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Sample records for weight heparin dalteparin

  1. A comparative study of dalteparin and unfractionated heparin in patients with unstable angina pectoris

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    Hanmant S Amane

    2011-01-01

    Conclusion : Dalteparin is as effective and safe as unfractionated heparin in the treatment of unstable angina. Dalteparin does not require routine laboratory monitoring as with unfractionated heparin.

  2. Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study

    DEFF Research Database (Denmark)

    Artang, Ramin; Frandsen, Niels J; Nielsen, Jørn Dalsgaard

    2009-01-01

    . At this point there are no point of care devices available in the market for monitoring the effect of LMWH. Thrombelastography (TEG) evaluates the viscoelastic properties of blood during coagulation. The clinical application of TEG in monitoring LMWH treatment is not yet well defined. The purpose...... volunteers (n = 7) were injected subcutaneously with the LMWH dalteparin 120 IU/kg. TEG parameters and antifactor Xa levels were measures at baseline, 2, 4, 5 and 24 hours after the injection. Correlation between TEG parameters and antiXa were calculated. The sensitivity and specificity of the TEG parameters...... of sensitivity and specificity for the therapeutic range of antiXa levels (r = 0.82, p

  3. 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.

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

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    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.

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

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    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. Dalteparin-sodium induced drug fever in a neonate.

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    Wackernagel, Dirk; Obaya, Sami; Nydert, Per

    2016-10-13

    Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as 'probable ADR' and 'definite ADR'. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.

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

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    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

  8. Low molecular weight heparin impairs tendon repair.

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    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.

  9. 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).

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    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.

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

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    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

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

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    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

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

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    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.

  13. 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.

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

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    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.

  15. 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

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    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..

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

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    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

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

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    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.

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

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    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.

  19. 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

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

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    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

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

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    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)

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

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

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    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.

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  19. 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...

  20. The binding of pentapeptides to biological and synthetic high affinity heparin.

    Science.gov (United States)

    Flengsrud, Ragnar; Antonsen, Simen Gjelseth

    2015-11-01

    Pentapeptides have been shown to bind the synthetic heparin fondaparinux (Arixtra) as well the biological heparins dalteparin (Fragmin) and salmon heparin. In contrast to heparin binding consensus sequences, the pentapeptides are acidic or neutral, with no arginine or histidine residue. The peptides showed an effect on in vitro heparin anti-factor X activity with a reduction of fondaparinux activity by 65-95%. Heparin binding was further studied by using peptide solid phase chromatography and NMR analysis.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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...

  6. 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

  7. 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 ...

  8. 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.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. [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.

  12. 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...

  13. 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.

  14. [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.

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. [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.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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. .

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  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. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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:

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

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    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.

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

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    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.

  11. Thromboprophylaxis with dalteparin in medical patients: which patients benefit?

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    Cohen, Alexander T; Turpie, Alexander G G; Leizorovicz, Alain; Olsson, Carl-Gustav; Vaitkus, Paul T; Goldhaber, Samuel Z

    2007-05-01

    It is unclear whether thromboprophylaxis produces a consistent risk reduction in different subgroups of medical patients at risk from venous thromboembolism. We performed a retrospective, post hoc analysis of 3706 patients enrolled in the PREVENT study. Patients were at least 40 years old with an acute medical condition requiring hospitalization for at least 4 days and had no more than 3 days of immobilization prior to enrolment. Patients received either subcutaneous dalteparin (5000 IU) or placebo once daily. The primary end point was the composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism, asymptomatic proximal DVT, or sudden death. Primary diagnosis subgroups were acute congestive heart failure, acute respiratory failure, infectious disease, rheumatological disorders, or inflammatory bowel disease. All patients, except those with congestive heart or respiratory failure, had at least one additional risk factor for venous thromboembolism. A risk reduction was shown in patients receiving dalteparin versus placebo. The relative risk (RR) was 0.73 in patients with congestive heart failure, 0.72 for respiratory failure, 0.46 for infectious disease, and 0.97 for rheumatological disorders. The RR was 0.52 in patients aged > or = 75 years, 0.64 in obese patients, 0.34 for patients with varicose veins, and 0.71 in patients with chronic heart failure. No subgroup had a significantly different response from any other. Importantly, multivariate analysis showed that all patient groups benefited from thromboprophylaxis with dalteparin. Our findings, therefore, support the broad application of thromboprophylaxis in acutely ill hospitalized medical patients.

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

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    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

  13. 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.

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

    Science.gov (United States)

    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

  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. 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.

  17. 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

  18. [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.

  19. 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.

  20. 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.

  1. 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.

  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. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  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. 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

  6. 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 ...

  7. 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.  ……

  8. 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.

  9. 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.

  10. 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

  11. Effects of Dalteparin on Structure of Hippocampal Neurons of Rats in Chronic Stress

    OpenAIRE

    Mansoureh Soleimani; Arezo Nahavandi; Fereshteh Farajdokht

    2012-01-01

    Introduction: Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke rodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats.Methods : the study was carried out on 60 adult male wistar rats, weighing 200-250 gr. The rats were randomly divided into three groups: control, stress and stre...

  12. 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

  13. 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

  14. 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.

  15. Current management of heparin-induced thrombocytopenia.

    Science.gov (United States)

    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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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...

  10. Dalteparin Injection

    Science.gov (United States)

    ... pa' rin)If you have an epidural or spinal anesthesia or a spinal puncture while using a 'blood ... left in your body, if you recently had spinal anesthesia (administration of pain medication in the area around ...

  11. Enhanced effect of fibroblast growth factor-2-containing dalteparin/protamine nanoparticles on hair growth

    Directory of Open Access Journals (Sweden)

    Takabayashi Y

    2016-05-01

    Full Text Available Yuki Takabayashi,1 Masaki Nambu,1 Masayuki Ishihara,2 Masahiro Kuwabara,1 Koichi Fukuda,2 Shingo Nakamura,2 Hidemi Hattori,2Tomoharu Kiyosawa1 1Department of Plastic and Reconstructive Surgery, 2Division of Biomedical Engineering, Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan Purpose: Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs can effectively carry growth factors (GFs such as fibroblast GF (FGF-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs on hair growth.Patients and methods: In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL and D/P NPs (56 μg/mL was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter.Results: The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience.Conclusion: The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia. Keywords: hair growth, dalteparin/protamine nanoparticles, fibroblast growth factor, transdermal application

  12. 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

  13. 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

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

    Science.gov (United States)

    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.

  15. 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.

  16. 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

  17. Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats.

    Science.gov (United States)

    Schönig, Jette C; Mischke, Reinhard H

    2016-07-01

    OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

  18. 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。

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. Inactivation of Heparin by Cationically Modified Chitosan

    Directory of Open Access Journals (Sweden)

    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.

  6. 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。

  7. 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.

  8. Heparin-Induced Thrombocytopenia Associated with Massive Intracardiac Thrombosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Atheer Ahmed

    2012-01-01

    Full Text Available A 60-years old patient was admitted to a community hospital with septic arthritis. He was treated with antibiotics and subcutaneous unfractionated heparin (UH was used for venous thromboprophylaxis. After three days, he developed leg deep venous thrombosis and was treated with IV heparin. One day later, the patient developed pulmonary emboli, which was found using ventilation/perfusion scan. He was transferred to the University Hospital for further management. Upon arrival, antibiotic and intravenous UH were continued. Trans-Esophageal Echocardiogram showed a thrombus in the right atrium, a small portion of which extended to the left atrium through a patent foramen ovale. Another large thrombus was noted in the right ventricle, which extended to the pulmonary artery. Review of the patient’s medical records revealed a halving of his platelet count three days following the heparin administration. Therefore, HIT seemed very likely. Intravenous UH was stopped and an emergency thrombectomy was performed. ELISA testing of HIT antibodies came negative. This made HIT diagnosis unlikely and the patient received dalteparin. A week later, as the platelet count declined again, HIT antibodies’ testing using ELISA and C-14 serotonin release was repeated, and both assays were positive. Argatroban was restarted and the platelet count normalized.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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。

  1. 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

  2. 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。

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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; ...

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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。

  17. 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.

  18. 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.

  19. 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.

  20. 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 treatment of acute multiple cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    邵志坚

    2015-01-01

    目的 探讨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.方法 88例急性多发性脑梗死患者随机分为对照组(43例, 采用肠溶阿司匹林、胞二磷胆碱治疗)和治疗组(45例, 采用氯吡格雷、低分子肝素钙、胞二磷胆碱治疗).对比两组疗效.结果 治疗组总有效率高于对照组(P<0.05);治疗后血液流变学改善优于对照组(P<0.05).结论 氯吡格雷联合低分子肝素钙治疗急性多发性脑梗死具有协同作用, 有明显控制病情发展作用.%Objective To investigate curative effect by clopidogrel combined with low molecular weight heparin calcium in the treatment of acute multiple cerebral infarction.Methods A total of 88 acute multiple cerebral infarction patients were randomly divided into control group (43 cases, received enteric-coated aspirin and citicoline for treatment) and treatment group (45 cases, received clopidogrel, low molecular weight heparin calcium and citicoline for treatment). Curative effects of the two groups were compared.Results The treatment group had higher total effective rate than the control group (P<0.05), and its hemorheological improvement was better than the control group after treatment (P<0.05).Conclusion Combination of clopidogrel and low molecular weight heparin calcium contains synergistic effect in treating acute multiple cerebral infarction, and this method can effectively control the progression of disease.

  1. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P;

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...... to investigate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied by significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti...

  2. 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...

  3. 硝普钠、多巴胺、低分子肝素钙治疗肺源性心脏病顽固性心功能衰竭的临床研究%The Clinical Research of Sodium Nitroprusside,Dopamine Combined with Low Molecular Weight Heparin Treating Intractable Heart Failure of Pulmonary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    王玉彩; 菅向东

    2013-01-01

    目的 总结硝普钠、多巴胺、低分子肝素钙治疗肺源性心脏病(肺心病)顽固性心功能衰竭的临床效果.方法 回顾性分析患者在原有治疗肺心病的基础上使用硝普钠、多巴胺、低分子肝素钙前后临床症状的变化、心功能改善情况及血压、心率、呼吸、24 h尿量改变的情况.结果 经硝普钠、多巴胺、低分子肝素钙治疗后,肺心病顽固性心功能衰竭疗效显著(P<0.05),且患者血压、心率、呼吸频率及24 h尿量均明显改善(P<0.05).结论 硝普钠、多巴胺、低分子肝素钙对治疗肺心病顽固性心功能衰竭疗效确切,值得临床推广.%Objective To study the effect of sodium nitroprusside,dopamine combined with low molecular weight heparin treating intractable heart failure of pulmonary heart disease. Methods The clinical of clinincal symptoms,cardiac function improvement and blood pressure,heart rate,breathing,24 h urine volume after the use of sodium nitroprusside, dopamine, low molecular weight heparin on the basis of pulmonary heart disease treatment were retrospectively analyzed. Results Sodium nitroprusside,dopamine,low molecular weight heparin calcium had significant effect on the intractable heart failure of pulmonary heart disease ( P <0.05 );blood pressure, heart rate, respiratory rate and 24 h urine volume were significantly improved (P<0.05). Conclusion Sodium nitroprusside, dopamine combined with low molecular weight heparin treating intractable heart failure of pulmonary heart disease is of affirmative effect,which is worthy of clinical promotion.

  4. Effect of Shenkang injection combined with low molecular weight heparin sodium injection on a hypercoagulable state of the primary nephrotic syndrome%肾康注射液联合低分子量肝素钠注射液对原发性肾病综合征高凝状态的影响

    Institute of Scientific and Technical Information of China (English)

    牛凯; 冯珍; 刘冰; 史亚男; 董春霞

    2011-01-01

    Objective To investigate the effect of Shenkang injection combined with low molecular weight heparin sodium injection on a hypercoagulable state of the primary nephrotic syndrome. Methods 88 patients with primary nephrotic syndrome (PNS) were randomly divided into four groups, Dipyridamole tablets group, Shenkang injection group, low molecular weight heparin sodium injection group and combination therapy group. Patients in four groups were treated by conventional blood pressure, lipid lowering therapy, and oral methylprednisolone. Dipyridamole tablets group ( n =21) received Dipyridamole tablets. Shenkang injection group ( n = 22) and low molecular weight heparin sodium injection group ( n = 22) separately received Shenkang injection and low molecular weight heparin sodium injection. Combination therapy group ( n =23) received Shenkang injection combined with low molecular weight heparin sodium injection. The course was four weeks in four groups. The changes of 24 h urinary protein excretion, serum albumin, prothrombin time (PT) , activated partial thromboplastin enzyme time (APTT) and fibrinogen ( FIB) were measured before and after treatment. Results 24 h urinary protein excretion and FIB in Shenkang injection group and low molecular weight heparin sodium injection group were decreased as compared with those in Dipyridamole tablets group ( P <0. 05). Plasma albumin, PT and APTT in Shenkang injection group and low molecular weight heparin sodium injection group were increased as compared with those in control group ( P < 0. 05 ). 24 h urine protein excretion in Shenkang injection group was decreased as compared with that in low molecular weight heparin sodium injection group ( P <0. 05) , plasma albumin was increased ( P <0. 05). 24 h urinary protein excretion and FIB in combination therapy group were significantly decreased as compared with those in other three treatment groups ( P < 0. 05 ). Plasma albumin, PT and APTT were obviously increased in comparison

  5. Efficacy of Flunarizine and low molecular weight heparin for the frequency of recurrent transient ischemic attacks%氟桂利嗪与低分子肝素联合应用对频发性短暂脑缺血发作的疗效分析

    Institute of Scientific and Technical Information of China (English)

    王德俊; 于灵灵; 孙东良

    2012-01-01

    目的 分析联合应用氟桂利嗪与低分子肝素治疗频发性短暂脑缺血发作的疗效.方法 选取146例频发性短暂脑缺血发作患者,按治疗方案不同分为两组:对照组,予以低分子肝素治疗,共77例;研究组,在低分子肝素基础上加用氟桂利嗪,共69例.治疗2周后,分别进行临床疗效及不良反应比较.结果 与对照组比较,研究组总有效率、显效率明显较高(P<0.05),两组治疗后全血黏度(低切)、全血黏度(高切)、血浆黏度、纤维蛋白原含量较治疗前明显下降(P< 0.05),但治疗后研究组较对照组明显改善(P<0.05).研究组的血细胞减少、皮疹、头痛、肝功能异常等不良反应较对照组差异无统计学意义(P>0.05).结论 应用氟桂利嗪与低分子肝素治疗频发性短暂脑缺血发作疗效可靠,不良反应少.%Objective To analyze the efficacy of the combination of Flunarizine and low molecular weight heparin for the frequency of recurrent transient ischemic attacks (TIA). Methods 146 cases of frequent TIA patients were randomly divided into 2 groups according to the treatment program. 77 patients of control group were given low molecular weight heparin, 69 patients of control group were treated with Klunarizine on the basis of low molecular weight heparin. The clinical efficacy and adverse reactions of two groups after treatment were compared. Results Compared with the control group, the utility and excellence rates of the study group were significantly higher (P 0.05). Conclusion The application of Flunarizine combined with low molecular weight heparin for the frequent TIA is reliable and has fewer adverse reactions.

  6. Heparinized poly(vinyl alcohol)-small intestinal submucosa composite membrane for coronary covered stents

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Tao; Wang Guixue; Qiu Juhui; Luo Lailong [Bioengineering College and ' 111 Project' Laboratory of Biomechanics and Tissue Repair, Chongqing University, Chongqing (China); Zhang Guoquan, E-mail: wjjt72@live.c [Histology and Embryology Department, Medical College of China People Armed Police Forces, Tianjin (China)

    2009-04-15

    To develop a novel coating material for coronary covered stents, we prepared a kind of composite membrane which contains polyvinyl alcohol (PVA) and porcine small intestinal submucosa (SIS) powders crosslinked and heparinized by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The amount of immobilized heparin increased with increasing ratios of EDC:heparin, and the maximum amount was approximately 60 {mu}g heparin per milligram SIS powder at a weight ratio of EDC:heparin of 2. Uniaxial tensile and balloon inflation testing suggested that the composite membrane crosslinked by lower EDC concentration is more flexible and elastic. The clotting time (APTT and PT) of the heparinized PVA-SIS membrane was longer than that of the unheparinized membrane. The number of adherent platelets on the heparinized PVA-SIS composite membrane was about 25% of the unheparininzed, and there was no sign of accumulation and almost no pseudopodium was observed. The endothelial cells were amicable with the heparinized and unheparinized PVA-SIS composite membranes. In in vivo implantation tests, we observed a thin capsule formed by several layers of fibroblasts surrounding the implants. These results showed that the heparinized PVA-SIS composite membrane has potential biomechanical and biological properties as a coating material for coronary covered stent.

  7. Structural Snapshots of Heparin Depolymerization by Heparin Lyase I

    Energy Technology Data Exchange (ETDEWEB)

    Han, Young-Hyun; Garron, Marie-Line; Kim, Hye-Yeon; Kim, Wan-Seok; Zhang, Zhenqing; Ryu, Kyeong-Seok; Shaya, David; Xiao, Zhongping; Cheong, Chaejoon; Kim, Yeong Shik; Linhardt, Robert J.; Jeon, Young Ho; Cygler, Miroslaw; (SNU); (Korea BSI); (McGill); (UST-Korea); (Rensselaer)

    2010-01-12

    Heparin lyase I (heparinase I) specifically depolymerizes heparin, cleaving the glycosidic linkage next to iduronic acid. Here, we show the crystal structures of heparinase I from Bacteroides thetaiotaomicron at various stages of the reaction with heparin oligosaccharides before and just after cleavage and product disaccharide. The heparinase I structure is comprised of a {beta}-jellyroll domain harboring a long and deep substrate binding groove and an unusual thumb-resembling extension. This thumb, decorated with many basic residues, is of particular importance in activity especially on short heparin oligosaccharides. Unexpected structural similarity of the active site to that of heparinase II with an ({alpha}/{alpha}){sub 6} fold is observed. Mutational studies and kinetic analysis of this enzyme provide insights into the catalytic mechanism, the substrate recognition, and processivity.

  8. [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.

  9. Heparin Characterization: Challenges and Solutions

    Science.gov (United States)

    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.

  10. 环氧合酶-2在低分子肝素干预大鼠酒精性肝病中的作用机制研究%Effect of cyclooxygenase-2 in alcoholic liver disease rats intervened with low molecular weight heparin

    Institute of Scientific and Technical Information of China (English)

    阎春英; 石军; 杨艳; 郝菁华; 任万华; 张捷

    2012-01-01

    目的 研究低分子肝素干预大鼠酒精性肝病模型的作用机制.方法 56% (V/v)的白酒平均以8 g/kg的剂量2次/d灌胃10周,初步制备大鼠酒精性肝病模型,成模后部分大鼠低分子肝素(100 IU/kg)皮下注射进行干预,4周后观察低分子肝素对大鼠的血清生物化学指标、肝组织中丙二醛及环氧化酶-2的影响.结果 与模型组比较,低分子肝素治疗组大鼠血清转氨酶、血脂及丙二醛含量明显下降(P<0.05);光学显微镜观察HE染色见脂肪变性、炎症反应程度明显减轻(P<0.01),免疫组织化学染色及逆转录聚合酶链反应显示环氧化酶-2的表达均明显降低(P<0.05).结论 低分子肝素通过改善脂肪代谢、抑制氧化应激及降低环氧化酶-2的表达而对酒精性肝病大鼠起到一定的保护治疗作用.%Objective To study the effect of low molecular weight heparin on alcohol-fed rats. Methods The model of alcoholic liver disease rats was made by alcohol gavage (infused with 56% of ethanol twice a day with a dose of 8 g/kg body weight for 10 weeks) , and then parts were treated with low molecular weight heparin (100 IU/kg). After 4 weeks, the effect of low molecular weight heparin on serum biochemical index, malondialdehyde and cyclooxygenase-2 in liver tissue was observed. Results Compared with model group, the levels of Iransaminases, lipids and malondialdehyde significantly decreased in low molecular weight heparin therapy group ( P <0. 05 ). Under the observation of optical microscope, the degree of liver steatosis, inflammation reaction were significantly reduced ( P < 0.01 ) . The levels of cyclooxygenase-2 in liver tissue were significantly lowered by immunohistochemical staining and semiquantitative reverse transcription-polymerase chain reaction. Conclusion Low molecular weight heparin has therapeutic effect on alcohol-induced liver disease rats by improving fat metabolism, reducing oxidative stress and decreasing the

  11. 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.

  12. Comparison of the effect of low molecular weight heparin sodium and that of heparin sodium on pre-disseminated intravascular coagulation stage in patients suffering from exertional heat stroke%低分子肝素钠与普通肝素钠治疗劳力性热射病非显性弥散性血管内凝血的比较研究

    Institute of Scientific and Technical Information of China (English)

    李玉堂; 郭春文; 刘辉; 元智昊; 林辉; 王雁; 闫红

    2015-01-01

    目的:观察低分子肝素钠(LMWHS)治疗劳力性热射病(EHS)非显性弥散性血管内凝血(DIC)患者的疗效。方法采用前瞻性随机对照临床试验(RCT),选择2012年4月至2014年11月解放军第一八〇医院重症医学科住院治疗的EHS非显性DIC患者36例,按随机数字表法分为肝素钠组(20例)和LMWHS组(16例)。所有患者入院后均接受集束化治疗,包括迅速降温、积极的液体复苏、维护器官功能(呼吸机辅助呼吸、酌情血液净化)、补充凝血底物抗凝等。肝素钠组加用肝素钠注射液12500 U,24 h持续静脉泵入,共5 d;LMWHS组加用希弗全2500 U,皮下注射,每日2次,共5 d。比较两组患者DIC发生率、出血发生率及病死率;观察治疗前后两组患者血小板计数(PLT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)和D-二聚体的变化情况。结果 LMWHS组与肝素钠组DIC发生率、病死率比较差异无统计学意义(31.2%比30.0%,χ2=0.007,P=0.936;6.2%比5.0%,χ2=0.026,P=0.871);LMWHS组治疗后出血发生率明显低于肝素钠组(12.5%比45.0%,χ2=4.425,P=0.035)。LMWHS组和肝素钠组治疗后PLT均较治疗前明显升高(×109/L:140.5±17.5比110.5±16.5,152.6±21.5比120.0±20.0,均P<0.05),D-二聚体较治疗前明显降低(mg/L:0.5±0.1比3.2±1.2,0.6±0.2比4.4±1.8,均P<0.05);肝素钠组治疗后APTT较治疗前明显延长(s:75.3±10.6比44.1±8.2,P<0.05),而LMWHS组治疗后APTT无明显变化(s:38.6±5.5比42.1±8.4, P>0.05);两组治疗前后PT、Fib均无明显变化。结论 LMWHS阻止EHS非显性DIC向DIC发展的疗效与肝素钠相当,但LMWHS治疗后患者出血发生率低,更为安全。%ObjectiveTo study the effect of low molecular weight heparin sodium (LMWHS) therapy for exertional heat stroke (EHS) patients with

  13. 奥扎格雷钠联合低分子肝素钙在治疗短暂性脑缺血发作中的临床疗效%Sodium Ozagrel Combined With Low Molecular Weight Heparin Clinical Efifcacy in the Treatment of Transient Ischemic Attack

    Institute of Scientific and Technical Information of China (English)

    王瑜

    2016-01-01

    Objective To investigate the clinical curative effect of sodium ozagrel combined with low molecular heparin calcium in the treatment of transient ischemic attack.MethodsSelected 60 cases of transient ischemic attack patients from November 2013 to February 2016 in our hospital as the research object and randomly divided into two groups, 30 cases in each group and received low molecular weight heparin calcium and sodium ozagrel combined with low molecular weight heparin calcium treatment.Results The total effective rate of the treatment group was 93.3%, significantly higher than the control group 76.7%, the difference was statistically signiifcant (P0.05). Conclusion Ozagrel sodium combined with low molecular heparin calcium has better clinical curative effect in the treatment of transient ischemic attack and adverse reactions occur rate is low and safe.%目的:探讨奥扎格雷钠联合低分子肝素钙在治疗短暂性脑缺血发作中的临床疗效。方法选取2013年11月~2016年2月我院收治的60例短暂性脑缺血发作患者作为研究对象,随机分成两组,各30例。分别采取低分子肝素钙与奥扎格雷钠联合低分子肝素钙进行治疗。结果治疗组患者治疗总有效率为93.3%高于对照组76.7%,差异具有统计学意义(P<0.05);两组患者不良反应的发生率差异无统计学意义(P>0.05)。结论奥扎格雷钠联合低分子肝素钙在治疗短暂性脑缺血发作中具有较好的临床治疗效果,且不良反应发生率低,治疗安全有效。

  14. Heparins and heparinoids: occurrence, structure and mechanism of antithrombotic and hemorrhagic activities.

    Science.gov (United States)

    Nader, Helena B; Lopes, Carla C; Rocha, Hugo A O; Santos, Elizeu A; Dietrich, Carl P

    2004-01-01

    The correlation between structure, anticlotting, antithrombotic and hemorrhagic activities of heparin, heparan sulfate, low molecular weight heparins and heparin-like compounds from various sources that are in used in clinical practice or under development is briefly reviewed. Heparin-like molecules composed exclusively of iduronic acid 2-O-sulfate residues have weak anticlotting activities, whereas molecules that contain both iduronic acid 2-O sulfate, iduronic acid and small amounts of glucuronic acid, such as heparin, or mixed amounts of glucuronic and iduronic acids (mollusk heparins) possess high anticlotting and anti-Xa activities. These results also suggest that a proper combination of these elements might produce a strong antithrombotic agent. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate derived from bovine pancreas and a sulfated fucan from brown algae have a potent antithrombotic activity in arterial and venous thrombosis model "in vivo" with a negligible activity upon the serine-proteases of the coagulation cascade "in vitro". These and other results led to the hypothesis that antithrombotic activity of heparin and other antithrombotic agents is due at least in part by their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate. All the antithrombotic agents derived from heparin and other heparinoids have hemorrhagic activity. Exceptions to this are a heparan sulfate from bovine pancreas and a sulfated fucan derived from brown algae, which have no hemorrhagic activity but have high antithrombotic activities "in vivo". Once the structure of these compounds are totally defined it will be possible to design an ideal antithrombotic.

  15. Heparins: process-related physico-chemical and compositional characteristics, fingerprints and impurities.

    Science.gov (United States)

    Liverani, Lino; Mascellani, Giuseppe; Spelta, Franco

    2009-11-01

    During the past 25 years, heparin extraction and purification processes have changed. The results of these changes are reflected by the continuous increase in potency of the International Standard for heparin. This increase is due not only to a higher purity, but also to a number of changes in the physico-chemical characteristics of heparin. For long time, all these changes have been disregarded as non-critical by regulatory authorities. Heparin marketing authorisation was reviewed only two years ago and Pharmacopoeia monographs were reviewed just for the addition of new tests, mainly aimed at tackling the oversulfated chondroitin sulfate (OSCS) crisis. Currently, heparin monographs are again under revision. Such changes, different for each manufacturer, have caused a further increase in the heterogeneity of individual batches of heparin. This review aims at showing that chemical, physical and biological characteristics of heparin (such as disaccharide composition, amount of low sulfated and high sulfated sequences, molecular weight profiles [MW], activities, structural artifacts, fingerprints and glycosaminoglycans impurities) are all process-dependent and may significantly vary when different processes are used to minimise the content of dermatan sulfate. The wide heterogeneity of the physico-chemical characteristics of currently marketed heparin and the lack of suitable and shareable reference standards for the identification/quantification of process-related impurities caused, and are still causing, heated debates among scientific institutions, companies and authorities.

  16. Fabrication of a heparin-PVA complex hydrogel for application as a vascular access.

    Science.gov (United States)

    Negishi, Jun; Nam, Kwangwoo; Kimura, Tsuyoshi; Hashimoto, Yoshihide; Funamoto, Seiichi; Higami, Tetsuya; Fujisato, Toshiya; Kishida, Akio

    2014-10-01

    A high hydrostatic pressure method, which can apply over 600 MPa pressure was employed for preparing a hydrogel of poly(vinyl alcohol) (PVA) loaded with heparin. The aim of this study was to fabricate a heparin-PVA hydrogel conduit and evaluate its potential for vascular access. Heparin-PVA complex hydrogel showed suppressed heparin release and prevented clot formation, depending on the molecular weight of the PVA. Strength of the hydrogel conduit was increased by embedding a Dacron mesh between two PVA layers. The tubular heparin-PVA complex hydrogel displayed a burst pressure of 750 mmHg. The tubular heparin-PVA complex hydrogel did not show any occlusion or burst for 2 weeks after implantation, implying that this heparin-PVA complex hydrogel shows high potential for use as a vascular access. This is the first report on the preparation of a multilayered PVA hydrogel with heparin embedded on one side only. The proposed approach could be expanded to the fabrication of various biomaterials for specific purposes.

  17. Observation on curative effects of low molecular weight heparin of prolongable curative course on treating unstable angina pectoris%低分子肝素延长疗程治疗不稳定型心绞痛疗效观察

    Institute of Scientific and Technical Information of China (English)

    胡亚力; 苏珍; 白洪雁; 苏晓燕; 刘怡

    2001-01-01

    目的:观察低分子肝素延长疗程治疗不稳定型心绞痛的疗效。方法:同期入院的不稳定型心绞痛患者168例,随机分为2组,均在常规治疗基础上应用低分子肝素(立迈青)皮下注射,每日2次。A组应用1周,B组应用3周,第1周用量2组均为每次120 IU/kg,第2~3周B组用量每次100 IU/kg。结果:早期(第7日)观察2组总有效率分别为75.9%、77.4%,疗效无显著差异(P>0.05);心血管意外事件(急性心肌梗死、心脏性或非心脏性死亡、药物无法控制病情需行急性血运重建术)及出血,在2组的发生率无显著差异(P>0.05) 。晚期(第8~30日)观察2组总有效率分别为87.2%、97.5%,有显著性差异(P0.05) 。结论:低分子肝素延长疗程治疗不稳定型心绞痛疗效较短程应用疗效为好,且不增加出血发生率。%Objective:To observe the curative effect of low molecular weight heparin of prolongable curative course on treating unstable angina pectoris.Methods:One hundred and sixtyeight cases with unstable angina pectoris who were admitted into hospital at the same period were randomly divided into two groups.Both groups were subcutaneously injected by low molecular weight heparin combined with conventional therapy,two times a day for one week in group A and three weeks in group B respectively.In the first week,the dosage of heparin in group A and B was 120 IU/kg every time,from second to third week,the dosage of heparin in group B was 100 IU/kg every time.Results:The total effective rates in group A and group B were 75.9% and 77.4% respectively in early stage (seventh day),and the difference was not significant (P>0.05).The incidences of cardiovascular accidental events (acute myocardial infarction,cardiac death,uncardiac death,the illness which could not be controlled by the medicine and should be treated with acute reconstruction of blood circulation) and haemorrhage in both groups had not significantly different

  18. Heparin-induced thrombocytopenia: a general review.

    Science.gov (United States)

    Swanson, Joseph M

    2007-01-01

    Unfractionated heparin is widely used for numerous clinical situations. A well-known adverse effect of heparin exposure is thrombocytopenia. Heparin-induced thrombocytopenia is a clinicopathologic syndrome that can be associated with severe complications and significant mortality. The pathophysiology of heparin-induced thrombocytopenia includes an immune-mediated reaction to heparin that activates platelets and results in an acquired hypercoagulability. Diagnosis of heparin-induced thrombocytopenia should incorporate clinical signs and symptoms and laboratory testing for heparin-induced thrombocytopenia antibodies. Therapy should include discontinuation of heparin, initiation of a direct thrombin inhibitor, and eventually therapy with warfarin (only after the platelet count is at least 100 x 10(9)/L).

  19. 辛伐他汀联合低分子肝素治疗急性心肌梗死的临床观察%Clinical observation of treatment of acute myocardial infarction by simvastatin with low molecular weight heparin

    Institute of Scientific and Technical Information of China (English)

    秦迁; 徐验; 张志伟

    2009-01-01

    目的 观察辛伐他汀联用低分子肝素钠治疗急性心肌梗死的临床疗效和安全性.方法 80例急性心肌梗死患者随机分为辛伐他汀联用低分子肝素钠治疗(联合组)40例,硝酸酯类药治疗(常规组)40例,观察治疗前后血清炎性因子水平、动态心电图及疗效指标.结果 常规组、联合组治疗后TC、TG、LDL、HDL-C、高敏C反应蛋白(hs-CRPs)、可溶性白细胞分化抗原40配体(sCD40L)水平均较治疗前下降(t=2.131,t=2.211,t=2.235,t=2.211,t=2.115,t=2.274,均P<0.05);联合组治疗后hs-CRP、sCD40L下降水平较常规组明显(t=2.231,t=2.245,均P<0.05);常规组IMT下降1.1%低于联合组3.4%(X2=4.01,P<0.05);常规组治疗后斑块积分11.5%高于联合组斑块积分下降16.9%(X2=4.25,P<0.05);联合组治疗后软斑数(7.7%)低于治疗前(28.2%)(X2=6.78,P<0.01);联合组治疗后EDV、ESV、EF较治疗前下降明显(t=2.221,t=2.342,t=2.245,P<0.05);常规组和联合组治疗后缺血发作次数、ST段最大下降幅度、ST段下降时间明显低于治疗前(t=2.731,t=2.781,t=2.785,t=2.781,t=2.815,t=2.874,均P<0.01);联合组总有效率90.0%高于常规组67.4%(X2=4.25,P<0.05).结论 辛伐他汀联用低分子肝素钠治疗急性心肌梗死疗效较好.%Objective To observe the clinical effect and side-effect of low molecular weight beparin (LMWH) and simvastatin on patients with acute myocardial infarction(AMI). Methods 80 cases of AMI were randomly divided into simvastatin with low-molecular-weight heparin treatment (joint group) 40 cases and nitrates drug treatment( conventional group) 40 cases Au the patiants were observed before and after treatment for serum inflammatory factor,quantitative gated tomography,Holter and analysis of the effectbefore and after treatment. Results The conventional group and joint group after the treatment of TC, TG, LDL, HDL-C, hs-CRPs, CD40L levels were decreased than before treatment (t=2. 131, t = 2. 211, t = 2. 235, t

  20. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  1. 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.

  2. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    Science.gov (United States)

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson

    2013-01-01

    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  3. 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.

  4. Low molecular weight heparin for the prevention of thrombosis after autologous bone marrow stem cell transplantation in animals%低分子肝素预防自体骨髓干细胞移植血栓形成的动物实验研究

    Institute of Scientific and Technical Information of China (English)

    蒋晶超; 韩明子; 刘佰玲; 高福来; 金世柱

    2011-01-01

    目的 探讨低分子肝素预防小鼠自体骨髓单个核细胞移植后血栓形成的作用.方法 应用CCI4/2-AAF制备小鼠急性肝损伤模型,然后行骨髓单个核细胞移植.实验A组于经尾静脉注入骨髓干细胞悬液;实验B组于经尾静脉先注入低分子肝素后注入骨髓干细胞悬液.分别于移植2周后处死小鼠,取2组小鼠心、肺、肝、肾、脑等重要脏器于显微镜下观察有无血栓.结果 HE染色观察发现:A组肝脏、心脏、肺脏、肾脏均有血栓形成(脑未发现血栓);B组肝脏、心脏、肺脏、肾脏及脑均无血栓形成.结论 低分子肝素可预防BALB/c小鼠尾静脉移植BMMCs后导致的血栓形成.%Objective To evaluate the low molecular weight heparin for the prevention of thrombosis after autologous bone marrow mononuclear cell transplantation. Methods Hepatic injury mice models were established by carbon tetra-chloride ( CC14) and administration of 2-acetylminofluorene(2-AAF). Group A; BMMNC were injected via the tail vein; group B; The low molecular weight heparin were injected via the tail vein before the BMMNC transfusion. Two weeks after transplantation, liver, kidney, lung, heart and brain were examined anatomically, and the thrombus in these organs were further observed under the microscope. Results Group A: Thrombous could be found in liver, kidney, lung,heart (not in brain. ) Group B; Thrombous could not be found in liver, kidney, lung, heart and brain. Conclusion The low molecular weight heparin can be used for the prevention of the thrombosis after the autologous bone marrow mononuclear cell transplantation.

  5. Clinical observation on low molecular weight heparin sodium in the treatment of chronic obstructive pulmonary disease in 74 cases%低分子肝素钠治疗慢性阻塞性肺疾病74例临床观察

    Institute of Scientific and Technical Information of China (English)

    王龙滨

    2015-01-01

    Objective:To explore the curative effect of low molecular weight heparin sodium in the treatment of chronic obstructive pulmonary disease.Methods:74 patients with chronic obstructive pulmonary disease were selected.They all had the tendency of pulmonary embolism.They were randomly divided into the experimental group and the control group.The control group was given conventional treatment.The experimental group was given low molecular weight heparin sodium on the basis of the control group.The change situations of symptoms,arterial blood gas analysis,hematocrit of patients in two groups were analyzed. Results:The change situations of symptoms, arterial blood gas analysis,hematocrit after treatment in the experimental group were significantly better than those of the control group.Conclusion:The chronic obstructive pulmonary disease patients with the tendency of pulmonary embolism should be given low molecular weight heparin sodium as soon as possible.It can prevent the occurrence of pulmonary embolism.%目的:探讨低分子肝素在慢性阻塞性肺疾病治疗中的疗效。方法:收治慢性阻塞性肺疾病患者74例,均有肺栓塞倾向,随机分为试验组和对照组。对照组给予常规治疗,试验组在对照组的基础上给予低分子肝素钠治疗。分析两组患者治疗后症状、动脉血气分析、红细胞比容变化情况。结果:试验组治疗后症状、红细胞比容及动脉血气分析变化情况明显优于对照组。结论:慢性阻塞性肺疾病有肺栓塞倾向患者应尽早使用低分子肝素钠,防止肺栓塞的发生。

  6. 低分子肝素钠联合酚妥拉明治疗矽肺合并慢性肺源性心脏病疗效观察%Observation of Effect of Low Molecular Weight Heparin and Phentolamine Mesylate on Pneumoconiosis Complicated with Chronic Pulmonary Disease in Acute Period

    Institute of Scientific and Technical Information of China (English)

    黎晓莉; 何亦龙; 陈利玲; 唐燕

    2014-01-01

    Objective: the effect of low molecular weight heparin and phentolamine mesylate on patients of coal worker's pneumoconiosis complicated with chronic pulmonary disease in acute Period. Methods: fourty-six coal worker's pneumoconiosis complicated with chronic pulmonary patients were randomly assingned into treatment group and control group ,each group was Tweety-three, low molecular weight heparin and phentolamine mesylate were taken oral y by treatment group, The control group gives the western medicine convention treatment. the therapeutic period is 10 days. Results:Compared with control group, the clinical manifestation was improved evidently in treatment group ,the dif erence was statistical y significant (P<0.05). Conclusion: low molecular weight heparin and phentolamine mesylate is effective in treating on chronic cor pulmonale patients in acute period.%目的:探讨低分子肝素钠联合酚妥拉明治疗矽肺合并慢性肺源性心脏病的临床效果。方法选择矽肺合并慢性肺源性心脏病患者共46例随机分为治疗组和对照组,两组患者均给予吸氧、抗感染、解痉平喘、祛痰止咳、改善心功能等基础治疗,治疗组患者在上述治疗基础上给予低分子肝素钠和酚妥拉明治疗,治疗后评定两组疗效。结果治疗组总有效率82.61%,对照组总有效率73.91%,治疗组总有效率明显高于对照组,差异有统计学意义(P<0.05)。结论低分子肝素钠联合酚妥拉明能够显著改善矽肺合并慢性肺源性心脏病患者临床症状和体征,提高治疗效果及患者生活质量,值得推广。

  7. 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.

  8. Clinical Study on Treatment of the Low Molecular Weight Heparin in Children Severe Sepsis%低分子肝素治疗小儿严重脓毒症临床研究

    Institute of Scientific and Technical Information of China (English)

    莫巧字; 贾雯

    2016-01-01

    Objective To explore therapy values of the low molecular weight heparin in children severe sepsis.Method 38 children with severe sepsis were randomly divided into the experimental group and the control group,each group had 19 chil-dren.Both of two groups were treated with symptomatic and supportive treatment.Besides,the former was to be treated with LM-WH.And comparison of coagulation indexes of two groups in before and after the treatment,time in PICU,acute physiology and chronic health evaluation (APACHEⅡscore)and case -fatality rate.Results After treatment,in the experimental group the blood coagulation indexes was obviously improved compared with before treatment,the difference was statistically significant (P 0.05).Experimental group PLT,FIB and PT was higher than the control group,the difference was statistically significant (P <0.05).D -dimer,APTT was lower than the control group,the difference was statistically significant (P <0.05).Experimental group in PICU was shorter than the control group,the difference was statistically significant (P <0.05).Experimental group A-PACHEⅡscore was lower than the control group,the difference was statistically significant (P <0.05).Experimental group case fa-tality rate was lower than the control group,the difference was statistically significant (P <0.05).Conclusion LMWH has impor-tant clinical significance because it can improve children with severe sepsis in coagulation disorders,reduce case -fatality rate,and improve prognosis.%目的:探讨低分子肝素(LMWH)治疗小儿严重脓毒症的临床价值。方法:将38例严重脓毒症患儿随机分成试验组和对照组各19例,两组患儿均予以对症支持治疗,试验组在此基础上加用 LMWH 治疗,比较治疗前后两组凝血指标、住 PICU 时间、急性生理与慢性健康状况评分(APACHEⅡ评分)及病死率。结果:治疗后,试验组各项凝血指标较治疗前有明显改善,差异有统计学意义(P

  9. 奥扎格雷钠联合低分子肝素治疗进展性脑梗死疗效观察%A clinical study of sodium ozagrel injection combined with low molecular weight heparin sodium on progressive cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    卢兰香

    2012-01-01

    目的 观察奥扎格雷钠联合低分子肝素治疗进展性脑梗死的疗效及安全性.方法 将85例进展性脑梗死患者随机分成联合组43例及对照组42例.2组均给予常规治疗及酌情对症处理,同时联合组给予奥扎格雷钠联合低分子肝素钠;对照组仅给予低分子肝素钠.2组患者于治疗前、治疗后14天依据美国国立卫生院卒中量表(N1HSS)评分及日常生活活动能力(ADL)评分评定神经功能缺损程度.结果 治疗14 d后,2组患者NIHSS及ADL评分均有显著改善,联合组改善优于对照组(P<0.05),联合组及对照组显效率分别为69.77%及47.62%(P<0.05).2组患者均无消化道出血、颅内出血等不良反应发生.结论 奥扎格雷钠联合低分子肝素钠治疗进展性脑梗死是一种有效、安全的治疗方法,值得临床推广使用.%Objective To observe the therapeutic effect of sodium ozagrel injection combined with low molecular weight heparin sodium in the treatment of progressive cerebral infarction. Methods Eighty patients were randomly divided into treatment group and control group, which were administered sodium ozagrel + low molecular weight heparin sodium and low molecular weight heparin sodium, respectively. The degree of neurological deficit were assessed according to the U. S. National Institutes of Health Stroke Scale (NIHSS) score and activities of daily living (ADL) in two groups before treatment, and 14 days after treatment. Results The excellence rates in the treatment and control group were 69. 77% and 47. 62% , respectively 14 days after treatment. The rate of improvement in the combined group was better than that of the control group( P< 0. 05). No complications of gastrointestinal bleeding, intracranial hemorrhage were identifed in both groups. Conclusion Sodium ozagrel injection combined with low molecular weight heparin sodium is safe and reliable in treating progressive cerebral infarction, which is worthy of clinical

  10. Heparin release from thermosensitive hydrogels

    NARCIS (Netherlands)

    Gutowska, Anna; Bae, You Han; Feijen, Jan; Kim, Sung Wan

    1992-01-01

    Thermosensitive hydrogels (TSH) were synthesized and investigated as heparin releasing polymers for the prevention of surface induced thrombosis. TSH were synthesized with N-isopropyl acrylamide (NiPAAm) copolymerized with butyl methacrylate (BMA) (hydrophobic) or acrylic acid (AAc) (hydrophilic) co

  11. Heparin-Coated Coronary Stents.

    Science.gov (United States)

    van Der Giessen WJ; van Beusekom HM; Larsson; Serruys

    1999-09-01

    The development of the heparin-coated (HC)-stent should be viewed against the backdrop of the early unfavorable results with noncoated stents in the pre-intravascular ultrasound and pre-ticlopidine era. Notwithstanding, results of pilot and randomized trials show a surprisingly low incidence of (sub)acute stent thrombosis under challenging circumstances, such as acute coronary syndromes. Considering the quite low incidence of early complications with noncoated second-generation stents, it may require large trials to prove the clinical efficacy of the heparin- coating against noncoated devices. However, even if the "added value" of the heparin-coating will never be clinically proven, it has helped to enhance the penetration of stent therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now disagree with the statement that stents contribute to the state-of-the-art treatment of patients with angina pectoris or acute myocardial infarction. A preliminary comparison of available trials also suggests that the heparin-coated Palmaz-Schatz stent (Cordis Corp., Waterloo, Belgium) is as effective as the noncoated stent plus abciximab treatment.

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

    Science.gov (United States)

    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.

  13. 抗血小板药物联合低分子肝素治疗糖尿病合并脑梗死的疗效分析%Curative effect analysis of antiplatelet drugs combined with low molecular weight heparin in the treatment of diabetes complicated with cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    张盛开

    2015-01-01

    目的:探讨抗血小板药物联合低分子肝素在糖尿病合并脑梗死中的疗效。方法以我院325例糖尿病合并脑梗死患者为研究对象,将其随机分成两组,A组(160例)联合奥扎格雷、低分子肝素治疗,B组(165例)联合氯吡格雷、低分子肝素治疗,比较两组的临床疗效。结果 A组治疗3个月后总有效率83.75%, B组总有效率92.12%,组间比较差异显著(P<0.05);A组NIHSS评分(9.2±2.6)分,B组NIHSS评分(7.2±2.3)分,组间比较差异有统计学意义(P<0.05)。结论相较于奥扎格雷,氯吡格雷联合低分子肝素治疗糖尿病合并脑梗死的疗效更佳,值得临床应用。%Objective To investigate the effect of antiplatelet drugs combined with low molecular weight heparin in the treatment of diabetes complicated with cerebral infarction.Methods 325 cases of patients with diabetes complicated with cerebral infarction were selected as research object in our hospital. They were divided into 2 groups randomLy. Ozagrel combined with low molecular weight heparin was used to treat group A (160 cases). Clopidogrel combined with low molecular weight heparin was used to treat group B (165 cases). The clinical effect between the two groups was then compared.Results After treatment of 3 months, total efficiency of group A was 83.64%, and that of the group B was 92.17%. There was significant difference between the two groups(P<0.05). The NIHSS score of group A was (9.2±2.6) points, and the group B was(7.2±2.3)points. There was significant difference between groups(P<0.05).Conclusion Compared with ozagrel, clopidogrel combined with low molecular heparin has a better effect in the treatment of diabetes complicated with cerebral infarction, which is worthy of application.

  14. Low Molecular Weight Heparin in the Treatment of Neonatal Sepsis with Diffuse effect Analysis of Intravascular Coagulation%低分子肝素治疗新生儿脓毒症合并弥散性血管内凝血的临床疗效

    Institute of Scientific and Technical Information of China (English)

    刘莲香; 王健; 李燕芳

    2015-01-01

    目的:探讨低分子肝素治疗新生儿脓毒症合并弥散性血管内凝血的临床疗效。方法收集我院2012年3月至2014年6月收治的66例脓毒症合并弥散性血管内凝血患儿资料,随机将其分为两组,均接受抗感染、对症处理等基础治疗,对照组患儿给予普通肝素治疗,观察组患儿则采取低分子肝素治疗,比较两组患者的临床疗效、不良反应及治疗前后凝血功能指标。结果观察组患儿总有效率为93.9%,对照组患儿总有效率为72.7%;观察组患儿治疗后凝血酶原时间(PT)、部分凝血酶原时间(APTT)、D-二聚体(D-D)及纤维蛋白原(FIB)均较对照组明显改善,差异均有统计学意义(均P<0.05);治疗期间均未发生明显不良反应。结论低分子肝素治疗新生儿脓毒症并弥散性血管内凝血安全有效,能明显改善患儿凝血功能。%Objective To investigate the efficacy of combined with diffuse intravascular coagulation in sepsis newborn babies with low molecular weight heparin treatment.Methods In 66 cases of sepsis in our hospital from 2012 March to 2014 June were children with diffuse intravascular coagulation as the object of study,and randomly divided into two groups,were treated with basic anti infection,symptomatic treatment and so on,in addition,the control group were given ordinary heparin therapy,the observation group with low molecular weight heparin treatment is taken,the adverse reactions were compared between the two groups before and after treatment,the clinical curative effect and the function indexes of blood coagulation.Results Observation group with total efficiency is 93.9%,control group the total effective rate was 72.7%;the observation group after treatment PT,APTT,D-D and FIB were significantly improved than control group,the difference was statistical y significant(P<0.05);during the treatment had no obvious adverse reaction.Conclusion Low molecular weight

  15. 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

  16. 低分子肝素钠对血液透析患者钙磷代谢影响的临床观察%Effect of Low Molecular Weight Heparin Sodium on Calcium Phosphorus Metabolism in Patients Undergoing Hemodialysis:Clinical Observation

    Institute of Scientific and Technical Information of China (English)

    王猛

    2015-01-01

    OBJECTIVE:To explore the effect of low molecular weight heparin sodium on calcium-phosphorus metabolism in patients undergoing hemodialysis.METHODS: From May 2012 to May 2013, a total of 166 patients undergoing hemodialysis were randomly divided into either control group receiving unfractionated heparin or experimental group receiving low molecular weight heparin sodium.The two groups were followed and compared with regard to serum levels of calcium, phosphorus, parathyroid hormone (PTH) and alkaline phosphatase (ALP), the incidences of bleeding and blood clotting during cardiopulmonary bypass.RESULTS:Before treatment, serum levels of calcium, phosphorus, PTH and ALP showed no significant difference between the two groups ( P >0.05 ) .Serum phosphorus and PTH levels did not change significantly in the control group before and after treatment ( P>0.05 ) . After hemodialysis, serum phosphorus and PTH levels were significantly reduced in the experimental group, and the differences were statistically significant between the experimental group and the control group ( P 0.05 ) .The incidence of bleeding in the experimental group was significantly lower than in the control group ( P0.05).CONCLUSION:The low molecular heparin sodium might be effective for improving calcium-phosphorus metabolism.%目的:探讨低分子肝素钠对维持性血液透析患者钙磷代谢的影响。方法:选取2012年5月至2013年5月收治的166例血液透析患者作为研究对象,按随机表法将其分成对照组和试验组,对照组予以普通肝素钠,试验组予以低分子肝素钠,对两组患者的血钙、血磷、甲状旁腺激素( PTH)、碱性磷酸酶( ALP)水平、出血发生率、体外循环凝血发生率进行观察比较。结果:治疗前两组患者血钙、血磷、PTH、ALP水平差异无统计学意义(P>0.05)。对照组治疗前后血磷、PTH水平无明显变化(P>0.05)。透析后,试验组血磷及PTH水平显

  17. 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

  18. Effects of heparin on liver fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jun Shi; Jing-Hua Hao; Wan-Hua Ren; Ju-Ren Zhu

    2003-01-01

    AIM: To evaluate the effects of heparin on liver fibrosis in patients with chronic hepatitis B.METHODS: Fifty-two cases under study were divided into two groups, group A and group B. The two groups were given regular treatment and heparin/low molecular weight heparin (LMWH) treatment respectively. Hepatic functions,serum hyaluronic acid (HA) and type IV collagen levels were measured before and after the treatment, and six caseswere taken liver biopsy twice.RESULTS: After treatment, hepatic functions became significantly better in both groups. Serum HA and type IV collagen levels in group B compared with group A, decreased significantly after treatment. Collagen proliferation also decreased in group B after treatment.CONCLUSION: Heparin/LMWH can inhibit collagen proliferation in liver tissues with hepatitis B.

  19. pH-sensitive genipin-cross-linked chitosan microspheres for heparin removal.

    Science.gov (United States)

    Kamiński, Kamil; Zazakowny, Karolina; Szczubiałka, Krzysztof; Nowakowska, Maria

    2008-11-01

    Chitosan hydrogel microspheres were obtained by cross-linking chitosan in its inverse emulsion using genipin as cross-linker. The genipin-cross-linked chitosan microspheres (ChGp) swell significantly in water at pH values below 6.5 and shrink to a smaller extent at pH values above 6.5. ChGp microspheres bind heparin in water. The kinetics of heparin binding was found to be pH dependent and was faster and more efficient at a lower pH. That can be also controlled by the weight of ChGp microspheres used. Rate and efficiency of heparin adsorption at pH 7.4, which is typical of blood, could be increased by quaternization of ChGp microspheres using glycidyltrimethylammonium chloride (GTMAC). The polymeric material obtained thus can be potentially useful for heparin removal in biomedical applications.

  20. Study the mechanism of low molecular weight heparin improving proteinuria of rats with L-NAME (NG-Nitro-L-arginine Methyl Ester) induced preeclampsia by regulation of synaptopodin%Synaptopodin参与低分子肝素改善子痫前期大鼠蛋白尿的机制研究

    Institute of Scientific and Technical Information of China (English)

    柳宛璐; 乔福元; 刘海意; 龚洵; 石鑫玮; 吴媛媛

    2015-01-01

    Objective:To study the mechanism of low weight molecular heparin treating proteinuria of rats with L-NAME induced preeclampsia by synaptopodin. Methods:We dynami-cally monitored the blood pressure of tail artery,the total amount of 24h urinary protein and the mean body weight of pups of pregnancy rats after different concentration of low molecular weight heparin ( LMWH) administration. Meantime we detected synaptopodin expression of kidneys in pregnant rats after different concentration low molecular weight heparin ( LMWH ) administra-tion using RT-PCR, Immunohistochemical staining and Western blot. Results:Compared with the control,synaptopodin expression of kidneys in pregnant rats was significantly decreased after L-NAME injection. Synaptopodin expression of kidneys in pregnant rats was significantly in-creased after high concentration of LMWH ( H-LMWH ) administration compared with the L-NAME group. But synaptopodin expression had no changes between the L-NAME group and low concentration of LMWH ( L-LMWH) group. In addition,the blood pressure of tail artery and proteinuria of pregnant rats with L-NAME injection were markedly deceased after low and high concentration of LMWH administration [(200IU/(kg·d) and 600IU/(Kg·d)] on the 15th and 19th day. But the body weights of pups and the number of embryos per female did not change among the three groups. Conclusion:LMWH improved proteinuria of pregnant rats with L-NAME induced preeclampsia by up-regulation of synaptopodin,while LMWH improved pro-teinuria and decreased blood pressure of tail artery.%目的::探讨synaptopodin在低分子肝素( LMWH)治疗子痫前期( PE)大鼠模型中的分子作用机制。方法:将PE孕鼠随机分为3组:(1) L-NAME组:于妊娠第9天起连续腹腔内注射亚硝基左旋精氨酸甲酯(L-NAME)至孕期结束;(2)L-LMWH组:注射L-NAME的同时,孕15天起连续腹腔内注射LMWH 200IU/(kg·d)至孕期结束;(3)H-LM-WH组:注射L-NAME的同时,孕15

  1. To Observe the Curative Effect of Phentolamine Combined With Low Molecular Weight Heparin in Treatment of Acute Exacerbation of Chronic Pulmonary Heart Disease%酚妥拉明与低分子肝素联合治疗肺心病急性加重期的疗效观察

    Institute of Scientific and Technical Information of China (English)

    吕一敏

    2015-01-01

    Objective To analyzed the clinical effect of low molecular heparin combine with phentolamine in treatment of acute exacerbation of pulmonary heart disease. Methods 69 cases of pulmonary heart disease in acute exacerbation period were randomly divided into two groups,compared two groups of patients with therapeutic effect. Results The total effective rate of the treatment group was signiifcantly higher than that of the control group, the whole blood viscosity, plasma viscosity, erythrocyte aggregation index improved signiifcantly than the control group, PaO2 was signiifcantly higher than the control group, PaCO2 was significantly lower than the control group, P<0.05. Conclusion Phentolamine and low molecular weight heparin combination therapy pulmonary heart disease acute exacerbation has signiifcant effect.%目的:分析酚妥拉明与低分子肝素联合治疗肺心病急性加重期的疗效。方法将69例肺心病急性加重期患者随机分为两组,对比两组患者治疗效果。结果治疗组治疗总有效率较对照组提高,治疗后全血粘度、血浆粘度、红细胞聚集指数改善程度优于对照组,PaO2较对照组提高,PaCO2较对照组降低,P<0.05。结论酚妥拉明与低分子肝素联合治疗肺心病急性加重期取得显著效果,显著改善患者心肺功能。

  2. A disposable, coated wire heparin sensor.

    Science.gov (United States)

    Yun, J H; Fu, B; Meyerhoff, M E; Yang, V C

    1994-01-01

    The development of an ion-selective electrode heparin sensor consisting of a specially formulated polymer membrane doped with tridodecylmethylammonium chloride as the heparin complexing agent was recently reported. Because of the simple nature of the membrane technology used, the authors envisioned that the sensor could be configured as a disposable single-use device for rapid clinical or bedside measurement of heparin in a small, discrete sample. To explore this possibility, an inexpensive, disposable heparin sensor was created by dip-coating a copper wire with the specially formulated heparin-sensing polymeric membrane. Coated wire heparin sensors with a broad range of membrane thicknesses, prepared by repeatedly dipping the wire in the membrane solution for various times, were examined. Data show that increasing the membrane thickness of the sensor to a certain degree (more than 10 microns) enhanced the sensor's potentiometric response to heparin, although the time required to achieve 90% of the steady-state potential change was also prolonged. In addition, increasing membrane thickness also magnified the stirring effect on the sensor's response. In undiluted plasma samples, the coated-wire sensor with an optimized membrane thickness yielded a significant (5 to 30 mV) and reproducible response to heparin in a clinically relevant concentration range (0.5 to 12 units/ml, respectively). The clinical utility of the coated wire heparin sensor was shown using the sensor during protamine titration of heparinized plasma to assess the titration end-point. Preliminary results showed that the titration end-points determined by the heparin sensor strongly correlated with those determined by the activated partial thromboplastin time clotting assay. The overall time requirement to complete the titration process using a set of prefabricated coated wire heparin sensors, however, was less than 3 minutes. Further titration studies using undiluted clinical whole blood samples are

  3. 低分子肝素联合硫酸镁治疗早发型子痫前期的研究%Studies of Low MoIecuIar Weight Heparin Combined with Magnesium SuI-fate in the Treatment of EarIy Onset PreecIampsia

    Institute of Scientific and Technical Information of China (English)

    温洁红

    2015-01-01

    目的:探讨维生素E、低分子肝素联合硫酸镁对早发型子痫前期凝血指标及妊娠结局的影响。方法选择84例早发型子痫前期孕妇为研究对象,采用随机数字表法分为观察组和对照组,每组42例,对照组给予硫酸镁治疗,观察组给予维生素 E、低分子肝素和硫酸镁联合治疗。对两组的凝血功能和妊娠结局进行对比。结果观察组 D-二聚体值明显低于对照组、活化部分凝血酶原时间和凝血酶时间值明显延长,与对照组比较,差异均有统计学意义(P<0.01),而血小板数和凝血酶原时间比较,差异无统计学意义(P>0.05)。观察组孕妇自觉症状改善率、胎儿平均孕龄、新生儿平均体重均高于对照组,差异均有统计学意义(P<0.01)。结论维生素E、低分子肝素联合硫酸镁治疗能降低血压、抑制血液高凝状态,延长胎儿宫内妊娠时间,提高妊娠结局。%OBJECTIVE To investigate the effects of vitamin E , low molecular weight heparin combined with Magnesium sulfate on pregnancy outcome and coagulation index in the treatment of early onset preeclamp -sia.METHODS 84patientswithearlyonsetpreeclampsiawerechoosedastheresearchobjects,andwererandomly divided into observation group and control group ,42 cases in each group.Patients in the control group received Mag-nesium sulfate ,patients in the observation group were received vitamin E ,low molecular weight heparin and Magnesi-um sulfate.The function of blood coagulation and the outcome of pregnancy were compared .RESULTS The D-di-mer values were significantly lower in the observation group than that in the control group ,activated partial thrombo-plastin time and thrombin time was significantly prolonged , compared with the control group , there was statistically significant(P0.05 ) .The pregnant symptoms improvement rate , the average gestational age , neonatal average weight were higher than those

  4. 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

  5. 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

  6. Synthetic heparin-binding factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  7. Efficacy and safety analysis of different doses of low molecular weight heparin combined with hormone in refractory nephrotic syndrome%不同剂量低分子肝素联合激素治疗难治性肾病综合征的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    刘海燕; 王亚莉

    2016-01-01

    Objective To discuss the efficacy and safety analysis of different doses of low molecular weight heparin combined with hormone in the treatment of refractory nephrotic syndrome.Methods 60 cases of patients with refractory nephrotic syndrome in our hospital from January 2014 to January 2016 were selected,According to the random number table,60 patients were divided into high,medium and low dose of low molecular weight heparin group and control group,control group were treated with hormonal therapy,the high,medium and low dose of low molecular weight heparin group were injected low-molecular-weight heparin calcium on the basis of the control group,twice daily,once daily and every other day,respectively.Results After treatment,the clinical total effective rate of the high,medium and low dose group and control group patients was 14(93.3%),12(80.0%),10(66.7%) and 9(60.0%)respectively,the total efficiency of the high dose group was significantly higher than that of the control group(P<0.05),while there was no significant difference among control,medium and low dose group.The 24 h urine protein quantitation,ALB and Cr in high dose group improved better than those in medium and low dose group(P<0.05).The TG,TC and LDL in high dose group improved better than those in control group(P<0.05). The prothrombin time(PT)and activated partial thromboplastin time(APTT)in high and medium dose group were longer than those in control group(P<0.05),while fibrinogen(FIB)was lower(P<0.05).The PT in low dose group was longer than control group(P<0.05),while there was no significant difference in other coagulation indicators compared with control group.The APTT in high dose group was longer than low dose group(P<0.05).There was no obvious adverse reactions among each dose group.Conclusion The clinical curative effect in different doses of low molecular weight heparin combined with hormone in the treatment of refractory nephrotic syndrome is better,which could be significantly improved in

  8. Analysis of the efficacy of low molecular weight heparin combined with Danshen injection in the treatment of acute cerebral infarction%低分子肝素联合丹参注射液治疗急性脑梗死的效果分析

    Institute of Scientific and Technical Information of China (English)

    赵海燕

    2016-01-01

    目的:探讨低分子肝素和丹参注射液联合治疗急性脑梗死的临床效果。方法选取2012-12—2015-01我院诊治的急性脑梗死患者95例,随机分为研究组(n=48例)和对照组(n=47例),对照组实施基础治疗与丹参注射液,观察组加用低分子肝素治疗。比较2组治疗前后血液流变情况、神经功能改变情况(NIHSS 评分),并评定临床疗效、并发症情况。结果2组治疗后血液流变学指标(纤维蛋白原、红细胞比积、血浆黏度、全血低切黏度、全血高切黏度)均明显低于治疗前(P<0.05),且研究组较对照组降低更明显(P<0.05);治疗后7、14、28 d 2组 NIHSS 评分均较治疗前明显降低(P <0.05),且研究组各时点 NIHSS 评分较对照组更低(P<0.05);研究组与对照组总有效率分别为91.67%和74.47%,研究组高于对照组(P<0.05);2组并发症发生情况无明显差异(P>0.05)。结论低分子肝素联合丹参注射液治疗急性脑梗死,患者脑部循环明显改善,效果显著,值得推广。%Objective To evaluate the clinical efficacy of low molecular weight heparin combined with Danshen injection in the treatment of acute cerebral infarction. Methods Totally 95 cases of acute cerebral infarction patients in our hospital from December 2012 to January 2015 were chosen ,and were randomly divided into the study group (48 cases) and the control group (47 cases). The control group received the basic treatment combined with Danshen injection ,while the study group trea-ted by the basic treatment combined Danshen injection and low molecular weight heparin. The change of blood rheology ,nerv-ous function (NIHSS score) before and after treatment in two groups were compared ,and clinical efficacy ,complication were e-valuated. Results After treatment ,the indexes of hemorheology (fibrinogen ,hematocrit ,plasma viscosity ,whole blood low shear viscosity

  9. 低分子肝素联合小剂量阿司匹林对复发性流产患者激素水平、免疫功能的影响%Effect of low molecular weight heparin combined with low dose aspirin on hormone level and immune function in patients with recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    张高; 程玲慧

    2015-01-01

    目的:探讨低分子肝素联合小剂量阿司匹林对复发性流产患者激素水平、免疫功能的影响。方法选取2013年1月~2014年12月就诊的118例复发性流产患者为研究对象,采用随机数字表法分为观察组和对照组各59例。对照组采用小剂量阿司匹林治疗,观察组采用低分子肝素联合小剂量阿司匹林治疗。比较2组激素水平、免疫功能、治疗效果。结果临床疗效:观察组患者保胎成功率86.44%明显高于对照组55.93%(χ2=13.387,P<0.05);激素水平:观察组血清绒毛膜促性腺激素( human choionic gonadotophin,HCG)、孕酮(progesterone,P)、雌二醇(estradiol,E2)含量含量均明显高于对照组(P<0.05);免疫功能:观察组干扰素-γ(interferon-γ,IFN-γ)明显低于对照组(P<0.05),白细胞介素-4(interleukin-4,IL-4)明显高于对照组(P<0.05),IFN-γ/IL-4明显低于对照组(P<0.05);不良反应:2组不良反应比较差异无统计学意义(22.03%vs 15.25%)(χ2=0.894,P>0.05)。结论低分子肝素联合小剂量阿司匹林治疗有助于改善复发性流产孕妇激素水平与免疫功能,提高保胎成功率。%Objective To study effect of low molecular weight heparin combined with aspirin on hormone level and immune function in treatment of recurrent spontaneous abortion.Methods 118 cases patients with recurrent spontaneous abortion from January 2013 to December 2013 were divided into observation group and control group, control group was given low-dose aspirin therapy, observation group was given low molecular weight heparin combined with low-dose aspirin.hormone levels, immune function, therapy effect were compared between two groups.Result Clinical curative effect:observation group prevent miscarriage success rate 86.44% was significantly higher than control group 55.93%(χ2 =13.387, P0.05).Conclusion

  10. 奥扎格雷钠联合低分子肝素钠与氯吡格雷治疗进展性脑梗死的临床研究%Sodium ozagrel combined with Iow molecular weight heparin sodium and clopidogrel for progressive cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    何以鉴; 梁中抻; 温泉

    2012-01-01

    Objective To observe the clinical efficacy of sodium ozagrel combined with Iow molecular weight heparin sodium and clopidogrel for progressive cerebral infarction,and to explore the best therapeutic regimen for this disorder.Methods 90 patients with progressive cerebral infarction were randomly divided into two groups,45 for each group.Both groups received conventional treatment for cerebral infarction and therapies for high blood pressure and diabetes mellitus.The study group received sodium ozagrel combined with low molecular weight heparin sodium and clopidogrel,while the conirol group was treated by acetylsalicylic acid alone for 15 days.The efficacy,Neurological Disability Scale ( NDS ),platelet count and coagulation function were eompared between the two groups after treatment.Results The total effectiveness rate differed significantly between the study group and the control group( 97.78% vs.82.22%,P< 0.01 ).The score on NDS after treatment was markedly lower in the study group than in the control group [( 8.59 ± 5.17 ) vs.( 13.93 ± 4.05 ),P < 0.01].The platelet count and the change in coagulation function were normal,with no significant statistical difference ( P > 0.05 ).Conclusions Sodium ozagrel combined with low molecular weight heparin sodium and clopidogrel for progressive cerebral infarction has a synergetic effect and is safe.It effectively prevents infarction from deterioration,with better compliance and no adverse reactions,and is worth popu larizing clinically.%目的 观察奥扎格雷钠(晴尔)联合低分子肝素钠与氯吡格雷治疗进展性脑梗死的临床疗效,探讨进展性脑梗死的最佳治疗方案.方法 选择90例确诊为进展性脑梗死患者,并随机分为两组,各45例,两组均采用脑梗死常规治疗,并对伴发的高血压、糖尿病等进行对症治疗.观察组用晴尔联合低分子肝素钠与氯呲格雷治疗;对照组单用肠溶阿司匹林片治疗,均连续15d.比较两组疗效、

  11. Sodium Tanshinone ⅡA Sulfonate Combined with Low Molecular Weight Heparin in Treating Unstable Angina: A Meta-analysis%丹参酮ⅡA磺酸钠联合低分子肝素治疗不稳定型心绞痛Meta分析

    Institute of Scientific and Technical Information of China (English)

    赵劲波; 李元红; 江洪

    2012-01-01

    目的 评价丹参酮ⅡA磺酸钠联合低分子肝素治疗不稳定型心绞痛的效果.方法 计算机检索中国学术期刊网络出版总库、CNKI( 1994-2011)、万方医学数据库(1999-2011)、维普中文科技期刊全文数据库(1989-2011年)中关于丹参酮ⅡA磺酸钠联合低分子肝素治疗不稳定型心绞痛的随机对照试验,对符合标准的随机对照试验进行Meta分析.结果 共命中7篇符合条件文献.Meta分析结果显示,治疗2周后试验组疗效优于对照组,总效应Z=6.12(P <0.00001),OR及其95%可信区间4.48(2.77,7.24),其中3项研究对心电图进行评价,治疗2周后心电图改善情况试验组亦显著优于对照组,总效应Z =3.80(P =0.0001),OR及其95%可信区间2.83(1.65,4.84).结论 不稳定型心绞痛患者在常规治疗基础上联合应用丹参酮ⅡA磺酸钠和低分子肝素可明显改善心绞痛症状,有效控制心绞痛发作.%Objective To evaluate the effectiveness of Sodium Tanshinone DA Sulfonate combined with Low Molecular Weight Heparin in treating unstable angina (UA). Methods We conducted Meta-analysis by the randomized controlled trails (RCT) for patients with Sodium Tanshinone DA Sulfonate combined with l>ow Molecular Weight Heparin in treating unstable angina ( UA) from CNKI database (1994—2012) , Wan Fang medicine database (1999—2012), VIP full-text data base (1989—2012) and Medline. Results There were 7 trials. After two weeks treatment Meta-analysis indicated that the rurative effect of combination therapy was better than that of regular group in treating angina pectoris. The total effect was Z =6. 12 (P <0.00001), and the total effect of therapy group was better than that of control group [OR =4.48, 95% CI (2.77, 7.24), P <0.00001 ]. Three items showed that the curative efficiency and significant efficiency in the improvement of electrocardiogram were dramatically better than that of control group, and the total effect was Z = 3.80 [OR = 2. 83

  12. 奥扎格雷钠注射液与低分子肝素钙治疗不稳定型心绞痛的疗效观察%Observation on the curative effect of Ozagrel Sodium Injection and low molecular weight heparin calcium on unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    周雷

    2014-01-01

    目的:探讨奥扎格雷钠注射液与低分子肝素钙联合应用在不稳定型心绞痛中的治疗效果。方法选择本院82例不稳定型心绞痛患者,上述患者随机分为观察组和对照组,两组均给予常规治疗,对照组同时给予奥扎格雷钠注射液,观察组给予奥扎格雷钠注射液联合低分子肝素。评定两组疗效,观察血液流变学指标改变情况。结果观察组总有效率为95.0%,对照组总有效率为75.6%,观察组总有效率高于对照组(P<0.05)。观察组治疗后全血粘度高切、全血粘度低切和血液粘度分别与对照组治疗后比较,差异有统计学意义(P<0.05)。结论奥扎格雷钠注射液与低分子肝素钙治疗不稳定型心绞痛效果显著,有助于改善患者血液流变学指标,值得借鉴。%Objective To explore the effect of combined application of Ozagrel Sodium Injection and low molecular weight heparin on unstable angina pectoris. Methods 82 cases with unstable angina patients, the patients were randomly divided into observation group and control group, two groups were given conventional treatment, the control group was treated ozagrel sodium Injection, the observation group was given ozagrel sodium Injection combined with low molecular weight heparin. the efficacy of two groups was evaluated, the changes of blood rheology was observed. Results The total effective rate in the observation group, was 95%, the total effective rate in the control group was 75.6%, the total effective rate in observation groupwas higher than that in the control group (P<0.05). The whole blood high shear viscosity, whole blood low shear viscosity and blood viscosity in the observation group after treatment compared with those in the control group after treatment, the difference was statistically significant (P<0.05). Conclusion Ozagrel sodium Injection combined with low molecular weight heparin calcium on unstable angina pectoris has significant effect

  13. 奥扎格雷联合低分子肝素治疗进展性脑梗死的临床疗效%Clinical effects of sodium ozagrel combined with low molecular weight heparin on patients with progressive cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    李红军; 陈春富

    2011-01-01

    Objective To observe efficacy and safety of combined sodium ozagrel with low molecular weight heparin on patients with progressive cerebral infarction. Methods 112 cases of progressive cerebral infarction were randomly divided into the treatment group (56 cases) and the control group (56 cases). The control group was only administered 80 mg of sodium ozagrel, bid, for 14 days. And the treatment group was administered 80 mg of sodium ozagrel, bid,for 14 days and 0.4 mL of low molecular weight heparin sodium injection, bid, for 14 days. The therapeutic effect was evaluated by the National Institutes of Health Stroke Scale (NIHSS) and the Bathal index (BI). Liver and renal function, blood and urinary routines, blood clotting routine and electrocardiogram (ECG) were detected before and after 14 days of treatment. Results Compared with the control group, grades of NIHSS and BI in the treatment group were significantly lower after one (P <0.05) and two weeks (P <0.01 ). Both the number of platelets and blood coagulation time were within the normal range. There was no obvious side effect in either groups. Conclusion Sodium ozagrel combined with low molecular weight heparin is an effective and safe therapy for progressive cerebral infarction.%目的 观察奥扎格雷钠与低分子肝素联合治疗进展性脑梗死的疗效及安全性.方法 随机将急性进展性脑梗死患者12例分为治疗组和对照组各56例.对照组在临床常规治疗的基础上加用奥扎格雷钠80mg,静脉滴注,2次/d,连用14 d;治疗组在对照组治疗方案的基础上再加用低分子肝素钠0.4mL皮下注射,2次/d,连用14 d;治疗前、后依据美国国立卫生院卒中量表(NIHSS)评分及日常生活能力(BI)评分评定神经功能缺损程度,并监测肝肾功能、血尿常规、凝血4项及心电图.结果 与对照组相比,治疗组NIHSS、BI评分在治疗后1、2周时差异具有统计学意义(P<0.05,P<0.01).血小板、凝血酶原时间均在正

  14. Low molecular weight heparin calium combined dopamine and phentolamine in treatment of pulmonary heart disease and cardiac failure%低分子肝素钙联合多巴胺和酚妥拉明治疗肺心病并发心力衰竭疗效评价

    Institute of Scientific and Technical Information of China (English)

    陈国华; 李小红

    2015-01-01

    Objective To explore the clinical therapeutic effect of low molecular weight heparin combined with dopami ne and phentolamine in treatment of pulmonary heart disease and cardiac failure. Methods A total of 118 patients with pulmonary heart disease and cardiac failure in this hospital from February 2012 to February 2013 were randomly divided into the control group and the treatment group,59 of each group. The two groups were treated with basic therapies,such as oxygen inhalation, phlegm elimination, asthma relief,anti-inflammatory,diuretic treatments. The control group was given low molecular weight hep-arin while the treatment group with an extra dopamine and phentolamine based on the control group. The clinical efficacy and re-lated indicators of the two groups were observed 10 days after the treatment. Results After the treatment,the total effective rate of the control group was higher than that of the control group[91.5%(54/59) vs 74.6%(44/59)],and there was a significant differ-ence between them(P<0.05);The improvement of arterial blood gas analysis and hemorheology indexes of the treatment group were much higher than those of the control group (P<0.05). Conclusion The low molecular weight heparin combined with dopamine and phentolamine could significantly improve the patients′ hemodynamics and cardiopulmonary function in treatment of pul-monary heart disease and cardiac failure ,which should be worthy to be applied and promoted widely.%目的:探讨低分子肝素钙联合多巴胺和酚妥拉明治疗肺源性心脏病(肺心病)并发心力衰竭临床疗效。方法将该院2012年2月至2013年2月收治的118例肺心病并发心力衰竭患者随机分为对照组和观察组,各59例,两组患者均行吸氧、祛痰、平喘、抗炎、利尿等基础治疗,对照组给予低分子肝素钙治疗,观察组在此基础上予以多巴胺和酚妥拉明治疗。观察治疗10 d后两组患者的临床疗效及相关指标。结果治疗

  15. The efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery. A double blind randomized multicentre trail with venographic assesment

    DEFF Research Database (Denmark)

    Bergkvist, A; Eldor, A; Thorlacius-Ussing, O.

    1997-01-01

    BACKGROUND: Surgery for malignant disease carries a high risk of deep vein thrombosis. The aim of this study was to evaluate the prophylactic effect of a low molecular weight heparin, enoxaparin, 40 mg once daily, beginning 2 h before surgery, compared with that of unfractionated low-dose heparin...

  16. 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.

  17. 雾化吸入低分子量肝素对慢性阻塞性肺疾病大鼠血栓前状态干预的实验研究%Effects of inhaled low molecular weight heparin on prethrombotic state in rat model of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    孙妮娜; 韩伟忠; 佟丽; 程兆忠

    2008-01-01

    Objective To investigate the activity of coagulation and fibrinolysis in blood, and to observe the precautionary effect of inhaled low molecular weight heparin (LMWH) on rat of chronic obstructive pulmonary disease(COPD). Methods The rat of COPD model (model group) was established byi ntratracheal instillation of lipopolysaccharide(LPS) twice and exposured to cigarette smoke, meanwhile given LMWH inhaled. The activity of coagulation and fibrinolysis in blood, the blood gas analysis, the pathologic characteristics of bronchial walls, the total and different white blood cell counts of bronchoalveolar iavage fluid were determined. Results The model group rats shared specific pathological features in trachea, bronchi and lung tissues with that of human chronic bronchitis and obstructive emphesema; significant increase of total white blood cells and neutrophils in BALF was found in COPD group compared with those of control group (P<0.05). The total white blood cells and neutrophils in BALF in precaution group decreased obviously than in COPD group(P improved significantly(P<0.05). Conclusions There is preventive and protective effect of LMWH inhaled in the early state of COPD in some extent.%目的 探讨早期雾化吸入低分子量肝素(low molecular weight heparin,LMWH)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠模型发生发展的预防保护作用.方法 采用香烟熏吸加气道内注入脂多糖法建立大鼠COPD模型,并用LMWH雾化吸人,观察支气管肺泡灌洗液(BALF)的细胞计数及分类、动脉血气、有关血液学指标、肺组织病理学改变.结果 本实验建立被动吸烟致肺损伤大鼠模型的肺组织病理学改变基本符合人类COPD组织病理学改变特点,应用LMWH后,BALF中白细胞总数及巨噬细胞数较模型组显著降低,血液中vWF因子含量明显减低,PaO2、PaCO2明显改善.结论 早期雾化吸入LMWH对大鼠COPD模型的发生发展有一定的预防保护作用.

  18. Mass Spectrometric Evidence of Heparin Disaccharides for the Catalytic Characterization of A Novel Endolytic Heparinase

    Institute of Scientific and Technical Information of China (English)

    Yapeng CHAO; Shaoxiang XIONG; Xiulan CHENG; Shijun QIAN

    2004-01-01

    Heparinase from different sources can eliminate heparin or/and heparan sulfate into various low-molecular weight heparins with different characteristics. Porcine intestinal mucosa heparin was degraded into a series of oligosaccharides by a novel heparinase from the species Sphingobacterium. Disaccharide components from the digests were separated and purified by ultrafiltration and HPLC. Five major peaks appeared as three types according to their retention time. The mass spectrometry of peak Ⅰ mainly gave the non-sulfated disaccharide with the mass of 379 Da. Peak Ⅱ and Ⅲ were indicated as two major monosulfated disaccharides with molecular mass of 417 and 459 Da respectively. Moreover, the peak Ⅲ represented an Nacetyl disaccharide. Both peak Ⅳ and Ⅴ showed the same mass of 496 Da, hinting that they were disulfatesubstituted disaccharides. No trisulfate-substituted disaccharides were detected in the mixture of the heparin digest though they were abundant in the heparin structure. The results revealed that the heparinase might specifically cut the sites with low sulfated domain in heparin.

  19. MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles.

    Science.gov (United States)

    Jung, Min Jin; Lee, Seung Soo; Hwang, Yong Hwa; Jung, Hae Song; Hwang, Jin Wook; Kim, Min Jun; Yoon, Sangwoo; Lee, Dong Yun

    2011-12-01

    Transplantation of insulin-secreting pancreatic islets can provide real-time regulation of blood glucose in patients with type 1 diabetes mellitus. Currently, noninvasive and repetitive monitoring of islet engraftment and function is an emerging and promising modality for successful islet transplantation. Here we report a new technique for highly sensitive in vivo magnetic resonance (MR) imaging of transplanted pancreatic islets. To this end, heparinized superparamagnetic iron oxide (heparin-SPIO) nanoparticle was newly synthesized for chemical conjugation onto islet surface. Compared to typical cellular labeling of Feridex(®) via random endocytosis, chemical conjugation of heparin-SPIO was stable and improved the hypointensity of transplanted islets due to surface modification of every islet. These heparin-SPIO-conjugated islets showed normal viability and insulin secretion, and were quantified by spin echo T(2)-weighted MR imaging with linear correlation depending on transplanted islet mass in vitro and in vivo for 30 days. Also, from the immunohistochemistry, we confirmed the existence of heparin-SPIO and insulin biosynthesis in transplanted islets. However, Feridex-uptake islets showed late glucose responsiveness according to changing glucose concentration although they could normally control the blood glucose levels in diabetic mouse. Thus, we anticipate that this surface labeling with heparin-SPIO can be directly applicable for MR imaging of transplanted islets.

  20. A multicentre study on LMW-heparin effectiveness in preventing postsurgical thrombosis.

    Science.gov (United States)

    Verardi, S; Casciani, C U; Nicora, E; Forzano, F; Origone, A; Valle, I; Catania, G; Salanitri, G; Salcuni, P; Azzarone, M

    1988-01-01

    A multicentric study was carried out involving six italian departments of general surgery to assess the efficacy of a low molecular weight (LMW) heparin called Fluxum compared to standard calcium heparin in low doses for prevention of postoperative thromboembolic complications (deep vein thrombosis and pulmonary embolism). 610 patients were treated; 308 (50.5%) of whom were treated with Fluxum at doses of 4,000 or 8,000 I.U. Axa once a day by subcutaneous injection and 302 (49.5%) with heparin calcium at doses of 5,000 I.U. two or three times a day by subcutaneous injection. We observed a total of 29 deep vein thrombosis (4.7%); 10 (3.2%) from the group treated with LMW heparin and 19 (6.3%) from the comparative group. During the study 4 (0.65%) pulmonary embolism were found, 1 (0.32%) in the group treated with LMW heparin and 3 (1%) in the group treated with calcium heparin. None serious hemorrhagic accident was reported during the study. The antithrombotic prophy laxis carried out with Fluxum was on the whole better tolerated than the treatment of the other group, registering a lower frequency of hematomas at the injection and surgical wound sites.

  1. 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.

  2. 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.

  3. Complex coacervation of lysozyme and heparin

    DEFF Research Database (Denmark)

    van de Weert, Marco; Andersen, Mia Bendix; Frokjaer, Sven

    2004-01-01

    To characterize complex coacervates/flocculates of lysozyme and heparin in terms of binding stoichiometry and to determine the effect of complexation on protein structure and stability.......To characterize complex coacervates/flocculates of lysozyme and heparin in terms of binding stoichiometry and to determine the effect of complexation on protein structure and stability....

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Análisis y caracterización de la farmacoterapéutica de las heparinas de bajo peso molecular prescritas en pacientes hospitalizados en el Hospital Clínica Bíblica (Costa Rica durante el periodo de marzo a agosto del 2010 Analysis and Characterization of the Pharmacotherapy of Low Molecular Weight Heparins Prescribed in Hospitalized Patients at the Hospital ClinicaBiblica (Costa Rica from March to August 2010

    Directory of Open Access Journals (Sweden)

    Gustavo Céspedes-Orozco

    2012-03-01

    ón adecuada de la farmacoterapia con HBPM en este hospital, donde existe una alta proporción de pacientes que pueden desarrollar eventos tromboembólicos.Aim: To analyze the prescription of low molecular weight heparins in hospitalized patients at the Clinica Biblica Hospital (private hospital in Costa Rica based on the guidelines established by the American College of Chest Physicians (ACCP;2008. Material and methods: This study included 1651 hospitalized patients in the period from March to August 2010 who were treated with low molecular weight heparins, 250 patients were analyzed and randomly selected. A compilation of documents and information required for each patient for the analysis was made. Results: A total of 43% of the hospitalized patients used low molecular weight heparins (707 patients. In 91% of cases low molecular weight heparins were used with a prophylactic purpose. 2% of patients did not need to use prophylactic heparin therapy. In 90% of cases the dose was correct. 18% of cases required dose adjustments. In 80% of the patients had clinically relevant drug interactions, 4% of patients had some form of bleeding, where 2% of cases this effect was linked to the use of low molecular weight heparins. In 9% of cases in which LMWH were used as treatment were addressed in accordance with established guidelines. Conclusion: In the Hospital Clinica Biblica low molecular weight heparins were used according to the recommendations established by the guidelines of the ACCP despite the non-existence at the time of a hospital protocol. A pharmacotherapeutic analysis by the clinical pharmacist can provide important information to the medical doctor in order to take corrective and / or preventive actions associated with the correct use of medications. Make correct risk stratification and individualization of treatment facilitates proper implementation of drug therapy with low molecular weight heparins in this hospital where there is a high proportion of patients that may

  7. Cutaneous reactions to heparin therapy: when are they caused by heparin allergy?

    Directory of Open Access Journals (Sweden)

    Giuliana Zisa

    2013-03-01

    Full Text Available Introduction: Little is known about the incidence and causes of heparin-induced skin lesions. The most commonly reported causes are delayed-type hypersensitivity reactions. We describe 3 patients who were referred to our staff between March and October 2009 for suspected heparin allergies. All were scheduled to undergo major surgery (cardiovascular or orthopedic. Materials and methods: All 3 patients reported the development of itchy, erythematous rashes a few days after the subcutaneous administration of heparin (nadroparin calcium in cases 1 and 2, unspecified in case 3. Each of them underwent a diagnostic work-up for heparin allergy, which included prick and intradermal tests with commonly used heparins and patch testing with undiluted heparins and disinfectants. Results: Patch tests with disinfectants were negative in all 3 cases. In case 2, all allergological tests were negative. In cases 1 and 3, delayed positivity emerged for nadroparin calcium and at least one other heparin tested. Intravenous and/or subcutaneous provocation testing was done with an alternative heparin which produced negative results in skin tests (heparin sodium in case 1, pentasaccharide fondaparinux in case 3. In both cases the alternative drug was tolerated. After our evaluation, all 3 patients underwent surgery with no heparin-related complications. Discussion: The presenting clinical features in these 3 cases provided no information on which reactions were likely to be allergic: all 3 patients presented with similar local delayed reaction. The allergic reactions were identified only after cutaneous testing.

  8. 利多卡因联合奥扎格雷钠、低分子肝素钙治疗短暂性脑缺血发作38例疗效观察%Effect Observation that United Ozagrel Lidocaine, Low Molecular Weight Heparin Treatment of Transient Ischemic Attack in 38 Cases

    Institute of Scientific and Technical Information of China (English)

    朱士奎; 王洪元; 方保锋; 李保军

    2011-01-01

    Objective:To observe the clinical effect of lidocaine、 sodium ozagral and low-molecular-weight heparins calcium in treatment of transient ischemic attack (TIA).Methods:76 patients with TIA were randomly divided into two groups,38 patients of treatment group with TIA was treated with lidocaine300mg, with 0.9% sodium chloride injection 250ml,intravenously, daily, sodium ozagrel 80mg,with 0.9% sodium chloride injection 250ml,intravenously,daily, low-molecular-weight heparins calcium5000U, injecrio hypodermica, twice per day; simvastatin 10mg, orally daily;aspirin 100mg, orally daily.38 patients of the control group with Xueshuantong injection 10ml,with 0.9% sodium chloride injection 250ml,intravenously,daily, low-molecular-weight heparins calcium 5000U, injecrio hypodermica, twice per day; simvastatin 10mg,orally daily;aspirin 100mg, orally daily. Clinical effect and hematological changes were observed after seven day.Results:The total effective rates of the treatment group was 76.3%,with cure rate of 55.2%,respectively for the control group were 42.1% and 26.3%,with a very difference between the two groups (P<0.01),After the treatment, whole blood viscosity at a high-shear rate, whole blood viscosity at a low-shear rate, plasma viscosity, erythrocyte sedimentation rate and fibringen were significantly dropped,while prothrombin time was prolong,compared with before, these were significantly difference(P<0.0 1),platelet aggregation was improved after treatment,but treatment group was better than the control (P<0.05);For the control group there was no significantly difference than before(P>0.05).Conclusion:Lidocaine,sodium ozagral and low-molecular-weight heparins calcium was an effective cure for TIA.%目的:观察利多卡因联合奥扎格雷钠、低分子肝素钙治疗短暂性脑缺血发作(TIA)的临床疗效.方法:将76例TIA患者随机分为两组,治疗组38例,给予利多卡因300mg、奥扎格雷钠80mg分别加入0.9%

  9. 低分子肝素钙对不同剂量灯盏花素注射剂在大鼠体内药动学特征的影响%Study on effect of low molecular weight heparin calcium on the pharmacokinetics of scutellarin injection in rats at different doses

    Institute of Scientific and Technical Information of China (English)

    李秋红; 鞠爱霞; 田冲冲; 崔明宇

    2011-01-01

    AIM To study the effect of low molecular weight heparin calcium on the phannacokinetics of scutellatin injection in mrs at different doses. METHODS Plasma concentration of scutellarin was determined by HPLC after intravenous or subcutancous administration at the doses of 50,25 and 12.5 mg'kg-1 and the data were processed by 3P97 software to calculate the pharmacokinetic parameters. The protein binding rate of scutellarin in plasma was determined by ultrafiltration. RESULTS Two compartment model was shown after administration of scutellarin or scutellarin combined with low molecular weight heparin calcium in mrs. An elimination process of linear dynamic characteristics was expressed and the mean protein binding rate of scutellarin in plasma was 94.46% which kept constant at different doses after administration of scutellarin. However, nonlinear dynamic characteristics were presented and the mean protein binding rate of scutellarin in plasma declined to 89.93 % which didn' t changed at different doses after administration of scutellarin combined with low molecular weight heparin calcium in rats. CONCLUSION The specifity, precision, accuracy and stability are in line with the requirement of biological sample detection. The result proves the effect of low molecular weight heparin calcium on the phannacokinetics of scutellarin injection in rats and provides reference for design of rational drug use regimen.%目的 研究低分子肝素钙对不同剂量灯盏花素注射剂在大鼠体内药动学特征的影响.方法 实验设单独用药组和联合用药组,其中单独用药组大鼠予灯盏花素注射剂50、25、12.5 mg·kg-1,经快速静脉注射;联合用药组大鼠皮下注射低分子肝素钙注射剂0.5 mL(2000 U)后,快速静脉注射灯盏花素注射剂50、25、12.5 mg·kg-1.采用HPLC法测定大鼠血浆中灯盏花素的浓度,用3P97数据处理软件计算药动学参数.应用超滤法对灯盏花素与大鼠血浆的蛋

  10. Preparation and characterization of microspheres of albumin-heparin conjugates

    NARCIS (Netherlands)

    Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Feijen, Jan

    1991-01-01

    Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form albumin-hepar

  11. 21 CFR 864.5680 - Automated heparin analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated heparin analyzer. 864.5680 Section 864....5680 Automated heparin analyzer. (a) Identification. An automated heparin analyzer is a device used to determine the heparin level in a blood sample by mixing the sample with protamine (a...

  12. Oral heparin results in the appearance of heparin fragments in the plasma of rats

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

    1986-05-01

    We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of (/sup 35/S)heparin or (/sup 3/H)heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Resonance Light Scattering Imaging Determination of Heparin

    Institute of Scientific and Technical Information of China (English)

    Hong Ping GUO; Cheng Zhi HUANG; Jian LING

    2006-01-01

    A laser-induced resonance light scattering (RLS) imaging method to determine heparin is described based on the high light scattering emission power of the aggregation species of heparin with α, β, γ, δtetra(4-trimethylaminoniumphenyl)prophyrin (TAPP) in solution. By imaging the light scattering signals of the aggregation species, we proposed the method to determine the heparin with a detection range of 0.02 - 0.6 μg/mL and the detection limit (3 σ) of 1.3 ng/mL.

  15. Unfractionated heparin: a nursing dilemma.

    Science.gov (United States)

    Oertel, Lynn B

    2004-08-01

    Nurses face challenges in all aspects of their practice, especially with administering and monitoring drugs in a safe, effective manner. Key factors known to affect drug administration include general drug knowledge, formal nurse education, continuing education needs, clinical experience, and the nationwide nursing shortage. Other factors are advances in technologic aids and quality improvement initiatives. Emphasis on patient safety is growing, especially as it relates to drug therapy and high-alert drugs such as unfractionated heparin (UFH). Specific interventions related to UFH administration can enhance patient care management. Because nurses are at the site of direct patient care, they are often in an opportune position for identifying medication errors. At the same time, and most important, nurses need to collaborate with other health care professionals to actively develop solutions to minimize these errors. Adopting a systems approach and working collaboratively with an interdisciplinary team can result in improved patient outcomes.

  16. Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage

    NARCIS (Netherlands)

    Kaandorp, Stef P.; Goddijn, Mariette; van der Post, Joris A. M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyak, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N. M.; Buller, Harry R.; van der Veen, Fulco; Middeldorp, Saskia

    2010-01-01

    BACKGROUND Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS In this randomized

  17. Cost-utility of enoxaparin compared with unfractionated heparin in unstable coronary artery disease

    Directory of Open Access Journals (Sweden)

    Milne Ruairidh

    2001-10-01

    Full Text Available Abstract Background Low molecular weight heparins hold several advantages over unfractionated heparin including convenience of administration. Enoxaparin is one such heparin licensed in the UK for use in unstable coronary artery disease (unstable stable angina and non-Q wave myocardial infarction. In these patients, two large randomised controlled trials and their meta-analysis showed small benefits for enoxaparin over unfractionated heparin at 30–43 days and potentially at one year. We found no relevant published full economic evaluations, only cost studies, one of which was conducted in the UK. The other studies, from the US, Canada and France, are difficult to interpret since their resource use and costs may not reflect UK practice. Methods We aimed to compare the benefits and costs of short-term treatment (two to eight days with enoxaparin and unfractionated heparin in unstable coronary artery disease. We used published data sources to estimate the incremental cost per quality adjusted life year (QALY, adopting a NHS perspective and using 1998 prices. Results The base case was a 0.013 QALY gain and net cost saving of £317 per person treated with enoxaparin instead of unfractionated heparin. All but one sensitivity analysis showed net savings and QALY gains, the exception (the worst case being a cost per QALY of £3,305. Best cases were a £495 saving and 0.013 QALY gain, or a £317 saving and 0.014 QALY gain per person. Conclusions Enoxaparin appears cost saving compared with unfractionated heparin in patients with unstable coronary artery disease. However, cost implications depend on local revascularisation practice.

  18. HEPARIN-INDUCED THROMBOCYTOPAENIA/THROMBOSIS: A ...

    African Journals Online (AJOL)

    2009-12-02

    Dec 2, 2009 ... acid and glucosamine residues. Heparin was ..... which is the amino acid preceding the third cysteine moiety ... In this test visual detection is employed for determination of .... polypeptides extracted from the salivary glands of.

  19. [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.

  20. 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.

  1. 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.

  2. 不同分子量肝素对肾炎患者血小板活化和凝聚功能影响的研究%Effects of Different Molecular Weight Heparin on Functions of Activation and Aggregation of Platelet in Patients with Glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    李宏向; 张纪云; 孙念政; 郑楠; 常向秀

    2001-01-01

    Objective:To investigate the effects of different molecular weight heparin on functions of activation and aggregation of platelet in the patients with glomerulonephritis(GN).Methods:We tested the platelet count(PLT),mean platelet volume(MPV),platelet distribution width(PDW) by automatic blood analytic apparatus,and detected the expressive levels of platelet granule membrane protein(GMP-140) and fibrinogen receptor(GPⅡb-Ⅲa)by flow cytometry.Results:The study showed low molecular weight heprin(LMWH) did not afected significantly PLT,MPV,PDW in the patients with GN(P>0.05) and the expressive levels of GMP-140 and GPⅡb-Ⅲa on the surface of platelet(P>0.05);general heparin(GH)led to PLT decreasing,MPV enlarging,PDW exceeding normal volume in the patients with glomerulosclerosis(GS),membranous nephropathy(MN) or proliferative glomerulonephritis(PGN)(P<0.01),GH also led to the expressive levels of GMP-140 and GPⅡb-Ⅲa on platelets in the patients with GS,MN,PGN significant increasing(P<0.01).Conclusion:LMWH may not significantly affect the functions of activation and aggregation of platelet in the patients with GN,however,GH may strengthen the functions of activation and aggregation of platelet in the patients with GN.%目的:探讨普通肝素(GH)和低分子量肝素(LMWH)对肾炎患者血小板活化和凝聚的影响。方法:用全自动血细胞分析仪测定血小板计数(PLT)、体积(MPV)、分布宽度(PDW),用流式细胞学方法测定血小板表面颗粒膜蛋白(GMP-140)和纤维蛋白原受体(GPⅡb-Ⅲa)。结果:文中显示LMWH对各型肾炎患者PLT、MPV、PDW无显著性影响,可使血小板GMP-140和GPⅡb-Ⅲa表达水平上调,但未达统计学意义(P>0.05);GH可使GS、MN、PGN患者PLT减少,MPV增大(P<0.01),PDW超过正常值,且5.1%患者PLT降至100×109/L以下,使血小板GMP-140和GPⅡb-Ⅲa表达水平显著性上调(P<0.01),且显著高于LMWH治疗

  3. 低分子肝素预防ICU 患者DVT的出血原因分析及护理对策%Bleeding risk analysis and nursing countermeasures to prevent deep vein thrombosis (DVT) for ICU patients with low molecule weight heparin (LMWH)

    Institute of Scientific and Technical Information of China (English)

    王绍丽; 赖美红

    2015-01-01

    The risk of deep vein thrombosis (DVT) for ICU patients is increased due to long-term bedridden ,mechanicalven-tilation ,sedation and muscle relaxtionandoperation of central venous catheter and other invasive operation ,prevention is more important than treatment in clinical .Low molecule weight heparin (LMWH ) is widely used in the prevention of DVT .Its pre-vention effect has also been recognized .But it also has led to bleeding clinically .In this paper ,through a retrospective analysis of 15 clinical cases ,with-LMWH causeds different degrees of bleeding ,wesystematicly summarized of the coping strategies and feasible scheme to eliminate effectively the hidden -hemorrhage .%重症监护病房(ICU )的患者因长期卧床、机械通气、镇静和肌松、手术以及中心静脉置管等有创操作使深静脉血栓(DVT)的发生风险增加。低分子肝素在预防DVT方面应用广泛,其预防效果也得到公认。但随之而来的出血也屡见不鲜,亦有导致大出血的案例报道。回顾性分析我院2014年11月至2015年4月期间15例低分子肝素导致不同程度出血的原因,提出应对策略,消除出血隐患。

  4. 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.

  5. Comparison of the impact of rivaroxaban and low molecular weight heparin on hidden blood loss after unilateral first half artificial hip replacement surgery%初次单侧人工半髋置换术后利伐沙班与低分子肝素对隐性失血的影响比较

    Institute of Scientific and Technical Information of China (English)

    杨东靕; 裘兴栋; 吕存贤

    2015-01-01

    目的 探讨利伐沙班与低分子肝素对初次单侧人工半髋置换术后隐性失血的影响.方法 收集因股骨颈骨折行单侧人工半髋置换术老年患者共80例,术后按随机数字表法分为利伐沙班组40例和低分子肝素组40例.两组均在术后12 h开始每天分别口服利伐沙班10 mg和皮下注射低分子肝素5000u,比较两组围手术期实际失血总量、显性失血量、隐性失血量及隐性失血量占实际失血总量百分比;并记录35 d内出血事件.结果 利伐沙班组实际失血总量、显性失血量、隐性失血、隐性失血量占实际失血总量百分比分别为(671.00±55.61) mL、(313.88±14.53)mL、(350.00±29.41)mL、(52.00±5.22)%,低分子肝素组分别为(662.00±30.19)mL、(288.87±15.33) mL、(372.00±35.10)mL、(56.00±6.71)%,两组差异均无统计学意义(t =0.93、0.93、0.83、1.03,均P>0.05).结论 对于初次行单侧人工半髋置换术的患者,围手术期使用利伐沙班与低分子肝素后隐性出血风险及出血事件发生率无明显差异.%Objective To investigate the impact of rivaroxaban and low molecular weight heparin on hidden blood loss after unilateral first half artificial hip replacement surgery.Methods According to the digital table,a total of 80 cases because of femoral neck fractures in elderly patients with unilateral arthroplasty artificial hip and a half after surgery were randomly divided into the rivaroxaban group and low molecular weight heparin (LMWH) group,40 cases in each group.In both groups,respectively,after 12 h begin daily oral rivaroxaban 10 mg and subcutaneous low molecular weight heparin 5 000 u,compared the two groups around the actual amount of perioperative blood loss,blood loss was dominant,recessive blood loss and hidden blood loss accounts,the actual percentage of total blood loss,and recorded 35d bleeding events.Results The total amount of blood loss,dominant blood loss,hidden blood loss and the hidden

  6. 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

  7. 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

  8. Inhalation of ipratropium bromide combined with low molecular weight heparin calcium in the treatment ofClinical study of COPD%吸入用异丙托溴铵联合低分子肝素钙治疗 AECOPD 临床研究

    Institute of Scientific and Technical Information of China (English)

    解鲁文

    2014-01-01

    Objective To investigate the effect of inhaled ipratropium bromide combined with low molecular weight heparin calcium in the treatment of acute exacerbations of chronic obstructive pulmonary disease(AECOPD)and its clinical significance. Methods 80 cases were diag-nosed as AECOPD patients,which were randomly divided into two groups(observation group,the control group with 40 cases in each group). The two patients were given conventional oxygen inhalation,anti - inflammatory,short acting beta agonist bronchodilators,relieving cough and phlegm, correcting water electrolyte imbalance of conventional treatment. The observation group plus ipratropium bromide aerosol inhalation,low molecular weight heparin calcium injection 5 000 IU subcutaneous injection,2 times a day,used in conjunction 7d. The clinical symptoms,blood plasma D -dimer,two arterial blood gas analysis,the incidence of adverse reaction were analyzed and compared of two groups of patients before and after treat-ment. Results The clinical control rate was 62. 5% ,22. 5% with obvious effect,7. 5% with good effective. The total effective rate was 92. 5% . While in the control group,the clinical control rate was 30% ,20% obvious effect,25% with good effect. The total effective rate was 75% . The total efficiency of two groups of patients were statistically significant( P ﹤ 0. 05). The clinical control rate,significant efficiency percentage was higher than that of control group. The plasma D - two groups of two concentration after treatment were lower in observation group,which decreased obviously ( P ﹤0. 01). The two groups before and after treatment,PaO2 ,PaCO2 and SaO2 showed uniform statistical significance( P ﹤0. 05). The observa-tion group after treatment,PaO2 increased and PaCO2 decreased than that in the control group( P ﹤0. 05). The clinical adverse reactions occurred in 10% of patients of the observation group,while it was 32. 5% in the control group. There was significant difference( P ﹤0. 05

  9. [Latin American regional reference materials for porcine heparin and bovine heparin].

    Science.gov (United States)

    Albertengo, M E; Cinto, R O; Araldi, H T; Vernengo, M J

    1990-02-01

    In agreement with the Regional Programme of Reference Materials of the Panamerican Health Organization the Instituto Nacional de Farmacología y Bromatología of Buenos Aires designed a study for the calibration of a Reference Material for Heparin, porcine, mucosal and a Reference Material for Heparin, bovine, mucosal. The assay methods used in this study were those described in the United States Pharmacopeia XXI Ed and British Pharmacopoeia 1980, Addendum 1983. The overall combined potency estimates of both heparin in preparations relative to 4th Int.St. was 1633.83 UI/ampoule (95% confidence limits 1609.70-1657.96 UI/ampoule) for porcine heparin and 1332.31 UI/ampoule (95% confidence limits, 1302.31-1361.77 UI/ampoule) for bovine heparin. The assigned unitage was 1630 UI/ampoule for the porcine Reference Material and 1330 UI/ampoule for the bovine Reference Material.

  10. 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

  11. Impact of autoclave sterilization on the activity and structure of formulated heparin.

    Science.gov (United States)

    Beaudet, Julie M; Weyers, Amanda; Solakyildirim, Kemal; Yang, Bo; Takieddin, Majde; Mousa, Shaker; Zhang, Fuming; Linhardt, Robert J

    2011-08-01

    The stability of a formulated heparin was examined during its sterilization by autoclaving. A new method to follow loss in heparin binding to the serine protease inhibitor, antithrombin III, and the serine protease, thrombin, was developed using a surface plasmon resonance competitive binding assay. This loss in binding affinity correlated well with loss in antifactor IIa (thrombin) activity as well as antifactor Xa activity as measured using conventional amidolytic assays. Autoclaving also resulted in a modest breakdown of the heparin backbone as confirmed by a slight reduction in number-averaged and weight-averaged molecular weight and an increase in polydispersity. Although no clear changes were observed by nuclear magnetic resonance spectroscopy, disaccharide composition analysis using high-performance liquid chromatography-electrospray ionization-mass spectrometry suggested that loss of selected sulfo groups had taken place. It is this sulfo group loss that probably accounts for a decrease in the binding of autoclaved heparin to antithrombin III and thrombin as well as the observed decrease in its amidolytic activity. Copyright © 2011 Wiley-Liss, Inc.

  12. 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...

  13. Conformation of heparin studied with macromolecular hydrodynamic methods and X-ray scattering.

    Science.gov (United States)

    Pavlov, Georges; Finet, Stéphanie; Tatarenko, Karine; Korneeva, Evgueniya; Ebel, Christine

    2003-08-01

    The hydrodynamic characteristics of heparin fractions in a 0.2 M NaCl solution have been determined. Experimental values varied over the following ranges: the sedimentation coefficient (at 20.0 degrees C), 1.3weights in the range 3.9heparin molecule, ML, was determined using the theory of hydrodynamic properties of a weakly bending rod, giving ML=570 +/- 50 g nm(-1) mol(-1). The equilibrium rigidity, Kuhn segment length (A=9 +/- 2 nm) and hydrodynamic diameter (d=0.9 +/- 0.1 nm) of heparin were evaluated on the basis of the worm-like coil theory without the excluded volume effect, using the combination of hydrodynamic data obtained from fractions of different sizes. Small-angle X-ray scattering for three heparin fractions allowed an estimate for the cross-sectional radius of gyration as 0.43 nm; from the evolution with the macromolecule contour length of the radius of gyration, a value for the Kuhn segment length of 9 +/- 1 nm was obtained. A good correlation is thus observed for the conformational parameters of heparin from hydrodynamic and X-ray scattering data. These values describe heparin as a semi-rigid polymer, with an equilibrium rigidity that is essentially determined by a structural component, the electrostatic contribution being negligible in 0.2 M NaCl.

  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. Preparation and characterization of albumin-heparin microspheres

    NARCIS (Netherlands)

    Cremers, H.F.M.; Kwon, G.; Bae, Y.H.; Kim, S.W.; Verrijk, R.; Noteborn, H.P.J.M.; Feijen, J.

    1994-01-01

    Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsph

  16. 78 FR 38058 - Guidance for Industry on Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for...

    Science.gov (United States)

    2013-06-25

    ... risks of crude heparin contaminants and to recommend strategies to ensure that the heparin supply chain... Management, Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER... ruminant materials. The control of the quality of crude heparin is important to ensure the safety of...

  17. 77 FR 7584 - Draft Guidance for Industry on Heparin for Drug and Medical Device Use; Monitoring Crude Heparin...

    Science.gov (United States)

    2012-02-13

    ... Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. See the... crude heparin contaminants and to recommend strategies to ensure that the heparin supply chain is not... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Heparin for Drug and...

  18. 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

  19. Effect of Low Molecular Weight Heparin Used at Different Time Postoperatively in Total Hip Arthroplasty and Total Knee Arthroplasty%对全髋与全膝关节置换术后LMWH应用时机的初步研究

    Institute of Scientific and Technical Information of China (English)

    尹文化; 陈沐吉; 刘国强; 雷英

    2011-01-01

    目的 探讨全髋与全膝关节置换术后应用低分子肝素(LMWH)预防深静脉血栓(DVT)的时机.方法 158例全髋与全膝关节置换者中髋关节置换(THA)81例、全膝关节置换(TKA)77例.观察术后不同时机使用LMWH对术后引流量、DVT发生率的影响.结果 THA术后开始使用LMWH组引流量与术后72 h组差异具有统计学意义(P=0.000),而TKA术后组与术后72 h组差异无统计学意义(P=0.552).在THA和TKA中,术后组与术后72 h组DVT发生率差异均有统计学意义(P=0.000).结论 THA术后LMWH的最佳应用时机是术后72 h,但术后即应用LMWH则是TKA术后预防DVT的最佳时机.%Objective To explore the effect of low molecular weight heparin (LMWH) used at different time postoperatively in total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods One hundred and fifty eight patients underwent resurfacing arthroplasy, including THA 81 patients and TKA 77 patients. The effect of LMWH used at different time after operation on the amount of blood loss and the DVT incidence rates were observed. Results In THA group, there were significant differences between the postoperative and 72 hours later postoperative LMWH using groups in the amount of lead flow, while in the TKA group there were no significant difference between the postoperative and 72 hours later postoperative LMWH using groups in the amount of lead flow. In THA and TKA groups, there were significant differences between the postoperative and 72 hours later postoperative LMWH using groups in the incidence rate of DVT. Conclusion LMWH used 72 hours later postoperatively can obviously decrease the incidence rate of DVT in THA,but in TKA the optimal time for using LMWH probably is immediately after operation.

  20. [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.

  1. Modulation of low molecular weight heparin and Netrin-1 on biological functions of human placental microvascular endothelial cells%低分子肝素及轴突导向因子-1对人胎盘微血管内皮细胞生物学功能的影响

    Institute of Scientific and Technical Information of China (English)

    勾晨雨; 张兰珍; 王销颖; 罗玉玲; 张嵩卉

    2016-01-01

    目的 研究低分子肝素及轴突导向因子-1(Netrin-1)对人胎盘微血管内皮细胞(microvascular endothelial cells,MECs)生物学功能的影响.方法 选取正常早孕(8~10周)绒毛,通过Percoll梯度离心法提取人胎盘微血管内皮细胞进行原代培养,将细胞分为6组,其中5组培养液中加入不同浓度低分子肝素(low molecular weight heparin,LMWH)(终浓度为0.01 U/ml、0.1 U/ml、1U/ml、10 U/ml、100 U/ml),未加低分子肝素的作为对照组.通过实时荧光定量-PCR和Western-Blot分别检测不同组别Netrin-1基因mRNA及蛋白表达情况;CCK-8检测不同组别细胞增殖率的变化;筛选出细胞增殖率最高组别进行流式细胞检测凋亡水平及细胞周期的变化;利用Transwell细胞迁移实验检测细胞侵袭和迁移能力的变化.结果 培养24 h 0.1U/ml、1U/ml组Netrin-1 mRNA及蛋白表达高于对照组(P<0.05);10 U/ml、100 U/ml组Netrin-1 mRNA表达与对照组比较差异无统计学意义(P>0.05),但蛋白表达低对照组(P<0.05);培养48 h 0.1U/ml、1 U/ml、10 U/ml组Netrin-1 mRNA及蛋白表达均高于对照组;培养24 h 0.1 U/ml组MECs增值率高于对照组,100U/ml组细胞增值低于对照组;培养48 h 0.1U/ml、1U/ml、10 U/ml组细胞增值率高于对照组;0.1U/ml组培养24、48hS期细胞比例及细胞迁移数目高于对照组;0.1U/ml组培养24 h晚期细胞凋亡低于对照组(P<0.05),各组细胞侵袭实验比较差异无统计学意义(P>0.05).结论 适当浓度的低分子肝素可以促进人胎盘MECs的增殖,降低凋亡,迁移能力增高,这一变化可能与低分子肝素促进Netrin-1基因表达有关.%Objective To investigate the effect of low molecular weight heparin (LMWH) and Netrin-1 on biological functions of human placental microvascular endothelial cells (MECs).Methods Human placental MECs were collected and cultured aseptically from villi tissue of normal pregnant women who accepted artificial abortion in first

  2. 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.

  3. A RANDOMIZED CLINICAL TRIAL ON THE ANTI - INFLAMATORY EFFECT OF INTRACAMERAL LOW MOLECULAR WE HEPARIN (ENOXAPAIN IN DIABETIC CATARACT SURGERY

    Directory of Open Access Journals (Sweden)

    Shivanand

    2015-08-01

    Full Text Available AIM: To study the effect intracameral low molecular weight on postoperative inflammation after cataract surgery in diabetic patients. SETTING: Department of Ophtha lmology J. N. Medical College. Belgaum. DESIGN: Randomized control trial . MATERIAL AND METHODS: Forty patients with diabetes undergoing small incision cataract surgery with posterior chamber intraocular lens (IOL implantation were randomly assigned to two groups, group A and group B. All patients in g roup A received low molecular weight heparin (enoxaparin in the concentration of 40 IU in 500ml in the irrigating solution and patients in group B received irrigating solution without low molecular weight heparin. In all patients polymethyl methacrylate ( PMMA IOLs were implanted. The patients were examined postoperatively on day 1, day 7, day 30 and day 60 for anterior chamber cells and flare and iris pigments on cell by slit lamp biomicroscopy. RESULTS: A statistically significant reduction in postoperat ive cells, flare and intraocular lens surface pigments was noted in group with addition of low molecular weight heparin (enoxaparin at day 1(p0.001 and 1 week (p<0.001. At 4 weeks and 8 weeks no statistically significant reduction in post - operative cell s and flare was seen between the two groups but there was a significant reduction in the intraocular lens pigments in the group with addition of low molecular weight heparin (enoxaparin. CONCLUSION: Intraoperative use of low molecular weight heparin (enox aparin reduced disturbance in the blood - aq ueous barrier in the early post - operative period evidenced by lower postoperative anterior chamber cells and flare, and also reduced iris pigments on the intraocular lens. At 8 weeks cells and flare in both the gr oups did not show significant difference.

  4. Use of Low-Molecular-Weight Heparins in the Management of Acute Coronary Artery Syndromes and Percutaneous Coronary Intervention%低分子肝素在急性冠脉综合征和经皮冠脉介入治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    Graham C.Wong; Robert P.Giugliano; Elliott M.Antman

    2004-01-01

    背景:作为抗栓药物,低分子肝素(low-molecular—weight heparins,LMWHs)与普通肝素相比有诸多的药理学优势。目的:与普通肝素相比较,系统总结LMWHs用于急性冠脉综合征(acute coronary syndromes,ACSs)以及作为经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)辅助措施的安全性和有效性的临床资料。资料来源:检索了MDELINE 1990~2002年的相关文章,检索词为heparin(肝素),enoxaparin(依诺肝素),dalteparin,nadroparin,tinzaparin,low molecular weight heparin(低分子肝素),myocardial infarction(心肌梗死),unstable angina(不稳定心绞痛),coronary angiography(冠状动脉造影术),coronary angioplasty(冠状动脉成形术),thrombolytic therapy(抗栓治疗),reperfusion(再灌注),drug therapy(药物治疗),combination(联合治疗)。此外,资料还来源于MEDLINE所列相关文章的参考书目,来自对专家和制药公司的调查,以及近年来国内和国际心血管会议发表的文章。研究选择:选择所有比较LMWHs与普通肝素或安慰剂对ACS治疗效果的随机试验综述,以及在某些试验和注册研究中LMWHs用于PCI的临床预后、药代动力学和/或药效学结果。在查到的39项研究中有31个符合分析标准。资料提取:资料质量根据是否在专家审阅的刊物上发表或是否为正式心血管学会举办的会议录用确定。资料综合:美国心脏病协会(AHA)和美国心脏学会(ACC)推荐LMWHs可用于治疗不稳定心绞痛/非ST段抬高的心肌梗死。临床试验证实,LMWH在PCI期间以及与GpⅡh/Ⅲa抑制剂合用时,与普通肝素的安全性相似。总之,LMWHs作为抗栓药物用于治疗ST段抬高的心肌梗死有着极好的前景。结论:LMWHs作为抗栓药物治疗ACSs的各种病症时,可以取代普通肝素。此外,LMWHs在PCI期间应用,是一种安全有效的抗栓药物。但是,

  5. Prevention of venous thromboembolism and safe use of heparin in Spanish hospitals.

    Science.gov (United States)

    Saturno, Pedro J; Gama, Zenewton A S; Fonseca, Yadira A

    2011-04-01

    To assess compliance with basic and actionable indicators in relation to prevention of venous thromboembolism (VTE) and safe use of heparin. We built, pilot tested and measured a set of evidence-based structure (existence of guidelines) and process (risk assessment for VTE, and dose adjustment to patient weight and renal function when prescribing heparin) indicators in a nation-wide random sample of 22 hospitals. Compliance with process indicators is estimated at national level and by groups of hospitals (stratified by size). At hospital level, compliance is assessed with Lot Quality Acceptance Sampling, for 85% compliance standard (α ≤ 0.05), 55% threshold (β ≤ 0.10). Contents of existing guidelines are analyzed, and their influence on performance is assessed using logistic regression. Acute care hospitals in Spain. None Problem identification through indicators assessment. Less than half of hospitals have guidelines and their contents are very variable and incomplete. No hospital complies with the standard for VTE prevention and only one for heparin dose adjustment. Nationally, VTE risk assessment is performed in 5.8% of patients (95% CI: 5.6-6.0), and heparin dose is explicitly adjusted in 17.5% (95% CI: 16.8-18.2). Performance is relatively higher in large hospitals and it is associated with the existence of guidelines for VTE prevention (OR: 8.3; 95% CI: 2.1-32.1). We have identified some actionable contributing factors to safety problems using evidence-based structure and process indicators. Explicit process design and key clinical interventions (risk assessment for VTE and heparin dose adjustment) should be addressed to improve the current situation.

  6. 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

  7. 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.

  8. A spectroscopic study of interaction of cationic dyes with heparin

    Directory of Open Access Journals (Sweden)

    R. Nandini

    2010-01-01

    Full Text Available The interaction of two cationic dyes namely, acridine orange and pinacyanol chloride with an anionic polyelectrolyte, heparin, has been investigated by spectrophotometric method.The polymer induced metachromasy in the dyes resulting in the shift of the absorption maxima of the dyes towards shorter wavelengths. The stability of the complexes formed between acridine orange and heparin was found to be lesser than that formed between pinacyanol chloride and heparin. This fact was further confirmed by reversal studies using alcohols, urea and surfactants. The interaction of acridine orange with heparin has also been investigated fluorimetrically.The interaction parameters revealed that binding between acridine orange and heparin arises due to electrostatic interaction while that between pinacyanol chloride and heparin is found to involve both electrostatic and hydrophobic forces. The effect of the structure of the dye in inducing metachromasy has also been discussed.

  9. Clinical Analysis on Therapeutic Effect of Low Molecular Weight Heparin and CSDP on Abnormal Umbilical Artery Blood Flow in the Third Trimester of Pregnancy%低分子肝素联合复方丹参滴丸治疗妊娠中晚期脐动脉血流异常的临床分析

    Institute of Scientific and Technical Information of China (English)

    汪群

    2013-01-01

    Objective To investigate the clinical effects of low molecular weight heparin (LMWH) combined with CSDP on pregnant women with umbilical cord blood flow S/D value abnormality in the third trimester of pregnancy. Methods According to different medications, 89 pregnant women with umbilical cord blood flow S/D value abnormality in the third trimester of pregnancy were divided into two groups. The control group was given LMWH, while the observation group was treated with LMWH plus CSDP. The changes in umbilical cord blood flow and coagulation function were observed before and after the treatment. Results Compared with before the treatment, S/D ratio, PI and RI of pregnant women of two groups were significantly reduced after the treatment, and the differences were statistically significant. There were statistically significant differences in PI between the two groups (Ρ<0.001). After the treatment, descending rate of umbilical artery S/D ratio and treatment duration in the observation group were superior to those of control group (P<0.001, P<0.01). Conclusions Combined use of LMWH and CSDP in treating umbilical cord blood flow S/D value abnormality has the advantages of increasing placental blood flow and faster descending umbilical artery S/D ratio; moreover, it has no effect on blood coagulation. The remedy is worthy of popularization and application.%目的 探讨低分子肝素联合复方丹参滴丸治疗妊娠中晚期脐动脉血流异常的临床效果. 方法 将89例妊娠中晚期脐动脉血流异常的患者,按治疗方案不同分为两组,对照组给予低分子肝素治疗;观察组加用复方丹参滴丸治疗.观察两组治疗前后脐血流变化及凝血功能的变化. 结果 两组孕妇治疗后S/D比值、PI、RI均明显降低,与治疗前比较差异均有统计学意义;对照组凝血指标搏动指数与观察组比较差异有统计学意义(P<0.001);观察组患者治疗后脐动脉血流S/D比值下降速度及治

  10. 低分子量肝素对慢性阻塞性肺疾病大鼠气道黏液分泌的影响%The Effect of Low-Molecular-Weight-Heparin on the Airway Mucus Secretion of a Rat Model of Chronic Obstructive Pulmonary Disease (COPD)

    Institute of Scientific and Technical Information of China (English)

    高光敏; 强丽霞; 王凤爽; 杨梅; 金寿德

    2013-01-01

    目的:观察低分子量肝素对慢性阻塞性肺疾病(COPD)大鼠血浆D-二聚体和气道黏液分泌的影响.方法:将30只Wistar大鼠随机分为正常对照组、COPD模型组、LMWH干预组,每组10只.采用熏吸香烟法加气管内注入脂多糖的方法建立COPD大鼠模型,LMWH干预组于COPD模型建立后皮下注射LMWH,检测各组大鼠血浆D-二聚体水平及气道黏液细胞数的变化.结果:COPD模型组血浆D-二聚体水平及气道黏液细胞数较正常对照组均明显升高(P<0.05),而低分子量肝素治疗组二者较COPD模型组均明显下降(P<0.05).血浆D-二聚体水平与气道黏液细胞数呈显著正相关(r=0.946,P=0.04).结论:低分子量肝素在改善凝血功能的同时可以减少COPD气道黏液分泌,有助于疾病的控制和转归.%Objective: To study the effect of low-molecular-weight-heparin (LMWH) on plasma D-dimer level and airway mucus secretion of COPD rats. Methods: Thirty Wistar rats were randomly divided into the control group, COPD group and LMWH group, ten rats in each group. COPD rat model was established by smoke inhalations and endointracheal instillations of lipopolysaccaride, LMWH was administered to rats 48 hours after the injection of LPS and smoke inhalations. The change of plasma D-dimer level and number of mucous cells were measured and compared between different groups. Results: The plasma D-dimer level and number of mucous cells were significantly higher in COPD group than those in the control group (P<0.05), which were significantly lower in the LMWH treated COPD rats than those in the COPD group. The plasma D-dimer level was positively related to the number of mucous cells in COPD group(r=0.946,P=0.04). Conclusion: LMWH could enhance the blood coagulation and reduce the airway mucus secretion to improve the development of COPD.

  11. 低分子肝素、间歇性气压治疗预防颅脑创伤患者下肢深静脉血栓形成的临床分析%Clinical analysis on the effect of low molecular weight heparin and intermittent pneumatic compression against deep venous thrombosis following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    邓永兵; 肖虹; 胡晞; 刘科

    2013-01-01

    目的探讨低分子肝素、间歇性气压治疗对颅脑创伤患者下肢深静脉血栓( DVT)形成的预防效果。方法回顾分析我科2010年3月~2013年3月682例颅脑创伤患者临床资料。有148例应用低分子肝素( LMWH)药物预防;173例行间歇性气压治疗( IPC)物理预防;169例行LMWH、IPC联合预防;有192例未实施LMWH、IPC预防。下肢深静脉彩超或下肢CTV诊断DVT。结果 LMWH药物预防组,DVT 19例(12.83%); IPC预防组,DVT 23例(13.29%); LMWH、IPC联合预防组,DVT 14例(8.28%);未实施LMWH、IPC预防组,DVT 38例(19.80%)。 LMWH、IPC联合预防组、LMWH预防组、IPC预防组DVT发生率明显低于未实施LMWH、IPC预防组(P<0.05); LMWH、IPC联合预防组DVT发生率明显低于LMWH预防组或IPC物理预防组( P<0.05)。结论 LMWH、IPC对预防颅脑创伤患者下肢深静脉血栓形成有一定的临床疗效,且LMWH、IPC联合预防效果更好。%Objective To explore the efficacy and safety of low molecular -weight heparin ( LMWH) and intermittent pneumatic compression ( IPC) against deep venous thrombosis ( DVT) following traumatic brain injury (TBI).Methods The clinical data of 682 patients with TBI from Mar.2010 to Mar.2013 were analyzed retro-spectively.In those cases,148 cases received LMWH injection,173 cases received IPC prevention,169 cases re-ceived LMWH and IPC ,192 cases did not receive LMWH or IPC prevention .DVT was diagnosed by color duplex ultrasonography or computed tomo-venography(CTV).Results There were 19 cases of DVT (12.83%),23 cases of DVT (13.29%),14 cases of DVT (8.28%) and 38 cases of DVT (19.80%) in the group of LMWH preven-tion,group of IPC prevention,group of LMWH+IPC prevention and group of non-preventive measure,respectively. The incidence of DVT in group 1,2 and 3 was significantly lower than that in group 4 (P<0.05).The incidence of DVT in group 3 was significantly lower

  12. 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.

  13. 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

  14. Dual chain synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  15. Dual chain synthetic heparin-binding growth factor analogs

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  16. Potentiometric sensor for sensitive and selective detection of heparin

    Institute of Scientific and Technical Information of China (English)

    Yan Chen; Rong Ning Liang; Wei Qin

    2012-01-01

    A polymeric membrane ion-selective electrode for determination of heparin is described in this paper,protamine is incorporated into the organic membrane phase and functions as sensing element for selective recognition of heparin.The proposed membrane electrode exhibits high selectivity for heparin over lipophilic anions such as thiocyanide and salicylate.The potentiometric response to the concentration of heparin is linear in the range of 0.01-0.4 U/mL and a lower detection limit of 0.005 U/mL can be achieved.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 78 FR 36786 - Linking Marketplace Heparin Product Attributes and Manufacturing Processes to Bioactivity and...

    Science.gov (United States)

    2013-06-19

    ... Manufacturing Processes to Bioactivity and Immunogenicity AGENCY: Food and Drug Administration, HHS. ACTION... be minimized in heparin manufacturing, leading to safer heparin drugs with better patient outcomes. B...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  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. Release of macromolecules from albumin-heparin microspheres

    NARCIS (Netherlands)

    Kwon, Glen S.; Bae, You Han; Cremers, Harry; Feijen, Jan; Kim, Sung Wan

    1992-01-01

    Hydrophilic microspheres based on albumin-heparin conjugates have been prepared as a macromolecular delivery system. The soluble albumin-heparin conjugate was synthesized and crosslinked in a water-in-oil emulsion with glutaraldehyde to form microspheres in the same manner as for albumin microsphere

  5. [Role of heparin in the formation of food lipemia].

    Science.gov (United States)

    Sokolik, V V; Bozhko, G Kh

    2005-01-01

    Influence of endogenic and exogenic heparin in vivo on the basic forms of serum lipids content: cholesterol ethers, triacylglycerols, free fatty acids; as well as that glycosaminoglycan effect in vivo and in vitro on total lipoproteine lipase (LPL) activity and lecithin-cholesterol acyltransferase (LCAT) activity of human blood serum were investigated on food lipidemia model. The decrease of intercell reserve heparin content and increase of the background and post-heparin levels of blood serum LPL activity were indicated after two hours food load. The role of two factors, endogenic heparin being one of them, in the increase of postprandial LPL activity of blood serum were discussed. At the same time, some inhibition of blood serum LCAT activity two hours after food reception (evidently, as a result of endogenic heparin action) and to a considerable extent inhibition of cholesterol etherification under the action of exogenic heparin in vivo were ascertain. Heparin in vitro (50 U/ml of blood serum) did not influence LCAT and total LPL activities. It was summarised that endogenic heparin is a factor, taking part in lipolysis processes regulation.

  6. Heparin-containing block copolymers, Part I: Surface characterization

    NARCIS (Netherlands)

    Vulić, I.; Pijpers, A.P.; Okano, T.; Kim, S.W.; Feijen, J.

    1993-01-01

    Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly(ethylene oxide) (PEO) and covalently bound heparin (Hep) as bioactive block, were coated on aluminium, glass, polydimethylsiloxane (PDMS), PS or Biomer sub

  7. 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.

  8. 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. 

  9. Heparin-containing block copolymers; Part I: Surface characterization

    NARCIS (Netherlands)

    Vulić, I.; Pijpers, A.P.; Okano, T.; Kim, S.W.; Feijen, Jan

    1993-01-01

    Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly(ethylene oxide) (PEO) and covalently bound heparin (Hep) as bioactive block, were coated on aluminium, glass, polydimethylsiloxane (PDMS), PS or Biomer

  10. 99m Tc-labeled heparin test in orthopaedic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Bouvier, J.F.; Lafon, J.C.; Colin, M.; Chatelut, J.; Beaubatie, F. (Hopital Universitaire Dupuytren, Limoges (France))

    1983-06-30

    99m Tc-labeled heparin test was performed for early detection of phlebitis or pulmonary embolism after orthopaedic prothesis. Heparinic treatment and surgery per se were demonstrated to have no effect on the results. If this test demonstrates a statistical difference for pathologic patients, it is of greater value to consider ratio between rates before and after intervention.

  11. 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

  12. 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.

  13. Heparin modulates the mitogenic activity of fibroblast growth factor by inducing dimerization of its receptor. a 3D view by using NMR.

    Science.gov (United States)

    Nieto, Lidia; Canales, Ángeles; Fernández, Israel S; Santillana, Elena; González-Corrochano, Rocío; Redondo-Horcajo, Mariano; Cañada, F Javier; Nieto, Pedro; Martín-Lomas, Manuel; Giménez-Gallego, Guillermo; Jiménez-Barbero, Jesús

    2013-09-23

    In vitro mitogenesis assays have shown that sulfated glycosaminoglycans (GAGs; heparin and heparan sulfate) cause an enhancement of the mitogenic activity of fibroblast growth factors (FGFs). Herein, we report that the simultaneous presence of FGF and the GAG is not an essential requisite for this event to take place. Indeed, preincubation with heparin (just before FGF addition) of cells lacking heparan sulfate produced an enhancing effect equivalent to that observed when the GAG and the protein are simultaneously added. A first structural characterization of this effect by analytical ultracentrifugation of a soluble preparation of the heparin-binding domain of fibroblast growth factor receptor 2 (FGFR2) and a low molecular weight (3 kDa) heparin showed that the GAG induces dimerization of FGFR2. To derive a high resolution structural picture of this molecular recognition process, the interactions of a soluble heparin-binding domain of FGFR2 with two different homogeneous, synthetic, and mitogenically active sulfated GAGs were analyzed by NMR spectroscopy. These studies, assisted by docking protocols and molecular dynamics simulations, have demonstrated that the interactions of these GAGs with the soluble heparin-binding domain of FGFR induces formation of an FGFR dimer; its architecture is equivalent to that in one of the two distinct crystallographic structures of FGFR in complex with both heparin and FGF1. This preformation of the FGFR dimer (with similar topology to that of the signaling complex) should favor incorporation of the FGF component to form the final assemblage of the signaling complex, without major entropy penalty. This cascade of events is probably at the heart of the observed activating effect of heparin in FGF-driven mitogenesis.

  14. 肝素与低分子肝素治疗ST段抬高性心肌梗死有效性和安全性的Meta分析%Meta-analysis of Effectiveness and Safety of Heparin and Low Molecular Heparin for ST-segment Elevation Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    李小华; 孙毅毅

    2011-01-01

    OBJECTIVE: To evaluate the effectiveness and safety of heparin and low molecular heparin for ST-segment elevation myocardial infarction (STEMI) with evidence-based medicine. METHODS: Clinical controlled trials were retrieved from Cochrane Library, Medline, EMBase, CNKI, CBMdisc. We also searched 8 kinds of Chinese journals by hand, such as Chinese Journal of Cardiology. Randomized controlled trials (RCT) on heparin in the treatment of STEMI were included and analyzed by RevMan 5.0. RESULTS: 8 RCTs involoving 28 179 were included, there was no statistical significance in mortality between low molecular heparin and normal heparin [RR=0.92, 95%CI(0.84, 1.01),P=0.09]. The mortality/nonfatal recurrent MI [RR= 0.81, 95%CI (0.76, 0.88) ,P<0.000 01], recurrent MI [RR=0.66, 95%CI(0.59, 0.74) ,P<0.000 01] of low molecular weight heparin group were lower than normal heparin group. The recirculation [RR=0.84, 95%CI(0.73, 0.97) ,P=0.02] and bleeding rate [RR=1.42,95 % CI (1.21, 1.68), P<0.000 1] of low molecular weight heparin group were higher than normal heparin group. There was statistical significances. CONCLUSION: In effectiveness and safety evaluation of heparin for STEMI, low-molecular weight heparin is prior to normal heparin while the bleeding rate of low-molecular weight heparin group is higher than normal heparin group. Low-molecular weight heparin is suitable for STEMI patients but we should pay attention to the occurrence of severe bleeding.%目的:采用循证医学的方法对肝素治疗ST段抬高性心肌梗死(STEMI)的有效性和安全性进行系统评价.方法:系统检索Cochrane图书馆、Medline、EMBase、CNKI、CBMdisc数据库,手工检索等8种杂志,纳入有关肝素治疗STEMI的随机对照试验(RCT),并采用RevMan 5.0软件进行数据分析.结果:最终纳入8个RCT,28 179例患者.低分子肝素组与普通肝素组比较,病死率[RR=0.92,95%CI(0.84,1.01),P=0.09]无统计学意义,但病死

  15. 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.

  16. 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...

  17. A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation.

    Science.gov (United States)

    Aoki, Nobuo; Matsuda, Tamotsu; Saito, Hidehiko; Takatsuki, Kiyoshi; Okajima, Kenji; Takahashi, Hoyu; Takamatsu, Junki; Asakura, Hidesaku; Ogawa, Nobuya

    2002-06-01

    A randomized prospective double-blind trial was performed to compare the safety and efficacy of human activated protein C (APC) and unfractionated heparin for the treatment of disseminated intravascular coagulation (DIC). One hundred thirty-two patients with DIC were enrolled in this study: 63 patients received APC (12.5 U [2.5 microg]/kg body wt per hour) and 69 patients received heparin (8 U/kg body wt per hour) by intravenous infusion for 6 days. Forty-nine APC-treated patients and 55 heparin-treated patients were evaluated for efficacy, and 52 APC-treated patients and 55 heparin-treated patients were evaluated for safety. The 2 groups were similar with respect to sex, age, body weight, underlying diseases, and coagulation/fibrinolysis parameters before treatment. Aggravation of bleeding was seen after treatment in 8 patients receiving heparin, but in none of the patients receiving APC. The number of patients who showed alleviation of bleeding was significantly higher in the APC group than the heparin group (P = .009). The effects on DIC-related organ dysfunction were not significantly different between the 2 groups. Fibrinogen-fibrin degradation products, D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PIC) were all significantly decreased by treatment in both groups. Fibrinogen, protein C, and antithrombin were significantly increased in the APC group, whereas only protein C was significantly increased in the heparin group. Platelet count in the nonleukemic group was significantly increased in those patients receiving APC but not increased in those patients receiving heparin. Improvement of coagulation/fibrinolysis was assessed by scoring 4 parameters (soluble fibrin monomers, D-dimer, TAT, and PIC), and the results indicated that the APC group showed significantly greater improvement than the heparin group (P = .046). There was, however, no significant difference in the rate of complete recovery from DIC between the 2

  18. 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.

  19. Release of glomerular heparan-/sup 35/SO/sub 4/ proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Klein, D.J.; Oegema, T.R. Jr.; Brown, D.M.

    1989-01-01

    Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli were isolated from normal and streptozocin-induced diabetic rats after in vivo exposure to 35S-labeled sulfate and were treated with heparin in vitro. Heparin treatment released a unique heparan sulfate proteoglycan from glomerular cell surface or extracellular matrix proteoglycan receptors. Another, smaller heparan sulfate proteoglycan was the most abundant proteoglycan released into medium and was released constitutively in medium with or without added heparin. While the two heparin-extracted proteoglycans copurified on anion-exchange and gel-filtration chromatographic columns, they were resolved by composite 0.6% agarose--1.8% polyacrylamide gel electrophoresis. Glomeruli from diabetic rats contained decreased proportions of the heparin-releasable heparan sulfate proteoglycan and more constitutively released heparan sulfate proteoglycan. The apparent molecular weight and intrinsic charge of the heparin-released proteoglycan mixture and the apparent molecular weight and sulfation pattern of their 35S-labeled glycosaminoglycan chains after nitrous acid deaminative cleavage were similar in the two groups. A brief trypsin digestion of heparin-treated glomeruli released proportionately less integral membrane and extracellular matrix 35S-labeled proteoglycans and 35S-labeled glycopeptides from diabetic glomeruli than form control glomeruli. Elution of these 35S-labeled macromolecules from anion-exchange columns and migration in agarose-polyacrylamide gels were similar in the two groups.

  20. Comparison of therapeutic efficacy between fondaparinux and low molecular weight heparin for patients with acute coronary syndrome%磺达肝癸钠和低分子肝素治疗急性冠脉综合征疗效比较

    Institute of Scientific and Technical Information of China (English)

    王琼康; 郭牧; 张云强; 宋昱

    2010-01-01

    Objective To compare the efficacy and safety of fondaparinux with that of low molecular weight heparin (LMWH) in the treatment of acute coronary syndrome (ACS). Methods One hundred and five patients with ACS admitted from November 2009 to August 2010 were randomly divided into two groups. They were all treated with nitrates, β-blockers, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), statins, clopidogrel, enteric-coated aspirin and other basic drugs. On the basis of the above treatment, the fondaparinux group patients (n=50) received hypodermic injection of fondaparinux 2.5 mg, once a day, and the LMWH group patients (n=55) received hypodermic injection of LMWH 0.4 ml, twice a day, the therapeutic course being 3- 8 days of both groups. The therapeutic efficacy, the cardiovascular event and bleeding incidences during 7 days and 30 days of the treatment were observed. Results There was no significant difference between the fondaparinux group and LMWH group in the total effective rate (96.0% vs. 92.7%, P>0.05), also no significant differences were found between the two groups in cardiovascular events (death, acute myocardial infarction and recurrence of myocardial infarction) during 7 days and 30 days (7 days: 4.0% vs. 7.3%, 30 days: 8.0% vs. 10.9%, both P>0.05). There was no major bleeding incident, and the incidence of minor bleeding in fondaparinux group was obviously lower than that in LMWH group (2.0% vs. 32.7%, P<0.01). Conclusion The efficacy of fondaparinux in the treatment of ACS is not inferior to that of LMWH, and adverse events during and after its administration were significantly lower than those in LMWH group, so that fondaparinux treatment for ACS is safe and can be highly recommended.%对比磺达肝癸钠与低分子肝素(LMWH)在治疗急性冠脉综合征(ACS)中的疗效及安全性.方法 选择2009年11月至2010年8月本院确诊的ACS患者105例,按随机原则分为两组,均给予硝酸酯

  1. 自体富血小板血浆联合低分子肝素对吸入性损伤大鼠治疗效果的研究%Experimental study on the therapeutic effects of autologous platelet rich plasma combined with low molecular weight heparin on inhalation pulmonary injury in rats

    Institute of Scientific and Technical Information of China (English)

    罗志军; 陈杏绮; 王和庚; 田举

    2016-01-01

    目的:探讨自体富血小板血浆( PRP )联合低分子肝素( LMWH )治疗吸入性损伤大鼠的治疗效果。方法选取SPF级健康雄性Wistar大鼠48只,随机分为正常组、模型组、单用组、联合组,每组12只,模型组、单用组和联合组均建立烟雾吸入性损伤大鼠模型,模型组、正常组气管内滴入0乔.9%氯化钠溶液,单用组致伤后气管内滴注PRP液、联合组致伤后气管内滴注PRP和LMWH混合液。结果模型组、单用组、联合组的肺组织含水量显著的高于正常组( P <0.05),联合组的肺组织含水量显著的低于模型组和单用组( P <0.05);模型组、单用组、联合组的血清TNF-α、IL-6、IL-1β、PDGF显著高于正常组( P <0.05),联合组的血清TNF-α、IL-6、IL-1β、PDGF显著的低于模型组和单用组( P <0.05);模型组、单用组、联合组的肺组织Brdu免疫组化阳性标记指数显著的高于正常组( P <0.05),联合组的肺组织Brdu免疫组化阳性标记指数显著的高于模型组和单用组( P <0.05)。结论 PRP联合LMWH治疗吸入性损伤大鼠能够显著的减轻肺水肿及炎性反应。%Objective To investigate the therapeutic effects of autologous platelet rich plasma ( PRP) combined with low molecular weight heparin ( LMWH) on inhalation pulmonary injury in rats.Methods Forty-eight healthy rats ( SPF grade) were randomly divided into control group, model group, with 12 rats in each group.The animal models with smoke inhalation pulmonary injury were established in rats of model group, singleu-se group and combination group,and the rats in model group and control group were given 0.9% sodium chloride solution by intratracheal instillation , however,after smoke inhalation pulmonary injury the rats in single-use group were given PRP liquor by intratracheal instillation , but the rats in combinationgroup were given mixed liquor of PRP with

  2. 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

  3. Analysis of crude heparin by (1)H NMR, capillary electrophoresis, and strong-anion-exchange-HPLC for contamination by over sulfated chondroitin sulfate.

    Science.gov (United States)

    Keire, David A; Trehy, Michael L; Reepmeyer, John C; Kolinski, Richard E; Ye, Wei; Dunn, Jamie; Westenberger, Benjamin J; Buhse, Lucinda F

    2010-03-11

    We previously published a strong-anion-exchange-high performance liquid chromatography (SAX-HPLC) method for the detection of the contaminant over sulfated chondroitin sulfate (OSCS) in heparin sodium active pharmaceutical ingredient (API). While APIs have been processed to remove impurities, crude heparins contain insoluble material, chondroitin sulfates, heparan sulfate, and proteins that may interfere with the recovery and measurement of OSCS. We examined 500MHz (1)H NMR, capillary electrophoresis (CE), and SAX-HPLC to quantify OSCS in crude heparin. Using our standard API protocol on OSCS spiked crude heparin samples; we observed a weight percent LOD and LOQ for the NMR approach of 0.1% and 0.3%, respectively, while the SAX-HPLC method gave values of 0.03% and 0.09%, respectively. CE data was not amenable to quantitative measurement of OSCS in crude heparin. We developed a modified HPLC sample preparation protocol using crude dissolved at the 100mg/mL level with a 2.5M NaCl solution. This SAX-HPLC approach gave a weight percent LOD of 0.02% and a LOQ of 0.07% and had better performance characteristics than that of the protocol used for APIs.

  4. Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment

    NARCIS (Netherlands)

    Wang, Xue-Ning; Chen, Chang-Zhi; Yang, Min; Gu, Y. John

    2007-01-01

    Heparin treatment of decellularized xenografts has been reported to reduce graft thrombogenicity. However, little is known about the in vivo comparison of heparin-treated with non-heparin-treated xenografts, especially for small-caliber vascular implants. We implanted either a heparin-treated or a n

  5. 前列腺素 E1联合低分子肝素钙对慢性肺源性心脏病患者肺动脉压和相关生化指标的影响%Effects of PGE1 combined with low - molecular - weight heparin calcium on pulmonary artery pressure and related biochemical indexes in patients with chronic pulmonary heart disease

    Institute of Scientific and Technical Information of China (English)

    倪挺; 刘奇良

    2016-01-01

    目的:探讨前列腺素 E1联合低分子肝素钙对慢性肺源性心脏病患者肺动脉压和相关生化指标的影响。方法选取2013年9月至2015年9月共收治的84例经诊断为慢性肺源性心脏病的患者,按照数字随机分组法将其分为对照组和观察组,每组42例。观察组给予静脉滴注前列腺素 E1和皮下注射低分子肝素钙进行治疗,对照组仅给予静脉滴注静脉滴注前列腺素 E1进行治疗,共1周。测定并比较两组患者肺动脉压、血浆神经递质内皮素(ET)、血栓素 B2(TXB2)、6-酮-前列腺素 Flα(6- K - PGFLα)、总胆红质、天门冬氨酸氨基转移酶和尿素氮的含量。结果经治疗后,观察组患者的肺动脉平均压(MPAP)、肺动脉收缩压(PASP)及肺动脉舒张压(PADP)与显著低于对照组( P ﹤0.05);观察组与对照组患者6- K - PGFLα的含量无显著性差异( P ﹥0.05),观察组患者的血浆 ET、TXB2、总胆红质、天门冬氨酸氨基转移酶和尿素氮含量均低于对照组( P ﹤0.05)。结论前列腺素 E1联合低分子肝素钙的应用可以有效改善慢性肺源性心脏病患者的肺动脉压,对血浆内 ET、TXB2、总胆红质、天门冬氨酸氨基转移酶和尿素氮起到良好的调节作用。%Objective To investigate the effect of PGE1 combined with low molecular weight heparin on pulmonary artery pressure and re-lated biochemical indexes in patients with chronic pulmonary heart disease. Methods 84 patients diagnosed as chronic pulmonary heart disease from September 2013 to September 2015 were divided into the control group and the observation group according to the digital random grouping method,42 cases in each group. The observation group was given intravenous injection of PGE1 and subcutaneous injection of low molecular weight heparin calcium treatment. The control group only received intravenous infusion of PGE1 for treatment. Treatment time

  6. A Heparin Purification Process Removes Spiked Transmissible Spongiform Encephalopathy Agent.

    Science.gov (United States)

    Bett, Cyrus; Grgac, Ksenija; Long, Dianna; Karfunkle, Michael; Keire, David A; Asher, David M; Gregori, Luisa

    2017-01-23

    In 2000, bovine heparin was withdrawn from the US market for fear of contamination with bovine spongiform encephalopathy (BSE) agent, the cause of variant Creutzfeldt-Jakob disease in humans. Thus, US heparin is currently sourced only from pig intestines. Availability of alternative sources of crude heparin, a life-saving drug, would benefit public health. Bovine heparin is an obvious option, but BSE clearance by the bovine heparin manufacturing process should be evaluated. To this end, using hamster 263K scrapie as a surrogate for BSE agent, we applied a four-step bench-scale heparin purification protocol resembling a typical heparin manufacturing process to investigate removal of the spiked scrapie agent. We removed aliquots from each step and analyzed them for residual abnormal prion protein (PrP(TSE)) using a sensitive in vitro method, real-time quaking-induced conversion (RT-QuIC) assay, and for infectivity using animal bioassays. The purification process reduced infectivity by 3.6 log10 and removed PrP(TSE), measured as seeding activity, by 3.4 log10. NaOH treatment was the most effective removal step tested. We also investigated NaOH at different concentrations and pH: the results showed that as much as 5.2 log10 of PrP(TSE) seeding activity was removed at pH 12.5. Thus, changes to the concentration, treatment time, and temperature of alkaline extraction might further improve removal. Our results, using a basic heparin manufacturing process, inform efforts to reintroduce safe bovine heparin in the USA.

  7. Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

    Science.gov (United States)

    Kobayashi, Kyousuke; Takano, Ryo; Takemae, Hitoshi; Sugi, Tatsuki; Ishiwa, Akiko; Gong, Haiyan; Recuenco, Frances C.; Iwanaga, Tatsuya; Horimoto, Taisuke; Akashi, Hiroomi; Kato, Kentaro

    2013-11-01

    Heparin, a sulfated glycoconjugate, reportedly inhibits the blood-stage growth of the malaria parasite Plasmodium falciparum. Elucidation of the inhibitory mechanism is valuable for developing novel invasion-blocking treatments based on heparin. Merozoite surface protein 1 has been reported as a candidate target of heparin; however, to better understand the molecular mechanisms involved, we characterized the molecules that bind to heparin during merozoite invasion. Here, we show that heparin binds only at the apical tip of the merozoite surface and that multiple heparin-binding proteins localize preferentially in the apical organelles. To identify heparin-binding proteins, parasite proteins were fractionated by means of heparin affinity chromatography and subjected to immunoblot analysis with ligand-specific antibodies. All tested members of the Duffy and reticulocyte binding-like families bound to heparin with diverse affinities. These findings suggest that heparin masks the apical surface of merozoites and blocks interaction with the erythrocyte membrane after initial attachment.

  8. 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

  9. Glycol chitosan/heparin immobilized iron oxide nanoparticles with a tumor-targeting characteristic for magnetic resonance imaging.

    Science.gov (United States)

    Yuk, Soon Hong; Oh, Keun Sang; Cho, Sun Hang; Lee, Beom Suk; Kim, Sang Yoon; Kwak, Byung-Kook; Kim, Kwangmeyung; Kwon, Ick Chan

    2011-06-13

    We described the preparation of the glycol chitosan/heparin immobilized iron oxide nanoparticles (composite NPs) as a magnetic resonance imaging agent with a tumor-targeting characteristic. The iron oxide nanoseeds used clinically as a magnetic resonance imaging agent were immobilized into the glycol chitosan/heparin network to form the composite NPs. To induce the ionic interaction between the iron oxide nanoseeds and glycol chitosan, gold was deposited on the surface of iron oxide nanoseeds. After the immobilization of gold-deposited iron oxide NPs into the glycol chitosan network, the NPs were stabilized with heparin based on the ionic interaction between cationic glycol chitosan and anionic heparin. FE-SEM (field emission-scanning electron microscopy) and a particle size analyzer were used to observe the formation of the stabilized composite NPs, and a Jobin-Yvon Ultima-C inductively coupled plasma-atomic emission spectrometer (ICP-AES) was used to measure the contents (%) of formed iron oxide nanoseeds as a function of reaction temperature and formed gold deposited on the iron oxide nanoparticles. We also evaluated the time-dependent excretion profile, in vivo biodistribution, circulation time, and tumor-targeting ability of the composite NPs using a noninvasive NIR fluorescence imaging technology. To observe the MRI contrast characteristic, the composite NPs were injected into the tail veins of tumor-bearing mice to demonstrate their selective tumoral distribution. The MR images were collected with conventional T(2)-weighted spin echo acquisition parameters.

  10. 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.

  11. 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...

  12. Study on Resistance of Human Sperm Chromatin to Heparin Decondensation

    Institute of Scientific and Technical Information of China (English)

    褚劲松; 李建国; 薛同一; 王一飞

    1995-01-01

    Resistance of human sperm chromatin to heparin deeondensatinn was investigated by image analysis. The level of DNA deeondensation was determined by measuring the α, [red fluorescence/(red + green) fluoreseence] of sperm. The optimal experimental conditions were incubating sperms with 1000 IU/ml of heparin at 37℃ for 13 minutes and analysing the sperms with excitation F488, red fluoreseenee F630, green fluoreseence F530. The result showed that 72.93±14.73 percent of 20 fertile human sperms resist heparin deeondensa tion.

  13. Quantitation of heparosan with heparin lyase III and spectrophotometry.

    Science.gov (United States)

    Huang, Haichan; Zhao, Yingying; Lv, Shencong; Zhong, Weihong; Zhang, Fuming; Linhardt, Robert J

    2014-02-15

    Heparosan is Escherichia coli K5 capsule polysaccharide, which is the key precursor for preparing bioengineered heparin. A rapid and effective quantitative method for detecting heparosan is important in the large-scale production of heparosan. Heparin lyase III (Hep III) effectively catalyzes the heparosan depolymerization, forming unsaturated disaccharides that are measurable using a spectrophotometer at 232 nm. We report a new method for the quantitative detection of heparosan with heparin lyase III and spectrophotometry that is safer and more specific than the traditional carbazole assay. In an optimized detection system, heparosan at a minimum concentration of 0.60 g/L in fermentation broth can be detected.

  14. Thermodynamic characteristics of the heparin-leucine-CaCl2 system in a diluted physiological solution

    Science.gov (United States)

    Nikolaeva, L. S.; Belov, G. V.; Rulev, Yu. A.; Semenov, A. N.

    2013-03-01

    Chemical equilibria in aqueous solutions of high-molecular weight heparin (Na4hep) and leucine (HLeu) are calculated through the mathematical modeling of chemical equilibria based on representative experimental pH titration data. In addition, chemical equilibria in the CaCl2-Na4hep-HLeu-H2O-NaCl system in the presence of 0.154M NaCl background electrolyte at a temperature of 37°C in the range of 2.30 ≤ pH ≤ 10.50 and initial concentrations of basic components n × 10-3 M ( n ≤ 4).

  15. Quantitative description of thermodynamic and kinetic properties of the platelet factor 4/heparin bonds

    Science.gov (United States)

    Nguyen, Thi-Huong; Greinacher, Andreas; Delcea, Mihaela

    2015-05-01

    Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly understood. In this study, single molecule force spectroscopy (SMFS) is utilized to characterize the interaction of PF4 with heparins of defined length (5-, 6-, 8-, 12-, and 16-mers). Analysis of the force-distance curves shows that PF4/heparin binding strength rises with increasing heparin length. In addition, two binding pathways in the PF4/short heparins (=8-mers) are identified. We provide a model for the PF4/heparin complexes in which short heparins bind to one PF4 tetramer, while long heparins bind to two PF4 tetramers. We propose that the interaction between long heparins and PF4s is not only due to charge differences as generally assumed, but also due to hydrophobic interaction between two PF4s which are brought close to each other by long heparin. This complicated interaction induces PF4/heparin complexes more stable than other ligand-receptor interactions. Our results also reveal that the boundary between antigenic and non-antigenic heparins is between 8- and 12-mers. These observations are particularly important to understand processes in which PF4-heparin interactions are involved and to develop new heparin-derived drugs.Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly

  16. Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis

    NARCIS (Netherlands)

    Laville, Maurice; Dorval, Marc; Ros, Joan Fort; Fay, Renaud; Cridlig, Joelle; Nortier, Joelle L.; Juillard, Laurent; Debska-Slizien, Alicja; Lorente, Loreto Fernandez; Thibaudin, Damien; Franssen, Casper; Schulz, Michael; Moureau, Frederique; Loughraieb, Nathalie; Rossignol, Patrick

    2014-01-01

    Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-in

  17. Influence of Layer-by-Layer Polyelectrolyte Deposition and EDC/NHS Activated Heparin Immobilization onto Silk Fibroin Fabric

    OpenAIRE

    M. Fazley Elahi; Guoping Guan; Lu Wang; Martin W. King

    2014-01-01

    To enhance the hemocompatibility of silk fibroin fabric as biomedical material, polyelectrolytes architectures have been assembled through the layer-by-layer (LbL) technique on silk fibroin fabric (SFF). In particular, 1.5 and 2.5 bilayer of oppositely charged polyelectrolytes were assembled onto SFF using poly(allylamine hydrochloride) (PAH) as polycationic polymer and poly(acrylic acid) (PAA) as polyanionic polymer with PAH topmost. Low molecular weight heparin (LMWH) activated with 1-ethyl...

  18. Fucans, sulfated polysaccharides extracted from brown seaweeds, inhibit vascular smooth muscle cell proliferation. I. Comparison with heparin for antiproliferative activity, binding and internalization.

    Science.gov (United States)

    Logeart, D; Prigent-Richard, S; Jozefonvicz, J; Letourneur, D

    1997-12-01

    Smooth muscle cell (SMC) proliferation is inhibited both in vivo and in vitro by heparin. However, the precise mechanisms of action are still not understood. The analogy between two sulfated polysaccharides, heparin and fucan, has led us to compare in detail their effects on SMC growth. We have prepared and characterized a 19 kDa fucan fraction from brown seaweed, Ascophyllum nodosum. Fucan affects the growth of SMCs in a time- and dose-dependent, reversible and non-toxic fashion. As determined by cell counting, [3H]thymidine incorporation, and microcytofluorimetry analysis, heparin was less active than fucan in inhibiting SMC growth. Fucan and heparin act by preferential blocking of G0/G1, thus decreasing the G0/S transition. Binding experiments with [125I]fucan indicated saturable, unlabeled-fucan displaceable binding sites with an apparent Kd of 30 nM. Moreover, displacement experiments performed with various polysaccharides revealed that antiproliferative compounds interacted with these membrane sites, but non-antiproliferative polysaccharides (dextran, chondroitin sulfate) did not, providing evidence of a correlation between binding to SMCs and their antiproliferative activity. When cells were exposed at 37 degrees C to a fluorescent 5-([4,6-dichlorotriazin-2-yl]-amino)fluorescein (DTAF)-fucan, internalization occurred and punctate vesicles were observed which accumulated rapidly in the perinuclear region as previously reported for heparin. Nuclear preparations (membranes + contents) of cultured SMCs previously incubated with radiolabeled heparin or fucan indicated the presence of radioactivity, suggesting an antiproliferative action of both polysaccharides at the nuclear level. Collectively, these observations indicated that fucan and heparin share some similar mechanisms of action, such as SMC growth inhibition, binding, and internalization. In the accompanying paper (Logeart et al., Eur. J. Cell Biol. 74, 1997, this issue), we describe the effect of fucans

  19. 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.

  20. 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.

  1. 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

  2. Effect of heparin administration on plasma binding of benzodiazepines.

    OpenAIRE

    1980-01-01

    1 The effect of intravenous administration of 100 units of heparin on plasma of diazepam, chlordiazepoxide, oxazepam and lorazepam was examined in fourteen normal subjects and five patients with cirrhosis. 2 In normal non-fasted subjects heparin caused a rapid 150--250% rise in the free fraction of diazepam, chlordiazepoxide and oxazepam but no change of lorazepam. The changes in free fraction were slightly smaller, but still significant, when the subjects were fasted. 3 These change in free ...

  3. 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 ...

  4. Antifibrotic effect of heparin on liver fibrosis model in rats

    Institute of Scientific and Technical Information of China (English)

    Binita; Shah; Gaurang; Shah

    2012-01-01

    AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.

  5. Anti-angiogenic activity of heparin functionalised cerium oxide nanoparticles.

    Science.gov (United States)

    Lord, Megan S; Tsoi, Bonny; Gunawan, Cindy; Teoh, Wey Yang; Amal, Rose; Whitelock, John M

    2013-11-01

    Cerium oxide nanoparticles (nanoceria) are widely reported to be non-cytotoxic and modulate intracellular reactive oxygen species (ROS). In this study, nanoceria (dxRD = 12 nm) were functionalised with either 130 or 880 molecules of unfractionated heparin using the organosilane linker, 3-aminopropyltriethoxysilane. Nanoceria with a low level of heparin functionalisation were found to scavenge intracellular ROS to the same extent as unfunctionalised nanoceria and significantly more than cells exposed to medium only. In contrast, nanoceria with the highest level of heparin functionalisation were not as effective at scavenging intracellular ROS. Nanoceria were localised predominantly in the cytoplasm, while heparin-nanoceria were localised in both the cytoplasm and lysosomes. Together these data demonstrated that the level of nanoceria surface functionalisation with heparin determined the intracellular localisation and ROS scavenging ability of these particles. Additionally, heparin-nanoceria were effective in reducing endothelial cell proliferation indicating that they may find application in the control of angiogenesis in cancer in the future.

  6. Hemorrhagic bullous dermatosis: a rare heparin-induced cutaneous manifestation.

    Science.gov (United States)

    Govind, Bhuvanesh; Gnass, Esteban; Merli, Geno; Eraso, Luis

    2016-01-01

    Heparin is one of the most widely prescribed medications. Cutaneous reactions distant to the injection site are rare and under-reported in the literature. We present an elderly man with history of CNS lymphoma who underwent treatment of a deep venous thrombosis with enoxaparin and subsequently developed well demarcated bullous lesions within days of heparin initiation. The exact pathophysiology is not well understood. Hemorrhagic bullous dermatosis is a rare cutaneous reaction that is temporally associated with the initiation of heparin products. The handful of cases thus far suggest that regression of these seemingly benign lesions may or may not be associated with dose reduction or discontinuation of heparin products and typically occur within a few weeks. Elderly age appears to be one potential risk factor for development of these rare asymptomatic lesions. Malignancy may have some contributing factor and differentiation between this rare cutaneous manifestation from heparin products and other dermatological findings in patients with malignancy is key. Because of the asymptomatic and self-limiting nature of hemorrhagic bullous dermatoses in the setting of heparin product use, we presume that the reported incidence does not reflect true clinical practice.

  7. 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.

  8. 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

  9. 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.

  10. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia: a case report.

    Science.gov (United States)

    Dickinson, Brian P; Lawrence, Peter F

    2007-01-01

    Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.

  11. Is liquid heparin comparable to dry balanced heparin for blood gas sampling in intensive care unit?

    Directory of Open Access Journals (Sweden)

    Viswas Chhapola

    2014-01-01

    Full Text Available Introduction: Blood gas (BG analysis is required for management of critically ill patients in emergency and intensive care units. BG parameters can be affected by the type of heparin formulations used-liquid heparin (LH or dry balanced heparin (DBH. This study was conducted to determine whether blood gas, electrolyte, and metabolite estimations performed by using DBH and LH are comparable. Materials and Methods: A prospective study was conducted at pediatric intensive care unit (PICU of a tertiary care hospital. Paired venous samples were collected from 35 consecutive children in commercially prepared DBH syringes and custom-prepared LH syringes. Samples were immediately analyzed by blood gas analyzer and compared for pH, pCO 2 , pO 2 , HCO 3 - , Na + , K + , Cl - , and lactate. Paired comparisons were done and agreement was assessed by Bland-Altman difference plots. The 95% limits of absolute agreement (LOA were compared with the specifications for total allowable error (TEa. Results: The P values were significant for all measured parameters, with the exception of pCO 2 and K +. Bland-Altman difference plots showed wide LOA for pCO 2 , pO 2 , HCO3 - , Na + , K + , and Cl - when compared against TEa. For pCO 2 , HCO3 - , Na + , K + , and Cl - , 40%, 23%, 77%, 34%, and 54% of samples were outside the TEa limits, respectively, with LH. Conclusion: Our study showed that there is poor agreement between LH and DBH for the BG parameters pCO2, pO2, HCO3 - , K + , Na + , and Cl - and, thus, are not comparable. But for pH and lactate, LH and DBH can be used interchangeably.

  12. 丹参酮 IIA 磺酸钠联合低分子肝素钙对普外科腹腔镜手术后下肢深静脉血栓形成的预防作用%The prevention of Sodium Tanshine IA combined with low molecular weight heparin calcium on patients with lower extremity deep vein thrombosis after laparoscopic surgery in General Surgery

    Institute of Scientific and Technical Information of China (English)

    丁爱民

    2013-01-01

      目的观察丹参酮 IA 磺酸钠联合低分子肝素钙(LMWH)在普科腹腔镜手术后下肢深静脉血栓(LEDVT)的防治效果.方法126例患者随机平均分为2组,A 组用 LMWH 治疗,B 组用丹参酮 IA 磺酸钠与 LMWH 联合治疗.结果① DVT 的发生率 A 组为4.76%,B 组为1.59%,两者比较有统计学差异(P<0.05);② B组用药后 APTT 和 PT 明显延长,与用药前和 A 组比较差异均有显著性意义(P<0.05).结论丹参酮 IA 磺酸钠结合 LMWH 可有效预防普科腹腔镜手术后 LEDVT 形成.%Abjective] To observe the efficacy of Sodium Tanshine IA combined with low molecular weight heparin calcium (LMWH)on patients with lower extremity deep vein thrombosis(LEDVT) after laparoscopic surgery in general surgery. [Methods] 126 patients are divided into two groups randomly and equaly. In A group, LMWH is used, while in B group, on the basic of the A group, Sodium Tanshine IA is intravenously dripped. [Results] ① the incidence of DVT is different between two groups(P<0.05),A group was 4.76%, B group was 1.59%; ② APTT and PT of B group was significantly prolonged in, compared with before treatment and A group,difference were statisticaly significant(P<0.05). [Conclusions] Sodium Tanshine IA combined with LMWH may be effective in preventing LEDVT after laparoscopic surgery.

  13. 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

  14. 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

  15. 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.

  16. Profiling Heparin-Chemokine Interactions Using Synthetic Tools

    Science.gov (United States)

    de Paz, Jose L.; Moseman, E. Ashley; Noti, Christian; Polito, Laura; von Andrian, Ulrich H.; Seeberger, Peter H.

    2009-01-01

    Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG endothelial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity. PMID:18030990

  17. 普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产疗效的Meta分析%Meta analysis of the efficacy of common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    杨晶晶; 刘帅斌; 胡丽娜

    2015-01-01

    目的:探讨普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产的疗效。方法:采用Cochrane协作网系统评价方法,对有关普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产研究进行质量评价。结果:低分子肝素组的胎儿流产风险是普通肝素组的0.59倍;低分子肝素组治疗复发性流产妇女最终导致其并发症的发生风险是普通肝素组的1.34倍,但差异均无统计学意义(P>0.05)。结论:普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产的临床疗效无差异。%Objective:To investigate the efficacy of common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion.Methods:We adopted the cochrane cooperative network system evaluation method,to do the quality evaluation of the common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion.Results:Low molecular heparin group fetal risk of miscarriage is unfractionated heparin group 0.59 times;low molecular weight heparin group treatment of women with recurrent spontaneous abortion ultimately lead to the complication risk is unfractionated heparin group of 1.34 times,but the difference was not statistically significant (P>0.05).Conclusion:There is no difference between the clinical efficacy of ordinary heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent miscarriage.

  18. Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus

    Directory of Open Access Journals (Sweden)

    Joseph W. Duncumb

    2016-01-01

    Full Text Available Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™ used for administering primary chemotherapy in breast cancer.

  19. Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus

    Science.gov (United States)

    Miyagi, Kana; Forouhi, Parto

    2016-01-01

    Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP) flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™) used for administering primary chemotherapy in breast cancer. PMID:27651974

  20. Effects of bemiparin and heparin on blood pressure, renal and liver function tests and platelet indices of salt-loaded uninephrectomized rats

    Directory of Open Access Journals (Sweden)

    K. Dizaye

    2011-01-01

    Full Text Available Low-molecular-weight Heparins (LMWHs are being preferred to unfractionated Heparin (UFH because of their superior convenience and comparable or slightly better toxicity profile. This study was designed to investigate and compare the effects of LMWH (Bemiparin and Heparin on hemodynamic parameters, liver and renal function tests and platelet indices of salt-loaded uninephrectomized hypertensive rats. The experimental rats divided into two groups. The first group included 18 hypertensive rats. Hypertension induced by unilateral nephrectomy and high NaCl loading with 4% NaCl in diet for 4 weeks. The rat models were subdivided into three groups, each subgroup consists of six rats. The first subgroup served as a positive control. The second subgroup received a daily intraperitoneal (I.P injection (250 unit/kg of Bemiparin for thirty days. The third sub group received daily I.P injection (250 unit/kg of Heparin for thirty days. The second group included six rats underwent sham operated surgery and served as a control group. Blood pressure was recorded in conscious rats by the tail-cuff plethmography method. At the end of the experiments, blood samples were collected from the rats for determination of serum creatinine, blood urea nitrogen, serum total bilirubin, serum sodium, potassium, calcium, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP concentrations and platelet indices. Compared to sham control rats, Systolic blood pressure in uninephrectomized loaded with a high salt was significantly reduced by administration of both Bemiparin and Heparin. Serum K+ and Na+ levels of hypertensive rats were significantly increased. Bemiparin significantly lowered serum K+ and Na+ levels of uninephrectomized rats, while Heparin did not change serum K+ and Na+ levels. The rise in both blood urea and serum creatinine of salt-loaded uninephrectomized hypertensive rats were significantly (P<0.05 reduced by Bemiparin and

  1. Heparin-like synthetic polymers, named RGTAs, mimic biological effects of heparin in vitro.

    Science.gov (United States)

    Rouet, Vincent; Meddahi-Pellé, Anne; Miao, Hua-Quan; Vlodavsky, Israel; Caruelle, Jean-Pierre; Barritault, Denis

    2006-09-15

    A family of biopolymers engineered to protect and stabilize heparin binding growth factors (HBGFs) show remarkable properties as wound healing agents in several in vivo tissue repair models to the extend that damaged tissues would recover almost its initial aspect and properties. These polymers where named RGTA for regenerating agents and proposed to act in vivo by enhancing the bioavailability of HBGFs at the site of the injury. To provide support for this hypothesis, we studied interaction of RGTA with FGF-2, taken as the paradigm of HBGFs, and its high- and low-affinity receptors as well as its ability to inhibit heparanase activity. We show that RGTA is comparable to heparin as it favors FGF-2 binding to FGFR-1 and FGF-2 dimerization and potentiates FGF-2-induced mitogenic activity. Furthermore, we show that RGTA inhibits the release of FGF-2 from its extracellular matrix storage sites by heparanase. Our data provide new evidence to support that RGTA may act in vivo both by enhancing HBGF activity and preserving HBGF availability by protecting the matrix low affinity heparan sulfates from rapid heparanase degradation. 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006.

  2. Ocorrência de hematoma peridural após anestesia geral associada à analgesia pós-operatória com cateter peridural em paciente em uso de heparina de baixo peso molecular: relato de caso Ocurrencia de hematoma postanestesia general asociada a analgesia postoperatoria con cateter peridural en paciente que usa heparina de bajo peso molecular: relato de caso Epidural hematoma after general anesthesia associated with postoperative analgesia with epidural catheter in patient using low molecular weight heparin: case report

    Directory of Open Access Journals (Sweden)

    Ranger Cavalcante da Silva

    2006-04-01

    drenaje del hematoma la paciente recuperó gradualmente la fuerza en los miembros inferiores, recibió alta en diez días con cuadro de disfunción de esfínteres. Después de tres meses el cuadro remitió y no hubo secuela neurológica definitiva. CONCLUSIONES: El rápido diagnóstico con intervención quirúrgica precoz es el tratamiento más eficaz para la reducción de la lesión neurológica, en pacientes que desarrollan hematoma peridural postoperatorio. La utilización de heparina de bajo peso molecular, con uso actual de catéter peridural, exige la adhesión estricta a protocolos establecidos, para que se reduzcan los riesgos del desarrollo de hematoma peridural.BACKGROUND AND OBJECTIVES: Presents a patient case with epidural hematoma, in the course of the use of epidural catheter and low molecular weight heparin, her clinical condition and treatment. CASE REPORT: A 75-year old female patient, submitted to the fixation of lumbar spine by anterior route, who, in the postoperative period, developed a clinical condition of progressive paralysis of the lower limbs, with loss of sensitivity and presenting no intense radicular pain. The treatment was the immediate medullar decompression, with drainage and surgical cleaning of a epidural hematoma, which extended from the 5th to the 10th thoracic vertebrae. After the drainage of the hematoma, the patient gradually recovered the strength in the lower limbs, was discharged in ten days with a condition of sphincterian dysfunction. After three months, the condition receded and there was no definitive neurological sequel. CONCLUSIONS: The quick diagnosis with early surgical intervention is the most effective treatment for the reduction of neurological damage, in patients that develop postoperative epidural hematoma. The use of low molecular weight heparin, in the course of the use of epidural catheter, requires the strict compliance with the established protocols so that the risks of epidural hematoma development can be

  3. Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial

    National Research Council Canada - National Science Library

    Dixon, Barry; Schultz, Marcus J; Smith, Roger; Fink, James B; Santamaria, John D; Campbell, Duncan J

    2010-01-01

    .... Heparin may reduce pulmonary inflammation and fibrin deposition. We therefore assessed whether nebulized heparin improved lung function in patients expected to require prolonged mechanical ventilation...

  4. EFFECT OF HEPARIN ON THE PATENCY OF ARTERIOVENOUS FISTULA

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    H Ravari

    2008-11-01

    Full Text Available "nPatients with end stage renal disease need a good vascular access for hemodialysis. Arteriovenous fistula is the method of choice for vascular access in these patients. However, failure of arteriovenous fistula due to thrombosis is a major problem. The aim of this study was to evaluate the effect of the heparin on the patency of the arteriovenous fistula. This prospective interventional case control study was performed from November 2003 through May 2005 in vascular surgery ward in Imam Reza Hospital. All the patients who underwent a surgery in order to perform an arteriovenous fistula in cubital or snuff box areas for the dialysis means were enrolled. They were randomly divided into two groups. The case group (n = 96 received intraoperative heparin whereas the controls (n = 102 did not. Early observation of arteriovenous fistula (immediately after surgery showed patency in 89% of heparin group and in 87% of the control group. The patency rate 2 weeks after the surgery was 85% in heparin group versus 74% in the control group, resulting in a statistically significant difference (P value = 0.046. According to higher patency rate of arteriovenous fistula in 2 weeks following surgery in case group, we recommend intraoperative use of heparin in arteriovenous fistula operations.

  5. Veno-venous bypass without systemic heparinization using a centrifugal pump: a blind comparison of a heparin bonded circuit versus a non heparin bonded circuit.

    Science.gov (United States)

    van der Hulst, V P; Henny, C P; Moulijn, A C; Engbers, G; ten Cate, H; Gründeman, P F; Klopper, P J

    1989-01-01

    Veno-venous bypass without the use of systemic heparinization has recently become of increasing interest for application during liver transplantation and surgery on the large abdominal veins. However, possible adverse effects on blood components as demonstrated by means of hematologic and hemostatic parameters or on the occurrence of thromboembolic complications are until now not excluded. No consensus has been reached as to the efficacy of heparin coated circuits in those procedures. In the present study veno-venous bypass was performed for four hours in ten dogs using heparin coated and non coated circuits without further heparinization in a randomized blind fashion. No changes or significant intergroup differences were noted in the hematological and coagulation parameters. Macroscopic evaluation of the circuits revealed small strands of fibrin on all connector rims and clots in the center part of the pump head and at the cannula tips. The lungs showed two small emboli in large size pulmonary arteries and also two minor emboli in small size arteries. In four animals the emboli were equally divided between the two groups. As expected regarding the size of the clots no influences could be seen on hemodynamic or respiratory parameters. With Scanning Electronic Microscopy a monolayer of activated thrombocytes was observed on the surface of the bypass circuits in the coated as well as in the uncoated group. This study suggests that a veno-venous bypass without systemic heparinization is possible without serious damage to blood cellular elements or impressive activation of the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Characterisation of the interaction of neuropilin-1 with heparin and a heparan sulfate mimetic library of heparin-derived sugars

    Directory of Open Access Journals (Sweden)

    Katarzyna A. Uniewicz

    2014-06-01

    Full Text Available Background. Neuropilin-1 (NRP-1 is a multidomain membrane protein with soluble isoforms interacting with a complex network of other membrane receptors, their respective ligands and heparan sulfate (HS. It is involved in the development of vasculature, neural patterning, immunological responses and pathological angiogenesis.Methods. We have characterised the binding of a Fc fusion of rat NRP-1 (Fc rNRP-1 and of a soluble isoform, corresponding to the first four extracellular domains of human NRP-1, shNRP-1, using optical biosensor-based binding assays with a library of heparin derivatives. Selective labelling of lysines protected upon heparin binding allowed their identification by mass spectrometry.Results. Fc rNRP-1 bound to heparin with high affinity (2.5 nM and fast ka (9.8 × 106 M−1s−1. Unusually, NRP-1 bound both highly sulfated and completely desulfated stretches of heparin and exhibited a complex pattern of preferences for chemically modified heparins possessing one or two sulfate groups, e.g., it bound heparin with just a 6-O sulfate group better than heparin with any two of N-sulfate, 6-O sulfate and 2-O sulfate. Mass-spectrometry based mapping identified that, in addition to the expected the b1 domain, the a1, and c domains and the L2 linker were also involved in the interaction. In contrast, shNRP-1 bound heparin far more weakly. This could only be shown by affinity chromatography and by differential scanning fluorimetry.Discussion. The results suggest that the interaction of NRP-1 with HS is more complex than anticipated and involving a far greater extent of the protein than just the b1–b2 domains. NRP-1’s preference for binding long saccharide structures suggests it has the potential to bind large segments of HS chains and so organise their local structure. In contrast, the four domain soluble isoform, shNRP-1 binds heparin weakly and so would be expected to diffuse away rapidly from the source cell.

  7. Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus.

    Science.gov (United States)

    Sakurai-Yamashita, Yasuko; Kinugawa, Hidekazu; Niwa, Masami

    2006-11-27

    Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was studied in ischemia-related hippocampal neuronal death and compared with a low molecular weight of heparin, named dalteparin in rats. Transient global ischemia was produced by four vessel-occlusion, the occlusion of the bilateral common carotid arteries following the electrocautherization of the vertebral arteries. 3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after 7min-occlusion/reperfusion. Seven days after the operation, the animals were perfused with 4% paraformaldehyde, and paraffinized coronal brain sections measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal damage was then estimated as a ratio of the number of degenerated neurons to that of both the surviving and degenerated neurons in three distinct area of the CA1 subfield. The ratio of neuronal death increased with the length of the occlusion-time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the neuronal damage induced by 7min-occlusion. These results demonstrated that both PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion-induced damage thus suggesting that they may be potentially useful therapeutic agents for acute ischemic stroke.

  8. How acidic are monomeric structural units of heparin?

    Science.gov (United States)

    Remko, Milan; Broer, Ria; Van Duijnen, Piet Th.

    2013-12-01

    Density functional theory methods with the B3LYP functional have been used to letter the acidity of carboxyl, O-sulfo and N-sulfo groups in six basic monomeric structural units of heparin (1-OMe ΔUA-2S, 1-OMe GlcN-S6S, 1,4-DiOMe GlcA, 1,4-DiOMe GlcN-S3S6S, 1,4-DiOMe IdoA-2S, and 1,4-DiOMe GlcN-S6S). The predicted gas-phase acidity of the acidic functional groups in the monomeric structural units of heparin is: O-sulfo > N-sulfo > carboxyl. The computed pKa values provide the same order of acidity as was observed in water solution. This implies that hydration does not change ordering of acidity of major acidic groups of monomeric structural units of heparin.

  9. Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

    Science.gov (United States)

    Ichikawa, Junko; Mori, Tetsu; Kodaka, Mitsuharu; Nishiyama, Keiko; Ozaki, Makoto; Komori, Makiko

    2017-09-01

    The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

  10. Severe preeclampsia cured by heparin in a patient with twin-twin transfusion syndrome

    Institute of Scientific and Technical Information of China (English)

    CHU Hong-nü; ZHOU Cai-yun

    2007-01-01

    @@ Heparin therapy for preeclampsia has been reported frequently.1-3 Most of the authors used heparin to prevent thrombosis and achieved good results. But its mechanism is not clear.4 Here we describe a case of severe early-onset preeclampsia complicated with hypercoagulable state, fetal growth restriction, and twin-twin transfusion syndrome, that responded well to heparin.

  11. A simple new competition assay for heparin binding in serum applied to multivalent PAMAM dendrimers.

    Science.gov (United States)

    Bromfield, Stephen M; Posocco, Paola; Fermeglia, Maurizio; Pricl, Sabrina; Rodríguez-López, Julián; Smith, David K

    2013-05-25

    We report a competition assay using our recently reported dye Mallard Blue, which allows us to identify synthetic heparin binders in competitive media, including human serum - using this we gain insight into the ability of PAMAM dendrimers to bind heparin, with the interesting result that low-generation G2-PAMAM is the preferred heparin binder.

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

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    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.

  13. Modernization of Enoxaparin Molecular Weight Determination Using Homogeneous Standards

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    Katelyn M. Arnold

    2017-07-01

    Full Text Available Enoxaparin is a low-molecular weight heparin used to treat thrombotic disorders. Following the fatal contamination of the heparin supply chain in 2007–2008, the U.S. Pharmacopeia (USP and U.S. Food and Drug Administration (FDA have worked extensively to modernize the unfractionated heparin and enoxaparin monographs. As a result, the determination of molecular weight (MW has been added to the monograph as a measure to strengthen the quality testing and to increase the protection of the global supply of this life-saving drug. The current USP calibrant materials used for enoxaparin MW determination are composed of a mixture of oligosaccharides; however, they are difficult to reproduce as the calibrants have ill-defined structures due to the heterogeneity of the heparin parent material. To address this issue, we describe a promising approach consisting of a predictive computational model built from a library of chemoenzymatically synthesized heparin oligosaccharides for enoxaparin MW determination. Here, we demonstrate that this test can be performed with greater efficiency by coupling synthetic oligosaccharides with the power of computational modeling. Our approach is expected to improve the MW measurement for enoxaparin.

  14. Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin.

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    Bartlomiej Kalaska

    Full Text Available Protamine, the only registered antidote of unfractionated heparin (UFH, may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3 is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.

  15. Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin.

    Science.gov (United States)

    Kalaska, Bartlomiej; Kaminski, Kamil; Sokolowska, Emilia; Czaplicki, Dominik; Kujdowicz, Monika; Stalinska, Krystyna; Bereta, Joanna; Szczubialka, Krzysztof; Pawlak, Dariusz; Nowakowska, Maria; Mogielnicki, Andrzej

    2015-01-01

    Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.

  16. 自拟抗栓方联合低分子肝素钠预防髋、膝部手术后深静脉血栓形成的临床研究%Clinical study on the self-designed antithrombotic prescription combined with low molecular weight heparin sodium in the prevention of deep vein thrombosis after operations in the hip and the knee

    Institute of Scientific and Technical Information of China (English)

    李可大; 冷重光; 赵江涛; 李忠强; 金冶华; 宫云昭

    2011-01-01

    .988;t=-0.106,P=0.921;t=-0.985,P=0.380).⑥红细胞聚集指数:两组治疗前后不同时间红细胞聚集指数比较,存在时间效应(F=24.763,P=0.000),但不存在分组效应(F=0.424,P=0.550);时间与组别之间存在交互效应(F=35.746,P=0.000);不同时点组间比较,差异均无统计学意义(t=-1.161,P=0.880;t=-1.106,P=0.921;t=-1.966,P=0.121).⑦纤维蛋白原:两组治疗前后不同时间纤维蛋白原比较,存在时间效应(F=12.496,P=0.003),但不存在分组效应(F=0.015,P=0.909);时间与组别之间存在交互效应(F=7.874,P=0.013);不同时点组间比较,差异均无统计学意义(t=-0.032,P=0.976;t=-0.178,P=0.867;t=-0.555,P=0.609).结论:自拟抗栓方联合低分子肝素钠能有效预防髋、膝部手术后深静脉血栓形成,可在临床推广应用.%Objective: To explore the clinical curative effects of the self- designed antithrombotic prescription in the prevention of deep vein thrombosis (DVT) after operations in the hip and the knee. Methods:One hundred and thirty - three patients met the criteria were randomly divided into 2 groups. Sixty - five cases in group Ⅰ , while the others in group Ⅱ. Treatment of preventing thrombus was carried out on that day after the operation. Patients in group Ⅰ were administrated with self - designed antithrombotic prescription combined with low molecular weight heparin sodium,while the others in group Ⅱ were administrated with low molecular weight heparin sodium only. Meanwhile,patients in the 2 groups were routinely given antibiotics to prevent infection and were administrated with functional exercise and rehabilitation therapy. Occurrences of DVT for patients in the 2 groups were recorded in the 8th day after operation, and their blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation indexes, fibrinogen and other blood rheology indexes were measured before the operation, in the 2nd and the 7th day after operation respectively. Results:①Two DVT cases were found

  17. [Automatization of heparin determination using chronometric evaluation of anti-Xa activity of the AT III-heparin complex].

    Science.gov (United States)

    Sampol, J; Rossi, J M; Lejay, G

    1984-01-01

    The authors describe an adaptation on a semi- automatique coagulometer KC 10 of a manual assay of anti-Xa activity of the Heparin-Antithrombin III Complex close to the technique described by Yin and al. ( Hepaclot - Stago ). The results show a good linearity and a good reproducibility, with a better sensitivity than the manuel method. Freezing has no influence. Significant differences were observed between our assay and the manuel anti-IIa assay. These last results neither depend on the administration route nor on the heparin batches.

  18. The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

    Science.gov (United States)

    Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

    2013-11-01

    Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

  19. 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.

  20. Heparin-based nanocapsules as potential drug delivery systems.

    Science.gov (United States)

    Baier, Grit; Winzen, Svenja; Messerschmidt, Claudia; Frank, Daniela; Fichter, Michael; Gehring, Stephan; Mailänder, Volker; Landfester, Katharina

    2015-06-01

    Herein, the synthesis and characterization of heparin-based nanocapsules (NCs) as potential drug delivery systems is described. For the synthesis of the heparin-based NCs, the versatile method of miniemulsion polymerization at the droplets interface was achieved resulting in narrowly distributed NCs with 180 nm in diameter. Scanning and transmission electron microscopy images showed clearly NC morphology. A highly negative charge density for the heparin-based NCs was determined by measuring the electro-kinetic potential. Measuring the activated clotting time demonstrated the biological intactness of the polymeric shell. The ability of heparin-based NCs to bind to antithrombin (AT III) was investigated using isothermal titration calorimetry and dynamic light scattering experiments. The chemical stability of the NCs was studied in physiological protein-containing solutions and also in medically interesting fluids such as sodium chloride 0.9%, Ringer's solution, and phosphate buffer saline using dynamic light scattering and measuring the fluorescence intensity. The impressive uptake of NCs in different cells was confirmed by fluorescence-activated cell sorting, confocal laser scanning microscopy, and transmission electron microscopy. The low toxicity of all types of NCs was demonstrated.

  1. Observational study of need for thrombolytic therapy and incidence of bacteremia using taurolidine-citrate-heparin, taurolidine-citrate and heparin catheter locks in patients treated with hemodialysis.

    Science.gov (United States)

    Solomon, Laurie R; Cheesbrough, John S; Bhargava, Ramya; Mitsides, Nicos; Heap, Michael; Green, Gerwyn; Diggle, Peter

    2012-01-01

    Catheter-related blood stream infections may be reduced by interdialytic locking with Taurolidine, a nontoxic antimicrobial agent. A formulation of 1.35% Taurolidine in 4% citrate (TC) is associated with a greater need for thrombolysis to maintain catheter patency than 5000 U/ml heparin. Our aim was to determine whether addition of 500 Units/ml of heparin to TC reduces the need for thrombolysis. TCH (1.35% taurolidine, 4% citrate and 500 U/ml heparin) was compared to TC and Heparin 5000 U/ml using retrospective data. Hundred and six adult hemodialysis patients with internal jugular tunnelled intravascular catheters using TCH were compared with 34 patients using TC and 34 patients using heparin 5000 U/ml respectively. Outcomes were time to first use of thrombolysis and bacteremia rates.TCH reduced the need for thrombolysis compared to TC (hazard ratio, 0.2; 95%CI: 0.06, 0.5; p < 0.001) and was not significantly different from heparin 5000 U/ml (hazard ratio, 1.4; 95%CI: 0.5, 3.9; p = 0.5). The bacteremia rates from all causes were 1.33, 1.22 and 3.25 per 1000 catheter- days (p < 0.001) in the TCH, TC and heparin groups respectively. Addition of 500 U/ml heparin to TC reduces the need for thrombolysis without increasing bacteremia and may achieve patency comparable to heparin 5000 U/ml.

  2. Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group.

    Science.gov (United States)

    Rossi, P; Bolognese, L

    1991-09-01

    In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar.

  3. 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.

  4. Immobilization of heparin on a silicone surface through a heterobifunctional PEG spacer.

    Science.gov (United States)

    Chen, Hong; Chen, Yang; Sheardown, Heather; Brook, Michael A

    2005-12-01

    A novel method of immobilizing heparin on a silicone surface through a heterobifunctional PEG spacer was used yield well defined surfaces with highly active surface immobilized heparin and low non-specific protein adsorption. The heparin surface density achieved using this technique was 0.68 microg/cm2. Sessile drop water contact angles showed increased hydrophilicity of the silicone surface after PEG modification and a further decrease in the contact angles following the grafting of heparin. High specificity for ATIII with little fibrinogen adsorption was noted in plasma adsorption studies. This ATIII adsorption was mediated by the heparin layer, since surfaces modified with PEG only did not adsorb significant quantities of AT. The thrombin resistance of the heparin modified surfaces was demonstrably greater as measured by a chromogenic thrombin generation assay. The results suggest that the heterbifunctional PEG linker results in a high density of active heparin on the surfaces.

  5. Synthesis and detection of N-sulfonated oversulfated chondroitin sulfate in marketplace heparin.

    Science.gov (United States)

    Mans, Daniel J; Ye, Hongping; Dunn, Jamie D; Kolinski, Richard E; Long, Dianna S; Phatak, Nisarga L; Ghasriani, Houman; Buhse, Lucinda F; Kauffman, John F; Keire, David A

    2015-12-01

    N-sulfonated oversulfated chondroitin sulfate (NS-OSCS), recently reported as a potential threat to the heparin supply, was prepared along with its intermediate derivatives. All compounds were spiked into marketplace heparin and subjected to United States Pharmacopeia (USP) identification assays for heparin (proton nuclear magnetic resonance [(1)H NMR], chromatographic identity, % galactosamine [%GalN], anti-factor IIa potency, and anti-factor Xa/IIa ratio). The U.S. Food and Drug Administration (FDA) strong-anionic exchange high-performance liquid chromatography (SAX-HPLC) method resolved NS-OSCS from heparin and OSCS and had a limit of detection of 0.26% (w/w) NS-OSCS. The %GalN test was sensitive to the presence of NS-OSCS in heparin. Therefore, current USP heparin monograph tests (i.e., SAX-HPLC and %GalN) detect the presence of NS-OSCS in heparin.

  6. Postpartum Osteoporosis and Thoracic Vertebral Fracture in a Patient Treated with Heparin During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ayse Aydemir Ekim

    2016-05-01

    Full Text Available Postpartum osteoporosis (PPO is a rare form of osteoporosis related to pregnancy. We report the case of a 35-year-old woman who consulted for severe low-back pain one week after her delivery. This woman had a personal history of protein C deficiency and was treated with low-molecular-weight heparin (LMWH 40 mg/day during her pregnancy. Her body mass index was 19.8 and she had only gained 8 kg during pregnancy. Magnetic resonance imaging (MRI revealed a fracture of thoracic 11. Dual-energy X-ray absorptiometry (DEXA measured T score = - 4,9 and Z score = -4,8 in Lumbar 1-4 vertebrae. These findings suggest that PPO may be one of the causes of severe back pain in postpartum patients. We think that PPO risk is higher in those patients with low BMI who were treated with LMWH during pregnancy.

  7. Weight Management

    Science.gov (United States)

    ... Anger Weight Management Weight Management Smoking and Weight Healthy Weight Loss Being Comfortable in Your Own Skin Your Weight Loss Expectations & Goals Healthier Lifestyle Healthier Lifestyle Physical Fitness Food & Nutrition Sleep, Stress & Relaxation Emotions & Relationships HealthyYouTXT ...

  8. Efficacy and safety of two unfractionated heparin dosing strategies with tenecteplase in acute myocardial infarction (results from Assessment of the Safety and Efficacy of a New Thrombolytic Regimens 2 and 3).

    NARCIS (Netherlands)

    Curtis, J.P.; Alexander, J.H.; Huang, Y.H.; Wallentin, L.; Verheugt, F.W.A.; Armstrong, P.W.; Krumholz, H.M.; Werf, F. van de; Danays, T.; Cheeks, M.; Granger, C.

    2004-01-01

    We investigated the effect of smaller dose, weight-adjusted heparin with earlier monitoring of activated partial thromboplastin time on the incidence of ischemic and hemorrhagic complications in patients with ST-elevation myocardial infarction treated with full-dose tenecteplase. We compared the out

  9. Heparin-coated circuit during cardiopulmonary bypass. A clinical study using closed circuit, centrifugal pump and reduced heparinization.

    Science.gov (United States)

    Sellevold, O F; Berg, T M; Rein, K A; Levang, O W; Iversen, O J; Bergh, K

    1994-05-01

    A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint-attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin-coated equipment (CBAS) and reduced i.v. heparin (1.5 mg.kg-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg.kg-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ng.ml-1 +/- 1.2 to 27.5 ng.ml-1 +/- 4.8 on day 2 and in the CBAS group from 10.7 ng.ml-1 +/- 1.2 to 35.6 ng.ml-1 +/- 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Development and validation of an ion-exchange chromatography method for heparin and its impurities in heparin products.

    Science.gov (United States)

    Thiangthum, Sumate; Vander Heyden, Yvan; Buchberger, Wolfgang; Viaene, Johan; Prutthiwanasan, Brompoj; Suntornsuk, Leena

    2014-11-01

    An anion-exchange liquid chromatography method for the determination of heparin and its impurities (dermatan sulfate and oversulfated chondroitin sulfate) was developed using chemometric-assisted optimization, including multivariate experimental design and response surface methodology. The separation of heparin, dermatan sulfate, and oversulfated chondroitin sulfate (Rs above 2.0) was achieved on a Dionex RF IC IonPac AS22 column with a gradient elution of 10-70% of 2.5 M sodium chloride and 20 mM Tris phosphate buffer (pH 2.1) at a flow rate of 0.6 mL/min and UV detection at 215 nm. Method validation shows good linearity (r > 0.99), acceptable precision (%relative standard deviations <11.4%) and trueness (%recovery of 92.3-103.9%) for all analytes. The limits of detection for dermatan sulfate and oversulfated chondroitin sulfate are equivalent to 0.11% w/w (10.5 μg/mL) and 0.07% w/w (7.2 μg/mL), while the limits of quantification are 0.32% w/w (31.5 μg/mL) and 0.22% w/w (22.0 μg/mL) relative to heparin, respectively. The method is specific for heparin, dermatan sulfate, and oversulfated chondroitin sulfate without interference from mobile phase and sample matrices and could be used for accurate quantitation the drug and its impurities in a single run. Applications of the method reveal contents of heparin between 90.3 and 97.8%. Dermatan sulfate and oversulfated chondroitin sulfate were not detected in any of the real-life samples.

  11. 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.

  12. Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin.

    Science.gov (United States)

    Pugh, Raymond J; Slee, Joshua B; Farwell, Sara Lynn N; Li, Yaqiu; Barthol, Trista; Patton, Walter A; Lowe-Krentz, Linda J

    2016-03-01

    Vascular cell responses to exogenous heparin have been documented to include decreased vascular smooth muscle cell proliferation following decreased ERK pathway signaling. However, the molecular mechanism(s) by which heparin interacts with cells to induce those responses has remained unclear. Previously characterized monoclonal antibodies that block heparin binding to vascular cells have been found to mimic heparin effects. In this study, those antibodies were employed to isolate a heparin binding protein. MALDI mass spectrometry data provide evidence that the protein isolated is transmembrane protein 184A (TMEM184A). Commercial antibodies against three separate regions of the TMEM184A human protein were used to identify the TMEM184A protein in vascular smooth muscle cells and endothelial cells. A GFP-TMEM184A construct was employed to determine colocalization with heparin after endocytosis. Knockdown of TMEM184A eliminated the physiological responses to heparin, including effects on ERK pathway activity and BrdU incorporation. Isolated GFP-TMEM184A binds heparin, and overexpression results in additional heparin uptake. Together, these data support the identification of TMEM184A as a heparin receptor in vascular cells.

  13. An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.

    Science.gov (United States)

    Min, Soon-Ki; Kwon, Oh-Choon; Lee, Sub; Park, Ki-Hyuk; Kim, Jong-Ki

    2012-05-01

    The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans.

  14. Surface Heparinization of Poly(ether ether ketone)

    Institute of Scientific and Technical Information of China (English)

    SUN Hui; CHEN Rui-chao; LIU Shu; XU Guo-zhi

    2012-01-01

    Photo-grafting of hydrophilic monomer and space arms was used to enhance the hydrophilicity of poly(ether ether ketone)(PEEK) with the aim of extending its application to biological fields.PEEK films were surface modified by UV grafting of acrylic acid(AA) to introduce-COOH on PEEK surface.Adipic amine was used as a.space ann to introduce heparin on PEEK surface based on the condensation reaction between -NH2 and -COOH.The modified PEEK(PEEK-COOH,PEEK-NH2 and PEEK-Hep) was characterized by energy-disperse spectroscopy (EDS),X-ray photoelectron spectroscopy(XPS) and water contact angle measurements,which show that heparin was grafted on PEEK surface.The contact angles of modified PEEK films were lower than those of original films,demonstrating a significant improvement of surface hydrophilicity.

  15. Surface Modification of Polyethylene by Heparin for Improvement of Antithrombogenicity

    Institute of Scientific and Technical Information of China (English)

    ZHAO Guowei; CHEN Yashao; DONG Tao; WANG Xiaoli

    2007-01-01

    The purpose of this paper was to enhance blood compatibility of polyethylene (PE)film.PE film pretreated by argon plasma was subjected to ultraviolet (UV) -induced graft polymerization with Acrylic acid(AAc) (AAc-grafted PE films,PE-g-PAAc) without photo-initiator,then heparin was covalently immobilized on the PE surface (PE-g-HPAAc).The surface properties and microstructure of PE-g-PAAc and PE-g-HPAAc were studied by static contact angle measurement,atomic force microscope (AFM),X-ray photoelectron spectroscopy (XPS) and Attenuated total reflectance Fourier transfer infrared spectroscopy (ATR-FTIR).It was confirmed that AAc and heparin were successfully immobilized onto the surface of PE film.Results of platelet adhesion experiments indicated that the antithrombogenicity of the modified PE film was remarkably improved.

  16. Semi-rigid solution structures of heparin by constrained X-ray scattering modelling: new insight into heparin-protein complexes.

    Science.gov (United States)

    Khan, Sanaullah; Gor, Jayesh; Mulloy, Barbara; Perkins, Stephen J

    2010-01-22

    The anionic polysaccharides heparin and heparan sulphate play essential roles in the regulation of many physiological processes. Heparin is often used as an analogue for heparan sulphate. Despite knowledge of an NMR solution structure and 19 crystal structures of heparin-protein complexes for short heparin fragments, no structures for larger heparin fragments have been reported up to now. Here, we show that solution structures for six purified heparin fragments dp6-dp36 (where dp stands for degree of polymerisation) can be determined by a combination of analytical ultracentrifugation, synchrotron X-ray scattering, and constrained modelling. Analytical ultracentrifugation velocity data for dp6-dp36 showed sedimentation coefficients that increased linearly from 1.09 S to 1.84 S with size. X-ray scattering of dp6-dp36 gave radii of gyration R(G) that ranged from 1.33 nm to 3.12 nm and maximum lengths that ranged from 3.0 nm to 12.3 nm. The higher resolution of X-ray scattering revealed an increased bending of heparin with increased size. Constrained molecular modelling of 5000 randomised heparin conformers resulted in 9-15 best-fit structures for each of dp18, dp24, dp30, and dp36 that indicated flexibility and the presence of short linear segments in mildly bent structures. Comparisons of these solution structures with crystal structures of heparin-protein complexes revealed similar ranges of phi (phi) and psi (psi) angles between iduronate and glucosamine rings. We conclude that heparin in solution has a semi-rigid and extended conformation that is preformed for its optimal binding to protein targets without major conformational changes.

  17. 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...

  18. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    DEFF Research Database (Denmark)

    Bitsch, M; Hermann, G G; Andersen, J P;

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid...... containing either 1.5% glycine with heparin or glycine solution alone. Tumor recurrence was determined by cystoscopy 4 to 6 months later. There were 70 patients evaluated: 38 in the heparin and 32 in the control group, respectively. The recurrence rate (heparin 74%, control 66%) and the median number...... of recurrences (heparin 3, range 1 to 15 and control 3, range 1 to 30) were similar (p greater than 0.05) in the 2 groups of patients. These observations show that low dose heparin administered in the irrigation fluid during transurethral resection does not decrease the recurrence rate of noninvasive (stage Ta...

  19. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia--a case report.

    Science.gov (United States)

    Dickinson, Brian P; De Ugarte, Daniel A; Reil, Todd D; Beseth, Bryce D; Lawrence, Peter F

    2006-01-01

    Heparin use, both prophylactically and therapeutically, is prevalent among hospitalized patients. Patients on heparin may develop a thrombocytopenia that is self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. The authors present a case report of heparin-induced thrombocytopenia in a patient who underwent aortic arch and aortic valve replacement that resulted in bilateral above-knee amputations. The patient developed limb ischemia related to heparin-associated thrombosis, but had a delay in antibody seroconversion. Early and accurate diagnosis of heparin-induced thrombocytopenia requires a high clinical suspicion and may be present despite the absence of serum antibodies.

  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. A quantitative PCR method to quantify ruminant DNA in porcine crude heparin

    OpenAIRE

    Concannon, Sean P.; Wimberley, P. Brett; Workman, Wesley E.

    2010-01-01

    Heparin is a well-known glycosaminoglycan extracted from porcine intestines. Increased vigilance for transmissible spongiform encephalopathy in animal-derived pharmaceuticals requires methods to prevent the introduction of heparin from ruminants into the supply chain. The sensitivity, specificity, and precision of the quantitative polymerase chain reaction (PCR) make it a superior analytical platform for screening heparin raw material for bovine-, ovine-, and caprine-derived material. A quant...

  2. Development and preclinical pharmacokinetics of a novel subcutaneous thermoresponsive system for prolonged delivery of heparin.

    Science.gov (United States)

    Matanović, Maja Radivojša; Grabnar, Pegi Ahlin; Voinovich, Dario; Golob, Samuel; Mijovski, Mojca Božič; Grabnar, Iztok

    2015-12-30

    Heparin is still widely used for treatment and prevention of thromboembolic diseases. Due to specific physicochemical properties, it requires frequent parenteral injections. In this study we present the development and in vitro evaluation of an advanced delivery system for prolonged subcutaneous release of heparin. The delivery system consisted of an in situ forming thermoresponsive poloxamer-based platform combined with pH-responsive polyelectrolyte heparin/chitosan nanocomplexes. Thermoresponsive hydrogels were tested for gelation temperature, gel dissolution and in vitro heparin release, whereas polyelectrolyte nanocomplexes were physico-chemically characterized, as well as tested for in vitro cytotoxicity and in vitro heparin release. Hydrogel combined of two poloxamers demonstrated the highest gelation temperature (28.6°C), while the addition of hydroxypropyl methylcellulose prolonged gel dissolution. On the other hand, nanocomplexes' dispersions, prepared at 1:1 heparin/chitosan mass ratio and in the concentration range 0.375-1.875mg/mL, demonstrated mean diameter 34mV. Pharmacokinetics of selected formulations (thermoresponsive hydrogel, nanocomplexes and a dual system consisting of nanocomplexes incorporated into thermoresponsive hydrogel) were studied in rats. Heparin plasma concentration-time profiles revealed a double-peak phenomenon, probably due to heparin diffusion inside the polymer matrix and gel dissolution. Pharmacokinetic parameters were determined by a non-linear mixed effects modeling approach. It was demonstrated that thermoresponsive hydrogel with heparin/chitosan nanocomplexes enabled the lowest absorption rate of heparin into systemic circulation and provided heparin concentration above the prophylaxis threshold for 5 days. In situ gelling thermoresponsive matrix combined with chitosan nanocomplexes present a promising delivery system for heparin, requiring less frequent administration during long-term treatment.

  3. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    Science.gov (United States)

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-12-16

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active.

  4. 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.

  5. Heparin-like properties of sulfated alginates with defined sequences and sulfation degrees.

    Science.gov (United States)

    Arlov, Øystein; Aachmann, Finn Lillelund; Sundan, Anders; Espevik, Terje; Skjåk-Bræk, Gudmund

    2014-07-14

    Sulfated glycosaminoglycans have a vast range of protein interactions relevant to the development of new biomaterials and pharmaceuticals, but their characterization and application is complicated mainly due to a high structural variability and the relative difficulty to isolate large quantities of structurally homogeneous samples. Functional and versatile analogues of heparin/heparan sulfate can potentially be created from sulfated alginates, which offer structure customizability through targeted enzymatic epimerization and precise tuning of the sulfation degree. Alginates are linear polysaccharides consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G), derived from brown algae and certain bacteria. The M/G ratio and distribution of blocks are critical parameters for the physical properties of alginates and can be modified in vitro using mannuronic-C5-epimerases to introduce sequence patterns not found in nature. Alginates with homogeneous sequences (poly-M, poly-MG, and poly-G) and similar molecular weights were chemically sulfated and structurally characterized by the use of NMR and elemental analysis. These sulfated alginates were shown to bind and displace HGF from the surface of myeloma cells in a manner similar to heparin. We observed dependence on the sulfation degree (DS) as well as variation in efficacy based on the alginate monosaccharide sequence, relating to relative flexibility and charge density in the polysaccharide chains. Co-incubation with human plasma showed complement compatibility of the alginates and lowering of soluble terminal complement complex levels by sulfated alginates. The sulfated polyalternating (poly-MG) alginate proved to be the most reproducible in terms of precise sulfation degrees and showed the greatest relative degree of complement inhibition and HGF interaction, maintaining high activity at low DS values.

  6. A HEPARIN-COATED CIRCUIT REDUCES COMPLEMENT ACTIVATION AND THE RELEASE OF LEUKOCYTE INFLAMMATORY MEDIATORS DURING EXTRACORPOREAL-CIRCULATION IN A RABBIT

    NARCIS (Netherlands)

    PLOTZ, FB; VANOEVEREN, W; HULTQUIST, KA; MILLER, C; BARTLETT, RH; WILDEVUUR, CRH

    1992-01-01

    Heparin coating modifies complement activation during extracorporeal circulation much more effectively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement act

  7. Cellular uptake and activity of heparin functionalised cerium oxide nanoparticles in monocytes.

    Science.gov (United States)

    Ting, S R Simon; Whitelock, John M; Tomic, Romana; Gunawan, Cindy; Teoh, Wey Yang; Amal, Rose; Lord, Megan S

    2013-06-01

    Cerium oxide nanoparticles (nanoceria) are effective in scavenging intracellular reactive oxygen species (ROS). In this study nanoceria synthesized by flame spray pyrolysis (dXRD = 12 nm) were functionalised with heparin via an organosilane linker, 3-aminopropyltriethoxysilane. Nanoceria were functionalised with approximately 130 heparin molecules per nanoparticle as determined by thermo gravimetric analysis. Heparin functionalised nanoceria were more effectively internalised by the human monocyte cell line, U937, and U937 cells that had been activated with phorbol 12 myristate 13-acetate (PMA) than bare nanoceria. The heparin functionalised nanoceria were also more effective in scavenging ROS than nanoceria in both activated and unactivated U937 cells. Heparin coupled nanoceria were found to be biologically active due to their ability to bind fibroblast growth factor 2 and signal through FGF receptor 1. Additionally, the heparin-coupled nanoceria, once internalised by the cells, were found to be degraded by 48 h. Together these data demonstrated that heparin enhanced the biological properties of nanoceria in terms of cellular uptake and ROS scavenging, while the nanoceria themselves were more effective at delivering heparin intracellularly than exposing cells to heparin in solution.

  8. Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

    Science.gov (United States)

    Kuchay, Mohammad Shafi; Farooqui, Khalid J; Bano, Tarannum; Khandelwal, Manoj; Gill, Harmandeep; Mithal, Ambrish

    2017-01-01

    Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

  9. 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.

  10. 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.

  11. Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump.

    Science.gov (United States)

    Campanella, C; Cameron, E; Sinclair, C; Feilberg, V L; Hider, C; Prasad, S; Boulton, F; Lamb, D

    1991-08-01

    To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time.

  12. [Heparin immune thrombocytopenia in a hemodialysis patient. A case report. Literature review].

    Science.gov (United States)

    Benítez, M; González Gómez, I; González Carmelo, I; Palma, A; Cruz, S; Rodríguez, E; Amián, A; Fernández M, F; Merino, M J; Fernández G, F; Suárez, C; Onaindía, J M; González, J

    2007-01-01

    Heparin-induced thrombocytopenia (HIT) is an important side effect of heparin therapy associated with significant morbidity and mortality if unrecognized. The platelet count typically falls below 150,000/ll 5-14 days after heparin is started. Thrombosis is the major clinical complication. We present the case gives a patient that develops a deep vein thrombosis ilio-femoral left, with trombocytopenia, one week after beginning treatment with haemodialysis in which Ac anti heparin is detected by test PaGIA (Particle Gel Inmuno Assay.

  13. From Farm to Pharma: An Overview of Industrial Heparin Manufacturing Methods.

    Science.gov (United States)

    van der Meer, Jan-Ytzen; Kellenbach, Edwin; van den Bos, Leendert J

    2017-06-21

    The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded industrial secrets which are not available to the general (scientific) public. However by reviewing the academic and patent literature, we aim to provide a comprehensive overview of the general methods used in industry for the extraction of heparin from animal tissue.

  14. A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor-like growth factor for maintaining hepatic functions in vitro and harvesting hepatocyte sheets

    Directory of Open Access Journals (Sweden)

    Yoshinori Arisaka

    2016-03-01

    Full Text Available A heparin-modified thermoresponsive surface bound with heparin-binding epidermal growth factor-like growth factor (HB-EGF was designed to allow creation of transferrable and functional hepatocyte sheets. A heparin-modified thermoresponsive surface was prepared by covalently tethering heparin onto poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide-grafted tissue culture polystyrene surfaces (Heparin-IC. HB-EGFs were able to stably bind to heparin-IC via affinity interaction. The survival of primary rat hepatocytes was maintained through HB-EGF-bound heparin-IC (HB-EGF/heparin-IC. Moreover, cultured rat primary hepatocytes on HB-EGF/heparin-IC exhibited higher albumin-secretion than hepatocytes cultured on PIPAAm-grafted and collagen-coated surfaces with soluble HB-EGF in the culture medium, regardless of whether soluble EGF was added. These results suggested that HB-EGF/heparin-IC is able to effectively maintain hepatic function via continuous signaling of HB-EGF. After a 4-day cultivation, the cultured hepatocytes on HB-EGF/heparin-IC detached as a cell sheet with fibronectin and HB-EGF only after the temperature was lowered to 20 °C. In addition, higher expression of hepatocyte-specific genes (albumin, hepatocyte nuclear factor 4 alpha, coagulation factor VII, and coagulation factor IX in hepatocyte sheets was detected on HB-EGF/heparin-IC than on a PIPAAm surface with soluble HB-EGF, indicating that HB-EGF/heparin-IC suppressed the dedifferentiation of cultured hepatocytes. Hence, heparin-modified thermoresponsive surfaces bound with HB-EGF facilitate the fabrication of transferrable hepatocyte sheets with intact hepatic functions and have the potential to provide an in vitro culture system using functional hepatocyte sheet tissues, which may serve as an effective hepatocyte-based tissue engineering platform for liver disease treatments.

  15. Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism.

    Science.gov (United States)

    Shirakawa, Takashi; Nakajima, Katsuyuki; Shimomura, Younosuke; Kobayashi, Junji; Stanhope, Kimber; Havel, Peter; Machida, Tetsuo; Sumino, Hiroyuki; Murakami, Masami

    2015-02-02

    A comparison of post-heparin and pre-heparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) on the metabolism of remnant lipoproteins (RLPs) has not been reported yet. Healthy volunteers were injected with heparin for LPL and HTGL determination in the fasting (8:00) and postprandial (20:00) plasma on the same day. Plasma total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, small dense LDL (sdLDL)-C, remnant lipoprotein (RLP)-C, RLP-TG, the RLP-TG/RLP-C ratio, adiponectin and apoCIII were measured. LPL activity and concentration in the post-heparin plasma exhibited a significant inverse correlation with TG, RLP-C, RLP-TG, and RLP particle size estimated as RLP-TG/RLP-C ratio and sdLDL-C, and positively correlated with HDL-C. HTGL was only inversely correlated with HDL-C. LPL concentration in the pre-heparin plasma was also inversely correlated with the RLP-TG/RLP-C ratio and other lipoprotein parameters. Adiponectin was inversely correlated with RLP-TG/RLP-C ratio and apoC III was positively correlated with RLP-TG/RLP-C ratio, but not correlated with LPL activity. LPL activity and concentration were inversely and significantly correlated with the particle size of RLP in both the post-heparin and pre-heparin plasma. Those results suggest that LPL concentration in pre-heparin plasma can take the place of LPL activity in the post-heparin plasma. Copyright © 2014. Published by Elsevier B.V.

  16. 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.

  17. 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.

  18. Weight Management

    Science.gov (United States)

    ... Health Information Weight Management English English Español Weight Management Obesity is a chronic condition that affects more ... Liver (NASH) Heart Disease & Stroke Sleep Apnea Weight Management Topics About Food Portions Bariatric Surgery for Severe ...

  19. Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia

    OpenAIRE

    Prechel, M Margaret; Walenga, Jeanine M.

    2013-01-01

    Heparin Induced Thrombocytopenia (HIT) is caused by antibodies that recognize platelet factor 4 (PF4) associated with polyanionic glycosaminoglycan drugs or displayed on vascular cell membranes. These antibodies are elicited by multimolecular complexes that can occur when heparin is administered in clinical settings associated with abundant PF4. Heparin binding alters native PF4 and elicits immune recognition and response. While the presence of heparin is integral to immunogenesis, the HIT an...

  20. 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

  1. Does heparin pretreatment affect the haemostatic system during and after cardiopulmonary bypass?

    NARCIS (Netherlands)

    Brinks, H.J.; Weerwind, P.W.; Bogdan, S.; Verbruggen, H.W.; Brouwer, M.H.J.

    2001-01-01

    In this clinical pilot study, the influence of heparin pretreatment on the haemostatic system during and after cardiopulmonary bypass (CPB) was investigated. Thirteen patients scheduled for elective coronary artery bypass grafting (CABG) were divided into two groups: heparin pretreated (HP, n = 6) a

  2. Poly(dimethylsiloxane)-poly(ethyleneoxide)-heparin block copolymers. I. Synthesis and characterization

    NARCIS (Netherlands)

    Grainger, D.W.; Kim, S.W.; Feijen, J.

    1988-01-01

    Amphiphilic block copolymers containing poly(dimethylsiloxane), poly(ethylene oxide), and heparin (PDMS-PEO-Hep) have been prepared via a series of coupling reactions using functionalized prepolymers, diisocyanates, and derivatized heparins. All intermediate steps of the synthesis yield quantifiable

  3. 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

  4. 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

  5. Molecular Spectroscopic Study on the Interaction between Heparin and Neutral Red

    Institute of Scientific and Technical Information of China (English)

    Li ZHANG; Na LI; Feng Lin ZHAO; Ke An LI

    2004-01-01

    The interaction between heparin and neutral red was investigated by molecular spectroscopic methods. The change of all spectra suggested that positively charged neutral red had interacted with negatively charged heparin. The study of influence factors indicated that electrostatic force and hydrophobic bond might be involved in the interaction. The total binding number per disaccharide unit and intrinsic binding constant were obtained using Scatchard model.

  6. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia

    NARCIS (Netherlands)

    Chong, B H; Burgess, J; Ismail, F

    1993-01-01

    The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platel

  7. Poly(vinyl alcohol)-heparin hydrogels as sensor catheter membranes

    NARCIS (Netherlands)

    Brinkman, E.; Does, van der L.; Bantjes, A.

    1991-01-01

    Poly(vinyl alcohol)-heparin hydrogels with varying water content were synthesized for use as sensor catheter membranes. Films were cast from aqueous mixtures of poly(viny) alcohol) (PVA), a photosensitive cross-linker p-diazonium diphenyl amine polymer (PA), glutaraldehyde (GA) and heparin. After dr

  8. Extracellular matrix heparin induces alteration of the cell adhesion during brain development

    NARCIS (Netherlands)

    Ushakova, GA; Nikonenko, IR; Nikonenko, AG; Skibo, GG

    2002-01-01

    The studies of neuronal cell-glycosaminoglycan interactions indicate an increasing interest in the question of how heparin can mediate adhesion properties of the cell. We have found that high levels of both N-CAM concentration and heparin-binding activity were noticed in the early stages of brain fo

  9. Inhibition of surface induced coagulation by preadsorption of albumin-heparin conjugates

    NARCIS (Netherlands)

    Hennink, W.E.; Kim, S.W.; Feijen, J.

    1984-01-01

    Surface coatings of the albumin-heparin conjugates were developed to improve the blood compatibility of polymeric materials. Glass, PVC, Biomer and cellulose acetate were coated with albumin-heparin conjugate and its adsorption and desorption behavior on glass in particular was studied using 3H and

  10. Design of a new type of coating for the controlled release of heparin

    NARCIS (Netherlands)

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

    1997-01-01

    Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and

  11. Bivalirudin is inferior to heparin in preservation of intraoperative autologous blood

    NARCIS (Netherlands)

    Huet, Rolf C. G. Gallandat; Cernak, Vladimir; de Vries, Adrianus J.; Lisman, Ton

    2012-01-01

    Introduction: Bivalirudin is used as an alternative to heparin in cardiac surgery, and may be superior to heparin with regard to platelet function. Bivalirudin however, is prone to cleavage by thrombin resulting in coagulation in areas of stasis. Material and Methods: We compared the preservation of

  12. HEPARINS MODULATE EXTRACELLULAR-MATRIX AND PROTEIN-SYNTHESIS OF CULTURED RAT MESANGIAL CELLS

    NARCIS (Netherlands)

    WOLTHUIS, A; BOES, A; BERDEN, JHM

    Heparins blunt the development of glomerulosclerosis in several disease models in the rat and this protective effect may be related to suppression of glomerular cell proliferation. In this study the direct effect of heparins on another key event in glomerulosclerosis, extracellular matrix (ECM)

  13. Poly(dimethylsiloxane)-poly(ethyleneoxide)-heparin block copolymers. I. Synthesis and characterization

    NARCIS (Netherlands)

    Grainger, D.W.; Kim, S.W.; Feijen, Jan

    1988-01-01

    Amphiphilic block copolymers containing poly(dimethylsiloxane), poly(ethylene oxide), and heparin (PDMS-PEO-Hep) have been prepared via a series of coupling reactions using functionalized prepolymers, diisocyanates, and derivatized heparins. All intermediate steps of the synthesis yield quantifiable

  14. Comprehensive safety analysis of concomitant drotrecogin alfa (activated) and prophylactic heparin use in patients with severe sepsis

    NARCIS (Netherlands)

    M. Levy; M. Levi; M.D. Williams; M. Antonelli; D. Wang; M.A. Mignini

    2009-01-01

    Purpose: The safety of using heparin concomitantly with drotrecogin alfa (activated) {DrotAA} was explored in the XPRESS study. No heparin effect on mortality was observed. Safety results from that study are explored in more detail. Methods: A randomized, double-blind trial of prophylactic heparin v

  15. Molecular docking of heparin oligosaccharides with Hep-II heparin-binding domain of fibronectin reveals an interplay between the different positions of sulfate groups.

    Science.gov (United States)

    Carpentier, Mathieu; Denys, Agnès; Allain, Fabrice; Vergoten, Gérard

    2014-02-01

    Fibronectin is a major component of the extracellular matrix and serves as support for cell adhesion and migration. Heparin and heparan sulfates (HS) have been reported to be high-affinity ligands for fibronectin. The strongest heparin/HS-binding site, named Hep-II, is located in the C-terminal repeat units FN12-14 of fibronectin. Mutational studies of recombinant fibronectin fragments and elucidation of the X-ray crystallographic structure of Hep-II in complex with heparin allowed localizing the main heparin/HS-binding site in FN13 to two parallel amino acid clusters: R1697, R1698, R1700 and R1714, R1716, R1745. Heparin, which is more sulfated than HS, is a better ligand for fibronectin, indicating that the sulfate density is important for the interactions. However, other studies demonstrated that the position of sulfate groups is also critical for high-affinity binding of the polysaccharides to fibronectin. In the current work, we used molecular docking of Hep-II domain of fibronectin with a series of differently sulfated dodecasaccharides of heparin to determine the implication of each sulfate position in the interaction. By using this approach, we confirmed the implication of R1697, R1698, R1700 and R1714 and we identified other amino acids possibly involved in the interaction. We also confirmed a hierarchic involvement of sulfate position as follows: 2S > 6S > NS. Interestingly, the formation of stable complexes required a mutual adaptation between Hep-II domain and oligosaccharides, which was different according to the pattern of sulfation. Finally, we demonstrated that 3-O-sulfation of heparin stabilized even more the complex with Hep-II by creating new molecular interactions. Collectively, our models point out the complexity of the molecular interactions between heparin/HS and fibronectin.

  16. HEPARIN OR 0.9% SODIUM CHLORIDE TO MAINTAIN CENTRAL VENOUS CATHETER PATENCY: A RANDOMISED TRIAL

    Directory of Open Access Journals (Sweden)

    Mahesh Babu

    2014-01-01

    Full Text Available BACKGROUND: Maintaining the lumen patency of Central venous catheters (CVCsusing low dose Heparin is recommended in many guidelines of CVC maintenance. This study is to compare the efficacy of low - dose Heparin 3ml (10U/ml and 0.9% Sodium chloride (10ml flush solutions to maintain Centra l venous catheter (CVC lumen patency. METHODS: We s tudied 100 adult patients between March 2012 and August 2012 who required short - term CVC insertion to compare two flush solutions , Heparin and0.9% Sodium Chloride on catheter lumen patency . RESULTS : The crude catheter non patency was 4% ( two lumensin Heparin group and 8% (four lumens in the Sodium Chloride group . There was no incidence of thrombocytopenia in both the study groups. CONCLUSION : This study has demonstrated no significant difference bet ween Heparin and 0.9% Sodium Chloride flushes with regards to catheter patency in adult patients with short - term use of CVCs .

  17. 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.

  18. Understanding Dermatan Sulfate-Heparin Cofactor II Interaction through Virtual Library Screening.

    Science.gov (United States)

    Raghuraman, Arjun; Mosier, Philip D; Desai, Umesh R

    2010-09-09

    Dermatan sulfate, an important member of the glycosaminoglycan family, interacts with heparin cofactor II, a member of the serpin family of proteins, to modulate antithrombotic response. Yet, the nature of this interaction remains poorly understood at a molecular level. We report the genetic algorithm-based combinatorial virtual libra