de primeira escolha na prática clínica é a enoxaparina, uma heparina de baixo peso molecular. Por ser de uso injetável, a enoxaparina pode diminuir a adesão do paciente ao tratamento, devido à insatisfação e à resistência quanto à via de administração. Este artigo revisa a literatura disponível sobre a utilidade total desses medicamentos inovadores ao abordar a farmacologia, a eficácia em comparação com os agentes atuais e os alvos potenciais para novos agentes, bem como aponta as novas tendências em pesquisa e desenvolvimento. O artigo também contribui

  20. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  1. Heparin-induced extracorporeal LDL-precipitation(HELP):Mode of action,safety and clinical experience(3)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Safety and practicability of the HELP procedure Compared to standard plasma exchange, HELP-apheresis is much better tolerated, primarily be-cause heparin rather than citrate is used for anti-coagulation and therefore problems due to hypercalce-mia do not play a role.

  2. Heparin-coated Palmaz-Schatz Stents in Human Coronary Arteries. . : Early Outcome of the Benestent-II Pilot Study

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); H.U. Emanuelsson (Hakan); A.C. Lunn; F. Kiemeneij (Ferdinand); C.M. Miguel (Carlos); W.R. Rutsch (Wolfgang); G.R. Heyndrickx (Guy); H. Suryapranata (Harry); V.M.G. Legrand (Victor); J-J. Goy (Jean-Jacques); P.H. Materne (Phillipe); J.J.R.M. Bonnier (Hans); M-C. Morice (Marie-Claude); J. Fajadet (Jean); J.A. Belardi (Jorge); A. Colombo (Antonio); E. Garcia (Eulogio); P.N. Ruygrok (Peter); M-A.M. Morel (Marie-Angèle); W.J. van der Giessen (Wim); P.P.T. de Jaegere (Peter)

    1996-01-01

    textabstractBackground The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. Methods and Results The study consisted of three initial phases (I, II

  3. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

    Science.gov (United States)

    Erlinge, David; Omerovic, Elmir; Fröbert, Ole; Linder, Rikard; Danielewicz, Mikael; Hamid, Mehmet; Swahn, Eva; Henareh, Loghman; Wagner, Henrik; Hårdhammar, Peter; Sjögren, Iwar; Stewart, Jason; Grimfjärd, Per; Jensen, Jens; Aasa, Mikael; Robertsson, Lotta; Lindroos, Pontus; Haupt, Jan; Wikström, Helena; Ulvenstam, Anders; Bhiladvala, Pallonji; Lindvall, Bo; Lundin, Anders; Tödt, Tim; Ioanes, Dan; Råmunddal, Truls; Kellerth, Thomas; Zagozdzon, Leszek; Götberg, Matthias; Andersson, Jonas; Angerås, Oskar; Östlund, Ollie; Lagerqvist, Bo; Held, Claes; Wallentin, Lars; Scherstén, Fredrik; Eriksson, Peter; Koul, Sasha; James, Stefan

    2017-09-21

    The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Among patients undergoing PCI for myocardial

  4. Low-molecular-weight heparin versus aspirin for acute ischemic stroke with large artery occlusive disease: subgroup analyses from the Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study.

    Science.gov (United States)

    Wang, Qiao Shu; Chen, Christopher; Chen, Xiang Yan; Han, Jing Hao; Soo, Yannie; Leung, Thomas W; Mok, Vincent; Wong, Ka Sing Lawrence

    2012-02-01

    The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies. The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries. Compared with aspirin, LMWH improved outcome among older patients >68 years (P=0.043; OR, 1.86; 95% CI, 1.02-3.41) without ongoing antiplatelet treatment on admission (P=0.029; OR, 1.85; 95% CI, 1.06-3.21) and with symptomatic posterior circulation arterial disease (P=0.001; OR, 5.76; 95% CI, 2.00-16.56). Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis. URL: www.strokecenter.org/trials. Unique identifier: registration no. 493.

  5. The preparation of patients taking anticoagulants for endoscopic procedures

    Directory of Open Access Journals (Sweden)

    Rafał Smoliński

    2016-12-01

    Full Text Available Drugs that inhibit platelet aggregation and  anticoagulants are widely used in  primary and  secondary prevention of thromboembolism and treatment of venous thrombosis. The use of these drugs is associated with an increased risk of bleeding during an endoscopic procedure, and their discontinuation leads to an increased risk of a thromboembolic event. The paper presents how to assess risk and how to prepare a patient treated with antiplatelet or anticoagulant drugs for endoscopic procedures. In each case, one should consider indications and planned duration of treatment as well as urgency of  the procedure. Diagnostic gastroscopy and  colonoscopy do  not usually require treatment modification, while the procedures with increased risk of bleeding require a change in therapy. In the case of antiplatelet drugs, it may be needed to stop it at a proper time before endoscopy. In the case of a dual antiplatelet therapy, when there are absolute indications for its use, one should consider postponing the procedure. Patients with increased risk of bleeding, treated with vitamin K antagonists, should have the treatment temporarily stopped and replaced with a bridging therapy with low molecular weight heparin; if the thromboembolic risk is assessed as low, a bridge therapy is not needed. The time to suspend the use of oral anticoagulants which are non-vitamin K antagonists depends on the risk of bleeding and renal function. Decisions concerning treatment may require consultation of a specialist ordering the anticoagulant or antiplatelet therapy as well as the opinion of an endoscopy centre in which the procedure is to be conducted. The doctor performing the examination should be informed about the treatment used by the patient and its modification.

  6. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  7. Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

    National Research Council Canada - National Science Library

    Lee, Soo Hyun; Lee, Wonhwa; Bae, Jong-Sup; Ma, Eunsook

    2016-01-01

    .... The aPTT results of 1 (33.2 ± 0.7 s) and 2 (43.5 ± 0.6 s) were compared with heparin (62.5 ± 0.8 s) in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity...

  8. Cataract surgery and anticoagulants

    NARCIS (Netherlands)

    Koopmans, SA; VanRij, G

    1996-01-01

    A questionnaire was sent to 240 members of the Netherlands Intraocular implant Club (NIOIC) to register their policy followed in 1993 with regard to anticoagulant therapy (ACT) and the use of aspirin in patients having cataract surgery. Ninety-one (32%) forms were suitable for analysis. Most eye sur

  9. The new oral anticoagulants.

    NARCIS (Netherlands)

    Verheugt, F.W.A.

    2010-01-01

    In patients with nonvalvular atrial fibrillation oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60%, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar ble

  10. Overestimation of canine albumin concentration with the bromcresol green method in heparinized plasma samples.

    Science.gov (United States)

    Stokol, Tracy; Tarrant, Jacqueline M.; Scarlett, Janet M.

    2001-01-01

    Albumin concentrations are routinely measured in dogs with bromcresol green (BCG)-binding assays on automated chemistry analyzers. Several variables affect this assay, including the length of reaction time, sample type, and lack of specificity of BCG for albumin. We observed that albumin concentrations measured with BCG appeared higher in heparinized plasma samples in sick dogs. The objective of this study was to determine the effect of anticoagulant and assay procedure on BCG albumin concentrations in clinically ill dogs. We hypothesized that albumin concentrations would be overestimated in heparinized plasma compared with serum because of the combination of heparin and fibrinogen. Furthermore, we hypothesized that the overestimation would be influenced by assay parameters. Blood was collected from 32 clinically ill dogs into tubes containing heparin, citrate, or no anticoagulant. Citrate was chosen to assess the effect of fibrinogen in the absence of heparin. Albumin concentration was measured in all 3 sample types from each dog using 2 different BCG procedures on an automated chemistry analyzer. The BCG procedures (standard and modified) differed in the wavelengths used for absorbance readings (standard, 600/700; modified, 570/505) and the time point at which absorbance was measured (standard, 100 seconds; modified, 40 seconds). In addition, the modified method incorporated a sample blank. Globulin fractions, fibrinogen concentration, and indices of lipemia, hemolysis, and icterus were evaluated for their contribution to the overestimation of albumin concentration in heparinized plasma compared with serum samples. Albumin concentrations were significantly higher (P heparinized plasma (mean +/- SE, 3.8 +/- 0.1 g/dL) than in serum (3.6 +/- 0.2 g/dL) or citrated plasma (3.2 +/- 0.1 g/dL). Overestimation was evident only with the standard BCG procedure. Multiple linear regression analysis indicated that fibrinogen was largely responsible for the higher

  11. Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents.

    Science.gov (United States)

    Levi, M; Eerenberg, E; Kamphuisen, P W

    2011-09-01

    The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In the case of severe bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, it may be useful to reverse anticoagulant treatment. Conventional anticoagulants such as vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates, whereas heparin and heparin derivatives can be counteracted by protamine sulphate. The anti-hemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors as well as new antiplatelet agents have been introduced and these drugs show promising results in clinical studies. A limitation of these new agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although experimental studies show hopeful results for some of these agents.

  12. Covalently bound conjugates of albumin and heparin: Synthesis, fractionation and characterization

    NARCIS (Netherlands)

    Hennink, Wim E.; Feijen, Jan; Ebert, Charles D.; Kim, Sung Wan

    1983-01-01

    Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10–16 weight % of heparin) were

  13. Preparation and stabilization of heparin/gelatin complex coacervate microcapsules.

    Science.gov (United States)

    Tsung, M; Burgess, D J

    1997-05-01

    The aims of this study are to optimize conditions for the preparation, stabilization, and harvesting of heparin/gelatin microcapsules prepared by complex coacervation. Microelectrophoresis and dry coacervate weight were used to determine the optimum conditions of pH and ionic strength for maximum heparin/gelatin coacervate yield. Heparin/gelatin microcapsules were formed by complex coacervation in the presence and absence of poly(1-vinyl-2-pyrrolidone) (PVP), which was used as a stabilizer. The microcapsules were collected using a spray-drying technique. Microcapsule particle size was analyzed using an AccuSizer optical sizer. Optimized conditions for maximum coacervate yield were pH 2.6, ionic strength 10 mM, and a 1:2 heparin/gelatin A ratio. PVP stabilized the heparin/gelatin coacervate droplets and reduced droplet aggregation during spray-drying. The mean particle diameter of the spray-dried coacervate droplets was lower in the presence of PVP and was unaffected by PVP concentration (in the range 0.5-2.0% w/w). Heparin/gelatin microcapsules, prepared under conditions optimized for maximum coacervate yield, were stabilized without the use of chemical cross-linking agents. Stabilization was achieved by a combination of the addition of PVP and spray-drying.

  14. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    Science.gov (United States)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  15. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; ZHANG Quanbin; ZHANG Zhongshan; HOU Yun; ZHANG Hong

    2011-01-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminariajaponica,an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content,sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  16. Therapeutic anticoagulation can be safely accomplished in selected patients with traumatic intracranial hemorrhage

    Directory of Open Access Journals (Sweden)

    Byrnes Matthew C

    2012-07-01

    Full Text Available Abstract Introduction Therapeutic anticoagulation is an important treatment of thromboembolic complications, such as DVT, PE, and blunt cerebrovascular injury. Traumatic intracranial hemorrhage has traditionally been considered to be a contraindication to anticoagulation. Hypothesis Therapeutic anticoagulation can be safely accomplished in select patients with traumatic intracranial hemorrhage. Methods Patients who developed thromboembolic complications of DVT, PE, or blunt cerebrovascular injury were stratified according to mode of treatment. Patients who underwent therapeutic anticoagulation with a heparin infusion or enoxaparin (1 mg/kg BID were evaluated for neurologic deterioration or hemorrhage extension by CT scan. Results There were 42 patients with a traumatic intracranial hemorrhage that subsequently developed a thrombotic complication. Thirty-five patients developed a DVT or PE. Blunt cerebrovascular injury was diagnosed in four patients. 26 patients received therapeutic anticoagulation, which was initiated an average of 13 days after injury. 96% of patients had no extension of the hemorrhage after anticoagulation was started. The degree of hemorrhagic extension in the remaining patient was minimal and was not felt to affect the clinical course. Conclusion Therapeutic anticoagulation can be accomplished in select patients with intracranial hemorrhage, although close monitoring with serial CT scans is necessary to demonstrate stability of the hemorrhagic focus.

  17. Curative effect of dabigatran etexilate versus low molecular weight heparin to prevent lower extremity deep venous thrombosis following femoral head prosthetic replacement%达比加群酯与低分子肝素预防髋关节置换术后下肢深静脉血栓的作用比较

    Institute of Scientific and Technical Information of China (English)

    赵伟; 曲虹; 丁美精; 胡小辉

    2016-01-01

    Objective To observe the clinical effects and security of low molecular weight heparin and dabigatran etexilate against deep venous thrombosis( DVT) following femoral head prosthetic replacement. Methods Totally 73 femoral head prosthetic replacement pa-tients were randomized into three groups: routine treatment group with 24 cases, dabigatran etexilate group with 25 cases and low heparin group with 24 cases. Change of platelet count and prothrombin time of the patients in three groups were observed and compared. Occurrence of DVT was observed under color Doppler of lower limbs. Results There was significant differences in DVT prevention between routine treat-ment group,the dabigatran etexilate group and low heparin group groups ( ( P 0.05)。 DE组和LMWH组在治疗期间均无严重出血。结论达比加群酯与低分子肝素均具有较好的预防髋关节置换后DVT的发生,达比加群酯疗效及安全性与低分子肝素作用相当。

  18. Heparin and protamine titration do not improve haemostasis in cardiac surgical patients.

    Science.gov (United States)

    Shore-Lesserson, L; Reich, D L; DePerio, M

    1998-01-01

    Weight-based heparin and protamine dosing strategies for cardiopulmonary bypass (CPB) do not take into account interpatient variability in drug sensitivity and may result in bleeding complications. We compared the Hemochron RxDx heparin and protamine titration system with standard weight based management with regard to heparin dose, protamine dose, and perioperative bleeding. One hundred and thirty-five cardiac surgical patients were randomised into four groups. Group 1 received standard heparin and protamine management: Group 2 received heparin and protamine by in vitro titration. Group 3 had the heparin dose titrated, and group 4 had the protamine dose titrated. Coagulation tests, bleeding, and transfusion requirements were measured. The initial heparin bolus predicted by the titration was < 300 U.kg-1 in all patients. Group 2 received a lower heparin bolus for the initiation of bypass but total heparin doses were not different among groups (group 1 = 365 +/- 43, group 2 = 348 +/- 73 U.kg-1, group 3 = 394 +/- 86 U.kg-1, group 4 = 376 +/- 60; P = 0.06). Groups 2 and 4 received a lower initial and a lower total protamine dose (total dose group 1 = 4.03 +/- 0.65 mg.kg-1, group 2 = 3.56 +/- 1.11 mg.kg-1, group 3 = 4.22 +/- 0.90 mg.kg-1, group 4 = 3.38 +/- 0.98 mg.kg-1, P = 0.001). The incidences of incomplete heparin neutralisation (P = 0.14) and heparin rebound (P = 0.1) were not different among groups. Postoperative bleeding and transfusion requirements did not differ. In cardiac surgical patients, heparin and protamine titration did predict a lower protamine dose but did not result in a measurable improvement in haemostasis during the perioperative period.

  19. Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

    Science.gov (United States)

    Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

    2017-05-01

    Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human placental amino acid transport.

    Directory of Open Access Journals (Sweden)

    Marc-Jens Kleppa

    Full Text Available BACKGROUND: Anticoagulants, e.g. low-molecular weight heparins (LMWHs and acetylsalicylic acid (ASA are prescribed to women at risk for pregnancy complications that are associated with impaired placentation and placental hypoxia. Beyond their role as anticoagulants these compounds exhibit direct effects on trophoblast but their impact on placental function is unknown. The amino acid transport systems A and L, which preferably transfer essential amino acids, are well-described models to study placental nutrient transport. We aimed to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental amino acid transport systems A and L and associated signalling mechanisms. METHODS: The uptake of C14-MeAIB (system A or H3-leucin (system L was investigated after incubation of primary villous fragments isolated from term placentas. Villous tissue was incubated at 2% O2 (hypoxia, 8% O2 and standard culture conditions (21% O2 or at 2% O2 and 21% O2 with dalteparin or ASA. Activation of the JAK/STAT or mTOR signalling pathways was determined by Western analysis of total and phosphorylated STAT3 or Raptor. RESULTS: Hypoxia decreased system A mediated MeAIB uptake and increased system L mediated leucine uptake compared to standard culture conditions (21% O2. This was accompanied by an impairment of STAT3 and a stimulation of Raptor signalling. System L activity increased at 8% O2. Dalteparin treatment reduced system A and system L activity under normoxic conditions and ASA (1 mM decreased system A and L transporter activity under normoxic and hypoxic conditions. CONCLUSIONS: Our data underline the dependency of placental function on oxygen supply. LMWHs and ASA are not able to reverse the effects of hypoxia on placental amino acid transport. These findings and the uncovering of the signalling mechanisms in more detail will help to understand the impact of LMWHs and ASA on placental function and fetal growth.

  1. [Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

    Science.gov (United States)

    Miyata, Shigeki; Maeda, Takuma

    2016-03-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  2. Clinical efficacy of Low-molecular-weight Heparin Sodium combined Aspirin in the treatment of unstable angina pectoris%低分子肝素钠联合阿司匹林治疗不稳定型心绞痛疗效分析

    Institute of Scientific and Technical Information of China (English)

    谢平

    2011-01-01

    目的:观察低分子肝素钠联合阿司匹林治疗不稳定型心绞痛(UA)的临床疗效.方法:将67例住院的UA患者随机分为对照组(34例)和治疗组(33例),治疗组使用低分子肝素钠加阿司匹林,对照组单用阿司匹林,疗程为1周,结果:治疗组总有效嘈<为96.96%,对照组为76.47%.两组疗效比较,差异有统计学意义(P<0.05).结论:低分子肝素钠联合阿司匹林治疗UA能明显减少心绞痛的发作,改善临床症状,具有安全有效的特点.%Objective: To observe the clinical efficacy of Low-molecular-weight Heparin Sodium combined Aspirin in the treatment of unstable angina pectoris. Methods: 67 cases of patients with unstable angina pectoris were randomly divided into control group (34 cases) and treatment group (33 cases). The control group was received Aspirin for 1 week. The treatment group was received Low-molecular-weight Heparin Sodium for 1 week based on the control group. Results: The total effective rate of treatment group was 96.96% and was significantly higher than that of control group (76.47%) (ρ<0.05). Conclusion: Low-molecular-weight Heparin Sodium combined with Aspirin is effective and safe in the treatment of unstable angina pectoris.

  3. 氯吡格雷联合低分子肝素钙治疗急性多发性脑梗死的疗效观察%Observation of curative effect by clopidogrel combined with low molecular weight heparin calcium in the treatm