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Sample records for antithrombins

  1. Antithrombin deficiency in pregnancy.

    Science.gov (United States)

    Durai, Shivani; Tan, Lay Kok; Lim, Serene

    2016-01-01

    We present a case of a 39-year-old, gravida 3 para 2, Chinese female with a history of inherited type 1 Antithrombin deficiency and multiple prior episodes of venous thromboembolism. She presented at 29+4 weeks' gestation with severe pre-eclampsia complicated by haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. She subsequently underwent an emergency caesarean section for non-reassuring fetal status, which was complicated by postpartum haemorrhage secondary to uterine atony, requiring a B-Lynch suture intraoperatively. PMID:27207982

  2. Antithrombin Dublin (p.Val30Glu)

    DEFF Research Database (Denmark)

    Navarro-Fernandez, José; de la Morena-Barrio, María Eugenia; Padilla, José; Miñano, Antonia; Bohdan, Nataliya; Águila, Sonia; Martínez-Martínez, Irene; Sevivas, Teresa S; de Cos, Carmen; Fernández-Mosteirín, Nuria; Llamas, Pilar; Asenjo, Susana; Medina, Pilar; Souto, Juan Carlos; Overvad, Kim; Kristensen, Søren R; Corral, Javier; Vicente, Vicente

    2016-01-01

    The key haemostatic role of antithrombin and the risk of thrombosis associated with its deficiency support that the low incidence of antithrombin deficiency among patients with thrombosis might be explained by underestimation of this disorder. It was our aim to identify mutations in SERPINC1 caus...

  3. Antithrombin, an Important Inhibitor in Blood Clots.

    Science.gov (United States)

    Zhu, Ying; Cong, Qing-Wei; Liu, Yue; Wan, Chun-Ling; Yu, Tao; He, Guang; He, Lin; Cai, Lei; Chou, Kuo-Chen

    2016-01-01

    Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin. PMID:26411319

  4. Generation of Humanized Mouse Models with Focus on Antithrombin Deficiency

    DEFF Research Database (Denmark)

    Jensen, Astrid Bøgh

    2015-01-01

    Antithrombin is one of the major inhibitors of the coagulation cascade. Antithrombin deficiency in humans significantly increases the risk of thrombosis. Mice homozygous for an antithrombin knock out die at day 16.5 of gestation, due to disseminated intravascular coagulation and organ failure. I ...

  5. Neuraxial anesthesia for labor and cesarean delivery in a parturient with hereditary antithrombin deficiency on recombinant human antithrombin infusion therapy.

    Science.gov (United States)

    Pamnani, Anup; Rosenstein, Megan; Darwich, Alaeldin; Wolfson, Alexander

    2010-09-01

    A recombinant human antithrombin (rhAT; generic name: antithrombin Alfa) has recently been developed. A 37 year-old parturient with hereditary antithrombin deficiency, receiving rhAT infusion therapy, who successfully received an epidural catheter for analgesia and anesthesia during labor and cesarean delivery, is presented. PMID:20868967

  6. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Afshari, Arash; Wetterslev, Jørn; Brok, Jesper Sune;

    2008-01-01

    Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ...

  7. Antithrombin III Basel. Identification of a Pro-Leu substitution in a hereditary abnormal antithrombin with impaired heparin cofactor activity.

    Science.gov (United States)

    Chang, J Y; Tran, T H

    1986-01-25

    Antithrombin III Basel is a hereditary abnormal antithrombin with normal progressive inhibition activity (normal reactive site) and reduced heparin cofactor activity (impaired heparin binding site). Structures of antithrombin III Basel and normal antithrombin III isolated from the same patient were compared by peptide mapping using the dimethylaminoazobenzene isothiocyanate precolumn derivatization technique. Of the approximately 50 tryptic peptides of normal and abnormal antithrombin III, one peptide comprising residues 40-46 had a different retention time in reversed-phase high performance liquid chromatography. The amino acid sequence of the peptide from antithrombin III Basel had a single substitution of Pro (normal) by Leu (abnormal) at position 41. This substitution is close to an Arg (residue 47) and a Trp (residue 49) which have previously been shown to be critical for heparin binding by antithrombin III. Although additional amino acid substitutions in antithrombin III Basel cannot be ruled out, this Pro-Leu replacement could cause a conformational change by increasing both the helical structure and the hydrophobicity around residue 41. These data suggest that: (i) the heparin binding site of antithrombin III encompasses the region containing residues 41, 47, and 49; and (ii) the impaired heparin cofactor activity of antithrombin III Basel is likely due to a conformational change of the heparin binding site induced by the Pro-Leu substitution at position 41. PMID:3080419

  8. 21 CFR 864.7060 - Antithrombin III assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antithrombin III assay. 864.7060 Section 864.7060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... assay. (a) Identification. An antithrombin III assay is a device that is used to determine the...

  9. Sulfated cellulose thin films with antithrombin affinity

    Directory of Open Access Journals (Sweden)

    2009-11-01

    Full Text Available Cellulose thin films were chemically modified by in situ sulfation to produce surfaces with anticoagulant characteristics. Two celluloses differing in their degree of polymerization (DP: CEL I (DP 215–240 and CEL II (DP 1300–1400 were tethered to maleic anhydride copolymer (MA layers and subsequently exposed to SO3•NMe3 solutions at elevated temperature. The impact of the resulting sulfation on the physicochemical properties of the cellulose films was investigated with respect to film thickness, atomic composition, wettability and roughness. The sulfation was optimized to gain a maximal surface concentration of sulfate groups. The scavenging of antithrombin (AT by the surfaces was determined to conclude on their potential anticoagulant properties.

  10. Antithrombin in the treatment of burn trauma.

    Science.gov (United States)

    Kowal-Vern, Areta; Orkin, Bruce A

    2016-02-01

    Antithrombin (AT) is a natural anticoagulant with anti-inflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma. PMID:26855890

  11. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B;

    2016-01-01

    BACKGROUND: Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in......, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple...... organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was -2.18 (95% Cl -4.36 to -0...

  12. Magnetic particles as affinity matrix for purification of antithrombin

    Science.gov (United States)

    Mercês, A. A. D.; Maciel, J. C.; Carvalho Júnior, L. B.

    2015-11-01

    Immobilization of biomolecules onto insoluble supports is an important tool for the fabrication of a diverse range of functional materials. It provides advantages: enhanced stability and easy separation. In this work two different magnetic composites were synthesized (MAG-PANI-HS and mDAC-HS) to human antithrombin purification. The magnetic particles (MAG) were obtained by co-precipitation method of iron salts II and III and subsequently coated with polyaniline (MAG-PANI particles). Dacron (polyethylene terephthalate) suffered a hydrazinolysis reaction to obtain a powder (Dacron hydrazide) which was subsequently magnetized (mDAC particles) also by co-precipitation method. Heparan sulfate (HS) was immobilized to MAG-PANI and mDAC retained respectively 35μg and 38.6μg per of support. The magnetic composite containing HS immobilized (MAG-PANI-HS and mDAC-HS) was incubated with human blood plasma (1mL) and then washed with NaCl gradients. Electrophoresis of proteins present in eluates showed bands of antithrombin (58kDa). A reduction in the antithrombin activity was detected in plasma that were incubated in the composites magnetic with HS immobilized, suggesting that the antithrombin was removed of the human blood plasma and then purified. Therefore, the above results suggest that both preparations: MAG-PANI-HS and mDAC-HS are able to affinity purify antithrombin, an important component of blood coagulation.

  13. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B.;

    2016-01-01

    PURPOSE: Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. METHODS: We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized cont...

  14. Use of recombinant human antithrombin concentrate in pregnancy

    Directory of Open Access Journals (Sweden)

    Baumann Kreuziger LM

    2013-09-01

    Full Text Available Lisa M Baumann Kreuziger,1 Tracy L Prosen,2 Mark T Reding1 1Division of Hematology, Oncology, and Transplantation, University of Minnesota, MN, USA; 2Obstetrics and Gynecology, Maternal Fetal Medicine Center, University of Minnesota, MN, USAWe read with great interest James et al’s article "Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency." The authors reported a case series of six women with antithrombin (AT deficiency treated with plasma derived antithrombin concentrate (pdAT; Thrombate III®, Grifols Therapeutics, Clayton, NC, USA.1 In contrast to these cases, we have managed three AT-deficient women over the past two years with low-molecular-weight-heparin during pregnancy and recombinant human antithrombin concentrate (rhAT; ATryn®, GTC Biotherapeutics, Framingham, MA, USA at delivery. In the Phase III trial leading to approval of rhAT, pregnant women required frequent dose modifications, and an alternate dosing regimen is currently recommended by the manufacturer.2,3 The detailed information provided in these cases may assist future providers in managing pregnant patients with AT deficiency.View original paper by James and colleagues.

  15. Inherited antithrombin deficiency and anabolic steroids: a risky combination.

    Science.gov (United States)

    Choe, Hannah; Elfil, Mohamed; DeSancho, Maria T

    2016-09-01

    A 20-year-old male with asymptomatic inherited type 1 antithrombin deficiency and a family history of thrombosis started injecting himself with testosterone 250 mg intramuscularly twice weekly for 5 weeks. He presented to the hospital with progressive dyspnea on exertion, chest pain and hemoptysis. Workup revealed bilateral submassive pulmonary embolism and proximal right lower extremity deep vein thrombosis. He was treated with intravenous (IV) unfractionated heparin and underwent catheter-directed thrombolysis with alteplase to the main pulmonary arteries. Postprocedure, he remained on IV alteplase infusion for 24 h and unfractionated heparin in the intensive care unit. Concomitantly he received plasma-derived antithrombin concentrate. He was transitioned to subcutaneous enoxaparin twice daily and discharged from the hospital on oral rivaroxaban 15 mg twice a day. This case highlights the heightened thrombogenic effect of anabolic steroids in the setting of underlying thrombophilia especially in younger subjects. PMID:26588446

  16. Interaction of antithrombin III with preadsorbed albumin-heparin conjugates

    OpenAIRE

    Hennink, W.E.; Ebert, C.D.; Kim, S. W.; Breemhaar, W.; Bantjes, A.; Feijen, J.

    1984-01-01

    The adsorption of antithrombin III (AT III) onto polystyrene surfaces preadsorbed with albumin or albuminheparin conjugates was studied using a two step enzyme immuno assay. When AT III-buffer solutions were used, the highest adsorption values were measured on high affinity albumin-heparin conjugate pretreated surfaces. Less AT III adsorption was found on nonfractionated albumin-heparin conjugate preadsorbed surfaces. AT III adsorption could also be detected on low affinity conjugate and albu...

  17. Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase

    Science.gov (United States)

    Luengo-Gil, Ginés; Calvo, María Inmaculada; Martín-Villar, Ester; Águila, Sonia; Bohdan, Nataliya; Antón, Ana I.; Espín, Salvador; Ayala de la Peña, Francisco; Vicente, Vicente; Corral, Javier; Quintanilla, Miguel; Martínez-Martínez, Irene

    2016-01-01

    Antithrombin is a key inhibitor of the coagulation cascade, but it may also function as an anti-inflammatory, anti-angiogenic, anti-viral and anti-apoptotic protein. Here, we report a novel function of antithrombin as a modulator of tumor cell migration and invasion. Antithrombin inhibited enteropeptidase on the membrane surface of HT-29, A549 and U-87 MG cells. The inhibitory process required the activation of antithrombin by heparin, and the reactive center loop and the heparin binding domain were essential. Surprisingly, antithrombin non-covalently inhibited enteropeptidase, revealing a novel mechanism of inhibition for this serpin. Moreover, as a consequence of this inhibition, antithrombin was cleaved, resulting in a molecule with anti-angiogenic properties that reduced vessel-like formation of endothelial cells. The addition of antithrombin and heparin to U-87 MG and A549 cells reduced motility in wound healing assays, inhibited the invasion in transwell assays and the degradation of a gelatin matrix mediated by invadopodia. These processes were controlled by enteropeptidase, as demonstrated by RNA interference experiments. Carcinoma cell xenografts in nude mice showed in vivo co-localization of enteropeptidase and antithrombin. Finally, treatment with heparin reduced experimental metastasis induced by HT29 cells in vivo. In conclusion, the inhibition of enteropeptidase by antithrombin may have a double anti-tumor effect through inhibiting a protease involved in metastasis and generating an anti-angiogenic molecule. PMID:27270881

  18. Discordant diagnoses obtained by different approaches in antithrombin mutation analysis

    DEFF Research Database (Denmark)

    Feddersen, Søren; Nybo, Mads

    OBJECTIVES: In hereditary antithrombin (AT) deficiency it is important to determine the underlying mutation since the future risk of thromboembolism varies considerably between mutations. DNA investigations are in general thought of as flawless and irrevocable, but the diagnostic approach can be...... critical. We therefore investigated mutation results in the AT gene, SERPINC1, with two different approaches. DESIGN AND METHODS: Sixteen patients referred to the Centre for Thrombosis and Haemostasis, Odense University Hospital, with biochemical indications of AT deficiency, but with a negative denaturing...... high-performance liquid chromatography (DHPLC) mutation screening (routine approach until recently) were included. As an alternative mutation analysis, direct sequencing of all exons and exon-intron boundaries without pre-selection by DHPLC was performed. RESULTS: Out of sixteen patients with a...

  19. Antithrombin gene Arg197Stop mutation-associated venous sinus thrombosis in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    Ang Li; Dexin Wang; Qiming Xue; Baoen Wang; Tianhui Liu; Zhandong Liu; Jimei Li; Chunling Zhang; Jun Chen; Jinmei Sun; YanfeiHan; Lili Wang

    2011-01-01

    This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed,leading to an arginine (CGA) to stop codon (TGA) change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.

  20. Antithrombin can modulate coagulation, cytokine production, and expression of adhesion molecules in abdominal aortic aneurysm repair surgery.

    Science.gov (United States)

    Nishiyama, Tomoki

    2006-04-01

    We investigated the effects of antithrombin on coagulation, fibrinolysis, and production of cytokines and adhesion molecules in abdominal aortic aneurysm repair surgery. Sixteen patients for Y-shaped graft replacement of abdominal aortic aneurysm were divided into an antithrombin group and a control group. In the antithrombin group, 3000 U antithrombin was infused over 30 min before heparin administration and 24 h later. White blood cell counts, platelet counts, prothrombin time ratio, and serum concentrations of antithrombin, polymorphonuclear leukocyte elastase, interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and adhesion molecules, and variables of coagulation and fibrinolysis were measured before surgery, at the end of surgery, and 1 and 2 days after surgery. The antithrombin concentration decreased in the control group, whereas it increased in the antithrombin group with significant differences between the groups. Prothrombin time ratio, concentrations of d-dimer, thrombin-antithrombin complex, and intercellular adhesion molecule-1 increased only in the control group and polymorphonuclear leukocyte elastase, IL-6, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1 increased in both groups. They were significantly less in the antithrombin group except for intercellular adhesion molecule-1. In conclusion, antithrombin could decrease hypercoagulation and inflammatory activation during abdominal aortic aneurysm surgery, which may decrease adverse events. PMID:16551889

  1. Activation of antithrombin III isoforms by heparan sulphate glycosaminoglycans and other sulphated polysaccharides.

    Science.gov (United States)

    Carlson, T H; Kolman, M R; Piepkorn, M

    1995-07-01

    Antithrombin III occurs naturally as two functionally distinct molecular species that differ in glycosylation at Asn135. Whereas the predominant, glycosylated isoform has high affinity for heparin, a quantitatively minor isoform lacking glycosylation at that site displays relatively higher affinity for both heparins and heparinoids. We characterized the ability of various sulphated polysaccharides to potentiate the rates of thrombin inhibition by the isoforms. High-molecular-weight dextran sulphate was the most effective of those studied, increasing thrombin inhibition by the higher-affinity antithrombin III isoform up to five-fold more efficiently than did heparin fractions with low-affinity for antithrombin III. In addition, dextran sulphate activated the higher-affinity isoform as much as twelve times more effectively than it did the lower-affinity isoform. Pentosan polysulphate was up to three-fold, and some heparan sulphate fractions up to two-fold, more effective with the higher, compared with the lower affinity, isoform. Heparan sulphate preparations less effectively increased the rate of thrombin inhibition than did the other low-affinity polysaccharides. Structure-function studies indicated positive correlations between activity and both polymer length and anionic group density of low-affinity sulphated polysaccharides. The observed effects of the heparan sulphates on this anticoagulant pathway, although of low potency, are consistent with the hypotheses that these substances naturally regulate blood homeostasis in vascular tissues and that much of this function may be mediated by the higher-affinity antithrombin III isoform. PMID:8589216

  2. Anticoagulant and anti-inflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis

    NARCIS (Netherlands)

    S.Q. van Veen; C.W. Cheung; J.C.M. Meijers; T.M. van Gulik; M.A. Boermeester

    2006-01-01

    Background: In sepsis, coagulation inhibition using high-dose systemic antithrombin (AT) tends to improve survival. However, systemic AT use is complicated by increased risk of bleeding (odds ratio 1,7) and clinically important survival increase is seen only in the non-heparinized subgroup. Local (i

  3. Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats

    NARCIS (Netherlands)

    Choi, Goda; Hofstra, Jorrit-Jan H; Roelofs, Joris J T H; Rijneveld, Anita W; Bresser, Paul; van der Zee, Jaring S; Florquin, Sandrine; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

    2008-01-01

    OBJECTIVE: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We

  4. Regions flanking exon 1 regulate constitutive expression of the human antithrombin gene.

    Science.gov (United States)

    Fernandez-Rachubinski, F A; Weiner, J H; Blajchman, M A

    1996-11-15

    We have identified cis-acting elements and trans-acting factors that regulate constitutive expression of the human antithrombin gene. The activity of the sequences flanking the first exon of the gene was investigated using a luciferase-based reporter assay in transiently transfected HepG2, COS1, BSC40, and HeLa cells. Deletion analysis allowed the mapping of two elements able to promote antithrombin gene transcription in HepG2 and COS1 cells. The first element is located upstream of the first exon (-150/+68 nucleotides). The second element is in the first intervening sequence (+300/+700 nucleotides) and functions in an orientation opposite to that of the first. Footprint analysis showed three protected areas in the 5' upstream element at -92/-68 (element A), -14/+37 (element B), and -126/-100 nucleotides (element C). These elements acted as enhancers in luciferase reporter assays. Gel retardation analysis demonstrated that two liver-enriched transcription factors, hepatocyte nuclear factor 4 (HNF4) and CCAAT enhancer-binding protein (C/EBPa), bound to the 5' upstream element. HNF4 bound to elements A and C, whereas C/EBPa bound to element B. Element A also interacted with the ubiquitous nuclear hormone receptors chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), thyroid hormone receptor alpha (TRalpha), peroxisome proliferator-activated receptor alpha(PPARalpha), and retinoid X receptor alpha (RXRalpha). In HepG2 and BSC40 cells, HNF4, C/EBPalpha, and RXRalpha activated luciferase expression from a reporter construct containing the 5'-upstream minimal antithrombin gene promoter, while COUP-TF1, TRalpha, and HNF3 (alpha or beta) repressed such expression. Our results show that constitutive expression of the human antithrombin gene depends in part upon the interplay of these transcription factors and suggest that signaling pathways regulated by these factors can modulate antithrombin gene transcription. PMID:8910619

  5. Antithrombin significantly influences platelet adhesion onto immobilized fibrinogen in an in-vitro system simulating low flow

    Directory of Open Access Journals (Sweden)

    Scharf Rüdiger E

    2006-10-01

    Full Text Available Abstract Background Adhesion of platelets onto immobilized fibrinogen is of importance in initiation and development of thrombosis. According to a recent increase in evidence of a multiple biological property of antithrombin, we evaluated the influence of antithrombin on platelet adhesion onto immobilized fibrinogen using an in-vitro flow system. Methods Platelets in anticoagulated whole blood (29 healthy blood donors were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 13 s-1 to 1500 s-1. Platelet adhesion onto fibrinogen-coated slips was assessed using a fluorescence laser-scan microscope and compared to the plasma antithrombin activity. Additionally the effect of supraphysiological AT supplementation on platelets adhesion rate was evaluated. Results Within a first minute of perfusion, an inverse correlation between platelet adhesion and plasma antithrombin were observed at 13 s-1 and 50 s-1 (r = -0.48 and r = -0.7, p -1, within first minute have been found. An in-vitro supplementation of whole blood with antithrombin increased the antithrombin activity up to 280% and platelet adhesion rate reached about 65% related to the adhesion rate in a non-supplemented blood (1.25 ± 0.17 vs. 1.95 ± 0.4 p = 0.008, respectively. Conclusion It appears that antithrombin in a low flow system suppresses platelet adhesion onto immobilized fibrinogen independently from its antithrombin activity. A supraphysiological substitution of blood with antithrombin significantly reduces platelet adhesion rate. This inhibitory effect might be of clinical relevance.

  6. Identification of antithrombin-modulating genes. Role of LARGE, a gene encoding a bifunctional glycosyltransferase, in the secretion of proteins?

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    María Eugenia de la Morena-Barrio

    Full Text Available The haemostatic relevance of antithrombin together with the low genetic variability of SERPINC1, and the high heritability of plasma levels encourage the search for modulating genes. We used a hypothesis-free approach to identify these genes, evaluating associations between plasma antithrombin and 307,984 polymorphisms in the GAIT study (352 individuals from 21 Spanish families. Despite no SNP reaching the genome wide significance threshold, we verified milder positive associations in 307 blood donors from a different cohort. This validation study suggested LARGE, a gene encoding a protein with xylosyltransferase and glucuronyltransferase activities that forms heparin-like linear polysaccharides, as a potential modulator of antithrombin based on the significant association of one SNPs, rs762057, with anti-FXa activity, particularly after adjustment for age, sex and SERPINC1 rs2227589 genotype, all factors influencing antithrombin levels (p = 0.02. Additional results sustained this association. LARGE silencing inHepG2 and HEK-EBNA cells did not affect SERPINC1 mRNA levels but significantly reduced the secretion of antithrombin with moderate intracellular retention. Milder effects were observed on α1-antitrypsin, prothrombin and transferrin. Our study suggests LARGE as the first known modifier of plasma antithrombin, and proposes a new role for LARGE in modulating extracellular secretion of certain glycoproteins.

  7. Mechanism of poly(acrylic acid) acceleration of antithrombin inhibition of thrombin: implications for the design of novel heparin mimics.

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    Monien, Bernhard H; Cheang, Kai I; Desai, Umesh R

    2005-08-11

    The bridging mechanism of antithrombin inhibition of thrombin is a dominant mechanism contributing a massive approximately 2500-fold acceleration in the reaction rate and is also a key reason for the clinical usage of heparin. Our recent study of the antithrombin-activating properties of a carboxylic acid-based polymer, poly(acrylic acid) (PAA), demonstrated a surprisingly high acceleration in thrombin inhibition (Monien, B. H.; Desai, U. R. J. Med. Chem. 2005, 48, 1269). To better understand this interesting phenomenon, we have studied the mechanism of PAA-dependent acceleration in antithrombin inhibition of thrombin. Competitive binding studies with low-affinity heparin and a heparin tetrasaccharide suggest that PAA binds antithrombin in both the pentasaccharide- and the extended heparin-binding sites, and these results are corroborated by molecular modeling. The salt-dependence of the K(D) of the PAA-antithrombin interaction shows the formation of five ionic interactions. In contrast, the contribution of nonionic forces is miniscule, resulting in an interaction that is significantly weaker than that observed for heparins. A bell-shaped profile of the observed rate constant for antithrombin inhibition of thrombin as a function of PAA concentration was observed, suggesting that inhibition proceeds through the "bridging" mechanism. The knowledge gained in this mechanistic study highlights important rules for the rational design of orally available heparin mimics. PMID:16078853

  8. Domain structure of antithrombin III. Tentative localization of the heparin binding region using 1H NMR spectroscopy

    International Nuclear Information System (INIS)

    The denaturation of human and bovine antithrombin III by guanidine hydrochloride has been followed by 1H NMR spectroscopy. The same unfolding transition seen previously from circular dichroism studies at low denaturant concentration was detected here by discontinuous changes in the chemical shifts of the C(2) protons of two of the five histidines in human antithrombin III and of three of the six histidines in bovine antithrombin III. These two histidines in human antithrombin III are assigned to residue 1 and, more tentatively, to residue 65. Two of the three histidines similarly affected in the bovine protein appear to be homologous to residues in the human protein. This supports the proposal of similar structures for the two proteins. In the presence of heparin, the discontinuous titration behavior of these histidine resonances is shifted to higher denaturant concentration, reflecting the stabilization of the easily unfolded first domain of the protein by bound heparin. From the tentative assignment of one of these resonances to histidine-1, it is proposed that the heparin binding site of antithrombin III is located in the N-terminal region and that this region forms a separate domain from the rest of the protein. The pattern of disulfide linkages is such that this domain may well extend from residue 1 to at least residue 128. Thermal denaturation also leads to major perturbation of these two histidine resonances in human antithrombin III, though stable intermediates in the unfolding were not detected

  9. Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin.

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    Sonia Aguila

    Full Text Available The inefficient glycosylation of consensus sequence on N135 in antithrombin explains the two glycoforms of this key anticoagulant serpin found in plasma: α and β, with four and three N-glycans, respectively. The lack of this N-glycan increases the heparin affinity of the β-glycoform. Recent studies have demonstrated that an aromatic sequon (Phe-Y-Asn-X-Thr in reverse β-turns enhances N-glycosylation efficiency and stability of different proteins. We evaluated the effect of the aromatic sequon in this defective glycosylation site of antithrombin, despite of being located in a loop between the helix D and the strand 2A. We analyzed the biochemical and functional features of variants generated in a recombinant cell system (HEK-EBNA. Cells transfected with wild-type plasmid (K133-Y-N135-X-S137 generated 50% of α and β-antithrombin. The S137T, as previously reported, K133F, and the double mutant (K133F/S137T had improved glycosylation efficiency, leading to the secretion of α-antithrombin, as shown by electrophoretic and mass analysis. The presence of the aromatic sequon did not significantly affect the stability of this conformationally sensitive serpin, as revealed by thermal denaturation assay. Moreover, the aromatic sequon hindered the activation induced by heparin, in which is involved the helix D. Accordingly, K133F and particularly K133F/S137T mutants had a reduced anticoagulant activity. Our data support that aromatic sequons in a different structural context from reverse turns might also improve the efficiency of N-glycosylation.

  10. Rapid high-performance liquid chromatographic quantification of recombinant human antithrombin III during production and purification

    OpenAIRE

    Büntemeyer, Heino; Tebbe, H.; Lütkemeyer, Dirk; Lehmann, Jürgen

    1994-01-01

    For monitoring of recombinant human antithrombin III during cell culture processes and subsequent purification steps a rapid method for quantitative determination was developed. The need for the introduction of this rapid method came from the limited availability of a quantitative enzyme-linked immunosorbent assay (ELISA) and the very time-consuming ELISA procedure. The developed method is based on reversed-phase high-performance liquid chromatography using a C 4 column. The separation by gra...

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

    Directory of Open Access Journals (Sweden)

    Lesley J. Smith

    2008-01-01

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

  12. Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

    Full Text Available The final most common pathway for the majority of coronary artery disease is occlusion of a coronary vessel. Under normal conditions, antithrombin III (AT III, protein C, and protein S as an active protein C cofactor, are natural anticoagulants (hemostatic control that balances procoagulant activity (thrombin antithrombin complex balance to prevent thrombosis. If the condition becomes unbalanced, natural anticoagulants and the procoagulants can lead to thrombosis. Thirty subjects with acute coronary syndrome (ACS were studied for the incidence of antithrombin III (AT III, protein C, and protein S deficiencies, and the result were compare to the control group. Among patients with ACS, the frequency of distribution of AT-III with activity < 75% were 23,3% (7 of 30, and only 6,7% ( 2 of 30 in control subject. No one of the 30 control subject have protein C activity deficient, in ACS with activity < 70% were 13,3% (4 of 30. Fifteen out of the 30 (50% control subjects had protein S activity deficiency, while protein S deficiency activity < 70% was found 73.3.% (22 out of 30. On linear regression, the deterministic coefficient of AT-III activity deficiency to the development ACS was 13,25 %, and the deterministic coefficient of protein C activity deficient to the development of ACS was 9,06 %. The cut-off point for AT-III without protein S deficiency expected to contribute to the development of vessel disease was 45%. On discriminant analysis, protein C activity deficiency posed a risk for ACS of 4,5 greater than non deficient subjects, and AT-III activity deficiency posed a risk for ACS of 3,5 times greater than non deficient subjects. On binary logistic regression, protein S activity acted only as a reinforcing factor of AT-III activity deficiency in the development of ACS. Protein C and AT III deficiency can trigger ACS, with determinant coefficients of 9,06% and 13,25% respectively. Low levels of protein C posed a greater risk of

  13. Comparison of antithrombin activity of the polysulphate chitosan derivatives in in vivo and in vitro system.

    Science.gov (United States)

    Drozd, N N; Sher, A I; Makarov, V A; Galbraikh, L S; Vikhoreva, G A; Gorbachiova, I N

    2001-06-01

    In order to choose the proper method for evaluating the antithrombin activity in samples of chitosan polysulphate (CP) with different polymerization degrees and sulphation degrees, we estimated the ability of direct anticoagulants to depress the coagulability of recalcified sheep blood using the third international heparin standard (A1 - in vitro system) and determined such activity on pharmacodynamic curve (A2 - in vivo system). The curve admits the kinetics of CP elimination to be nonlinear in case of intravenous injection to rabbits, as it is observed in heparin: Ct = C(o)exp(-K(e)lt), where Ct is the CP concentration at the time moment t; C(o) is the CP concentration at the injection moment; Kel is the elimination constant. Besides, it is assumed that there is a linear approximation of the anticoagulant effect on the dose, which finally makes it possible to calculate the specific activity A2: T = KTCt+T(in), where T is the time of clot formation at different time intervals after CP injection; T(in) is the time of clot formation prior to CP injection. T value was assessed in two tests: blood coagulation time (BCT) and activated partial thromboplastin time (APTT). No correlation was observed between A1 and A2. At the same time, the values of Kel and the period of semi-elimination, with the use of the biospecific cetylpyridinium chloride electrophores for the quantitative determination of CP in rabbit's blood taken at different time intervals after injection, showed a close correlation (r = .94, P < .05) between the same parameters, obtained with the help of the rectilinear pharmacodynamic plot in BCT test. Thus, experimentally, it was proven that the assumption of the CP nonlinear elimination and the CP effect-dose dependence was true, which is necessary for A2 calculation. Relatively low molecular weights (MW 61-82 kDa, polymerization degree 188-252 ) and high sulphation patterns (sulphur amounts 15.6-16.9%, sulphation degree 1.58-1.86) were slowly cleared and

  14. Histidine-rich glycoprotein does not interfere with interactions between antithrombin III and heparin-like compounds on vascular endothelial cells

    International Nuclear Information System (INIS)

    The role of histidine-rich glycoprotein in controlling heparin-like compounds on the endothelial cell surface is still unclear. The effects of this heparin-neutralizing protein on the interaction between antithrombin III and cultured porcine aortic endothelial cells were examined. Displacement of 125I-labeled antithrombin III specifically bound to endothelial cells by unlabeled histidine-rich glycoprotein was much less potent than that by unlabeled antithrombin III. One hundred-fold molar excess of histidine-rich glycoprotein displaced specific 125I-antithrombin III binding only by 20%. Furthermore, the endothelial cell-mediated acceleration of thrombin inactivation by antithrombin III was diminished by protamine sulfate, but was not affected by histidine-rich glycoprotein even at a histidine-rich glycoprotein/antithrombin III molar ratio of approximately 7:1. These data indicate that histidine-rich glycoprotein does not interfere with the interaction of endothelial cell heparin-like compounds with antithrombin III. Thus, it may not play an important role in the modulation of anticoagulant activity of endothelial cells in vivo, suggesting that the commonly accepted view of the probable function of this protein is erroneous

  15. Dynamic properties of the native free antithrombin from molecular dynamics simulations: computational evidence for solvent- exposed Arg393 side chain.

    Science.gov (United States)

    Tóth, László; Fekete, Attila; Balogh, Gábor; Bereczky, Zsuzsanna; Komáromi, István

    2015-09-01

    While antithrombin (AT) has small basal inhibitory activity, it reaches its full inhibitory potential against activated blood coagulation factors, FXa, FIXa, and FIIa (thrombin), via an allosteric and/or template (bridging) mechanism by the action of heparin, heparan sulfate, or heparin-mimetic pentasaccharides (PS). From the numerous X-ray structures available for different conformational states of AT, only indirect and incomplete conclusions can be drawn on the inherently dynamic properties of AT. As a typical example, the basal inhibitory activity of AT cannot be interpreted on the basis of "non-activated" free antithrombin X-ray structures since the Arg393 side chain, playing crucial role in antithrombin-proteinase interaction, is not exposed. In order to reveal the intrinsic dynamic properties and the reason of basal inhibitory activity of antithrombin, 2 μs molecular dynamics simulations were carried out on its native free-forms. It was shown from the simulation trajectories that the reactive center loop which is functioning as "bait" for proteases, even without any biasing potential can populate conformational state in which the Arg393 side chain is solvent exposed. It is revealed from the trajectory analysis that the peptide sequences correspond to the helix D extension, and new helix P formation can be featured with especially large root-mean-square fluctuations. Mutual information analyses of the trajectory showed remarkable (generalized) correlation between those regions of antithrombin which changed their conformations as the consequence of AT-PS complex formation. This suggests that allosteric information propagation pathways are present even in the non-activated native form of AT. PMID:25483839

  16. Polyurethane films modified by antithrombin-heparin complex to enhance endothelialization: An original impedimetric analysis

    International Nuclear Information System (INIS)

    In this paper, polyurethane (PU) was deposited as a thin layer onto the surface of ITO (indium tin oxide) and was then modified with an antithrombin-heparin complex (ATH). The resulting films were characterized by ATR spectroscopy, contact angle measurements and electrochemical impedance spectroscopy (EIS). Physicochemical characterization confirmed the surface modifications. The obtained films were used as substrates for endothelial cell attachment and growth. These processes were characterized using electrochemical impedance spectroscopy (EIS). We observed that the addition of a small amount of heparin and AT additives onto the polymer surface resulted in a considerable change in the surface characteristics, and we found that PU films that were modified by the ATH complex were able to greatly enhance adhesion and proliferation of endothelial cells (ECs).

  17. Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study

    OpenAIRE

    Rehberg, S; Yamamoto, Y; Bartha, E; Sousse, L.E. (Linda); Jonkam, C. (Collette); Zhu, Y; Traber, L.D. (Lillian); Cox, R. A.; Traber, D.L. (Daniel); Enkhbaatar, P

    2013-01-01

    Introduction: We hypothesized that maintaining physiological plasma levels of antithrombin attenuates myocardial dysfunction and inflammation as well as vascular leakage associated with burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. Methods: Following 40% of total body surface area, third degree flame burn and 4 × 12 breaths of cold cotton smoke, chronically instrumented sheep were randomly assigned t...

  18. A recurrent deletion in the antithrombin gene, AT106-108(-6 bp), identified by DNA heteroduplex detection

    Energy Technology Data Exchange (ETDEWEB)

    Olds, R.J.; Thein, S.L. (John Radcliffe Hospital, Oxford (United Kingdom)); Lane, D.A. (Charing Cross and Westminster Medical School, London (United Kingdom)); Beresford, C.H.; Hughes, P.M. (Univ. of Otago Medical School, Dunedin (New Zealand)); Abildgaard, U. (Aker Hospital, Oslo (Norway))

    1993-04-01

    Antithrombin is the major physiological inhibitor of the activated serine proteinases of the coagulation system. Hereditary deficiency of the inhibitor is transmitted in an autosomal dominant pattern and is associated with a risk of venous thromboembotic disease in affected individuals. In the classical form of deficiency, type Ia, plasma antithrombin is reduced to approximately half normal in both functional and immunological assays. The authors report here the identification of a recurrent mutation as the basis for type Ia deficiency in two independent kindreds, one from New Zealand and the other from Norway, and demonstrate the utility of DNA heteroduplex detection as a method for screening for the presence of mutations. Standard functional and immunological assays for plasma antithrombin showed levels of approximately half normal in several members of both kindreds, consistent with the classification as type Ia deficiency. The plasma of the proband from the Norwegian kindred was examined by crossed immunoelectrophoresis, in the presence or absence of heparin in the first dimension, and an abnormal component that may have represented a variant form of the inhibitor was not identified. In both families affected members have had episodes of venous thrombosis, although some carriers of the abnormal allele, as confirmed in the current study, so far have not had clinical thrombotic disease. 7 refs., 2 figs.

  19. Fondaparinux bei Herz-Kreislauf-Erkrankungen: Ein neues Antithrombin mit herausragenden Eigenschaften

    Directory of Open Access Journals (Sweden)

    Huber K

    2008-01-01

    Full Text Available Fondaparinux, ein synthetisches Pentasaccharid, führt zu einer indirekten Hemmung des Gerinnungsfaktors Xa und behindert in der Folge die Bildung von Thrombin. Fondaparinux wurde als Vergleichssubstanz gegenüber unfraktioniertem (Standard- Heparin oder dem niedermolekularen Heparin Enoxaparin in der Prophylaxe oder Therapie von venösen Thrombosen getestet. Zuletzt wurde Fondaparinux auch bei Patienten mit akuten Koronarsyndromen (ACS untersucht: bei Patienten mit ACS ohne ST-Hebung (NSTE-ACS waren sowohl die Blutungsrate als auch die Kurz- und Langzeitmortalität im Fondaparinuxarm (2,5 mg/Tag s. c. signifikant geringer als in den Enoxaparin-behandelten Patienten (1 mg/kg KG 2×/Tag s. c. (OASIS-5-Studie. Bei Patienten mit akutem ST-Strecken-Hebungsinfarkt (STEMI war Fondaparinux in den Subgruppen der konservativ behandelten Patienten (ohne Reperfusion und der Patienten, die eine pharmakologische Reperfusion erhielten (Thrombolyse von Vorteil gegenüber Placebo oder unfraktioniertem Heparin. Hingegen zeigte sich bei Patienten mit STEMI, die einer Akut-PCI unterzogen wurden, eine starke Tendenz zugunsten von unfraktioniertem Heparin gegenüber Fondaparinux (OASIS-6-Studie. Daher wird Fondaparinux in den internationalen Richtlinien als das Antithrombin mit der günstigsten Risiko/Nutzen-Ratio bei NSTEMI aber auch bei STEMI-Patienten mit Ausnahme jener Patienten, die sich einer Akut-PCI unterziehen, empfohlen. Fondaparinux könnte schon in der nahen Zukunft die Heparine in diesen Indikationen weitgehend ersetzen.

  20. Comparative study of antithrombin III. Protease complex metabolism by fibroblasts and vascular endothelial cells

    International Nuclear Information System (INIS)

    125I-labeled human antithrombin III (125I-AT III).protease complexes are specifically bound to both cultured human skin fibroblast (HSF) cells and adult bovine aortic endothelial (ABAE) cells; however, there is a significant difference in the rate and degree of metabolism of the complexes by these two cell types. HSF cells appear to internalize the complexes at a rate of about 2.5 pmole/1 X 10(6) cells/h and subsequently degrade them at a rate of 0.6 pmole/1 X 10(6) cells/h. ABAE cells internalize and degrade the complexes at rates approximately 100 and 30 times lower, respectively. Neither cell type interacts with free 125I-AT III but only with its combined form with either thrombin or trypsin. These data indicate the major role of HSF cells in the removal of AT III.protease complexes from extravascular spaces in the body, in contrast to the inert vascular surface with regard to AT III.protease complexes provided by the vascular endothelium

  1. A capillary zone electrophoresis method to detect conformers and dimers of antithrombin in therapeutic preparations.

    Science.gov (United States)

    Marie, Anne-Lise; Tran, Nguyet Thuy; Saller, François; Abdou, Youmna Mohamed; Zeau, Pascal; Plantier, Jean-Luc; Urbain, Rémi; Borgel, Delphine; Taverna, Myriam

    2016-07-01

    Antithrombin (AT) is a human plasma glycoprotein that possesses anticoagulant and anti-inflammatory properties. However, the native (active) form of AT is unstable and undergoes conformational changes, leading to latent, cleaved, and heterodimeric forms. The presence of these alternative forms mostly inactive can highly impact the quality and therapeutic activity of pharmaceutical AT preparations. We developed a capillary zone electrophoresis method, based on a neutral polyethylene oxide-coated capillary and a buffer close to physiological conditions, enabling the separation of more than eight forms of AT. Several peaks were identified as native, latent, and heterodimeric forms. The CZE method was reproducible with intraday relative standard deviations less than 0.5 and 2% for migration times and peak areas, respectively. The method was applied to the comparison of AT preparations produced by five competitive pharmaceutical companies, and statistical tests were performed. Important differences in the proportion of each form were highlighted. In particular, one AT preparation was shown to contain a high quantity of heterodimer, and two preparations contained high quantities of latent form. In addition, one AT preparation exhibited additional forms, not yet identified. PMID:26989842

  2. Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Masanao Kurata; Kenji Okajima; Toru Kawamoto; Mitsuhiro Uchiba; Nobuhiro Ohkohchi

    2006-01-01

    AIM: To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-α-induced expression of E-selectin in rats.METHODS: Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically.The number of metastatic nodules was counted on day 7after I/R. TNF-α and E-selectin mRNA in hepatic tissue,serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2,were measured.RESULTS: AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-αand E-selectin in animals subjected to hepatic I/R.Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1αwere significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT.Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenit.al AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice.CONCLUSION: AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.

  3. Biological Variations of Lupus Anticoagulant, Antithrombin, Protein C, Protein S, and von Willebrand Factor Assays.

    Science.gov (United States)

    Shou, Weiling; Chen, Qian; Wu, Wei; Cui, Wei

    2016-02-01

    The results of lupus anticoagulant (LA), antithrombin (AT), protein C (PC), and protein S (PS) testing, and the values of von Willebrand factor antigen (VWF:Ag) are important in diagnosis and therapeutic monitoring of thrombosis and hemostasis diseases. Till now, no published study has focused on the biological variations in LA testing, and only a few studies have examined the biological variations of AT, PC, PS, and VWF:Ag. With the latest fully automated instruments and improved reagents, the analytical, within-subject, and between-subject biological variations were estimated for these five coagulant parameters in a cohort of 25 apparently healthy subjects. Blood specimens were collected at 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5. The analytical biological variation (CV(A)) values of all the parameters were less than 3%. The within-subject biological variation (CV(W)) and between-subject biological variation (CV(G)) values of the LA normalized ratio were 4.64 and 6.83%, respectively. No significant differences were observed in the intraday and interday biological variations of LA tests, or in AT, PC, PS, and VWF:Ag values. Additionally, the utility of the conventional population-based reference intervals of the five coagulation parameters was evaluated by the index of individuality, and data on CV(W) and CV(A) were used to calculate the reference change value to identify the significance of changes in serial results from the same individual. PMID:26516946

  4. Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency

    Directory of Open Access Journals (Sweden)

    James AH

    2013-05-01

    Full Text Available Andra H James,1 Barbara A Konkle,2,3 Kenneth A Bauer4 1Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia, 2Puget Sound Blood Center, Seattle, Washington, 3Department of Medicine, University of Washington, Seattle, Washington, 4Department of Medicine, Beth Israel Deaconess Medical Center and VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts, USA Objective: The aims of the study reported here were to provide data from six pregnant subjects who were enrolled in a clinical trial of antithrombin (AT concentrate, discuss other published case series and case reports, and provide general guidance for the use of AT concentrate for inherited AT deficiency in pregnancy. Methods: In the late 1980s, 31 AT-deficient subjects were enrolled in a prospective treatment trial of the plasma-derived AT concentrate Thrombate III®. Herein, newly available treatment data about the six pregnant subjects in the trial is tabulated and summarized. Results: All six experienced venous thromboembolism (VTE during pregnancy, were dosed according to a weight-based protocol, and were treated concomitantly with anticoagulation. Loading doses of AT concentrate of 54–62 units/kg were followed by maintenance doses of 50%–100% of the loading dose for 3–10 days. At the time of labor, loading doses of 46–50 units/kg were followed by maintenance doses of 50%–75% of the loading dose for 5–7 days. None of the six experienced recurrent thrombosis while receiving treatment with AT concentrate. Conclusion: Currently we suggest that women with AT deficiency who are pregnant or postpartum and have a personal history of VTE or current VTE receive AT concentrates. Keywords: thrombophilia, thrombosis, plasma-derived concentrate, labor, delivery, heparin.

  5. Interaction of antithrombin III with bovine aortic segments. Role of heparin in binding and enhanced anticoagulant activity.

    OpenAIRE

    Stern, D.; Nawroth, P; Marcum, J; Handley, D; Kisiel, W; Rosenberg, R; Stern, K.

    1985-01-01

    Bovine antithrombin III (AT III) interaction with the luminal surface of bovine aortic segments with a continuous layer of endothelium was examined. Incubation of 125I-AT III with vessel segments, previously washed free of endogenous AT III, demonstrated specific, time-dependent binding to the protease inhibitor to the endothelium. Half-maximal binding was observed at an added AT III concentration of 14 nM. Binding of 125I-AT III to the vessel wall was reversible (50% dissociated in 4 min), a...

  6. Resolution of preoperative portal vein thrombosis after administration of antithrombin III in living donor liver transplantation: case report.

    Science.gov (United States)

    Imai, H; Egawa, H; Kajiwara, M; Nakajima, A; Ogura, Y; Hatano, E; Ueda, M; Kawaguchi, Y; Kaido, T; Takada, Y; Uemoto, S

    2009-11-01

    A 59-year-old man with hepatitis C virus-associated liver cirrhosis was transferred to our hospital to undergo living donor liver transplantation. Coagulation was impaired (prothrombin time [International Normalized Ratio], 3.27), and antithrombin III (AT-III) activity was 23% (normal, 87%-115%). Contrast-enhanced computed tomography scans revealed portal vein thrombosis (PVT) from the junction between the splenic and superior mesenteric vein to the porta hepatica; the portal vein was completely obstructed (PVT). To prevent further development of PVT, 1500 U of AT-III was administered for 3 days, elevating the AT-III activity to 50%. A contrast-enhanced computed tomography scan obtained 9 days after AT-III administration showed resolution of PVT. Living donor liver transplantation was safely performed without portal vein grafting. Thus, a low AT-III concentration may have an important role in the pathogenesis of PVT in patients with cirrhosis. PMID:19917415

  7. Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS)

    OpenAIRE

    Zhao, Yuejie; Singh, Arunima; Li, Lingyun; Linhardt, Robert J.; Xu, Yongmei; Liu, Jian; Woods, Robert J.; Amster, I. Jonathan

    2015-01-01

    We validate the utility of ion mobility to measure protein conformational changes induced by the binding of glycosaminoglycan ligands, using the well characterized system of Antithrombin III (ATIII) and Arixtra, a pharmaceutical agent with heparin (Hp) activity. Heparin has been used as a therapeutic anticoagulant drug for several decades through its interaction with ATIII, a serine protease inhibitor that plays a central role in the blood coagulation cascade. This interaction induces conform...

  8. Development of Methods for Measuring Protein C Inhibitor and Antithrombin: Use of Monoclonal Antibodies against the Reactive Center Loop-Inserted Forms of the Serpins

    OpenAIRE

    Kjellberg, Margareta

    2007-01-01

    Protein C inhibitor (PCI) and antithrombin (AT) are serine protease inhibitors (serpins) that are involved in the regulation of coagulation. Like other inhibitory serpins, PCI and AT adopt different structural conformations that are related to their functions. The cleaved, inactive form is a result of cleavage by a protease, and the latent form, which is also inactive, can arise due to a mutation in the serpin. Methods that quantify the different forms can be useful as diagnostic tools. The a...

  9. Purified radiolabeled antithrombin III metabolism in three families with hereditary AT III deficiency: application of a three-compartment model

    International Nuclear Information System (INIS)

    Purified human radioiodinated antithrombin III (125I-AT III) was used to study its metabolism in six members from three different families with a known hereditary AT III deficiency. Six healthy volunteers served as a control group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and crossed immunoelectrophoresis (CIE) showed the purified AT III to be homogeneous. Amino acid analysis of the protein revealed a composition identical to a highly purified internal standard. The specific activity was 5.6 U/mg. Analysis of plasma radioactivity data was performed, using a three-compartment model. Neither plasma disappearance half-times nor fractional catabolic rate constants differed significantly between patients and control subjects. The mean absolute catabolic rate in the patient group was significantly lower than that of the control group at 2.57 +/- 0.44 and 4.46 +/- 0.80 mg/kg/day, respectively. In addition, the mean patient alpha 1-phase, flux ratio (k1,2 and k2,1) of the second compartment alpha 2-phase and influx (k3,1) of the third compartment were significantly reduced as compared with control values. It has been tentatively concluded that the observed reduction in the second compartment may be caused by a decrease in endothelial cell surface binding

  10. Localization of anticoagulantly active heparan sulfate proteoglycans in vascular endothelium: Antithrombin binding on cultured endothelial cells and perfused rat aorta

    International Nuclear Information System (INIS)

    We have studied the interaction of 125I-antithrombin (125I-AT) with microvascular endothelial cells (RFPEC) to localize the cellular site of anticoagulantly active heparan sulfate proteoglycans (HSPG). The radiolabeled protease inhibitor bound specifically to the above HSPG with a Kd of approximately 50 nM. Confluent monolayer RFPEC cultures exhibited a linear increase in the amount of AT bound per cell for up to 16 d, whereas suspension RFPEC cultures possessed a constant number of protease inhibitor binding sites per cell for up to 5 d. These results suggest that monolayer RFPEC cultures secrete anticoagulantly active HSPG, which then accumulate in the extracellular matrix. This hypothesis was confirmed by quantitative light and EM level autoradiography which demonstrated that the AT binding sites are predominantly located in the extracellular matrix with only small quantities of protease inhibitor complexed to the cell surface. We have also pinpointed the in vivo position of anticoagulantly active HSPG within the blood vessel wall. Rat aortas were perfused, in situ, with 125I-AT, and bound labeled protease inhibitor was localized by light and EM autoradiography. The anticoagulantly active HSPG were concentrated immediately beneath the aortic and vasa vasorum endothelium with only a very small extent of labeling noted on the luminal surface of the endothelial cells. Based upon the above data, we propose a model whereby luminal and abluminal anticoagulantly active HSPG regulate coagulation mechanism activity

  11. Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S.

    Science.gov (United States)

    Campello, Elena; Spiezia, Luca; Radu, Claudia M; Bulato, Cristiana; Gavasso, Sabrina; Tormene, Daniela; Woodhams, Barry; Dalla Valle, Fabio; Simioni, Paolo

    2016-01-01

    Many subjects carrying inherited thrombophilic defects will never experience venous thromboembolism (VTE) while other individuals developed recurrent VTE with no known additional risk factors. High levels of circulating microparticles (MP) have been associated with increased risk of VTE in patients with factor V Leiden and prothrombin G20210A mutation, suggesting a possible contribution of MP in the hypercoagulability of mild genetic thrombophilia. The role of MP as additional risk factor of VTE in carriers of natural clotting inhibitors defects (severe thrombophilia) has never been assessed. Plasma levels of annexin V-MP, endothelial-derived MP (EMP), platelet-derived MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) were measured in 132 carriers of natural anticoagulant deficiencies (25 antithrombin, 63 protein C and 64 protein S defect) and in 132 age and gender-matched healthy controls. Carriers of natural anticoagulant deficiencies, overall and separately considered, presented with higher median levels of annexin V-MP, EMP, PMP, TF+MP and PPL activity than healthy controls (pEMP and PMP had an adjusted OR for VTE of 3.36 (95% CI, 1.59 to 7.11), 9.26 (95% CI, 3.55 to 24.1) and 2.72 (95%CI, 1.16 to 6.38), respectively. Elevated levels of circulating MP can play a role in carriers of mild and severe inherited thrombophilia. The clinical implications of this association remain to be defined. PMID:26354831

  12. Impact of antithrombin Ⅲ on hepatic and intestinal microcirculation in experimental liver cirrhosis and bowel inflammation: An in vivo analysis

    Institute of Scientific and Technical Information of China (English)

    Sasa-Marcel Maksan; Zilfi (U)lger; Martha Maria Gebhard; Jan Schmidt

    2005-01-01

    AIM: To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease (IBD) and to characterize the anti-inflammatory action of antithrombin Ⅲ (ATⅢ) on leukocyte kinetics and liver damage.METHODS: Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups (n = 6/group): controls, animals with cirrhosis,animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATⅢ.RESULTS: Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids (1.91±0.28 sticker/μm vs0.5±0.5 sticker/μm in controls, P<0.05). The effect enhanced in animals with cirrhosis and IBD (5.4±1.65sticker/μm), but reversed agter ATⅢ application (3.97±1.04sticker/μm, P<0.05). Mucosal blood flow showed no differences in cirrhotic animals and controls (5.3±0.31nL/min vs5.4±0.25 nL/min) and was attenuated in animals with cirrhosis and IBD significantly (3.49±0.6 nL/min). This effect was normalized in the treatment group (5.13±0.4nL/min, P<0.05). Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATⅢ application (P<0.05).CONCLUSION: Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.

  13. Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

    Science.gov (United States)

    Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

    2016-05-01

    The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

  14. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin.

    NARCIS (Netherlands)

    Mahmoodi, B.K.; Brouwer, J.L.P.; Kate, M.K. Ten; Lijfering, W.M.; Veeger, N.J.; Mulder, A.B.; Kluin-Nelemans, H.C.; Meer, J. van der

    2010-01-01

    BACKGROUND: Absolute risks of venous thromboembolism (VTE) in protein S-, protein C-, or antithrombin-deficient subjects are mainly based on retrospective data. Screening asymptomatic relatives of these patients is disputed, though studies addressing this issue have yet to be conducted. METHODS: We

  15. An antithrombin-dependent sulfated polysaccharide isolated from the green alga Caulerpa cupressoides has in vivo anti- and prothrombotic effects Um polissacarídeo sulfatado dependente de antitrombina isolado da alga verde Caulerpa cupressoides possui efeitos anti- e pró-trombótico in vivo

    OpenAIRE

    José Ariévilo Gurgel Rodrigues; Ismael Nilo Lino de Queiroz; Ana Luíza Gomes Quinderé; Bruno Cunha Vairo; Paulo Antônio de Souza Mourão; Norma Maria Barros Benevides

    2011-01-01

    Red algae sulfated polysaccharides (SPs) have been widely described as anticoagulant and antithrombotic agents; however no description of antithrombotic activity regarding green algae SPs has been reported. Caulerpa cupressoides (Chlorophyta) has three different SPs fractions (SP1, SP2 and SP3). We investigated the effects of SP2 on thrombin activity by antithrombin and in an experimental model of venous thrombosis in rats. The inhibition of thrombin assay was evaluated using antithrombin (AT...

  16. PEGylation of Hirudin and Analysis of Its Antithrombin Activity in vitro%水蛭素聚乙二醇化及其体外抗凝活力分析

    Institute of Scientific and Technical Information of China (English)

    秦海娜; 修志龙; 张代佳; 包永明; 李晓晖; 韩国柱

    2007-01-01

    Hirudin is the most anticoagulant drug found in nature, but its short serum half-life significantly inhibits its clinical application. The PEGylation of hirudin, the most promising anticoagulant drug, was performed in this paper. The optimal reaction conditions for PEGylated hirudin were investigated. When the PEGylation reaction was conducted under 4℃ after 10h, in the borate buffer at pH 8.5, with the molar ratio 250: 1 of PEG to hirudin, a higher modification extent was achieved. Finally, the bioactivity of PEGylated hirudin was measured in vitro.Compared with unmodified hirudin, 26% of anti-thrombin activity was retained.

  17. Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS).

    Science.gov (United States)

    Zhao, Yuejie; Singh, Arunima; Li, Lingyun; Linhardt, Robert J; Xu, Yongmei; Liu, Jian; Woods, Robert J; Amster, I Jonathan

    2015-10-21

    We validate the utility of ion mobility to measure protein conformational changes induced by the binding of glycosaminoglycan ligands, using the well characterized system of Antithrombin III (ATIII) and Arixtra, a pharmaceutical agent with heparin (Hp) activity. Heparin has been used as a therapeutic anticoagulant drug for several decades through its interaction with ATIII, a serine protease inhibitor that plays a central role in the blood coagulation cascade. This interaction induces conformational changes within ATIII that dramatically enhance the ATIII-mediated inhibition rate. Arixtra is the smallest synthetic Hp containing the specific pentasaccharide sequence required to bind with ATIII. Here we report the first travelling wave ion mobility mass spectrometry (TWIMS) investigation of the conformational changes in ATIII induced by its interaction with Arixtra. Native electrospray ionization mass spectrometry allowed the gentle transfer of the native topology of ATIII and ATIII-Arixtra complex. IM measurements of ATIII and ATIII-Arixtra complex showed a single structure, with well-defined collisional cross section (CCS) values. An average 3.6% increase in CCS of ATIII occurred as a result of its interaction with Arixtra, which agrees closely with the theoretical estimation of the change in CCS based on protein crystal structures. A comparison of the binding behavior of ATIII under both denaturing and non-denaturing conditions confirmed the significance of a folded tertiary structure of ATIII for its biological activity. A Hp oligosaccharide whose structure is similar to Arixtra but missing the 3-O sulfo group on the central glucosamine residue showed a dramatic decrease in binding affinity towards ATIII, but no change in the mobility behavior of the complex, consistent with prior studies that suggested that 3-O sulfation affects the equilibrium constant for binding to ATIII, but not the mode of interaction. In contrast, nonspecific binding by a Hp

  18. Antithrombin III (AT and recombinant tissue plasminogen activator (R-TPA used singly and in combination versus supportive care for treatment of endotoxin-induced disseminated intravascular coagulation (DIC in the neonatal pig

    Directory of Open Access Journals (Sweden)

    Gardner Renee'

    2006-05-01

    Full Text Available Abstract Background Disseminated intravascular coagulation (DIC is a pathological disturbance of the complex balance between coagulation and anticoagulation that is precipitated by vascular injury, acidosis, endotoxin release and/or sepsis and characterized by severe bleeding and excessive clotting. The innately low levels of coagulation factors found in newborn infants place them at extremely high risk for DIC. Anecdotal reports suggest that either anticoagulant or fibrinolytic therapy may alleviate some of the manifestations of DIC. To test the hypothesis that replacement of both anticoagulants and fibrinolytics may improve survival and outcome better than either single agent or supportive care alone, we utilized a neonatal piglet model of endotoxin-induced DIC. Methods DIC was induced in twenty-seven neonatal pigs (7 to 14 days of age by intravenous administration of E. coli endotoxin (800 μg/kg over 30 min. The piglets were divided into 4 groups on the basis of treatment protocol [A: supportive care alone; B: Antithrombin III (AT, 50 μg/kg bolus, 25 μg/kg per hr continuous infusion and supportive care; C: Recombinant Tissue Plasminogen Activator (R-TPA, 25 μg/kg per hr continuous infusion and supportive care; D: AT, R-TPA and supportive care] and monitored for 3 primary outcome parameters (survival time, macroscopic and microscopic organ involvement and 4 secondary outcome parameters (hematocrit; platelet count; fibrinogen level; and antithrombin III level. Results Compared with supportive care alone, combination therapy with AT and R-TPA resulted in a significant improvement of survival time, hematocrit, AT level, macroscopic and microscopic organ involvement, p Conclusion The findings suggest that combining AT, R-TPA and supportive care may prove more advantageous in treating the clinical manifestations of DIC in this neonatal pig model than either single modality or supportive care alone.

  19. Correlative Analysis of the Relationships and Differences on D-dimer, Fibrinogen and Antithrombin Ⅲ Between Varied Clinical Periods of Cerebral Infarction%D-D、Fb和AT-Ⅲ在脑梗死不同时期的变化及相关性分析

    Institute of Scientific and Technical Information of China (English)

    徐威香; 武蓉珍; 胡晓蕾

    2012-01-01

    目的:探讨血浆D-二聚体(D-D)、纤维蛋白原(Fb)和抗凝血酶Ⅲ(AT-Ⅲ)在脑梗死(CI)不同时期的变化及其临床意义.方法:根据临床特征,对260例CI患者进行分组,其中CI急性期组80例、进展期组41例、非进展期组65例、康复期组74例;90例体检健康者为正常对照组.采用SYSMEX CA7000血凝仪分别检测其血浆D-D、Fb和AT-Ⅲ水平.结果:CI急性期、进展期、非进展期患者D-D、Fb含量均明显高于正常对照组(P<0.01),AT-Ⅲ低于正常对照组(P<0.01);脑梗死组中,D-D与AT-Ⅲ呈负相关(P<0.01),D-D与Fb呈正相关(P<0.01),AT-Ⅲ与Fb无相关性.结论:CI患者D-D、Fb、AT-Ⅲ变化显著,D-D升高伴随AT-Ⅲ含量降低,提示D-D、Fb、AT-Ⅲ共同参与了梗死发生发展的病理生理过程,可作为CI临床危险分级和病情监测的指标.%Objective To investigate the differences and its clinical significance of D-dimer, fibrinogen and antithrombin Ⅲ between varied clinical periods of cerebral infarction( CI). Methods 328 CI patients were rolled into the study, and they were divided into four groups due to their different clinical periods as follows: group acute period (80) , group progressing(41) , group non-pro-gressing(65) , group convalescence(74). And, 90 healthy volunteers were rolled into the normal control group. Their plasma D-dimer, fibrinogen and antithrombin HI were detected on SYSMEX CA7000 automatic coagulation analyzer. Results D-dimer and fibrinogen of CI patients in the acute, progressing and non-progressing periods were significantly higher (P <0.01) than those of healthy volunteers, while antithrombin Ⅲ of them was significantly lower (P<0.01) than that of healthy volunteers. In CI patients, D-dimer correlated negatively with antithrombin Ⅲ, while positively with fibrinogen. No significant relationship was observed between antithrombin Ⅲ and fibrinogen. ConclUSin D-dimer, fibrinogen and antithrombin Ⅲ of CI patients varied significantly

  20. Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke [Teikyo Univ. School of Medicine, Tokyo (Japan)] [and others

    1997-01-20

    We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,de1(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient. 16 refs., 4 figs.

  1. The functional study of antithrombin L99 mutation%抗凝血酶L99氨基酸位点突变对其功能的影响

    Institute of Scientific and Technical Information of China (English)

    郁婷婷; 戴菁; 丁秋兰; 傅启华; 王学锋

    2014-01-01

    Objective To study the molecular mechanisms of inherited antithrombin (AT)defiency caused by AT L99 mutation.Methods Wild type (WT),L99V,L99A,L99I and L99S AT were purified from drosophila expression system.The binding capacity of AT and the low molecular weight heparin sodium was analyzed by the heparin binding assay.Surface plasmon resonance (SPR) was used to detect the binding ability of AT to thrombin (F Ⅱ a) or AT to coagulation factor X a (F X a).The activity of AT (AT∶ A) was detected by chromogenic assay.Results The purified WT and mutant AT were at the same size.No additional band was observed by coomassie blue staining and western blot assay.Compared to the WT AT,the binding abilities of the low molecular weight heparin sodium to the AT L99V,L99A,L99I and L99S were (44.8±3.6)%,(118.9±14.0)%,(15.2±8.8)%,and (23.0±8.2)%,respectively.The binding abilities of F Ⅱ a to AT L99V,L99A,L99I and L99S were 13%,57%,3%,and 29%,while the binding of F X a to AT L99V,L99A,L99I and L99S were 7%,51%,1%,and 25%.The AT∶A of WT,L99V,L99A,L99I and L99S AT were 146.5%,21.4%,120.9%,10.8%,and 39.0%,respectively.Conclusion The binding abilities of AT to heparin,F Ⅱ a and F X a were damaged by the L99 mutation,which resulted in decreased AT∶ A and inherited AT deficiency.%目的 研究抗凝血酶(AT)L99氨基酸位点突变导致遗传性AT缺陷症的分子机制.方法 利用果蝇细胞表达系统表达纯化野生型AT以及L99V、L99A、L99I和L99S等突变型AT蛋白;采用肝素结合实验检测重组AT蛋白与低分子量肝素钠的结合能力;采用表面等离子共振(SPR)技术检测重组AT蛋白与凝血酶(FⅡa)及活化凝血因子X(FXa)的结合能力;将野生型及各突变型AT蛋白的浓度调整至正常AT血浆浓度后,采用发色底物法检测重组AT蛋白活性.结果 考马斯亮蓝染色及免疫印迹法显示各突变蛋白与野生型AT蛋白大小一致,未见明显杂带.

  2. An antithrombin-dependent sulfated polysaccharide isolated from the green alga Caulerpa cupressoides has in vivo anti- and prothrombotic effects Um polissacarídeo sulfatado dependente de antitrombina isolado da alga verde Caulerpa cupressoides possui efeitos anti- e pró-trombótico in vivo

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2011-04-01

    Full Text Available Red algae sulfated polysaccharides (SPs have been widely described as anticoagulant and antithrombotic agents; however no description of antithrombotic activity regarding green algae SPs has been reported. Caulerpa cupressoides (Chlorophyta has three different SPs fractions (SP1, SP2 and SP3. We investigated the effects of SP2 on thrombin activity by antithrombin and in an experimental model of venous thrombosis in rats. The inhibition of thrombin assay was evaluated using antithrombin (AT in the presence of SP2 and the antithrombotic activity was investigated in rats with thromboplastin as the thrombogenic stimulus. The anticoagulant effects of SP2 are suggested be due to the potentiation of thrombin inhibition by antithrombin (IC50 ~ 10.0µg mL-1 and this mechanism of interaction is different when compared to other studied Caulerpa polysaccharides. SP2 exhibited antithrombotic effects at doses of 1.0 and 2.0mg kg-1 body weight, but at higher doses (>2.0mg kg-1 body weight this polysaccharide revert the antithrombotic property. No hemorrhagic effect (2.0mg kg-1 was observed. As occurs with red algae SPs, these results indicate that green algae SPs are also capable of exhibiting different in vivo properties.Os polissacarídeos sulfatados (PSs de algas vermelhas têm sido relatados mundialmente como agentes anticoagulantes e antitrombóticos. Entretanto, nenhuma descrição de atividade antitrombótica tem sido relacionada com os PSs de algas verdes. A clorofícea Caulerpa cupressoides possui três frações de PSs (PS1; PS2 e PS3. Dessa forma, objetivou-se investigar os efeitos da fração PS2 sobre a atividade da trombina por antitrombina e usando um modelo experimental de trombose venosa em ratos. O ensaio de inibição da trombina foi avaliado usando a antitrombina (AT na presença de PS2 e a atividade antitrombótica foi investigada em ratos, usando a tromboplastina como o estímulo trombogênico. Os efeitos anticoagulantes de PS2 devem

  3. Deficiencies of Natural Anticoagulants, Protein C, Protein S, and Antithrombin

    Science.gov (United States)

    ... citing article information Citing articles via Google Scholar Google Scholar Articles by Lipe, B. Articles by Ornstein, D. L. Search for related content PubMed PubMed citation Articles by Lipe, B. Articles by Ornstein, D. ... Reddit StumbleUpon Twitter What's this? Navigate This ...

  4. Clinical significance on changes of platelet aggregation test, von Willebrand factor,antithrombin and D-dimer assayin acute cerebral infarction patients%急性脑梗死患者血小板聚集功能、血管性血友病因子、抗凝血酶及 D-二聚体测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    叶青跃; 程鹏飞; 周有利; 饶汉武; 黄承芳; 周立

    2015-01-01

    目的:探讨急性脑梗死患者血小板聚集功能( PAgT)、血管性血友病因子( vWF)、抗凝血酶( AT)和D-二聚体( D-dimer)水平变化及临床意义。方法选用相应的方法和仪器测定112例脑梗死及80例健康对照者血(浆) PAgT、vWF、AT和D-dimer水平变化,同时对部分患者进行治疗前、后的对比分析。结果脑梗死患者血中PAgT、vWF、D-dimer等指标均明显高于健康对照组,AT活性较对照组显著降低,差异有统计学意义(P<0.05或P<0.01)。选取经治疗效果明显好转的78例脑梗死患者,出院前取空腹静脉血测定PAgT、vWF、AT、D-dimer等指标,并与治疗前对照,结果治疗后PAgT、vWF、D-dimer降低,AT活性升高,差异有统计学意义(P<0.05或P<0.01)。结论脑梗死患者体内存在明显的凝血及纤溶功能异常,与血管内皮损伤、血小板聚集功能增强、凝血及纤溶功能亢进、抗凝功能降低等多因素有关。 PAgT、vWF、AT、D-dimer可以作为脑梗死患者诊断、治疗监测和预后判断的参考指标。%Objective To evaluate the clinical signification of coagulation ,anti-coagulation and fibrinolysis indexes i.e.platelet aggrega-tion test(PAgT),von Willebrand factor(vWF),antithrombin(AT),D-dimer in acute cerebral infarction patients.Methods vWF was as-sayed using ELISA method,AT was determined by chromogenic substances assay,and Latex enhanced immune turbidimetry for D-dimer. vWF,AT and D-dimer all the parameters were finished by SysmexCA-7000 automated blood coagulation analyzer.PAgT was measured sim-ultaneously using a whole-blood Lumi-Aggregometer by CHRMNO-LOG platelet aggregation apparatus.Results PAgT, vWF, D-dimer were significantly higher in acute cerebral infarction patients group,compared with those in the control group(P<0.05 or P<0.01). while AT was significantly lower(P<0.05).After effective treatment,PAgT,vWF,AT,D-dimer Indicators are all

  5. Correlation of the activities of protein C,antithrombin and coagulation factor Ⅷ with the treatment of lung cancer with pulmonary embolism%蛋白 C、抗凝血酶及凝血因子Ⅷ活性变化与肺癌合并肺栓塞后治疗的关系

    Institute of Scientific and Technical Information of China (English)

    陈环; 张鹏; 刘军锋

    2014-01-01

    Objective To investigate the correlation of the activities of protein C(PC),antithrombin(AT)and coagulation factor Ⅷ(FⅧ)with the treatment of lung cancer with pulmonary embolism(PE).Methods A total of 98 patients with lung cancer and PE were enrolled as lung cancer with PE group.A total of 1 00 patients with lung cancer were enrolled as lung cancer group.Their sex and age were recorded,and lipoprotein(a)[Lp(a)],total cholesterol (TC),triglyceride (TG),C-reactive protein(CRP),thrombin time(TT),platelet (PLT)and fibrinogen(Fbg)in the 2 groups were determined,respectively.PC,AT,FⅧ and D-dimer were determined in lung cancer with PE group after 5-7 d of treatment.Logistic regression analysis was used to analyze the factors influencing coagulation-fibrinolysis after 5-7 d of treatment in lung cancer with PE group.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of these factors.Results Lp (a),TC,TG and TT in lung cancer with PE group were significantly higher than those in lung cancer group (P 0.90.Conclusions The influence of PC,AT and FⅧ on coagulation-fibrinolysis should be concerned in midterm treatment of lung cancer with PE,and their activities can be used to assess the therapeutic efficiency and treatment program in a given period.%目的:探讨蛋白C(PC)、抗凝血酶(AT)及凝血因子Ⅷ(FⅧ)活性变化与肺癌合并肺血栓栓塞[简称肺栓塞(PE)]后治疗的关系。方法选择肺癌合并 PE 患者(肺癌+PE 组)98例及肺癌患者(肺癌组)100例。记录两组性别、年龄并检测脂蛋白(a)[Lp(a)]、总胆固醇(TC)、甘油三酯(TG)、C 反应蛋白(CRP)、凝血酶时间(TT)、血小板数量(PLT)、纤维蛋白原(Fbg)等指标。检测肺癌+PE 组治疗5~7 d 及肺癌组入院时的 PC、AT、FⅧ、D-二聚体水平。应用 Logistic 回归分析肺癌合并 PE 后治疗5~7 d 凝血-纤溶状态的影响因素,

  6. Clinical Significance of von Willebrand Factor and Antithrombin in Diabetes Mellitus with Retinopathy%血管性血友病因子与抗凝血酶在糖尿病视网膜病变中的临床意义

    Institute of Scientific and Technical Information of China (English)

    张鹏; 汤荣华

    2012-01-01

    目的 探讨糖尿病微血管视网膜病变患者血管性血友病因子(vWF)、抗凝血酶(AT)的变化及临床意义.方法 将100例2型糖尿病患者分为两组,糖尿病无微血管视网膜病变并发症组53例,糖尿病微血管视网膜病变并发症组47例,设健康人群对照组50例.所有人群入院或体检时即采集静脉血,进行vWF:Ag、AT:A检测.结果 2型糖尿病无微血管视网膜病变并发症组患者血浆vWF:Ag含量较正常对照组增高(P<0.05),2型糖尿病微血管视网膜病变并发症组患者血浆vWF:Ag含量与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆vWF:Ag含量比较有显著性差异(P<0.05).2型糖尿病无微血管视网膜病变并发症组患者血浆AT活性与正常对照组相比无显著性差异(P>0.05),2型糖尿病微血管视网膜病变并发症组患者血浆AT活性与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆AT活性比较有显著性差异(P<0.05).结论 血浆vWF:Ag、AT:A的变化与糖尿病微血管视网膜病变的发生、发展有密切关系,监测其水平与活性对糖尿病微血管并发症的治疗和预防有重要的临床意义.%Objective To explore the changes of von Willebrand factor(vWF) and antithrombin(AT) in diabetic patients with retinopathy and its clinical implications. Methods 100 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups,one group included 53 T2DM patients without retinopathy,another group included 47 T2DM patients with retinopathy, 50 healthy peoples were enrolled as control group. Venous blood was collected from all groups and vWF:Ag, AT; A were determined. Results The level of vWF;Ag in T2DM

  7. Developmental expression of chicken antithrombin III is regulated by increased RNA abundance and intracellular processing.

    Science.gov (United States)

    Amrani, D L; Rosenberg, J; Samad, F; Bergtrom, G; Banfield, D K

    1993-01-23

    We isolated and sequenced a 432 bp cDNA to cAT-III, that encoded 115 nucleotides of 5' untranslated sequence, a 17 amino acid long signal peptide and residues 1-88 of the mature protein, and used it to prepare a probe for measuring and correlating the developmental changes of steady-state cAT-III mRNA levels with known changes in antigen levels. Densitometric analysis of nuclease protection (n = 2), Northern blot (n = 4), and slot blots (n = 3) of total RNA from chick livers of 16-day-old embryos to 6-day-old chicks showed a 2.6 +/- 0.5-fold increase in steady-state cAT-III mRNA levels. Assay of functional mRNA levels by in vitro translation of poly(A)+ RNA and specific immunoprecipitation of 35S-Met-labelled cAT-III was comparable to RNA analysis (16-day-old embryos vs. 10-day-old hatchlings). We evaluated whether there were developmental differences in post-translational secretion which may also contribute to the regulation of the circulating level of this protein. Pulse-chase studies of freshly-isolated hepatocytes from 16-day-old embryos and 10-day-old hatchlings maintained in suspension demonstrated a approx. 5.0-5.5-fold increase in cAT-III levels at steady-state secretion. The above findings indicate that changes in circulating cAT-III levels during late embryonic development are primarily due to increased abundance of cAT-III mRNA. In addition, we postulate that post-translational intracellular processing may account for further differences in circulating protein levels. PMID:8424948

  8. Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency

    OpenAIRE

    James AH; Konkle BA; Bauer KA

    2013-01-01

    Andra H James,1 Barbara A Konkle,2,3 Kenneth A Bauer4 1Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia, 2Puget Sound Blood Center, Seattle, Washington, 3Department of Medicine, University of Washington, Seattle, Washington, 4Department of Medicine, Beth Israel Deaconess Medical Center and VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts, USA Objective: The aims of the study reported here were to provide data from six pregnan...

  9. Anti-thrombin therapy during warm ischemia and cold preservation prevents chronic kidney graft fibrosis in a DCD model

    OpenAIRE

    Favreau, F.; Thuillier, R.; Cau, J; S. Milin; Manguy, E; Mauco, G; Zhu, X.; Lerman, LO; Hauet, T.

    2009-01-01

    Ischemia reperfusion injury (IRI) is pivotal for renal fibrosis development via peritubular capillaries injury. Coagulation represents a key mechanism involved in this process. Melagatran® (M), a thrombin inhibitor, was evaluated in an autotransplanted kidney model, using Large White pigs. To mimic deceased after cardiac death donor conditions, kidneys underwent warm ischemia (WI) for 60 min before cold preservation for 24 hours in University of Wisconsin solution. Treatment with M before WI ...

  10. Antitrombina: 25 años después: Un tributo a una permanente fuente de conocimiento en Hemostasia Antithrombin: 25 years later: A tribute to a long lasting source of knowledge in Hemostasis

    OpenAIRE

    Jorge Korin

    2006-01-01

    En los últimos 25 años se ha revolucionado el conocimiento de la fisiología de la Hemostasia con un rápido traslado de muchos de los nuevos hallazgos a la fisiopatología de los estados trombofílicos. El presente artículo condensa algunos de dichos avances en torno a las serpinas en general y a la antitrombina en especial. Se analiza el papel de la principal inhibidora de trombina en la hemostasia normal y en patologías trombóticas congénitas y adquiridas como así también la importante contrib...

  11. Deep venous thrombosis

    Science.gov (United States)

    ... Blood clot in the legs; Thromboembolism; Post-phlebitic syndrome; Post-thrombotic syndrome ... for the Factor V Leiden mutation) Antithrombin levels Antiphospholipid antibodies Complete blood count (CBC) Genetic testing to ...

  12. Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women Efeitos da terapia de reposição hormonal estroprogestativa sobre o sistema de coagulação e de fibrinólise em mulheres na pós-menopausa

    OpenAIRE

    Claudio E Bonduki; Dayse M Lourenço; Eduardo L.A. da Motta; José Maria Soares Jr; Mauro Abi Haidar; Baracat, Edmund C

    2007-01-01

    OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus m...

  13. 非ST段抬高急性冠脉综合征患者随机应用依诺肝素或普通肝素抗凝治疗的疗效和出血并发症系统综述%Efficacy and Bleeding Complications Among Patients Randomized to Enoxaparin or Unfractionated Heparin for Antithrombin Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes A Systematic Overview

    Institute of Scientific and Technical Information of China (English)

    John L. Petersen; James A. de Lemos; Christopher C. Nessel; Robert A. Harrington; James J. Ferguson; Eugene Braunwald; Robert M. Califf; 徐成斌; Kenneth W. Mahaffey; Vic Hasselblad; Elliott M. Antman; Marc Cohen; Shaun G. Goodman; Anatoly Langer; Michael A. Blazing; Anne Le-Moigne-Amrani

    2005-01-01

    背景:抗凝疗法已成为急性冠脉综合征(acute coronary syndrome,ACS)治疗指南推荐的标准疗法.但是,最近某些试验在ACS患者中对依诺肝素(enoxaparin)与普通肝素(unfractionated heparin)的应用进行了比较,发现这些抗凝疗法的疗效及安全性并不及既往试验结果.目的:有6项随机对照试验对依诺肝素与普通肝素治疗ACS患者进行了比较,对其终点(即全因死亡及非致死性心肌梗死)、输血与大出血进行系统评估.资料来源:从杜克临床研究所(Duke Clinical Research Institute)获取ESSENCE、A to Z及SYNERGY试验的原始数据.由TIMI 11B、ACUTEⅡ及INTERACT研究的主要研究人员提供各自的基线特征和事件发生频率.研究选取:在非ST段抬高ACS患者中比较依诺肝素与普通肝素的6项随机对照试验均入选进行分析.数据提取:从全部试验人群和随机分组前未接受抗凝治疗的亚人群中获取疗效终点和安全性终点.数据综合:应用随机效应经验性贝叶斯模型(random-effects empirical Bayes model),系统评估21 946例患者的结果.依诺肝素与普通肝素30天死亡率无显著差异(3.0%比3.0%,优势比[odds ratio,OR],1.00;95%可信区间[confidence interval,CI],0.85~1.17).在所有试验人群中,依诺肝素与普通肝素相比,30天死亡或非致死性心肌梗死(myocardial infarction,MI)联合终点显著下降,具有统计学差异(10.1%比11.0%;OR,0.91;95%CI,0.83~0.99;所需治疗例数107).随机分组前未接受抗凝治疗的依诺肝素组患者30天死亡或MI联合终点亦显著下降,具有统计学差异(8.0%比9.4%;OR,0.81;95%CI,0.70~0.94;所需治疗例数72).随机分组后第7天,总体安全人群或者随机分组前未接受抗凝治疗的人群输血(OR,1.01;95%CI,0.89~1.14)或大出血的发生率(OR,1.04;95%CI,0.83~1.30)无显著差异.结论:对近22 000例各类ACS患者进行系统回顾发现,在预防死亡或MI联合终点方面依诺肝素较普通肝素更有效.

  14. The fabrication, characterization and application of aptamer-functionalized Si-nanowire FET biosensors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Su; Lee, Hyun-Seung; Yang, Jeong-A; Jo, Moon-Ho; Hahn, Sei Kwang [Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784 (Korea, Republic of)], E-mail: skhanb@postech.ac.kr

    2009-06-10

    An aptamer-functionalized silicon-nanowire (Si-NW) field effect transistor (FET) biosensor was successfully fabricated, characterized and applied to real-time electrical detection of binding with the target protein for biomedical applications. Surface modifications were carried out using 3-aminopropyl diethoxysilane and succinic anhydride to introduce amine and carboxyl groups onto Si substrates. Anti-thrombin aptamers with 5{sup '}-end amine groups were chemically grafted onto the surface-modified Si substrates through amide bond formation. Atomic force microscopic (AFM) analyses confirmed the successful immobilization of anti-thrombin aptamers on Si-NWs and their binding with thrombin samples. The anti-thrombin aptamers bound to Si-NWs through the linker appeared to have a mean height of approx. 4 nm and the thrombin/aptamer complex to have a mean height of approx. 8 nm. Fluorescence micrographs visualized the FITC-labeled thrombin after binding to anti-thrombin aptamers immobilized on Si-NWs. Furthermore, the anti-thrombin Si-NW FET biosensor was successfully applied to the real-time detection of electronic signals during and after binding with a thrombin sample at a concentration of approx. 330 pmol l{sup -1} and the thrombin in blood samples.

  15. Combination of a SAW-biosensor with MALDI mass spectrometric analysis.

    Science.gov (United States)

    Treitz, G; Gronewold, T M A; Quandt, E; Zabe-Kühn, M

    2008-05-15

    A S-sens K5 surface acoustic wave biosensor was coupled with mass spectrometry (SAW-MS) for the analysis of a protein complex consisting of human blood clotting cascade factor alpha-thrombin and human antithrombin III, a specific blood plasma inhibitor of thrombin. Specific binding of antithrombin III to thrombin was recorded as a function of time with a S-sens K5 biosensor. Two out of five elements of the sensor chip were used as references. To the remaining three elements coated with RNA anti-thrombin aptamers, thrombin and antithrombin III were bound consecutively. The biosensor measures mass changes on the chip surface showing that 20% of about 400fmol/cm2 thrombin formed a complex with the 1.7-times larger antithrombin III. Mass spectrometry (MS) was applied to identify the bound proteins. Sensor chips with aptamer-captured (1) thrombin and (2) thrombin-antithrombin III complex (TAT-complex) were digested with proteases on the sensor element and subsequently identified by peptide mass fingerprint (PMF) with matrix assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry. A significant identification of thrombin was achieved by measuring the entire digest with MALDI-ToF MS directly from the sensor chip surface. For the significant identification of both proteins in the TAT-complex, the proteolytic peptides had to be separated by nano-capillary-HPLC prior to MALDI-ToF MS. SAW-MS is applicable to protein interaction analysis as in functional proteomics and to miniaturized diagnostics. PMID:18316185

  16. Dicty_cDB: Contig-U05497-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 4 8.4 1 ( DJ452293 ) Method for analysing genome using microsatellite ... 44 8.4 1 ( DJ047936 ) CD10-specific antibody composition.... 44 8.4 1 ( DI155118 ) Process for producing Antithrombin III composition. 44 8.4 1 (...( DD152135 ) Fusion protein composition. 44 8.4 1 ( DD152031 ) Method of producing Antithrombin III composition.... 44 8.4 1 ( DD152009 ) IL-5 receptor-specific antibody composition. 44 8.4 1 ( DD151990 ) CCR4-specific antibody composition...sition. 44 8.4 1 ( DD151869 ) Ganglioside GD3-specific antibody composition. 44 8.4

  17. The Anopheles gambiae cE5, a tight- and fast-binding thrombin inhibitor with post-transcriptionally regulated salivary-restricted expression

    Czech Academy of Sciences Publication Activity Database

    Ronca, R.; Kotsyfakis, Michalis; Lombardo, F.; Rizzo, C.; Currà, C.; Ponzi, M.; Fiorentino, G.; Ribeiro, J.M.C.; Arcà, B.

    2012-01-01

    Roč. 42, č. 9 (2012), s. 610-620. ISSN 0965-1748 R&D Projects: GA ČR GAP502/12/2409 Institutional research plan: CEZ:AV0Z60220518 Keywords : Anopheles * Salivary protein * Anti-thrombin * Anophelin * Hematophagy * Post-transcriptional regulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2012

  18. Kombineret antitrombinmangel og faktor VLeiden-mutation i en dansk familie

    DEFF Research Database (Denmark)

    Nielsen, Christiane; Gram, Jørgen

    Factor VLeiden (FVL) and antithrombin (AT) deficiency are both known genetic risk factors for venous thromboembolism (VTE). The combination is rare and leads to significantly increased risk for VTE. In this case we present a 22-year-old woman with VTE while treated with oral contraceptives. Labor...

  19. Drug: D08795 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available BR:br08301] 6 Agents against pathologic organisms and parasites 63 Biological preparation...s 634 Human blood preparations 6343 Plasma preparations D08795 Human anti-thrombin III, freeze-dried concentrated PubChem: 96025478 ...

  20. A rare case of alpha 1-antitrypsin deficiency associated with hypogammaglobulinemia and recurrent pulmonary thrombosis

    Directory of Open Access Journals (Sweden)

    Raghav Gupta

    2014-01-01

    Full Text Available Alpha 1-antitrypsin (AAT belongs to the family of serpins (serine protease inhibitors. Loop sheet polymerization is the pathology behind serpinopathies which encompasses AAT, anti-thrombin III and neuroserpin deficiency. To the best of our knowledge, we report the first case of alpha 1-antitrypsin deficiency associated with hypogammaglobulinemia and recurrent pulmonary thrombosis without any concomitant use of drugs.

  1. Deficiency of the natural anticoagulant proteins in women with pregnancy related venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Mitić Gorana

    2009-01-01

    Full Text Available Inherited thrombophilia can be defined as a predisposition to thrombosis caused by heritable defects, such as mutations in genes encoding the natural anticoagulants or clotting factors. Pregnancy related risk of VTE is sixfold increased comparing to non pregnant age matched women. Pregnancy is an independent risk factor for the development of venous thromboembolism and this risk is further increased by the presence of thrombophilia. Aim of the study: The aim of the study was to evaluate the association between deficiency of natural anticoagulants: antithrombin, protein C and protein S and pregnancy related thromboembolism. We have determined the activities of antithrombin, proten C and protein S in 74 women with pregnancy related thrombosis and in 45 healthy women who had at least two uncomplicated pregnancies. Among the women with the history of venous thromboembolism antithrombin deficiency was found in 4 (5.4%, protein C deficiency in 2 (2.7% and protein S deficiency in 5 (6.76%. The total of 11 (14.6% women was found to be deficient. Not a single woman in the control group was found to be deficient in natural anticoagulants. Deficiencies of coagulation inhibitors are associated with an increased risk of venous thrombosis during pregnancy and puerperium (p= 0.006. Antithrombin, protein C and protein S deficient women are at higher risk of developing venous thromboembolism during antepartal period (p= 0.0097. Prophylactic treatment with heparin should be recommended from the very beginning of the following pregnancy in women with antithrombin, protein C or protein S deficiency.

  2. [Congenital thrombophilia].

    Science.gov (United States)

    Kojima, Tetsuhito

    2016-03-01

    Congenital thrombophilia is a thrombotic diathesis caused by a variety of genetic abnormalities in blood coagulation factors or their inhibitory factors associated with physiological thrombus formation. Patients with congenital thrombophilia often present with unusual clinical episodes of venous thrombosis (occasionally combined with pulmonary embolism, known as venous thromboembolism) at a young age and recurrence in atypical vessels, such as the mesenteric vein and superior sagittal sinus, often with a family history of this condition. Studies in Japan as well as in western countries have shown congenital thrombophilia to be caused by a wide variety of genetic abnormalities in natural anticoagulant proteins, such as antithrombin, protein C, and protein S. However, there may still be many unknown causes of hereditary thrombosis. We recently reported a case of hereditary thrombosis induced by a novel mechanism of antithrombin resistance, that is, congenital thrombophilia caused by a gain-of-function mutation in the gene encoding the coagulation factor prothrombin. PMID:27076244

  3. Effect of a single plasma transfusion on thromboembolism in 13 dogs with primary immune-mediated hemolytic anemia.

    Science.gov (United States)

    Thompson, Mary F; Scott-Moncrieff, J Catharine; Brooks, Marjory B

    2004-01-01

    Thirteen dogs with primary immune-mediated hemolytic anemia received fresh-frozen plasma within 12 hours of admission, in addition to unfractionated heparin and other therapies, such as prednisone, azathioprine, and packed red blood cell transfusion. Antithrombin activity was quantified prior to transfusion and at 30 minutes and 48 hours after transfusion. Plasma antithrombin activity did not change significantly after a single plasma transfusion. There were no deaths in the first 48 hours of treatment. Thromboembolism was identified at necropsy in six of 10 dogs that died within 12 months of admission. There was no significant difference in the incidence of thromboembolism between the current treatment group and a historical control group. PMID:15533964

  4. Localization of blood coagulation factors in the germinal centers of human Peyer's patches

    OpenAIRE

    Kudo, S.; Yamakawa, Mitsunori; Imai, Yutaka; Tsukamoto, M.

    1992-01-01

    The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factos XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin 111 and inactive alpha-thrombin were found, showing a lace-like s...

  5. Multiple presence of prothrombotic risk factors in Croatian children with arterial ischemic stroke and transient ischemic attack

    OpenAIRE

    Leniček Krleža, Jasna; Đuranović, Vlasta; Bronić, Ana; Coen Herak, Desiree; Mejaški-Bošnjak, Vlatka; Zadro, Renata

    2013-01-01

    Aim To determine the frequency of inherited and acquired prothrombotic risk factors in children with arterial ischemic stroke (AIS) and transient ischemic attacks (TIA) in Croatia. Methods We investigated 14 prothrombotic risk factors using blood samples from 124 children with AIS or TIA and 42 healthy children. Prothrombotic risk factors were classified into five groups: natural coagulation inhibitors (antithrombin, protein C, protein S), blood coagulation factors (FV Leiden and FII 20210), ...

  6. Changes in Blood Parameters and the Expression of Coagulation-Related Genes in Lactating Sprague–Dawley Rats

    OpenAIRE

    Urasoko, Yoshinaka; He, Xi Jun; Masao, Takano; KINOSHITA, YUICHI; Edamoto, Hiroshi; Hatayama, Kazuhisa; Asano, Yuzo; Tamura, Kazutoshi; Mochizuki, Masahiro

    2012-01-01

    This study measured blood parameters, particularly those related to coagulation, and alterations in the expression levels of blood-coagulation–related genes in lactating Sprague–Dawley rats. The day of delivery was designated as lactation day 0 (LD 0). On the day after delivery (LD 1), prothrombin time and overall activity of vitamin-K–dependent coagulation factors were decreased, whereas fibrinogen contents, platelet counts and antithrombin III concentrations were increased as compared with ...

  7. Evaluation of the plasma quality after filtration

    OpenAIRE

    M Mahmoodian Shooshtari; Mousavi Hosseini, K.

    2010-01-01

    "n  "n "nBackground and the purpose of the study: The quality of some of the human plasma derived drugs such as coagulation factor VIII and coagulation factor IX which can be used for the treatment of hemophilia A and B, depends on their activity which may be affected by filtration. In this study the quality of plasma with respect to coagulation factors FVII, FVIII, FIX, FV, FXI, Fibrinogen, antithrombin III, anti-plasmin and antitrypsin activities obtained after plasm...

  8. inherited thrombophilia and recurrent pregnancy loss Trombofilias heredadas y pérdida gestacional recurrente

    OpenAIRE

    Angela Patricia Cadavid Jaramillo; Wálter Darío Cardona Maya; Serguei Abel Castañeda Ospina

    2002-01-01

    One of the causes of recurrent pregnancy loss is thrombophilia, defined as a tendency to thrombosis or hypercoagulability, with various clinical manifestations dependent on the vascular region affected by the absence of blood flow. Thrombophilias can be classified as inherited or acquired, according to the nature of their cause. The former are factor V Leiden, the prothrombin G20210A, the methilenetetrahydrofolate reductase C677T, deficiencies of the natural anticoagulants antithrombin III, p...

  9. Platelet and coagulation factors in proliferative diabetic retinopathy.

    OpenAIRE

    Borsey, D. Q.; Prowse, C. V.; Gray, R S; Dawes, J.; James, K.; Elton, R A; Clarke, B F

    1984-01-01

    Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and...

  10. Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women

    DEFF Research Database (Denmark)

    Petersen, K R; Sidelmann, Johannes Jakobsen; Skouby, S O;

    1993-01-01

    concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between...... generation and resolution of fibrin was maintained during treatment with both hormonal compounds. Our findings suggest that the risk of thrombosis in normal women should not be increased....

  11. Den haemostatiske balance under behandling med nyere p-pillepraeparater

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen;

    1994-01-01

    concentration of tissue plasminogen activator inhibitor. The ratio between thrombin-antithrombin-III-complexes and fibrin degradation products were unchanged signifying no effect of hormonal intake on the balance between thrombin formation and fibrin resolution. In conclusion, the dynamic balance between...... generation and resolution of fibrin was undisturbed during treatment with both hormonal compounds and our findings do not provide evidence for increased risk of thrombosis in normal women....

  12. High incidence of thrombophilia detected in Chinese patients with venous thrombosis

    OpenAIRE

    Liu, HW; Kwong, YL; BOURKE, C; Lam, CK; Lie, AKW; Wei, D; Chan, LC

    1994-01-01

    Venous thromboembolism is rare in Chinese. To determine the incidence and disease profile of thrombophilia in Chinese patients with thrombosis, 52 unselected Chinese patients with documented venous thrombosis were studied for the presence of thrombophilia. Levels of antithrombin III (AT III), protein C (PC) and protein S (PS) as well as the presence of acquired lupus anticoagulant (LA) and anticardiolipin antibody (ACA) were investigated. Thirty patients were found to be abnormal. These consi...

  13. Aptamer Based Microsphere Biosensor for Thrombin Detection

    OpenAIRE

    Xudong Fan; White, Ian M.; Suter, Jonathan D.; Hongying Zhu

    2006-01-01

    We have developed an optical microsphere resonator biosensor using aptamer as receptor for the measurement of the important biomolecule thrombin. The sphere surface is modified with anti-thrombin aptamer, which has excellent binding affinity and selectivity for thrombin. Binding of the thrombin at the sphere surface is monitored by the spectral position of the microsphere's whispering gallery mode resonances. A detection limit on the order of 1 NIH Unit/mL is demonstrated. Control experiments...

  14. Functional domains of rabbit thrombomodulin.

    OpenAIRE

    Bourin, M C; Boffa, M C; Björk, I.; Lindahl, U

    1986-01-01

    Thrombomodulin isolated from rabbit lung was separated by ion-exchange chromatography on DEAE-cellulose into a retarded (acidic) and a nonretarded (nonacidic) fraction. Both fractions contained the cofactor required for the activation of protein C. In addition, the acidic fraction (but not the nonacidic fraction) prevented the clotting of fibrinogen by thrombin ("direct" anticoagulant activity) and accelerated the inhibition of thrombin by antithrombin (effect corresponding to 2-10 internatio...

  15. The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

    Directory of Open Access Journals (Sweden)

    Hadil A. Al Otair

    2016-05-01

    Full Text Available Objective: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI. The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the lowmolecular-weight heparin enoxaparin. Materials and Methods: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa. Results: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived. Conclusion: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go

  16. PROTEIN C ROLE IN MICROCIRCULATION DISTURBANCE IN PATIENTS WITH GINGIVITIS

    OpenAIRE

    T.V. Simonyan; V.F. Kirichuk

    2008-01-01

    The research purpose is focused on studying the role of protein С system in coagulation component disturbance of hemostasis and fibrinolysis system in patients with different forms of gingivitis. The decrease of protein С and antithrombin inactivity, the decrease ofplasminogen reserve in blood, thrombin time shortening and the resistance of factor Va Via to protein Care watched in patients with different forms of gingivitis. The most marked changes in protein С system may be observed in exace...

  17. Haematological stress syndrome in atherosclerosis.

    OpenAIRE

    Stuart, J; George, A J; Davies, A. J.; Aukland, A; Hurlow, R. A.

    1981-01-01

    Forty patients with atherosclerotic peripheral vascular disease, as compared to 29 healthy controls, showed a significant increase in platelet number and activity, a neutrophil leucocytosis, and a raised level of several acute-phase reactant proteins (fibrinogen, antithrombin III, factor VIII, and serum globulin). The hyperproteinaemia was associated with increases in plasma-, serum-, and blood-viscosity and is the likely cause of the hyperviscosity of vascular disease. These multiple haemost...

  18. Structural Determinants of the Capacity of Heparin to Inhibit the Formation of the Human Amplification C3 Convertase

    OpenAIRE

    Kazatchkine, Michel D.; Fearon, Douglas T.; Metcalfe, Dean D.; Rosenberg, Robert D.; Austen, K. Frank

    1981-01-01

    The ability of heparin glycosaminoglycan to prevent formation of the properdin-stabilized amplification C3 convertase is independent of antithrombin binding activity and requires substitution of the amino sugar and a degree of oxygen (O)-sulfation which could be on the uronic acid or the amino sugar. Preparations of heparin glycosaminoglycan isolated by different techniques from different species (rat, human, and porcine) exhibited an equivalent capacity to inhibit generation of the amplifica...

  19. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    OpenAIRE

    Sinuhe eHahn

    2015-01-01

    It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells...

  20. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    OpenAIRE

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem c...

  1. Hydrogels by irradiation of a synthetic heparinoid polyelectrolyte

    OpenAIRE

    Sederel, L.C.; Does, van der, Leen; Euverman, B.J.; Bantjes, A.; Kluft, C.; Kempen, H.J.M.

    1983-01-01

    Gamma irradiation of aqueous solutions of a synthetic heparinoid polyelectrolyte results in the formation of hydrogels, varying in water content and mechanical strength. The equilibrium water content and the mechanical strength of the hydrogels are dependent on the initial polyelectrolyte concentration, the molecular weight of the polyelectrolyte, the percentage of double bonds in the polyelectrolyte and the radiation dose. The polyelectrolyte hydrogels do not deplete Antithrombin III from bl...

  2. Contraception and Thrombophilia - A statement from the German Society of Gynecological Endocrinology and Reproductive Medicine (DGGEF e. V.) and the Professional Association of the German Gynaecologists (BVF e. V.)

    OpenAIRE

    Rabe T; Luxembourg B; Ludwig M.; Dinger JC; Bauersachs R; Rott H; Mueck AO; Albring C

    2011-01-01

    Venous thromboembolism (VTE) is responsible for more than half a million deaths annually in the European Union, most in older people following surgery, but some in women of reproductive age using various hormonal contraceptives. In some parts of the population inherited defects of the blood coagulation system (factor V Leiden, prothrombin G20210A, protein C, protein S and antithrombin deficiency) are responsible for an increased risk of VTE, which is also influenced by concomitant factors:...

  3. In vivo antithrombotic properties of a heparin from the oocyte test cells of the sea squirt Styela plicata(Chordata-Tunicata)

    OpenAIRE

    L. Cardilo-Reis; M.C.M. Cavalcante; C.B.M. Silveira; M.S.G. Pavão

    2006-01-01

    In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10% of mammalian heparin and about 5% as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porc...

  4. [Hypercoagulable workup in ophthalmology. When and what].

    Science.gov (United States)

    Muñoz-Negrete, F J; Casas-Lleras, P; Pérez-López, M; Rebolleda, G

    2009-07-01

    Most ophthalmologic disorders secondary to hypercoagulabe state are due to the confluence of congenital and adquired factors. A systematic workup is mandatory. Most of congenital coagulation disorders cause venous trombosis and are inherited autosomal dominantly. In order of frequency these are factor V Leiden mutation (activated protein C resistance), G20210A mutation of the prothrombin gen and protein C, protein S, and antithrombin III deficiencies. Sickle cell anemia can determine arerial and venous thrombosis. In relation with arterial occlusion, the markers most frequently involved are homcysteine fasting levels and the markers of antiphospholipid antibody syndrome. Both of them can also determine venous thrombosis. Several acquired factors can lead to hypoercoagulable state, especially hyperhomocysteinemia, antiphospholipid antibody syndrome, hepatic disease, alcohol and tobacco intake, oral contraceptives, immobilization, surgeries and malignancies. In central venous occlusion is only necessary to rule out hyperhomocysteinemia and antiphospholipid antibody syndrome in young patients without known risk factors. In central artery occlusion, hypercoagulable workup is only recommended for patients less than 50 years-old with unknown emboli source. In this cases protein C, protein S, and antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome will ruled out. In non arteritic ischemic optic neuropathy hypercoagulable work up is not necessary. In amaurosis fugax without known emboli source, it is recommended to rule out etiologies of arterial occlusion, especially antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome. PMID:19658050

  5. sEPCR Levels in Chronic Myeloproliferative Diseases and Their Association with Thromboembolic Events: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Figen Atalay

    2014-06-01

    Full Text Available OBJECTIVE: Venous, arterial, and microcirculatory events are frequently encountered in the clinical course of essential thrombocytosis and polycythemia vera. We aimed to investigate the levels of soluble endothelial protein C receptor (sEPCR in myeloproliferative diseases to see whether there was a difference between the patients with and without history of thromboembolism. METHODS: The study included patients with polycythemia vera (n=12, patients with essential thrombocytosis (n=13, and controls (n=29. In all groups, we measured proteins C and S, antithrombin and sEPCR levels, and plasma concentrations of thrombin-antithrombin complex, prothrombin fragments 1+2, and D-dimer. RESULTS: Comparing the patients with and without history of thromboembolic attack, statistically significant differences were not observed in terms of sEPCR, D-dimer, thrombin-antithrombin complex, prothrombin fragments 1+2, and hematocrit levels (p=0.318, 0.722, 0.743, 0.324, and 0.065, respectively. CONCLUSION: Significant increase in the parameters that reflect activation of coagulation, such as sEPCR, thrombinantithrombin complex, prothrombin fragments 1+2, and D-dimer, reflects the presence of a basal condition that leads to a tendency toward thrombosis development in ET and PV when compared to healthy controls.

  6. Selected thrombosis and atherosclerosis risk factors in children with idiopathic nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Beata Bieniaś

    2012-04-01

    Full Text Available The purpose of our study was to evaluate selected thrombosis and atherosclerosis risk factors in children with idiopathic nephrotic syndrome (INS at three  stages of the disease (I – in acute phase before steroid therapy, II – during steroid therapy after resolution of proteinuria, III – in remission after completion of steroid therapy.In all children, serum total homocysteine, lipoprotein (a, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels were measured at three stages of the disease. Plasma antithrombin III, fibrinogen and D-dimer levels were also determined.  At all stages of INS, the serum t-HCY levels were similar and significantly higher than in controls.  Serum lipoprotein (a level, plasma antithrombin III, fibrinogen and D-dimer levels were significantly higher at stage I than at stages II, III and controls.In conclusion, children with INS are at high risk of thrombosis and atherosclerosis. Keywords: Idiopathic nephrotic syndrome, Homocysteine, Lipoprotein (a, Antithrombin III, fibrinogen, D-dimer

  7. Evaluation of the plasma quality after filtration

    Directory of Open Access Journals (Sweden)

    M Mahmoodian Shooshtari

    2010-06-01

    Full Text Available "n  "n "nBackground and the purpose of the study: The quality of some of the human plasma derived drugs such as coagulation factor VIII and coagulation factor IX which can be used for the treatment of hemophilia A and B, depends on their activity which may be affected by filtration. In this study the quality of plasma with respect to coagulation factors FVII, FVIII, FIX, FV, FXI, Fibrinogen, antithrombin III, anti-plasmin and antitrypsin activities obtained after plasma filtration with CPD (citrate-phosphate-dextrose using integral filter was evaluated. "nMethods:Sixty units of plasma were individually separated from whole blood by centrifugation and immediately filtered by integral filter system. Specific plasma filtration was carried out between 4 and 20 hrs after blood donation. Before filtration, 60 units of non filtered fresh plasmas were kept as control. "nCoagulation factors were determined by one-stage clotting assay in an automated system. Antithrombin III activity was determined by immunochrom assay in an automated system. Activity of anti-plasmin was determined by Berichrom α2 - antiplasmin and antitrypsin activity was assayed with human neutrophil elastase. "n  "nResults:The activity of coagulation factors FVIII, FIX, Fibrinogen, FV, and FXI, were not affected by filtration, in all experiments. Filtration only caused negligible change in FVII activity. Antithrombin III, anti-plasmin and antitrypsin activities were not influenced by filtration. Non-filtrated and filtrated plasma values were not significantly different (P> 0.05. Conclusions:Plasma filtration dose not result in a measurable impairment of coagulation factors and inhibitors. Although a little changes in FVII activity was observed after filtration, but these filtration-dependent changes apparently have no impact on the therapeutic quality of whole blood- filtered fresh plasma for transfusion.

  8. Test of hirudin activity by tracking the binding of hirudin to thrombin in the presence of BS3 cross-linking.

    Science.gov (United States)

    Liu, Yanfang; Yang, Jian; Wang, Jiangmin; Huang, Qingmei; Yang, Xiaohong; Zhang, Jianhua

    2015-10-01

    Hirudin has a great potential in inhibiting thrombin, and its antithrombin activity has direct bearing on its clinical application. Using bovine alpha-thrombin and recombinant hirudin of Poecilobdella javanica purified from Phichia pastoris as materials, this study introduced a novel method to testing antithrombin activity of hirudin visually and dynamically by tracking the binding of hirudin to thrombin. After incubating the mixture of thrombin and hirudin at 37 °C for 5 min, the binding of hirudin to thrombin was cross-linked by bis[sulfosuccinimidyl] suberate for 30 min and visualized by SDS-polyacrylamide gel electrophoresis. With the aid of image analysis on the basis of INRA-Noésis E1D analysis software, antithrombin activity of hirudin was calculated through intensity variations of protein bands of either thrombin-hirudin compound, unbound thrombin, or unbound hirudin. In this regard, activity of the given hirudin was tested to be 5625 ATU/mg based on a single reaction, and 5675.3 ATU/mg based on a series of reactions in a stepwise manner, close to the result of 6000 ATU/mg concluded by titration method. The superiorities of the method include good accuracy (the minimum testable concentration of hirudin is 1.5 μg/ml) and little sample consumption (sample consumption of hirudin is generally 1-11.5 μl using the apparatus of Mini Protean 3 Cell). Easy operation, low input, and equipment requirement also grant it as an effective way. PMID:26332983

  9. Human recombinant interleukin-1 beta- and tumor necrosis factor alpha-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells

    International Nuclear Information System (INIS)

    Cytokines are known to tip the balance of the coagulant-anticoagulant molecules on the endothelial cell surface toward intravascular coagulation. Their effects on endothelial cell surface-associated heparin-like compounds have not been examined yet. Incorporation of [35S]sulfate into heparan sulfate on cultured porcine aortic endothelial cells was suppressed by human recombinant interleukin-1 beta (rIL-1 beta) or tumor necrosis factor alpha (rTNF alpha) in a dose- and time-dependent manner with little effect on cell number, protein content, and [3H]leucine incorporation of cells. Maximal inhibition was achieved by incubation of cells with 100 ng/ml of rIL-1 beta or 5 ng/ml of rTNF alpha for 12-24 hours, resulting in a reduction of the synthesis of heparan sulfate on the cell surface by approximately 50%. The dose dependency was consistent with that seen in the stimulation of endothelial cell procoagulant activity by each cytokine. The suppression of heparan sulfate synthesis was sustained for at least 48 hours after pretreatment of cells with cytokines and was unchanged after the addition of indomethacin or polymyxin B. The rate of degradation of prelabeled 35S-heparan sulfate on the cell surface was not altered by cytokine treatments. Neither the size, the net negative charge, nor the proportion of the molecule with high affinity for antithrombin III of endothelial cell heparan sulfate was changed by cytokines. Furthermore, specific binding of 125I-labeled antithrombin III to the endothelial cell surface was reduced to 40-60% of control by cytokines. In parallel with reduction in binding, antithrombin III cofactor activity was partially diminished in cytokine-treated endothelial cells. Thus, cytokine-mediated suppression of heparin-like substance on endothelial cells appears to be another cytokine-inducible endothelial effects affecting coagulation

  10. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

    Directory of Open Access Journals (Sweden)

    Larsen Claus F

    2011-10-01

    Full Text Available Abstract Background Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG and biomarker profiles upon admission in trauma patients. Methods Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments, sympathoadrenal activation (adrenaline, noradrenaline, coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII. Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. Results Trauma patients had normal (86%, hypercoagulable (11% or hypocoagulable (1% TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p 10 red blood cells the initial 24 h. Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles. Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. Conclusions Trauma patients displayed

  11. Influence of dabigatran and rivaroxaban on routine coagulation assays. A nationwide Belgian survey.

    Science.gov (United States)

    Van Blerk, Marjan; Bailleul, Els; Chatelain, Bernard; Demulder, Anne; Devreese, Katrien; Douxfils, Jonathan; Jochmans, Kristin; Mullier, François; Wijns, Walter; Soumali, Mohamed Rida; Coucke, Wim; Vernelen, Kris; Van de Walle, Philippe

    2015-01-01

    The Belgian national External Quality Assessment Scheme performed a nationwide survey using lyophilised plasma samples spiked with dabigatran or rivaroxaban to demonstrate to the Belgian clinical laboratories how these drugs affect their routine coagulation assays prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin. Virtually all Belgian laboratories performing routine coagulation testing (189/192) participated in the survey. Both, dabigatran and rivaroxaban significantly prolonged the PT and aPTT in a concentration- and reagent-dependent manner. PT reagents were more influenced by rivaroxaban than by dabigatran and aPTT reagents more influenced by dabigatran than by rivaroxaban. Among PT reagents, Neoplastin R® was the most sensitive to rivaroxaban and Innovin® and Thromborel S® the least sensitive. Converting PT results to INR only increased the variability between reagents. Among aPTT reagents, Actin FSL® was the least sensitive to dabigatran while the other aPTT reagents showed slightly higher sensitivities. The presence of dabigatran led to falsely reduced fibrinogen concentrations when measured with a low thrombin concentration reagent. The presence of dabigatran caused an overestimation of the antithrombin level when measured with a thrombin-based activity assay and the presence of rivaroxaban an overestimation of the antithrombin level when measured with a FXa-based assay. Instrument-related differences were found for all tested parameters. In conclusion, this paper provides detailed information on the effect of dabigatran and rivaroxaban on routine coagulation assays as performed with a large number of reagent/instrument combinations. PMID:25231101

  12. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Science.gov (United States)

    Tsunaka, Misae; Arai, Reina; Ohashi, Ayaka; Koyama, Takatoshi

    2016-01-01

    Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox) led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma), Molt4 (acute T-lymphoblastic leukemia), and Ramos (Burkitt lymphoma) were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs. PMID:27504186

  13. Effect of whole-body irradiation on the level of blood clotting factors in rats

    International Nuclear Information System (INIS)

    Rats were irradiated with 6.0, 7.0 or 9.5 Gy of X-rays. Blood was collected on the 1,3,7,14 or 30th day after exposure. Fibrinogen, thrombin, prothrombin, factor X and antithrombin 3 levels were determined in blood plasma. In irradiated rats the level of these factors underwent a change which depended to some extent on the radiation dose absorbed. In general, there was a temporary elevation of all factors, lasting longer when the dose applied was higher. 24 refs., 6 tabs. (author)

  14. Synthetic oligosaccharides as heparin-mimetics displaying anticoagulant properties.

    Science.gov (United States)

    Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J

    2003-01-01

    Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394

  15. Range of fractionated plasma products to optimize plasma resources

    Institute of Scientific and Technical Information of China (English)

    Thierry Burnouf

    2010-01-01

    @@ HUMAN PLASMA is a source material that is crucial for the production of unique therapeutic fractionated products. Indeed, plasma contains hundreds of proteins ensuring many physiological functions. The most abun-dant proteins, albumin and immunoglobulin G (IgG) ,are present at about 35 and 10 g/L,respectively,repre-senting about 80% of all plasma proteins. However,other important therapeutic proteins include the coagu-lation factors (factor Ⅷ (F Ⅷ) ; FIX ; Von Willebrand Factor (VWF), fibrinogen) various protease inhibitors (alpha 1-antitrypsin ; antithrombin; C1-esterase) and anticoagulants (protein C) which exhibit potent physi-ological activity.

  16. Assessing the relative importance of the biophysical properties of amino acid substitutions associated with human genetic disease

    DEFF Research Database (Denmark)

    Terp, Bent N; Cooper, David N; Christensen, Inge T; Jørgensen, Flemming Steen; Bross, Peter Gerd; Gregersen, Niels; Krawczak, Michael

    2002-01-01

    five human genes encoding arylsulphatase A (ARSA), antithrombin III (SERPINC1), protein C (PROC), phenylalanine hydroxylase (PAH), and transthyretin (TTR). These proteins were chosen on the basis of 1) the availability of a crystallographic structure, and 2) a sufficiently large number of amino acid...... replacements being logged in HGMD. A total of 9,795 possible mutant structures were modeled and 20 different biophysical parameters assessed. Together with the HGMD-derived spectra of clinically detected mutations, these data allowed maximum likelihood estimation of RCOL profiles for the 20 parameters studied...

  17. METHODS OF TREATING OR PREVENTING DEMYELINATION USING THROMBIN INHIBITORS AND METHODS OF DETECTING DEMYELINATION USING NEUROFASCIN 155 | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (“NICHD”), seek CRADA partner or collaboration for development of agents to treat multiple sclerosis or other conditions associated with myelin remodeling by administering an agent that inhibits cleavage of Neurofascin 155 or Caspr1. The agent could be a thrombin inhibitor, an agent that inhibits thrombin expression, an anti-thrombin antibody that specifically inhibits thrombin mediated cleavage of Neurofascin 155, a mutated version or fragment of Neurofascin 155 or Caspr1, or antibodies to Neurofascin 155 or Caspr1.

  18. Purpura fulminans in a patient with mixed connective tissue disease.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2013-01-01

    A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud\\'s syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made.

  19. Kontrazeption & Thrombophilie - Eine Stellungnahme der Deutschen Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin (DGGEF) e. V. und des Berufsverbands für Frauenärzte (BVF) e.V.

    OpenAIRE

    Rabe T; Luxembourg B; Ludwig M; Dinger JC; Bauersachs R; Rott H; Mueck AO; Albring C

    2012-01-01

    Mehr als eine halbe Million Menschen sterben jährlich in der EU an venösen Thromboembolien (VTE), meist in höherem Alter oder im Zusammenhang mit Operationen, aber auch junge Frauen im reproduktiven Alter unter Anwendung hormonaler Kontrazeptiva. In einigen Teilen der Bevölkerung sind angeborene Störungen im Gerinnungssystem (Faktor-V-Leiden, Prothrombin-Mutation G20210A, Protein C-, Protein S- und Antithrombin-Mangel) für ein erhöhtes VTE-Risiko verantwortlich. Das VTE-Risiko wird durch f...

  20. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    Science.gov (United States)

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  1. Thrombotic actions of nonionic intravascular contrast agents

    International Nuclear Information System (INIS)

    Experimental studies show that nonionic contrast media (NICM) produce markedly lower or no anticoagulant effects and, on extended contact, can produce procoagulant actions in native blood. Patients with hemostatic imbalance (such as a decrease of antithrombin III, protein C, thrombocytosis, hyperfibrinogenemia, rheologic disorders, hemoconcentration, and dehydration) are at high thrombotic risk during angiography. Exogenous compensation of the hemostatic deficit minimizes the thrombogenic actions of NICMs. Anticoagulants such as hirudin and low-molecular-weight heparin can antagonize the procoagulant actions of NICM. In a primate model (Macaca mulatta), thrombogenic properties of nonionic contrast media have been successfully antagonized with anticoagulant drugs

  2. Hormone replacement therapy and hypercoagulability. Results from the Prospective Collaborative Danish Climacteric Study

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, Jørgen; Andersen, Lars F.;

    2003-01-01

    norethindrone acetate, (E). E(2) combined with local delivery of levonorgestrel and (F). E(2)V plus medroxyprogesterone. HRT-induced changes in the concentration of inhibitors of coagulation and markers of fibrin turnover during 12 months of treatment. RESULTS: Significant decreases of antithrombin and protein......-normalised ratio were measured at baseline and after 6 and 12 months of HRT in six groups of healthy postmenopausal women: (A). no HRT (reference group), (B). continuous oestradiol valerate (E(2)V) plus cyproterone acetate, (C). cyclic E(2)V plus cyproterone acetate, (D). continuous combined oestrogen (E(2)) plus...

  3. Anesthetic management of a child with nephrotic syndrome undergoing open heart surgery: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Vishnu Datt

    2012-01-01

    Full Text Available The congenital nephrotic syndrome (NS in infancy and childhood is an important entity but combination with acyanotic congenital heart disease is uncommon. Anesthesia in such cases is challenging because of associated problems like hypo-protienemia, anti-thrombin III deficiency, edema, hyperlipidemia, coagulopathy, cardiomyopathy, immunodeficiency, increased lung water etc. We describe anesthetic management of a patient with childhood NS and sinus venosus atrial septal defect (ASD undergoing open heart surgery. We also suggest guidelines for safe conduct of anesthesia and CPB in such patients.

  4. Drug: D03674 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03674 Drug Enoxaparin sodium (JAN/USAN/INN); Lovenox (TN) Antithrombotic intended ...olism 33 Blood and body fluid agents 333 Anticoagulants 3334 Heparins D03674 Enoxaparin sodium (JAN/USAN/INN...ITHROMBOTIC AGENTS B01A ANTITHROMBOTIC AGENTS B01AB Heparin group B01AB05 Enoxaparin D0367...lume Expanders Anticoagulants Enoxaparin D03674 Enoxaparin sodium (JAN/USAN/INN) Target-based classification... of drugs [BR:br08310] Others Heparin binding proteins antithrombin III [HSA:462] [KO:K03911] Enoxaparin [ATC:B01AB05] D0367

  5. Cerebral Vein Thrombosis:Screening of Acquired and Hereditary Thrombophilic Risk Factors

    Directory of Open Access Journals (Sweden)

    Sarraf Payam

    2009-10-01

    Full Text Available Cerebral vein thrombosis (CVT is an infrequent condition with a large variety of causes that can lead to serious disabilities. However, in 20% to 35% of cases, no cause is found. In this study we evaluated the hereditary (P & C Proteins, antithrombin, mutation of prothrombin G20210A and factor V Leiden, other risk factors (hyperhomocycteinemia, factor VIII, ACL-ab, APL-ab, and OCP and clinical manifestations among a population of Iranian patients with CVT. 18 women and 10 men aged 16 to 50 years with CVT were screened for inherited and acquired coagulation risk factors. No one had an abnormal ACL-ab, APL-ab or antithrombin III deficiency. One had prothrombin G20210A mutation (heterozygot (3.6%. Hyperhomocycteinemia was observed in 5 patients (17.9%. APC-R was decreased in 3 (10.7%. 2 had positive factor V Leiden mutation (heterozygot (7.1%. 17 had an increased of factor VIII (60.7. PS and PC deficiencies were each detected in two cases (7.1%. Conclusion: Our study suggests that screening for inherited thrombophilia may be an integral part in the diagnostic workup and duration of treatment in patients with CVT.

  6. New anticoagulants for the prevention of venous thromboembolism

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    Cecilia Becattini

    2010-04-01

    Full Text Available Cecilia Becattini, Alessandra Lignani, Giancarlo AgnelliInternal and Cardiovascular Medicine and Stroke Unit, University of Perugia, ItalyAbstract: Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future.Keywords: anticoagulant therapy, antithrombotic therapy, anticoagulants, direct thrombin inhibitors, factor Xa inhibitors

  7. New anticoagulants for the prevention of venous thromboembolism

    Science.gov (United States)

    Becattini, Cecilia; Lignani, Alessandra; Agnelli, Giancarlo

    2010-01-01

    Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future. PMID:20531960

  8. Hemostatic system changes predictive value in patients with ischemic brain disorders

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    Raičević Ranko

    2002-01-01

    Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

  9. Effect of Age on the Hemostatic Function in Patients with Degenerative Diseases of the Large Joints

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    Igor L. Shlykov, PhD¹, ScD¹

    2013-06-01

    Full Text Available Background: Aging is associated with an increased hypercoagulable state. Degenerative diseases of the large joints are also accompanied by increased coagulation activity. We investigated the effect of age on the hemostatic function in patients with osteoarthritis. Material and Methods: The study included 192 patients with osteoarthritis admitted to the clinic for primary hip or knee arthroplasty. The patients were categorized into 5 age groups: the age group under 40 years, the 41–to-50 -year age group, the 51–to-60-year age group, the 61-to-70- year age group, and the age group over 70 years. The general blood clotting tests, platelet number, fibrinogen, antithrombin, protein C, TAT, D-dimer, vonWillebrand factor (vWF, PAI-1, ß-thromboglobulin were determined. Results: Among patients with osteoarthritis, the antithrombin III level significantly decreased by the age of 50; however, above the age of 60 there was a distinct decrease in platelet count, and over the age of 70 the activity of the extrinsic coagulation pathway and the plasminogen level dropped significantly. TAT and D-dimer levels were elevated in most of the patients. Conclusion: The decrease in platelet count coupled with the activity of the extrinsic coagulation pathway in elderly osteoarthritic patients may increase blood loss during total arthroplasty; also, the drop in the anticoagulant and fibrinolytic potential may play a negative role in strengthening the prothrombotic state during the postoperative period.

  10. Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity.

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    Xavier Stephenne

    Full Text Available Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs, ii to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts or liver origin (liver myofibroblasts, and iii to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry, we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans.

  11. Effects of fused hirudin on activity of thrombin and function of platelets

    Institute of Scientific and Technical Information of China (English)

    SHEN Li; CHEN Shao-ping; CAI Zai-long; YANG Sheng-sheng; QIN Yong-wen

    2005-01-01

    Objective: To investigate whether fused hirudin peptide has both antithrombin and antiplatelet functions. Methods: The core region of fused hirudin was the C-terminal tail of hirudin(hirudin53-64),which could bind to the anion binding exosite (ABE) of thrombin.Arg-Pro-Pro-Gly-Phe(RPPGF) amino acid sequence,a metabolite of bradykinin,was added to the N-terminus of hirudin53-64.It bound to the active site of thrombin.Additionally,Arg-Gly-Asp(RGD)amino acid sequence,an inibitor of glycoprotein Ⅱb/Ⅲa( GP Ⅱb/Ⅲa) receptor,was linked to C-terminus of hirudin53-64.This 26-animo acid-fused hirudin peptide was artificially synthesized,purified and analysed. Results: Fused hirudin peptide significantly lengthened the activated partial thromboplastin time(APTT),thrombin time(TT)and prothrombin time(PT) and inhibited the amidolytic activity of thrombin.The ADP-induced platelet aggregation was markedly inhibited by fused hirudin peptide. Conclusion: Fused hirudin peptide has activity of antithrombin as well as antiplatelet.Therefore bifunctional anticoagulation peptide has capacity to target various components of haemostatic process and may become more powerful antithrombosis agent.

  12. Interaction of basic amino acids, polypeptides and proteins with heparin

    International Nuclear Information System (INIS)

    A study has been made of the relative binding affinities for heparin of L-lysine, L-arginine, poly-L-lysine, poly-L-arginine, protamine, thrombin and antithrombin III. The destruction by different concentrations of organic cations of the heparin-methylene blue complex was determined by visible absorption spectroscopy. The strength of binding of the basic amino acids and polypeptides increased with increasing molecular weight, and decreased at low pH. Pulse radiolysis experiments were used to show the effects of increasing concentrations of L-lysine, poly-L-lysine and protamine sulphate on the reaction of e-sub(aq) with the heparin-methylene blue complex. The results indicate that the binding of basic amino acids and polypeptides to heparin is ionic, and that the enhanced rate of association of antithrombin III to thrombin in the presence of heparin is due to partial or complete charge neutralization of the basic groups in the proteins. (U.K.)

  13. Coagulation inhibitors and activated protein C resistance in recurrent pregnancy losses in Indian women

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    P Lalita Jyotsna

    2011-01-01

    Full Text Available Background: Thrombophilias, both acquired and inherited, have been investigated in the etiopathogenesis of unexplained recurrent pregnancy loss. Aim: To study coagulation inhibitors and activated protein C resistance (APCR in recurrent pregnancy losses (RPL occurring in second and third trimesters. Materials and Methods: A total of 30 pregnant women (group A with two or more recurrent unexplained fetal loses were evaluated for APCR, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies (APLA. Thirty age-matched controls were taken (group B comprising of pregnant women with at least one live issue. Statistical Analysis: Comparisons between two group frequencies and group means were made using Chi square test and Student′s t test, respectively. Results: Protein C and protein S levels were reduced in group A compared with group B and the difference was statistically significant (P=0.005 and P=0.032, respectively. The mean value of antithrombin was slightly reduced in group A compared with group B. APCR was observed in 16.6% cases and 3.3% controls. However, the difference was not statistically significant. APLA was observed in 20% cases and none of the controls. Of these, lupus anticoagulant was positive in 16.6% cases and anticardiolipin antibodies in 10% cases. Combined defects were seen in seven patients. Conclusion: There is a significant risk of RPL in pregnant women with thrombophilias. Therefore, screening for thrombophilias may be justified in pregnant women with unexplained recurrent fetal wastage, especially in second and third trimester.

  14. Arteriovenous thrombosis in chronic renal failure patients receving renal replacement therapy

    International Nuclear Information System (INIS)

    To determine the frequency of thrombotic complications and to identify factors associated with arteriovenous thrombosis in patients of chronic renal failure receiving renal replacement therapy. Of the 3000 patients evaluated, 61 End Stage Renal Disease (ESRD) patients on regular dialysis, having recent renal transplant, were selected for the study after informed consent. These patients had arteriovenous thrombosis with temporary central lines thrombosis and vascular access problems. Cases of congenital or acquired thrombotic disorders, e.g. with malignancy, DIC, liver disease, systemic lupus erythematosus or other immunologic diseases, pregnancy or women using oral contraceptives, were excluded. Similarly, patients taking any type of anticoagulant therapy during the preceding one week were not included in the study. Findings were recorded in a structured questionnaire. Laboratory analysis was done after clinical and radiological evaluation. Thrombophilia screening included antithrombin, protein C, protein S deficiencies and lupus anticoagulant. Forty-seven out of 61 patients selected were positive for thrombophilia screening with protein C deficiency in 26.2%, protein S deficiency in 16.3%, antithrombin in 5%, lupus anticoagulant in 13.1% and combined deficiency was observed in 16.3%. Of the 3000 patients, 61 with frequency of 2% were found to be deficient in one or had combined deficiency of these. Thus, the study of ESRD patients presenting with arteriovenous thromboembolism emphasizes the need to reconsider the perception that this clinical entity is rare and requires further studies. (author)

  15. [A case report of hereditary angioedema and studies on the serum components of complement, C1-inactivator and proteinase inhibitors during edema attack].

    Science.gov (United States)

    Mikami, A; Kohno, M

    1987-05-01

    Sixteen years old girl was admitted because of for the past ten years' frequent edema attack and abdominal pain. Laboratory examination revealed hypocomplementemia, marked depletion of the fourth component of complement and low level of C1-inactivator. Familial studies revealed that her mother was also hypocomplementemic and in low level of C1-inactivator. Serial studies performed on the alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin during edema attack. The fourth component of complement and C1-inactivator were markedly depleted in remission and attack. Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator during attack. In contrast, alpha 1-antitrypsin and alpha 2-macroglobulin did not change. The present study may explain that Hageman factor fragments, activated by C1s, promotes kinin generation via kalikrein activation. And the condition that complete functional deficiency of C1-inactivator was main role in this circuit. Fibrynolysis and late components of complement was less influence on edema attack. PMID:3610041

  16. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

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    Ishioka M

    2015-02-01

    Full Text Available Masamichi Ishioka, Norio Yasui-Furukori, Norio Sugawara, Hanako Furukori, Shuhei Kudo, Kazuhiko Nakamura Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan Objective: The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation.Method: The participants included 182 patients with schizophrenia (male =89, female =93 who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex and serum prolactin concentrations were measured.Results: Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002 and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026 but not of the thrombin–antithrombin complex level (r=0.117, ns among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion: The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. Keywords: prolactin, antipsychotics, venous thromboembolism

  17. Biosynthesis of heparin. Effects of n-butyrate on cultured mast cells

    International Nuclear Information System (INIS)

    Murine mastocytoma cells were incubated in vitro with inorganic [35S]sulfate, in the absence or presence of 2.5 mM n-butyrate, and labeled heparin was isolated. The polysaccharide produced in the presence of butyrate showed a lower charge density on anion exchange chromatography than did the control material and a 3-fold increased proportion of components with high affinity for antithrombin. Structural analysis of heparin labeled with [3H] glucosamine in the presence of butyrate showed that approximately 35% of the glucosamine units were N-acetylated, as compared to approximately 10% in the control material; the nonacetylated glucosamine residues were N-sulfated. The presence of butyrate thus leads to an inhibition of the N-deacetylation/N-sulfation process in heparin biosynthesis, along with an augmented formation of molecules with high affinity for antithrombin. Preincubation of the mastocytoma cells with butyrate was required for manifestation of either effect; when the preincubation period was reduced from 24 to 10 h the effects of butyrate were no longer observed. A polysaccharide formed on incubating mastocytoma microsomal fraction with UDP-[3H]glucuronic acid, UDP-N-acetylglucosamine, and 3'-phosphoadenylylsulfate in the presence of 5 mM butyrate showed the same N-acetyl/N-sulfate ratio as did the corresponding control polysaccharide, produced in the absence of butyrate. These findings suggest that the effect of butyrate on heparin biosynthesis depends on the integrity of the cell

  18. [The indicators of hemostasis and functions of liver in patients with acute lymphoblastic leucosis under manifestation of disease and induction therapy].

    Science.gov (United States)

    Tarasova, L N; Vladimirova, S G; Skolskaya, O Yu; Tcherepanova, V V

    2013-05-01

    The function of liver and synthesized by it components of blood coagulation were studied on sampling of 25 patients with acute lymphoblastic leucosis in the debut of disease and under implementation of induction of remission. Before treatment the hepatotoxicity was detected in 40% of patients. The reliable correlation between level of aspartataminotransferase and number of leucocytes and blasts (rs = 0.401 and rs = 0.406 correspondingly) testifies the role of leucosis cells in functional disorders of liver during this period of disease. Against the background of cytostatic therapy the signs of liver damage were presented in 76% of patients. The maximum expressed hepatotoxicity was observed at 9-14 day of treatment. The decrease of components of hemostasis synthesized in liver was observed at 16-21 day of treatment. During this time the synthesis of factors of thrombin complex, antithrombin III and plasminogen was disordered. The plasminogen also decreased at the expense of its consumption as a result of fibrinolysis activation validated by decreased level of D-dimers. It is proved that in the debut and under treatment acute lymphoblastic leucosis the danger of development of thrombotic hemorrhagic complications is related both with derangement of synthesis of procoagulants, antithrombin III and plasminogen and with their consumption in case of activation of intravascular coagulation with leucosis process and cytostatic. PMID:24006640

  19. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

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    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  20. Heparin cofactor II is degraded by heparan sulfate and dextran sulfate.

    Science.gov (United States)

    Saito, Akio

    2015-02-20

    Heparan sulfate normally binds to heparin cofactor II and modulates the coagulation pathway by inhibiting thrombin. However, when human heparin cofactor II was incubated with heparan sulfate, heparin cofactor II became degraded. Other glycosaminoglycans were tested, including hyaluronic acid, chondroitin sulfates, dermatan sulfate, and heparin, but only dextran sulfate also degraded heparin cofactor II. Pretreatment of heparan sulfate with heparinase reduced its heparin cofactor II-degrading activity. Heparan sulfate and dextran sulfate diminished the thrombin inhibitory activity of heparin cofactor II. Other serpins, including antithrombin III and pigment epithelium-derived factor, were also degraded by heparan sulfate. This is the first evidence of acidic polysaccharides exhibiting protein-degrading activity without the aid of other proteins. PMID:25600805

  1. Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders.

    Science.gov (United States)

    Cherniack, E Paul

    2011-03-01

    In this second of a two-part series analyzing the evidence for the use of organisms as medicine, the use of a number of different "bugs" (worms, leeches, snails, ticks, centipedes, and spiders) is detailed. Several live organisms are used as treatments: leeches for plastic surgery and osteoarthritis and the helminths Trichuris suis and Necator americanus for inflammatory bowel disease. Leech saliva is the source of a number of anticoagulants, including the antithrombin agent hirudin and its synthetic analogues, which have been approved for human use. Predatory arthropods, such as certain species of snails, spiders, scorpions, centipedes, and ticks provide a trove of potential analgesic peptides in their venom. A synthetic analogue of a snail venom peptide, ziconotide, has been approved for human use and is used as an alternative to opioids in severe pain cases. Arthropods, such as ticks, have venom that contains anticoagulants and centipede venom has a protein that corrects abnormalities in lipid metabolism. PMID:21438646

  2. Heparin kinetics

    International Nuclear Information System (INIS)

    The author has studied the kinetics of heparin and heparin fractions after intravenous administration in humans and in this thesis the results of this study are reported. Basic knowledge about the physico-chemical properties of heparin and its interactions with proteins resulting in anticoagulant and lipolytic effects are discussed in a review (chapter II), which also comprises some clinical aspects of heparin therapy. In chapter III the kinetics of the anticoagulant effect are described after intravenous administration of five commercial heparin preparations. A mathematical model is presented that fits best to these kinetics. The kinetics of the anticoagulant and lipolytic effects after intravenous injection of various 35S-radiolabelled heparin fractions and their relationship with the disappearance of the radiolabel are described in chapter IV. Chapter V gives a description of the kinetics of two radiolabels after injection of in vitro formed complexes consisting of purified, 125I-radiolabelled antithrombin III and various 35S-radiolabelled heparin fractions. (Auth.)

  3. Chorioamnionitis caused by Serratia marcescens in a non-immunocompromised host.

    Science.gov (United States)

    Shimizu, S; Kojima, H; Yoshida, C; Suzukawa, K; Mukai, H Y; Hasegawa, Y; Hitomi, S; Nagasawa, T

    2003-11-01

    A 26 year old pregnant woman with antithrombin III deficiency developed recurrent septicaemia with Serratia marcescens. In spite of the administration of antibiotics, high grade fever persisted. She subsequently manifested lower abdominal pain, and spontaneous abortion occurred. After the abortion, she became completely afebrile. The amnion was turbid, and microscopic examination of the placenta showed haemorrhage and massive infiltration of neutrophils, suggestive of infectious chorioamnionitis. Pulsed field gel electrophoresis showed that isolates from the blood, urine, and vaginal discharge were genetically identical. Intravenous pyelography revealed that she had a bilateral completed double ureter. It was thought that a urinary tract anomaly caused infection with S marcescens, and the pathogen spread to the chorioamnion via the bloodstream. This is the first report of chorioamnionitis caused by S marcescens in a non-immunocompromised host. In addition, these findings indicate that the chorioamnion can serve as a site for persistent infection in normal pregnancies. PMID:14600137

  4. A STUDY ON EARLY ONSET CORONARY ARTERY DISEASE IN RELATION TO HYPER HOMOCYSTEINEMIA IN PATIENTS YOUNGER THAN 40 YEARS OF AGE

    Directory of Open Access Journals (Sweden)

    Sugunakar

    2013-12-01

    Full Text Available ABSTRACT: There has been a rising incidence of myocardial infarction as a whole in recent times much because of changing pattern of life style , urbanization , changing food habits , and increase in cigarette smoking , psycho social stress and increase in the incidence of diabete s mellitus. Adding to this there is drastic increase in the incidence of MI in young people much to the influence of novel risk factors which are of current debate especially homocysteine , lipoprotein little (a , fibrinogen , anticardiolipin antibody , prote in C , protein S and antithrombin deficiency. The first ever positive prospective study on plasma homocystein and CAD was reported in 1992 by Selhubetal who showed an association of plasma homocysteine with extracranial carotid stenosis in the elderly. We r eport our study to analyze the special risk factors of MI in patients younger than 40years of age in special reference to serum homocysteine levels.

  5. Cerebral venous sinus thrombosis as presenting feature of ulcerative colitis.

    Science.gov (United States)

    Ennaifer, R; Moussa, A; Mouelhi, L; Salem, M; Bouzaidi, S; Debbeche, R; Trabelsi, S; Najjar, T

    2009-01-01

    Thrombosis is a well recognized complication of inflammatory bowel disease that occurs in 1.3 to 6.4% of patients, however, cerebral vascular involvement is unusual. We present the case of a 16-year-old female in whom cerebral venous thrombosis was the presenting symptom of an active ulcerative pancolitis. Thrombophilia screen (plasma levels of proteins C and S, antithrombin, antibeta2-glycoprotein, lupus anticoagulant and anticardiolipin antibodies, activated protein C resistance, homocystein level antinuclear antibodies) was negative. The patient was successfully treated with anticoagulant therapy, phenobarbital and sulfasalazine. Cerebral venous thrombosis is an exceptional presenting feature of ulcerative colitis. Disease activity may play a major role in the occurrence of thrombosis. PMID:19902870

  6. Etiological analysis of presumed perinatal stroke.

    Science.gov (United States)

    Kocaman, Canan; Yilmaz, Yuksel

    2012-02-01

    This study aimed to investigate the maternal, pre- and perinatal, and prothrombotic factors with congenital hemiparesis due to presumed perinatal stroke (PPS). Prothrombotic risk factors including protein C and S, antithrombin III, lipoprotein (a), homocystein, factor VIII levels; anticardiolipin antibodies and lupus anticoagulant; methylenetetrahydrofolate reductase mutations, factor V Leiden, prothrombin G20210A mutations were investigated. Arterial ischemic stroke was detected in 60% and periventricular venous infarction in 40%. At least one prothrombotic risk factor was present in 69%, two in 17%, and three or more in 8.5% of cases. The most common combination was methylenetetrahydrofolate reductase C677T and factor V Leiden heterozygosity. The etiology and pathogenesis of PPS is still unclear. According to this study, most of the patients with PPS might have one or more prothrombotic risk factors and certain prenatal risk factors including intrauterine growth retardation, twin gestation and preeclampsia might be related to PPS. PMID:21561729

  7. 一例接受阿那曲唑和预防性那屈肝素治疗的乳腺癌妇女发生肺动脉栓塞%Pulmonary thromboembolism in a breast cancer woman receiving anastrozole and prophylactic nadroparin

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hormonal treatment is widely accepted for the adjuvant treatment of breast carcinoma, in order to get a reduction in the synthesis of estrogen or to block estrogen receptors in tumors that are hormone dependent. There are multiple risk factors that contribute to hypercoagulability in cancer patients. Hormonal therapy and chemotherapy are the main one. Type and stage of malignancy are other risk factors; so age, immobility and surgery are. The main antineoplastic therapy with definitive hypercoagulable effect is tamoxifen, because it can cause reduction in the concentrations of antithrombin Ⅲ and protein C. Here, we explain the case of a 75-year-old postmenopausal woman presenting with breast carcinoma who suffered from pulmonary thromboembolism during the treatment with anastrozole although she was taking nadroparin.

  8. The coagulopathy in sepsis: significance and implications for treatment

    Directory of Open Access Journals (Sweden)

    Berardino Pollio

    2011-09-01

    Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

  9. COAGULATION ACTIVITY IN LIVER DISEASE

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    Dr. Sheikh Sajjadieh Mohammad Reza

    2009-07-01

    Full Text Available Patients with advanced hepatic failure may present with the entire spectrum of coagulation factor deficiencies. This study was designed to determine laboratory abnormalities in coagulation in chronic liver disease and the association of these abnormalities with the extent of chronic hepatitis and cirrhosis. Coagulation markers were assayed in 60 participants: 20 patients with chronic hepatitis, 20 patients with cirrhosis, and 20 healthy individuals (control. Plasma levels of anti-thrombin III were determined by a chromogenic substrate method, and plasma concentrations of fibrinogen were analyzed by the Rutberg method. Commercially available assays were used for laboratory coagulation tests. The levels of coagualation activity markers in patients with chronic liver disease were significantly different in comparison to those in healthy participants. These results indicate the utility of measuring markers for coagulation activity in determining which cirrhosis patients are more susceptible to disseminated intravascular coagulation.

  10. Inhibition of coagulation factors by recombinant barley serpin BSZx

    DEFF Research Database (Denmark)

    Dahl, Søren Weis; Rasmussen, S.K.; Petersen, L..C.;

    1996-01-01

    leukocytes, a fungal trypsin and three subtilisins, Thrombin, plasma kallikrein, factor VIIa/tissue factor and factor Xa were inhibited by BSZx at heparin independent association rates (k(ass)) of 4.5 x 10(3)-1.3 x 10(5) M(-1) s(-1) at 22 degrees C. Only factor Xa turned a significant fraction of BSZx over...... as substrate, Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P-1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass) = 1-2 x 10(2) M(-1) s(-1)) whereas...... factor XIIa, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected, The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while...

  11. Structural characterization of pharmaceutical heparins prepared from different animal tissues.

    Science.gov (United States)

    Fu, Li; Li, Guoyun; Yang, Bo; Onishi, Akihiro; Li, Lingyun; Sun, Peilong; Zhang, Fuming; Linhardt, Robert J

    2013-05-01

    Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient. PMID:23526651

  12. [The correction of functional disorders of the hemostatic system and of the rheological properties of the blood in dogs in the late period of hemorrhagic shock by the intravenous transfusion of lactoprotein].

    Science.gov (United States)

    Oborin, A N; Uspenskiĭ, B A; Kondratskiĭ, B A; Mindiuk, M V

    1992-01-01

    In 9 dogs with severe hemorrhagic shock, the effect of hemocorrector "Lactoprotein" on the indices of coagulative hemostasis and rheologic blood properties was studied. It was established that in intravenous transfusion of lactoprotein at a dose of 10 ml/kg permitting to lead the animals out from the state of shock, the syndromes of disseminated intravascular coagulation and high viscosity of the blood were cupped off. However, by the end of 48 hours of observation, fibrinogen level in the blood of the animals increased sharply, while antithrombin-III concentration and hematocrit decreased. Together with recommendation to use lactoprotein in the complex of shock therapy at all the stages of medical evacuation, the conclusion about necessity to perform at the early postshock period the differential component hemo- and anticoagulative therapy has been made. PMID:1291772

  13. [Variations in hemostasis and fibrinolysis during the treatment of acute myocardial infarct (AMI) with tissue-type plasminogen activator (TTPA). A study of 17 cases].

    Science.gov (United States)

    Izaguirre Avila, R; Ruiz de Chávez Cervantes, A; Villavicencio, R; Gómez Trigos, A; Mar Chavira, R; Spíndola, M del C; Casanova, J M

    1993-01-01

    The aim of this trial was to estimate changes in the coagulation and fibrinolysis systems during the thrombolytic treatment with recombinant human tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction and correlate with hemorrhagic complications. We studied 17 patients with a 3 hours-continuous systemic infusion of 100 mg of rt-PA. Prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen splits products, plasminogen, alfa-2-antiplasmin (a-2AP) and antithrombin III (AT-III) were performed before, during and after infusion. Most patients showed lengthening coagulation times. Fibrinogen and plasminogen were decreased and PDF was increased. No variations in alpha-2AP or AT-III were observed. The recuperation of fibrinogen levels occurred in 3 hours and there was hyperfibrinogenemia after day 3. No hemorrhagic complication was observed in patients with abnormalities in these coagulation or fibrinolytic tests. PMID:8347053

  14. Integrated laboratory coagulation tests in hypercoagulation diagnosis and thrombosis risk assessment. Part I. The pathophysiology of thrombosis and hypercoagulation

    Directory of Open Access Journals (Sweden)

    E. N. Lipets

    2015-01-01

    Full Text Available Thrombosis is a fatal hemostatic disorders occurring in various conditions ranging from pregnancy and surgery to cancer, sepsis and heart attack. Despite the availability of different anticoagulants and accumulated clinical experience, proving their effectiveness, thrombosis remains a major cause of morbidity and mortality. This is largely due to the fact that conventional laboratory coagulation tests are not sufficiently sensitive to the hypercoagulable state, and they are difficult to use for assessing the risk of thrombosis. Specific molecular markers (D-dimers, fibrinopeptide, thrombin-antithrombin complex are more effective, but also have a large number of disadvantages. A possible solution is the use of integrated test, which simulate in vitro the majority of the physiological coagulation processes. In the first part of this paper the biochemical processes that cause the risk of thrombosis were discussed.

  15. Molecular evolution of serpins: homologous structure of the human α1-antichymotrypsin and α1-antitrypsin genes

    International Nuclear Information System (INIS)

    α1-Antichymotrypsin belongs to a supergene family that includes α1-antitrypsin, antithrombin III, ovalbumin, and angiotensinogen. The human chromosomal α1-antichymotrypsin gene has been cloned and its molecular structure established. The gene is approximately 12 kb in length and contains five exons and four introns. The locations of the introns within the α1-antichymotrypsin gene are identical with those of the human α1-antitrypsin and angiotensinogen genes. Other members of this supergene family contain introns located at nonhomologous positions of the genes. The homologous organization of the α1-antichymotrypsin and α1-antitrypsin genes corresponds with the high degree of homology between their protein sequences and suggest that these loci arose by recent gene duplication. A model is presented for the evolution of both the genomic structure and the protein sequences of the serine protease inhibitor superfamily

  16. Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications.

    Science.gov (United States)

    Erginer, Merve; Akcay, Ayca; Coskunkan, Binnaz; Morova, Tunc; Rende, Deniz; Bucak, Seyda; Baysal, Nihat; Ozisik, Rahmi; Eroglu, Mehmet S; Agirbasli, Mehmet; Toksoy Oner, Ebru

    2016-09-20

    Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications. PMID:27261753

  17. [Anticoagulant activity of low-molecular-weight sulfated derivatives of galactomannan from Cyamopsis tetragonoloba (L.) seeds].

    Science.gov (United States)

    Mestechkina, N M; Shcherbukhin, V D; Bannikova, G E; Varlamov, V P; Drozd, N N; Tolstenkov, A S; Makarov, V A; Tikhonov, V E

    2008-01-01

    Galactomannan from seeds of Cyamopsis tetragonoloba (L.) Taub. (guar) was depolymerized using immobilized enzymatic preparation celloviridin. A set of fragments whose molecular weights varied from 12.6 to 245.6 kDa was obtained. Sulfated derivatives of components of all fractions were synthesized, in which the content of HSO3(-) groups was 48.05% +/- 2.31. All preparations exhibited anticoagulant activity, which was recorded in vitro in two tests--aIIa and aXa. The antithrombin activity (aIIa) was high (up to 65-87 U/mg) and did not depend on the molecular weight of a sulfated derivative; in the second test (aXa), the effect of molecular weight was observed. Biospecific electrophoresis allowed us to detect the ability of galactomannan sulfates to form complexes with protamine sulfate, a classic antidote to heparin. PMID:18491607

  18. Hemostatic response to surgical neutering via ovariectomy and ovariohysterectomy in dogs

    DEFF Research Database (Denmark)

    Moldal, Elena R.; Kristensen, Annemarie Thuri; Peeters, Marijke E.;

    2012-01-01

    Objective-To investigate the hemostatic response to surgery and compare the response for ovariohysterectomy with that for ovariectomy and to evaluate the usefulness of thromboelastography on plasma samples. Animals-42 female dogs. Procedures-Dogs were assigned to undergo ovariohysterectomy or...... antigen, fibrinogen, antithrombin, and protein C; activity of factor VIII; activated partial thromboplastin time; prothrombin time; and thrombin time. The fibrinolytic response was assessed via concentrations of D-dimer, plasminogen, and α-2-antiplasmin (plasmin inhibitor). Results-Substantial hemostatic...... prothrombin and thrombin times. The dogs also typically had activation of the fibrinolytic system, as evidenced by increased postoperative concentrations of D-dimer, plasminogen, and plasmin inhibitor. Differences between the 2 groups could not be detected for any variables. Conclusions and Clinical Relevance...

  19. TACTIC: Trans-Agency Consortium for Trauma-Induced Coagulopathy.

    Science.gov (United States)

    Mann, K G; Freeman, K

    2015-06-01

    Trauma-induced coagulopathy (TIC) includes heterogeneous coagulopathic syndromes with different underlying causes, and treatment is challenged by limited diagnostic tests to discriminate between these entities in the acute setting. We provide an overview of progress in understanding the mechanisms of TIC and the context for several of the hypotheses that will be tested in 'TACTIC'. Although connected to ongoing clinical trials in trauma, TACTIC itself has no intent to conduct clinical trials. We do anticipate that 'early translation' of promising results will occur. Functions anticipated at this early translational level include: (i) basic science groundwork for future therapeutic candidates; (ii) development of acute coagulopathy scoring systems; (iii) coagulation factor composition-based computational analysis; (iv) characterization of novel analytes including tissue factor, polyphosphates, histones, meizothrombin and α-thrombin-antithrombin complexes, factor XIa, platelet and endothelial markers of activation, signatures of protein C activation and fibrinolysis markers; and (v) assessment of viscoelastic tests and new point-of-care methods. PMID:26149052

  20. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014.

    Science.gov (United States)

    Byrne, Robert A; Joner, Michael; Kastrati, Adnan

    2015-12-14

    Modern-day stenting procedures leverage advances in pharmacotherapy and device innovation. Patients treated with contemporary antiplatelet agents, peri-procedural antithrombin therapy and new-generation drug-eluting stents (DES) have excellent outcomes over the short to medium term. Indeed, coupled with the reducing costs of these devices in most countries there remain very few indications where patients should be denied treatment with standard-of-care DES therapy. The two major causes of stent failure are stent thrombosis (ST) and in-stent restenosis (ISR). The incidence of both has reduced considerably in recent years. Current clinical registries and randomized trials with broad inclusion criteria show rates of ST at or strategies which circumvent the need for chronically indwelling stents--such as drug-coated balloons or fully bioresorbable stents-more data are needed before the wider use of these therapies can be advocated. PMID:26417060

  1. Inherited thrombophilia and reproductive disorders

    Science.gov (United States)

    Liatsikos, Spyros A.; Tsikouras, Panagiotis; Manav, Bachar; Csorba, Roland; von Tempelhoff, Georg Friedrich; Galazios, Georgios

    2016-01-01

    Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia. PMID:27026779

  2. Predictors of fatal outcomes resulting from acute Escherichia coli mastitis in dairy cows.

    Science.gov (United States)

    Hagiwara, Seiichi; Mori, Kouichiro; Nagahata, Hajime

    2016-06-01

    To evaluate the prognostic criteria for identifying cows at an increased risk of a fatal outcome from acute Escherichia coli mastitis, the potential cut-off values for five diagnostic parameters associated with a high mortality were determined by receiver operator characteristic curve analysis. These criteria were hematocrit value >32%, blood non-esterified fatty acid concentration >0.4 mEq/l, antithrombin activity <120%, platelet count <15 × 10(4)/ml and presence of dysstasia. Exceeding the cut-off values for at least three parameters on day 2 after onset predicted fatality (predictive value 87.5). When these prognostic criteria were applied to 34 clinical cases, cows that met three criteria were seven times more likely to die than cows that met fewer than three criteria. PMID:26875836

  3. Alterations in coagulation following major liver resection.

    Science.gov (United States)

    Mallett, S V; Sugavanam, A; Krzanicki, D A; Patel, S; Broomhead, R H; Davidson, B R; Riddell, A; Gatt, A; Chowdary, P

    2016-06-01

    The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period. Levels of the procoagulant factors II, V, VII and X initially fell, but V and X returned to or exceeded normal range by postoperative day five. Levels of factor VIII and Von Willebrand factor were significantly elevated from postoperative day one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained significantly depressed on postoperative day five (p = 0.01). Overall, the imbalance between pro- and anticoagulant factors suggested a prothrombotic environment in the early postoperative period. PMID:27030945

  4. Modeling the microscopic electrical properties of thrombin binding aptamer (TBA) for label-free biosensors

    CERN Document Server

    Alfinito, Eleonora; Cataldo, Rosella; De Nunzio, Giorgio; Giotta, Livia; Guascito, Maria Rachele

    2016-01-01

    Aptamers are chemically produced oligonucleotides, able to bind a variety of targets such as drugs, proteins and pathogens with high sensitivity and selectivity. Therefore, aptamers are largely employed for producing label-free biosensors, with significant applications in diagnostics and drug delivery. In particular, the anti-thrombin aptamers are biomolecules of high interest for clinical use, because of their ability to recognize and bind the thrombin enzyme. Among them, the DNA 15-mer thrombin-binding aptamer (TBA), has been widely explored concerning both its structure, which was resolved with different techniques, and its function, especially about the possibility of using it as the active part of biosensors. This paper proposes a microscopic model of the electrical properties of TBA and the aptamer-thrombin complex, combining information from both structure and function. The novelty consists in describing both the aptamer alone and the complex as an impedance network, thus going deeper inside the issues...

  5. 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. PMID:26666430

  6. Cerebral venous thrombosis in adults: A study of 50 cases from Iran

    Directory of Open Access Journals (Sweden)

    Lotfi J

    2001-08-01

    Full Text Available The study was conducted to determine the clinical pattern and etiology of cerebral venous thrombosis in Iran. Records of all adult patients admitted with a clinical diagnosis and MRI of cerebral venous thrombosis from 1993 through 1999 in three major hospitals of Tehran, Iran were reviewed. Fifty patients (39 women, 11 men aged 14 to 56 years were identified. Headache the most frequent and often the earliest symptom, was encountered in 82 percent and papilledema, the most frequent sign in 56 percent of cases. Infection was the cause of cerebral venous thrombosis in 26 percent of our cases. Other causes included oral contraceptive (32 percent, vasculitis (6 percent, Behcet's disease (4 percent, postpartum state (4 percent, myeloproliferative disease (2 percent, ulcerative colitis (2 percent, antithrombin III deficiency (2 percent and diabetic ketoacidosis (2 percent. Oral contraceptive was recognized as the most common etiology. Infection is an important cause whereas procoagulation disorders are uncommon.

  7. 肿瘤性DIC实验室指标诊断阳性率分析%Analysis of Laboratory Index Positive Diagnostic Rate of Malignancy Tumor with Disseminated Intravascular Coagulation

    Institute of Scientific and Technical Information of China (English)

    尹茜

    2015-01-01

    目的探讨恶性肿瘤合并弥散性血管内凝血(Dis eminated Intravascular Coagulation,DIC)时,实验室检测指标DIC三项咱D-二聚体(D-dimer,DD)、纤维蛋白原降解产物(Fibrinogen Degradation Product,FDP)、抗凝血酶原II(AntithrombinII,ATII)暂和凝血常规咱凝血酶原时间(Prothrombin Time,PT)、活化部分凝血酶原时间(Activated Partial Prothrombin Time,APTT)、纤维蛋白原(Fibrinogen,FIB)检测阳性率的情况,并比较各组之间的有效性。方法回顾性分析78例恶性肿瘤患者的临床及实验室资料。结果 DD是恶性肿瘤合并DIC时诊断阳性率最高的指标。结论在肿瘤合并DIC时,DD的诊断价值最有意义。%Objective To explore malignancy tumor with disseminated intravascular coagulation,which laboratory index of D-dimer、fibrinogen degradation product、AntithrombinI I、prothrombin time、activated partial prothrombin time、fibrinogen are the positive indicator.Methods Clinical and laboratory data for 78 cases of DIC with malignancy tumor were retrospectively analysed.Result:D-dimer is the most ef ective indicator of DIC with malignancy tumor.Results The diagnosis index of:DD is the highest positive rate of malignant tumor complicated with DIC. Conclusion In the tumor with DIC, the diagnostic value of DD was the most significant.

  8. Systemic coagulation parameters in mice after treatment with vascular targeting agents

    Directory of Open Access Journals (Sweden)

    Gottstein Claudia

    2005-12-01

    Full Text Available Abstract Background Vascular targeting of malignant tumors has become a clinically validated new treatment approach with clear patient benefit. However clinical studies have also revealed that some types of vascular targeting agents (VTAs are prone to coagulation system side effects. It is therefore essential to predetermine coagulation parameters in preclinical studies. As of to date, this has rarely been done, predominantly due to technical issues. The goal of this study was to establish and apply a standardized process, whereby systemic coagulation activation can be routinely measured in mice. Results We have evaluated a number of sampling techniques and coagulation tests regarding their suitability for this purpose. We were able to adapt two assays measuring soluble fibrin, a marker for a prethrombotic status. Thus, soluble fibrin could be measured for the first time in mice. All assays were validated in a positive control model for systemic coagulation activation, i.e. lipopolysaccharide-induced endotoxemia. Based on our results, we selected a panel of coagulation tests, which are both feasable and informative for preclinical testing of VTAs: soluble fibrin, thrombin-antithrombin complexes, free antithrombin III, white blood cell counts and platelet counts. The effect of tumor transplants on coagulation parameters was evaluated using this panel. We then applied this set of assays in treatment studies with a VTA developed in our laboratory to investigate a potential systemic coagulation activation. Conclusion We have established a standardized panel of assays that can be used to test murine blood samples for coagulation activation in preclinical studies. All tests are feasible to perform in any research laboratory without specialized equipment. In addition, this is the first report to measure soluble fibrin, an early marker of systemic coagulation activation, in mice. The panel was applied on tumor bearing mice and mice treated with a VTA

  9. Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

    Science.gov (United States)

    George, Reema; Sivadasanpillai, Harikrishnan; Jayakumari, Narayani; Bhatt, Anugya; Thulaseedharan, Jissa V; Tharakan, Jaganmohan A

    2016-07-01

    Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD. PMID:27382201

  10. Deciphering the main venom components of the ectoparasitic ant-like bethylid wasp, Scleroderma guani.

    Science.gov (United States)

    Zhu, Jia-Ying

    2016-04-01

    Similar to venom found in most venomous animals, parasitoid venoms contain a complex cocktail of proteins with potential agrichemical and pharmaceutical use. Even though parasitoids are one of the largest group of venomous animals, little is known about their venom composition. Recent few studies revealed high variated venom composition existing not only in different species but also between closely related strains, impling that increasing information on the venom proteins from more greater diversity of species of different taxa is key to comprehensively uncover the complete picture of parasitoid venom. Here, we explored the major protein components of the venom of ectoparasitic ant-like bethylid wasp, Scleroderma guani by an integrative transcriptomic-proteomic approach. Illumina deep sequencing of venom apparatus cDNA produced 49,873 transcripts. By mapping the peptide spectral data derived from venom reservoir against these transcripts, mass spectrometry analysis revealed ten main venom proteins, including serine proteinase, metalloprotease, dipeptidyl peptidase IV, esterase, antithrombin-III, acid phosphatase, neural/ectodermal development factor IMP-L2 like protein, venom allergen 3, and unknown protein. Interestingly, one serine proteinase was firstly identified with rarely high molecular weight about 200 kDa in parasitoid venom. The occurrence of abundant acid phosphatase, antithrombin-III and venom allergen 3 demonstrated that S. guani venom composition is similar to that of social wasp venoms. All identified venom genes showed abundantly biased expression in venom apparatus, indicating their virulent functions involved in parasitization. This study shed light on the more better understanding of parasitoid venom evolution across species and will facilitate the further elucidation of function and toxicity of these venom proteins. PMID:26853496

  11. Evaluation of selected thrombotic factors among pregnant women with preeclampsia and normal pregnant women

    Science.gov (United States)

    Saghafi, Nafiseh; Mohammadzadeh Vatanchi, Atieh; Tara, Fatemeh; Pourali, Leila; Dadgar, Salmeh

    2014-01-01

    Background: Preeclampsia is one of the common complications during pregnancy with considerable maternal and fetal mortality and morbidity. Hypercoagulability due to thrombophilic factors is discussed as the etiology involved in this disease. Objective: The aim of this study was to evaluate selected thrombotic factors among pregnant women with preeclampsia and normal pregnant women. Materials and Methods: This case-control study was performed on 200 pregnant women at third trimester of pregnancy between 2012 and 2013. 100 pregnant women admitted to Qaem and Imam Reza hospitals of Mashhad, due to preeclampsia, were selected as case group and 100 pregnant women without preeclampsia referred to OB/GYN clinic of these hospitals as control group. Blood samples were taken from two groups for evaluation of the coagulation factors including factor V Leiden, protein C, protein S, antithrombin III, anti-cardiolipin antibodies, and lupus anticoagulant antibodies. Results: Two groups were not significantly different in terms of maternal age and parity (p>0.05). Levels of factor V Leiden, protein C, protein S, antithrombin III, anti-cardiolipin antibodies and lupus anticoagulant antibodies were compared between two groups. The number of patients with abnormal factor V Leiden and protein C was significantly higher in case group than in the control group (p<0.01 respectively), but other factors were not significant different between two groups. Thrombophilia disorders were significantly more in case group compared to control (p<0.001). Conclusion: The risk of thrombophilia disorders is higher in preeclamptic patients than normal pregnant women. PMID:25709635

  12. Expression and Characterization of Gly-317 Variants of Factor IX Causing Variable Bleeding in Hemophilia B Patients.

    Science.gov (United States)

    Lu, Qiuya; Yang, Likui; Manithody, Chandrashekhara; Wang, Xuefeng; Rezaie, Alireza R

    2015-06-23

    We recently identified two hemophilia B patients who carried Gly-317 to Arg (FIX-G317R) or Gly-317 to Glu (FIX-G317E) substitutions in their FIX gene. The former mutation caused severe and the latter moderate bleeding in afflicted patients. To understand the molecular basis for the variable clinical manifestation of Gly-317 mutations, we prepared recombinant G317R and G317E derivatives of FIX and compared their kinetic properties to those of recombinant wild-type FIX in appropriate assay systems. Both physiological activators, factor XIa and extrinsic Tenase (factor VIIa-tissue factor), activated both zymogen variants with an ∼1.5-fold elevated K(m); however, extrinsic Tenase activated FIX-G317E with an ∼2-fold improved k(cat). By contrast to zymogen activation, the catalytic activities of both FIXa-G317R and FIXa-G317E enzymes toward the natural substrate, factor X, were dramatically (>4 orders of magnitude) impaired, but their apparent affinity for interaction with factor VIIIa was only slightly (<2-fold) decreased. Further studies revealed that the reactivity of FIXa-G317R and FIXa-G317E with antithrombin has been impaired 10- and 13-fold, respectively, in the absence and 166- and 500-fold, respectively, in the presence of pentasaccharide. As expected, the clotting activities of FIX variants could not be measured by the aPTT assay. These results implicate a critical role for Gly-317 in maintaining normal catalytic function for FIX/FIXa in the clotting cascade. The results further suggest that improved k(cat) of FIX-G317E activation in the extrinsic pathway together with dramatically impaired reactivity of FIXa-G317E with antithrombin may account for the less severe bleeding phenotype of a hemophilia B patient carrying the FIX-G317E mutation. PMID:26023895

  13. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor.

    Science.gov (United States)

    de Agostini, A; Lijnen, H R; Pixley, R A; Colman, R W; Schapira, M

    1984-06-01

    To define the factors responsible for the inactivation of the active fragment derived from Factor XII (Factor XIIf ) in plasma, we studied the inactivation kinetics of Factor XIIf in various purified and plasma mixtures. We also analyzed the formation of 125I-Factor XIIf -inhibitor complexes by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In purified systems, the bimolecular rate constants for the reactions of Factor XIIf with C-1-inhibitor, alpha 2-antiplasmin, and antithrombin III were 18.5, 0.91, and 0.32 X 10(4) M-1 min-1, respectively. Furthermore, SDS-PAGE analysis revealed that 1:1 stoichiometric complexes were formed between 125I-Factor XIIf and each of these three inhibitors. In contrast, kinetic and SDS-PAGE studies indicated that Factor XIIf did not react with alpha 1-antitrypsin or alpha 2-macroglobulin. The inactivation rate constant of Factor XIIf by prekallikrein-deficient plasma was 14.4 X 10(-2) min-1, a value that was essentially identical to the value predicted from the studies in purified systems (15.5 X 10(-2) min-1). This constant was reduced to 1.8 X 10(-2) min-1 when Factor XIIf was inactivated by prekallikrein-deficient plasma that had been immunodepleted (less than 5%) of C-1-inhibitor. In addition, after inactivation in normal plasma, 74% of the active 125I-Factor XIIf was found to form a complex with C-1-inhibitor, whereas 26% of the enzyme formed complexes with alpha 2-antiplasmin and antithrombin III. Furthermore, 42% of the labeled enzyme was still complexed with C-1-inhibitor when 125I-Factor XII was inactivated in hereditary angioedema plasma that contained 32% of functional C-1-inhibitor. This study quantitatively demonstrates the dominant role of C-1-inhibitor in the inactivation of Factor XIIf in the plasma milieu. PMID:6725552

  14. Contraception and Thrombophilia - A statement from the German Society of Gynecological Endocrinology and Reproductive Medicine (DGGEF e. V. and the Professional Association of the German Gynaecologists (BVF e. V.

    Directory of Open Access Journals (Sweden)

    Rabe T

    2011-01-01

    Full Text Available Venous thromboembolism (VTE is responsible for more than half a million deaths annually in the European Union, most in older people following surgery, but some in women of reproductive age using various hormonal contraceptives. In some parts of the population inherited defects of the blood coagulation system (factor V Leiden, prothrombin G20210A, protein C, protein S and antithrombin deficiency are responsible for an increased risk of VTE, which is also influenced by concomitant factors: e.g. long-distance travel, immobilisation, advanced age, cigarette smoking, high BMI, surgery, malignancy, fluid loss, pregnancy, oral contraceptive use and hormone replacement therapy (HRT. Laboratory testing: General screening for thrombophilia prior to the prescription of oral contraceptives (OC is not recommended. Laboratory testing for thrombophilia should be limited to women with a positive family and/or personal history of VTE or vascular occlusion. – Factor V Leiden is by far the most common congenital thrombophilia. Heterozygous factor V Leiden (5-fold increased VTE risk is present in 3–13%, homozygous factor V Leiden (10-fold increased VTE risk in up to 0.2–1% of people of European origin. – Prothrombin mutation G20210A: Autosomal dominant mutation inheritance (2% of people of European origin leads to a 3-fold increase in VTE risk is substantially increased if one or more additional risk factors are present such as factor V Leiden or protein C, S, or antithrombin deficiency. – Protein C and protein S: VTE risk increases with protein C or S deficiency (odds-ratio 3–15 and 5–11, respectively. – Antithrombin deficiency leads to a 4 to 50-fold increase in VTE risk depending on the type of deficiency. Female hormonal contraceptives containing progestogens with or without combination with a synthetic estrogens (mainly ethinylestradiol [EE] or a natural estrogen (e.g. estradiol or its derivative estradiol valerate affect the incidence of VTE in

  15. 体积排阻色谱法测定低分子量肝素抗凝血因子Xa的活性%An assay for anti-factor Xa activity of low molecular weight heparins by high performance liquid size exclusion chromatography

    Institute of Scientific and Technical Information of China (English)

    张倩倩; 康经武

    2013-01-01

    发展了一种基于体积排阻色谱测定低分子量肝素(LMWH)抗凝血活性的方法.利用肝素与抗凝血酶Ⅲ(ATⅢ)结合后可增强ATⅢ对凝血因子Xa (FXa)抑制作用的原理,通过测定加入LMWH后FXa水解其生色底物产生对硝基苯胺(pNA)这一反应的抑制程度确定LMWH的活性.首先将含有一定浓度LMWH的缓冲溶液与ATⅢ溶液混合,然后依次加入FXa和生色底物,分别孵育一段时间.底物被FXa水解,产生游离的pNA.体积排阻色谱可将小分子产物pNA与其他大分子分离开,因而可以在pNA的最大吸收波长下得到高灵敏度的测定,并且不再受其他成分的干扰.该方法重复性好,灵敏度高,极大地减少了样品的消耗量,降低了成本,并且还可进行各种复杂样品(如血浆)中LMWH抗FXa活性的监测.%The "gold standard" assay for monitoring low molecular weight heparins (LMWHs) activity is the chromogenic-based anti-factor Xa assay.The methodology of an anti-factor Xa assay is that LMWH is added to a known amount of excess factor Xa and excess antithrombin.It will bind to antithrombin and form a triplet complex with factor Xa,inhibiting the activity of factor Xa.However,the residual factor Xa can still hydrolyze chromogenic peptide substrate,releasing the chromophore for photometric detection.The absorbance is inversely proportional to the amount of heparin/LMWH.The results are given in anticoagulant concentration in units/ mL of anti-factor Xa,such that high values indicate high levels of anticoagulation and low values indicate low levels of anticoagulation.Herein,a novel assay method for anti-FXa activity of LMWHs using high performance liquid size exclusion chromatography (SEC) is reported,in which antithrombin m (AT m) was diluted by the buffer solution contained LMWHs.Subsequently,exogenous FXa and p-nitroaniline coupled peptide substrate were added and incubated for a period,separately.The resulting mixture was separated based on size by SEC

  16. Análise da freqüência de trombofilia em pacientes com atrofia branca de Milian Frequency analysis of thrombophilia in patients with atrophie blanche

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    Aline Donati Jorge

    2007-02-01

    Full Text Available FUNDAMENTOS - Atrofia branca de Milian ou vasculopatia livedóide é entidade clinicopatológica rara, cuja patogênese não é completamente compreendida. OBJETIVOS - Avaliar casos de atrofia branca de Milian para verificar a prevalência de diversas trombofilias. MATERIAL E MÉTODOS - Quatorze pacientes foram submetidos a exames laboratoriais incluindo pesquisa de fator V (Leiden, protrombina mutante, dosagem de antitrombina, proteína S e C, pesquisa de anticorpos anticardiolipina e anticoagulante lúpico, dosagem de homocisteína e pesquisa da mutação da metilenotetraidrofolatoredutase. RESULTADOS - Dos nove doentes cujos critérios de inclusão foram preenchidos para análise da freqüência de trombofilia, foram encontrados quatro com fatores relacionados à trombofilia: deficiência da antitrombina (um caso, deficiência da proteína S (um caso, mutação da metilenotetraidrofolatoredutase com hiperhomocisteinemia (um caso e presença de anticorpo anticardiolipina (um caso. CONCLUSÃO - Apesar de este estudo não apresentar casuística que possibilite a comparação com a população geral, os dados sugerem a presença de eventos geradores de trombofilia nesses doentes, contribuindo para adoção sistemática de um protocolo de investigação de trombofilia nos doentes portadores de vasculopatia livedóide no Brasil.INTRODUCTION: Atrophie blanche, or livedoid vasculopathy, is a rare clinicopathological entity of unknown etiology. A "thrombo-occlusive process" theory has recently been accepted. OBJECTIVES: To search the presence of several thrombophilic abnormalities in patients with livedoid vasculopathy. METHODS: Fourteen patients were evaluated and tested for factor V Leiden, prothrombin 20210G/A variant, antithrombin, C and S proteins, anticardiolipin and lupus anticoagulant antibodies, homocysteine and methylenetetrahydrofolate reductase mutation. RESULTS: Nine patients met all criteria to be included in the analysis and four of

  17. Quality of therapeutic plasma-requirements for marketing authorization.

    Science.gov (United States)

    Heiden, Margarethe; Seitz, Rainer

    2002-10-31

    Fresh frozen plasma (FFP) contains higher levels of intact coagulation factors and coagulation and fibrinolysis inhibitors than solvent/detergent-treated plasma (SD plasma), and also greater residual cell contamination. SD plasma is a particle-free plasma of uniform quality. SD treatment, however, has the specific result of reducing the activities of some inhibitors. Both plasma types carry a minimal residual risk of transmitting human immunodeficiency virus (HIV)-1/2, hepatitis virus B (HBV), and hepatitis virus C (HCV), but SDP is, in addition, also safe with respect to other lipid-enveloped viruses and perhaps with respect to hepatitis virus A (HAV), also due to its antibody (Ab) content. Future revisions of therapeutic plasma safety and quality standards should consider the following points:For FFP:reduce residual cell count in all FFP units to values below 5 x 10(6) leukocytes/l;screen donors for Parvovirus B19 genome and antibodies in order to establish a sufficiently large collection of genome-negative and antibody-positive donors whose FFP can be used for selected patients;For SDP:introduce pool testing for Parvovirus B19 genome; fix an upper limit for genome and a lower limit for antibody content;in addition to the standard quality control methods for therapeutic plasma, focus on assays to test for functionally intact proteinase inhibitors such as alpha(2)antiplasmin (alpha(2)AP) and alpha(1)proteinase inhibitor (alpha(1)PI) that are important for plasma indications. Commercially available kits may not be sufficient to show changes in inhibition kinetics. For both types:introduce an activation marker such as thrombin-antithrombin complex (TAT) as a random test to monitor activation processes during withdrawal, separation, manufacturing, and storage;abolish inappropriate parameters like Antithrombin III (AT III) and coagulation factor XI that are not relevant for changes in plasma quality;finally, support every effort towards establishing an efficient

  18. Efficacy L-Arginine In Patients With Nonalcoholic Steatohepatitis Associated With Metabolic Syndrome

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    Oleksandr Fediv

    2015-01-01

    Full Text Available Abstract Background and Purpose Recent research in the field of hematology indicate that among the many pathogenic mechanisms of development and progression of nonalcoholic steatohepatitis NASH which occurs on the background of the metabolic syndrome an important role is played by endothelial dysfunction and violations of haemocoagulation. The aim of this research was to study the effectiveness of L-arginine as it corrects endothelial dysfunction and disorders of homeostasis haemocoagulation link in patients with NASH associated with the metabolic syndrome. Subjects and Methods 128 patients with nonalcoholic steatohepatitis associated with metabolic syndrome were examined. Some patients 63 persons received standard treatment according to national guidelines. To another group 65 patients on the background of basic therapy L-arginine hydrochloride followed by transition to oral form of L-arginine aspartate was administered. Blood levels of stable nitrogen monoxide metabolites nitrites nitrates endothelin-1 and plasma recalcification time prothrombin time thrombin time activated partial thromboplastin time fibrinogen plasma level activity of antithrombin III and coagulation factor XIII potential activity of plasminogen plasma fibrinolytic blood activity were studied. Results Originally significantly increased levels of endothelin-1 decreased after the therapy in all studied groups but more noticeable changes in the group with L-arginine appointment were observed p0.05. In the studied groups normalization of stable nitrogen monoxide metabolites after treatment was also noticed. Significant p0.05 increase in all haemocoagulation time characteristics and activities of antithrombin-III and factor XIII was found. The positive effect of L-arginine on blood fibrinolytic activity was noted. Discussion and Conclusion Combined therapy of nonalcoholic steatohepatitis associated with metabolic syndrome with a differentiated degreeal L-arginine assignment by

  19. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  20. A study of some aspects of auto immunity in children with thalassemia major

    International Nuclear Information System (INIS)

    This study is subjected to estimate the study of the most common autoimmune complications in thalassemia and the prevalence of different auto antibodies so as to evaluate its correlation with personal data including age, sex, growth parameters, Hepatitis C virus infection ferritin level and type of iron chelation therapy methodology : Different Abs including anti cardiolipin, antitistone, ANA, Anti erythropoietin by ELISA technique Hepatitis C virus by ELISA. Ferritin by IRMA (Immune radiometric assay), Protein C, S. Antithrombin III by ELISA result of the study were analyzed by appropriate statistical methods .The results showed that age of Hepatitis C virus negative cases was significantly lower than Hepatitis C virus Positive cases, ferritin levels were significantly higher in patients on defripone than those as desferrioxamine, anti erythropoietin was detected in 93.3% of cases regarding the antithrombotic factors deficiency. Protein C was deficient in 26.67% of cases. Protein S was deficient in 13.33% only and no cases showed anti thrombin III deficiency. No special relation was found between these abnormalities and type of chelation , Conclusions: Auto immunity may be a cofactor in the development of life threatening complication

  1. Fumonisin mycotoxicosis in broilers: plasma proteins and coagulation modifications.

    Science.gov (United States)

    Espada, Y; Ruiz de Gopegui, R; Cuadradas, C; Cabañes, F J

    1997-01-01

    The effects of fumonisin B1 (FB1) intoxication in chickens were evaluated in three experiments. Two-day-old broiler chicks were fed a diet containing 10 mg pure FB1/kg feed for 6 days; some chicks were necropsied at this time, and others were allowed to recover for 5 wk before necropsy. In two other experiments, 2-day-old chicks were fed a broiler starter ration prepared with Fusarium moniliforme culture material containing FB1; one group received 30 mg/kg for 2 wk, and another received 300 mg FB1/kg for 8 days. Compared with controls, intoxicated chicks exhibited decreased prothrombin time, increased plasma fibrinogen (not included for the group receiving 30 mg/kg of culture material), and increased antithrombin III activity. Simultaneously decreased serum albumin concentration and increased serum globulins could be observed in groups intoxicated with F. moniliforme culture material containing FB1. The group allowed to recover for 5 wk did not exhibit modifications in hemostasis or serum proteins compared with controls. The results indicate that low doses of pure FB1 (10 mg/kg) and FB1 from F. moniliforme culture material (30 mg/kg) may alter hemostasis and serum proteins in young chicks. PMID:9087322

  2. Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica.

    Science.gov (United States)

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Kusaykin, Mikhail I; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

    2016-05-01

    A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core → 3)-β-D-GalNAc-(1 → 4)-β-D-GlcA-(1 →. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ∼ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin. PMID:26681734

  3. Anticoagulant, antiplatelet and antianemic effects of Punica granatum (pomegranate) juice in rabbits.

    Science.gov (United States)

    Riaz, Azra; Khan, Rafeeq A

    2016-04-01

    Pomegranate (Punica granatum L., Punicaceae) is a good source of minerals and phytochemicals with diverse pharmacological activities such as anxiolytic, antidepressant, hypoglycemic, hypolipidemic, and anti-inflammatory activities. Effects of P. granatum on blood parameters and coagulation have, however, been little studied. The aim of the study was to assess the outcome of P. granatum on coagulation and anticoagulation factors at different doses on blood samples of healthy white rabbits. Blood samples of the animals were collected twice during the study and biochemical assays were performed to assess the effect on hematological, coagulation, anticoagulation, and platelet aggregation. Significant changes were observed in erythrocytes, hemoglobin, and mean corpuscular hemoglobin concentration, while bleeding and thrombin time were also prolonged significantly. There was significant increase in protein C, thrombin antithrombin complex levels, and decrease in platelet aggregation and fibrinogen concentration, in a dose-dependent manner. The results of hematological and coagulation assays lead to the speculation about a possible antianemic and cardioprotective effect of P. granatum. PMID:26881853

  4. Plasma functionalization of polycarbonaturethane to improve endothelialization--Effect of shear stress as a critical factor for biocompatibility control.

    Science.gov (United States)

    Lukas, Karin; Thomas, Ulrich; Gessner, André; Wehner, Daniel; Schmid, Thomas; Schmid, Christof; Lehle, Karla

    2016-04-01

    Medical devices made of polycarbonaturethane (PCU) combine excellent mechanical properties and little biological degradation, but restricted hemocompatibility. Modifications of PCU might reduce platelet adhesion and promote stable endothelialization. PCU was modified using gas plasma treatment, binding of hydrogels, and coupling of cell-active molecules (modified heparin, anti-thrombin III (ATIII), argatroban, fibronectin, laminin-nonapeptide, peptides with integrin-binding arginine-glycine-aspartic acid (RGD) motif). Biocompatibility was verified with static and dynamic cell culture techniques. Blinded analysis focused on improvement in endothelial cell (EC) adhesion/proliferation, anti-thrombogenicity, reproducible manufacturing process, and shear stress tolerance of ECs. EC adhesion and antithrombogenicity were achieved with 9/35 modifications. Additionally, 6/9 stimulated EC proliferation and 3/6 modification processes were highly reproducible for endothelialization. The latter modifications comprised immobilization of ATIII (A), polyethyleneglycole-diamine-hydrogel (E) and polyethylenimine-hydrogel connected with modified heparin (IH). Under sheer stress, only the IH modification improved EC adhesion within the graft. However, ECs did not arrange in flow direction and cell anchorage was restricted. Despite large variation in surface modification chemistry and improved EC adhesion under static culture conditions, additional introduction of shear stress foiled promising preliminary data. Therefore, biocompatibility testing required not only static tests but also usage of physiological conditions such as shear stress in the case of vascular grafts. PMID:26762398

  5. Hemostatic abnormalities in liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Kendal YALÇIN

    2009-06-01

    Full Text Available In this study, 44 patients with liver cirrhosis were investigated for hemostatic parameters. Patients with spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome and cholestatic liver diseases were excluded. Patients were classified by Child-Pugh criterion and according to this 4 patients were in Class A, 20 in Class B and 20 in C. Regarding to these results, it was aimed to investigate the haematological disturbances in liver cirrhotic patients.In the result there was a correlation between activated partial thromboplastin time, serum iron, ferritin, transferrin, haptoglobin and Child-Pugh classification. Besides there was no correlation between prothrombin time, factor 8 and 9, protein C and S, anti-thrombin 3, fibrinogen, fibrin degradation products, serum iron binding capacity, hemoglobin, leukocyte, mean corpuscular volume and Child-Pugh classification.There were significant difference, in terms of AST, ferritin, haptoglobulin, sex and presence of ascites between groups (p0.05. In the summary, we have found correlation between hemostatic abnormalities and disease activity and clinical prognosis in patients with liver cirrhosis which is important in the management of these patients. This is also important for identification of liver transplant candidiates earlier.

  6. Heparin coating of tantalum coronary stents reduces surface thrombin generation but not factor IXa generation.

    Science.gov (United States)

    Blezer, R; Cahalan, L; Cahalan, P T; Lindhout, T

    1998-07-01

    In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed. These findings indicate that tantalum triggers blood coagulation, but that (adherent) platelets are essential for thrombin generation. Heparin-coated tantalum stents exposed to flowing platelet-rich plasma showed that factor IXa generation was slightly reduced compared with the bare stent. However, the heparin coating drastically delayed the onset of thrombin generation and largely reduced the steady-state production of thrombin. We found a clear relationship between the antithrombin binding capacity and the antithrombogenic potential of the heparin-coated stents. The mode of action of immobilized heparin is thought to abrogate thrombin generation by inhibiting thrombin-dependent positive feedback reactions at the surface of the coronary stent. PMID:9712292

  7. 3,4,9,10-Perylenetetracarboxylic dianhydride functionalized graphene sheet as labels for ultrasensitive electrochemiluminescent detection of thrombin.

    Science.gov (United States)

    Gan, Xianxue; Yuan, Ruo; Chai, Yaqin; Yuan, Yali; Cao, Yaling; Liao, Yuhong; Liu, Huijing

    2012-05-13

    A novel tracer, 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) functionalized graphene sheet (GS) composite (GS-TCDA), is employed to label the secondary anti-thrombin aptamer (TBA) to construct an ultrasensitive electrochemiluminescent sandwich-type aptasensor. The GS provided large surface area for loading abundant PTCDA and TBA with good stability and biocompatibility. Because of the excellent electroconductivity of GS and the desirable optical properties of PTCDA, the as-formed Apt II bioconjugate considerably amplified the electrochmiluminescence (ECL) signal of peroxydisulfate (S(2)O(8)(2-)) and worked as the desirable label for Apt II. On the basis of the considerably amplified ECL signal and sandwich format, an extremely wide range from 1 fM to 1 nM with an ultralow detection limit of 0.33 fM for thrombin was obtained. Additionally, the selectivity and stability of the proposed aptasensor were also excellent. Thus, this procedure has great promise for detection of thrombin present at ultra-trace levels during early stage of diseases. PMID:22541015

  8. [A sudden rise in INR due to combination of Tribulus terrestris, Avena sativa, and Panax ginseng (Clavis Panax)].

    Science.gov (United States)

    Turfan, Murat; Tasal, Abdurrahman; Ergun, Fatih; Ergelen, Mehmet

    2012-04-01

    Warfarin sodium is an antithrombin agent used in patients with prosthetic valve and atrial fibrillation. However, there are many factors that can change the effectiveness of the drug. Today, herbal mixtures promoted through targeted print and visual media can lead to sudden activity changes in patients using warfarin. In this case report we will present two cases with a sudden rise in INR due to using combination of Tribulus terrestris, Avena sativa and Panax ginseng (Panax Clavis). Two patients who used warfarin due to a history of aortic valve replacement (case 1) and atrial fibrillation (case 2) were admitted to the hospital due very high levels of INR detected during routine follow-up. Both patients had used an herbal medicine called ''Panax'' during the last month. The patients gave no indication regarding a change in diet or the use of another agent that might interact with warfarin. In cases where active bleeding could not be determinated, we terminated the use of the drug and re-evaluated dosage of warfarin before finally discharging the patient. PMID:22864323

  9. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Truelove, E; Fielding, A K; Hunt, B J

    2013-03-01

    The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking. PMID:23099335

  10. Glycoprotein fucosylation is increased in seminal plasma of subfertile men

    Directory of Open Access Journals (Sweden)

    Beata Olejnik

    2015-04-01

    Full Text Available Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL. Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.

  11. Extensive cerebral venous thrombosis in a renal allograft recipient

    International Nuclear Information System (INIS)

    An increased risk of venous thromboembolism has been demonstrated following renal transplantation. Commonly reported sites have been deep vein thrombosis, pulmonary thromboembolism and vascular thrombosis involving the graft. Cerebral venous thrombosis (CVT) has not been reported in literature so far. A 36-year-old male patient, transplanted in January 2005 with normal graft functions, was admitted with history of headache, blurring of vision and vomiting. Examination revealed papilledema and no neurological deficits. Baseline investigations and analysis of cerebrospinal liquid were normal. Cerebral magnetic resonance venogram revealed extensive CVT involving superior sagittal sinus, bilateral transverse sinuses and the right sigmoid sinus. He was investigated for a thrombophilic disorder; serum homocysteine, protein C and S levels, antiphospholipid antibody and antithrombin-III levels were done despite which no conclusive diagnosis could be arrived at. To our knowledge, this is the first report of extensive CVT described in a transplant recipient. Ne definite prothrombotic or predisposing factors could be identified in our patient and the cause of CVT remains unclear. (author)

  12. Is the size of an abdominal aortic aneurysm associated with coagulopathy?

    Science.gov (United States)

    Shindo, Shunya; Matsumoto, Harunobu; Kubota, Kenji; Kojima, Atsuo; Matsumoto, Masahiko; Satoh, Kaneo; Ozaki, Yukio

    2005-07-01

    Abdominal aortic aneurysm (AAA) volume and intraluminal thrombi were analyzed with respect to the number and function of platelets, blood cells, and coagulation factors. A group of 43 patients who underwent repair of an AAA were enrolled in this study. The maximum diameter and volume of the AAA, and the volume of intraluminal thrombi and lumen were measured by computed tomography with planimetry. The platelet count and platelet function, prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen, antithrombin 3, fibrin degradation products (FDP), D-dimer, and blood cell counts were measured. Spontaneous platelet aggregation and the FDP, and D-dimer levels were elevated; all other factors remained within the normal range. Intraluminal thrombus volume was strongly correlated with the volume and diameter of the AAA. However, no correlation was observed between the size of the AAA and coagulating factors, including the number and aggregation value of platelets. AAAs are frequently associated with a coagulating disorder. However, its size and thrombus volume are not correlated with coagulation changes. Although an intraluminal thrombus increases along with fee enlargement of the AAA, the clinical manifestation of bleeding is rarely associated with an AAA. Therefore coagulopathy in patients with an AAA is not fully explained by its morphology. PMID:15951938

  13. Antiplatelet treatment and prothrombotic diathesis following endovascular abdominal aortic aneurysm repair.

    Science.gov (United States)

    Trellopoulos, G; Georgiadis, G S; Nikolopoulos, E S; Kapoulas, K C; Georgakarakos, E I; Lazarides, M K

    2014-10-01

    Prothrombotic diathesis expressed by elevated levels of coagulation-specific biomarkers has been reported in patients with abdominal aortic aneurysm (AAA) and after AAA endovascular repair (EVAR). This study investigates the effect of antiplatelet agents (APLs) on the prothrombotic diathesis in the post-EVAR period. Forty elective EVAR patients had thrombin-antithrombin complex, d-dimer, fibrinopeptide A, and high-sensitivity C-reactive protein measured before, at 24 hours, 1 month, and 6 months after EVAR. Patients receiving APLs postoperatively were compared with those not receiving APLs. All biomarkers were above the normal limits preoperatively and increased significantly 24 hours postoperatively followed by a drop at 1 and 6 months. No statistically significant changes were noted among patients receiving APLs in comparison with those not receiving APLs. The preoperative and postoperative prothrombotic diathesis of AAA following EVAR was confirmed in line with other reports. There was however no significant alteration of the examined biomarkers in patients receiving APLs. PMID:24101707

  14. Coagulation and fibrinolysis after open infrarenal abdominal aortic aneurysm repair in a long-term perspective.

    Science.gov (United States)

    Holmberg, A; Bergqvist, D; Siegbahn, A

    1999-10-15

    In patients with abdominal aortic aneurysms (AAA) the coagulation and fibrinolytic systems have been found to be activated preoperatively. Does the increased activity of the coagulation and fibrinolytic systems persist after AAA surgery in a long-term perspective? Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), tissue plasminogen activator (tPA), human plasminogen activator inhibitor type 1, and human cross-linked fibrin degradation product (D-dimer) were analysed in 18 patients after open AAA surgery (postop-AAA). The median time between surgery and blood sampling was 19 months (range, 5-37 months). Comparisons were made with both preoperative values of 23 patients with AAA (preop-AAA) as well as 20 age-matched healthy controls (AMC). F1+2, TAT, and D-dimer in preop-AAA were significantly higher compared to AMC (pD-dimer). However, TAT and D-dimer levels were still higher in postop-AAA than in AMC (paneurysmal sac but still higher than in a nonaneurysmal aorta. PMID:10574587

  15. Compensated activation of coagulation in patients with abdominal aortic aneurysm: effects of heparin treatment prior to elective surgery.

    Science.gov (United States)

    Jelenska, Maria Magdalena; Szmidt, Jacek; Bojakowski, Krzystof; Grzela, Tomasz; Palester-Chlebowczyk, Magorzata

    2004-11-01

    Elective surgery of abdominal aortic aneurysm (AAA) sometimes leads to excessive bleeding and disseminated intravascular coagulation (DIC), even in patients with normal preoperative coagulation parameters. Coagulation screen, performed routinely before surgery is of limited value in the assessment of compensated activation of the haemostatic system. In this study, we used a number of additional tests (D-dimer, prothrombin fragment 1+2, antithrombin, and activation of fibrinolysis in the platelet poor plasma) for the diagnosis of compensated activation of the haemostatic system in AAA-patients. D-dimer and marker of thrombin generation (prothrombin fragment 1+2) positively correlated with each other (r = 0.768, P D-dimer and prothrombin fragment 1+2 decreased significantly) and resulted in the increase of platelet number and fibrinogen concentration, indicating their previous consumption. Despite differences in aneurysm diameters between the groups of 15 LMWH treated patients (mean 70.9 +/- 16 mm) and the reference group of 20 untreated AAA patients (mean 52.3 +/- 8.0 mm), intraoperative parameters (operation time, blood loss and transfusion demands) were similar. PMID:15543326

  16. Treatment of Venous Thromboembolism With New Anticoagulant Agents.

    Science.gov (United States)

    Becattini, Cecilia; Agnelli, Giancarlo

    2016-04-26

    Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE. PMID:27102510

  17. Changes in the coagulation profile of cattle with left abomasal displacement.

    Science.gov (United States)

    Sobiech, P; Radwińska, J; Krystkiewicz, W; Snarska, A; Stopyra, A

    2008-01-01

    The purpose of this study was to determine changes in coagulation profile parameters in cattle with left abomasal displacement (LAD). The study was performed on 20 Holstein-Friesian (H-F) cows divided into two groups: group I--10 cows with diagnosed left abomasal displacement and group II--10 clinically healthy cows. Coagulation tests, including TT (thrombin time), PT (prothrombin time) and APTT (activated partial thromboplastin time), were conducted, and fibrinogen content, D-dimer content, AT III (antithrombin III) activity and platelet (PLT) count were determined in all the animals. Prolonged TT, PT and APTT, a higher fibrinogen and D-dimer content, a drop in AT III activity and thrombocyte count were observed in the cattle with LAD. The above abnormal coagulation profiles were most predominant in three cows which died after surgical repositioning of the abomasum. The results of the study indicate that in cattle with abomasal displacement, the disseminated intravascular coagulation (DIC) syndrome was the most significant risk factor for mortality. PMID:19227127

  18. A study of some aspects of auto immunity in children with thalassemia major

    International Nuclear Information System (INIS)

    This study is subjected to estimate the study of the most common autoimmune complications in thalassaemic and the prevalence of different auto anti-bodies so as to evaluate its correlation with personal data including age, sex, growth parameters, Hepatitis C virus infection ferritin level and type of iron chelation therapy methodology : Different Abs including anti-cardiolipin, anti-tistone, ANA, Anti-erythropoietin by ELISA technique Hepatitis C virus by ELISA. Ferritin by IRMA (Immune radiometric assay), Protein C, S. Anti-thrombin III by ELISA result of the study were analyzed by appropriate statistical methods .The results showed that age of Hepatitis C virus negative cases was significantly lower than Hepatitis C virus Positive cases, ferritin levels were significantly higher in patients on defripone than those as desferrioxamine, anti-erythropoietin was detected in 93.3% of cases regarding the antithrombotic factors deficiency. Protein C was deficient in 26.67% of cases. Protein S was deficient in 13.33% only and no cases showed anti thrombin III deficiency. No special relation was found between these abnormalities and type of chelation , Conclusions: Auto-immunity may be a cofactor in the development of life threatening complication

  19. Factor V Leiden mutation does not affect coagulopathy or outcome in lethal H1N1 influenza.

    Science.gov (United States)

    Schouten, M; van der Sluijs, K F; Roelofs, J J T H; Levi, M; Van't Veer, C; van der Poll, T

    2010-12-01

    Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined. Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study. Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection. In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A. PMID:20413539

  20. [Biological and clinical safety of nomegestrol acetate administered alone then associated in inverse sequence with transdermal 17 beta estradiol, in women at risk of dyslipoproteinemia type IIa].

    Science.gov (United States)

    Zartarian, M; Chevallier, T; Micheletti, M C; Leber, C; Jamin, C

    1998-12-01

    In this study including 26 patients with dyslipoproteinemia classified IIa, we evaluated biochemical and clinical safety of Nomegestrol acetate (Lutenyl) used for its antigonadotrophin property. It was administered alone, during 3 cycles at the dose of 5 mg/d for 21 days by cycle and then it was associated (at the same sequence and dose), without any wash out, for the next 6 cycles, with a 17 beta estradiol patch (Estraderm TTS 50), 50 micrograms/d from the 11th to the 21st day of each cycle. Nomegestrol acetate, alone, had no significant effect on glycemia, antithrombin III, triglycerides, total cholesterol, apoprotein A1, and LpA1 values compared to those at baseline but apoprotein B and Lp (a) values tended to decrease slightly. Serum progesterone levels were collapsed, and FSH values were low. Weight and blood pressure remained constant. Adding 17 beta estradiol enabled to significantly decrease and normalize the apoprotein B values after the first 3 cycles compared to the baseline values, then these values remained constant during the next 3 cycles. There was no effect on the other parameters (except for a significant increase in plasmatic estradiol values) on the antigonadotrophin property of Nomegestrol acetate, nor on weight and blood pressure which remained constant. Moreover, we observed an important decrease in the rate of amenorrheic cycles compared to those with Nomegestrol acetate alone. PMID:9949893

  1. Fondaparinux sodium.

    Science.gov (United States)

    Keam, Susan J; Goa, Karen L

    2002-01-01

    black triangle Fondaparinux sodium, a selective factor Xa inhibitor, is the first in a new class of antithrombotics. It binds selectively with high affinity to antithrombin III and specifically catalyses the inactivation of factor Xa. The elimination half-life of fondaparinux sodium permits once daily treatment. black triangle A randomised, double-blind, parallel-group, dose-ranging, multicentre phase IIb study in 933 eligible patients established that a subcutaneous dose of between 1.5 and 3mg of fondaparinux sodium has the optimum efficacy and safety profile for prophylaxis of venous thromboembolism in patients undergoing major orthopaedic surgery. black triangle Fondaparinux sodium, given to more than 3600 patients undergoing major orthopaedic surgery who participated in prospective, randomised, double-blind, multicentre phase III clinical trials, significantly reduced the incidence of venous thromboembolism, with an overall risk reduction of 55.2% compared with enoxaparin. black triangle Fondaparinux sodium was well tolerated by patients undergoing major orthopaedic surgery, and at the recommended clinical dose of 2.5mg has a similar tolerability profile, including bleeding events, to standard enoxaparin regimens. Fondaparinux sodium has not been reported to cause antibody-induced thrombocytopenia. PMID:12109927

  2. Structural features and inactivation of coagulation proteases of a sulfated polysaccharidic fraction from Caulerpa cupressoides var. lycopodium (Caulerpaceae, Chlorophyta - doi: 10.4025/actascitechnol.v35i4.16709

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2013-10-01

    Full Text Available Studies on biopolymers from macroalgae suggested sulfated polysaccharides (SPs as research agents to investigate events related to haemostasis. Caulerpa cupressoides var. lycopodium is a marine green alga containing three SPs fractions (SP1, SP2 and SP3. SP2 had anticoagulant (in vitro and anti- and prothrombotic (in vivo actions; however, its effect on the coagulation system is not fully understood. This study aimed to determine the infrared (IR spectroscopy, chemical composition (CC, elemental microanalysis (EM, molecular weight (MW and the effect on coagulation proteases of SP2. The presence of sulfate ester, galactose-6-sulfate, uronic acid and glycoside linkages for IR spectrum; contents of sulfate (28%, total sugars (40% and uronic acids (7.18% for CC; and content of carbon (21.98%, sulfate (4.27%, nitrogen (1.3% and hydrogen (4.86% for EM were obtained. The average molecular weights of four different SPs (SP-1, SP-2, SP-3 and SP-4 subfractions from the SP2 ranged from ~ 8 to >100 kDa. SP2 was tested on coagulation proteases (thrombin and factor Xa in the presence of antithrombin (AT and heparin cofactor II (HCII using human plasma, being both thrombin and factor Xa target proteases inhibited, but requiring a concentration of about 2.5-fold higher of HCII than the thrombin inactivation by AT.   

  3. Leech therapeutic applications

    Directory of Open Access Journals (Sweden)

    A M Abdualkader

    2013-01-01

    Full Text Available Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin, antiplatelet (calin, saratin, factor Xa inhibitors (lefaxin, antibacterial (theromacin, theromyzin and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20 th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial.

  4. Hematologic and hemostatic changes induced by different columns during LDL apheresis.

    Science.gov (United States)

    Hovland, Anders; Hardersen, Randolf; Nielsen, Erik Waage; Mollnes, Tom Eirik; Lappegård, Knut Tore

    2010-01-01

    Low density lipoprotein (LDL) apheresis is a long-term treatment and its impact on risk factors other than lipoproteins could be of importance. Three patients with familial hypercholesterolemia participated in six consecutive treatments with three different LDL apheresis columns in random order: DL-75, LA-15, and EC-50W. We compared treatment effects on hemoglobin, leukocytes, platelets, fibrinogen, thrombin-antithrombin complexes (TAT), plasminogen activator inhibitor-1 (PAI-1), and homocysteine. Hemoglobin, leukocytes and platelets decreased significantly with DL-75 (P < 0.05). Hemoglobin and leukocytes increased significantly with LA-15 and EC-50W (P < 0.05). Platelets were unchanged. The DL-75 column was statistically different from LA-15 and EC-50W regarding these parameters. With the columns DL-75, LA-15, and EC-50W fibrinogen decreased significantly by 28%, 32%, and 42%, PAI-1 decreased significantly by 72%, 58%, and 30% while TAT increased significantly by 138%, 3%, and 251%, respectively (P < 0.05 for all). When comparing the columns there were significant differences between all of them regarding fibrinogen, no differences regarding TAT and a difference between DL-75 and EC-50W regarding PAI-1. With the columns DL-75, LA-15 and EC-50W homocysteine decreased 22%, 9%, and 13%, respectively, but there were no inter column differences. In conclusion, the three LDL apheresis columns affected important hematological and hemostatic risk factors differently. PMID:20806414

  5. Coagulation disorders in the patients with deep vein thrombosis of lower extremity

    Directory of Open Access Journals (Sweden)

    Milić Dragan J.

    2003-01-01

    Full Text Available PURPOSE Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality and long-term sequelae which may be disabling (post-thrombotic syndrome and ulceration. PROCEDURES The aim of our work was to establish the presence of coagulation disorders (hypercoagulable states in the patients with deep vein thrombosis (DVT of the leg. Prospectively we have analyzed a group of 30 patients with echosono-graphicaly verified DVT of the leg who were admitted to the department of vascular surgery from August 1st 2000 to July 31st 2001.The following parameters were monitored: prothrombin time (PT partial thromboplastin time (PTT, fibrinogen (Fib, alpha 2 antiplasmin (A-2 AP, D-dimer (DD, antithrombin III (AT III and factor VII. FINDINGS Activation of the coagulation process was registered. The values of monitored coagulation parameters are shown in table 1. Plasma levels of monitored parameters in the patients with DVT of the leg were significantly higher than in the control subjects. CONCLUSION In patients with a DVT a hypercoagulable state is common finding. Some parameters of coagulation activity such as D-dimer might be of great interest in the diagnostic strategy of DVT.

  6. What neurosurgeons need to know about dabigatran etexilate (pradax®/pradaxa®/prazaxa®)

    Science.gov (United States)

    Dwyer, Christopher Michael; Damodaran, Omprakash; Heckelmann, Michael; Sheridan, Mark Michael

    2015-01-01

    Dabigatran etexaliate is a novel oral anticoagulant that directly inhibits thrombin. It offers a number of substantial medical benefits over other oral and parenteral anticoagulants but its advent raises important neurosurgical considerations. Dabigatran has important potential benefits. Unlike warfarin, it does not require routine blood tests to monitor its anticoagulative effect and there is no need for dose titration. Drug interactions are greatly simplified when compared to warfarin as dabigatran is not metabolized by cytochrome p450 isoenzymes. As a result, dabigatran has been approved in many jurisdictions for DVT prophylaxis after orthopaedic surgery and also for the prevention of embolic events associated with non-valvular atrial fibrillation. There are, however, important neurosurgical challenges associated with regular dabigatran use. Unlike current anti-coagulants, there is no specific reversal agent for dabigatran. Known reversal options include activated charcoal (within one to two hours of intake) and renal dialysis. Protamine sulfate and vitamin K are unlikely to affect the activity of dabigatran. Platelet concentrates will not inactivate dabigatran's anti-thrombin properties. Assessing the degree of anticoagulation is difficult as conventional markers of serum coagulability are typically normal in patients taking dabigatran. The potential neurosurgical challenges of dabigatran were cast in sharp relief by a recent case report from the United States that is considered in this note. In the absence of a clear reversal pathway, we propose a treatment algorithm for chronic dabigatran use based on the replacement of any deficient factors and rapid access to renal dialysis. PMID:25972932

  7. What neurosurgeons need to know about dabigatran etexilate (pradax(®)/pradaxa(®)/prazaxa(®)).

    Science.gov (United States)

    Dwyer, Christopher Michael; Damodaran, Omprakash; Heckelmann, Michael; Sheridan, Mark Michael

    2015-01-01

    Dabigatran etexaliate is a novel oral anticoagulant that directly inhibits thrombin. It offers a number of substantial medical benefits over other oral and parenteral anticoagulants but its advent raises important neurosurgical considerations. Dabigatran has important potential benefits. Unlike warfarin, it does not require routine blood tests to monitor its anticoagulative effect and there is no need for dose titration. Drug interactions are greatly simplified when compared to warfarin as dabigatran is not metabolized by cytochrome p450 isoenzymes. As a result, dabigatran has been approved in many jurisdictions for DVT prophylaxis after orthopaedic surgery and also for the prevention of embolic events associated with non-valvular atrial fibrillation. There are, however, important neurosurgical challenges associated with regular dabigatran use. Unlike current anti-coagulants, there is no specific reversal agent for dabigatran. Known reversal options include activated charcoal (within one to two hours of intake) and renal dialysis. Protamine sulfate and vitamin K are unlikely to affect the activity of dabigatran. Platelet concentrates will not inactivate dabigatran's anti-thrombin properties. Assessing the degree of anticoagulation is difficult as conventional markers of serum coagulability are typically normal in patients taking dabigatran. The potential neurosurgical challenges of dabigatran were cast in sharp relief by a recent case report from the United States that is considered in this note. In the absence of a clear reversal pathway, we propose a treatment algorithm for chronic dabigatran use based on the replacement of any deficient factors and rapid access to renal dialysis. PMID:25972932

  8. The relationship between thrombophilic mutations and preeclampsia: a prospective case-control study

    International Nuclear Information System (INIS)

    Preeclampsia and its association with thrombophillia remain controversial, due to inconsistent results in different studies, which different ethnic groups, selection criteria, and patient numbers. The aim of this study was to determine the relationship between thrombophillia and preeclamptic patients in our region. In a prospective case-control study, we compared 100 consecutive women with preeclampsia and eclampsia (group 1) with 100 normal pregnant women (group 2). All women were tested two months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase (MTHFR), and prothrombin gene mutation mutataion as well as for deficiencies of protein C, protein S, and antithrmbin III. A thrombophilic mutation was found in 42 (42%) and 28(28%) women in group I and group II, respectively (P+0.27, OR 1.5, 95% CI 1.0-2.2). The incidence of Factor V Leiden mutation (heterozygous), prothrombin mutation (heterozygous), prothrombin mutation (homozygous), MTHFR mutation (homozygous) was not statistically significant in group 1 compared with group 2 (P>0.05). Also, deficiencies of protein S, protein c and antithrombin III were not statistically significant in group I com pared with group II (P>0.05). There was no difference in thrombophilic mutations between preeclamptic patients and normal pregnant women in our region. Therefore, we suggest that preeclamptic patients should not be tested for thrombophilia. (author)

  9. Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients

    Directory of Open Access Journals (Sweden)

    Henry Cardona

    2012-01-01

    Full Text Available Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases and 206 healthy multiparous women (controls in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population.

  10. Predilution versus postdilution during continuous venovenous hemofiltration: a comparison of circuit thrombogenesis.

    Science.gov (United States)

    de Pont, Anne-Cornélie J M; Bouman, Catherine S C; Bakhtiari, Kamran; Schaap, Marianne C L; Nieuwland, Rienk; Sturk, Augueste; Hutten, Barbara A; de Jonge, Evert; Vroom, Margreeth B; Meijers, Joost C M; Büller, Harry R

    2006-01-01

    During continuous venovenous hemofiltration, predilution can prolong circuit survival time, but the underlying mechanism has not been elucidated. The aim of the present study was to compare predilution with postdilution, with respect to circuit thrombogenesis. Eight critically ill patients were treated with both predilutional and postdilutional continuous venovenous hemofiltration in a crossover fashion. A filtration flow of 60 ml/min was used in both modes. We chose blood flows of 140 and 200 ml/min during predilution and postdilution, respectively, to keep the total flow through the hemofilter constant. Extracorporeal circuit pressures were measured hourly, and samples of blood and ultrafiltrate were collected at five different time points. Thrombin-antithrombin complexes and prothrombin fragments F1 + 2 were measured by ELISA, and platelet activation was assessed by flow cytometry. No signs of thrombin generation or platelet activation were found during either mode. During postdilution, baseline platelet count and maximal prefilter pressure had a linear relation, whereas both parameters were inversely related with circuit survival time. In summary, predilution and postdilution did not differ with respect to extracorporeal circuit thrombogenesis. During postdilution, baseline platelet count and maximal prefilter pressure were inversely related with circuit survival time. PMID:16883122

  11. [Complex assessment of vasomotor function of vascular endothelium in patients with hypertension].

    Science.gov (United States)

    Gel'tser, B I; Savchenko, S V; Kotel'nikov, V N; Plotnikova, I V

    2004-01-01

    Vasomotor function of vascular endothelium was studied in 62 patients with grade 1-2 hypertension with moderate and high added risk. Methods included study of brachial and middle cerebral artery endothelium dependent and independent vasodilation/vasoconstriction, measurement of plasma levels of nitric oxide metabolites (NO(n)-), endothelin-1, and antithrombin, as well as registration of their changes during vasomotor tests with calculation of integral indexes. Most patients with hypertension differed from controls by preponderance of vasoconstrictor over vasodilator reactions both in peripheral and cerebral vascular bed. At the same time patients with hypertension had pronounced dissociation between vasomotor responses of cerebral and peripheral vessels compared with subjects with normal blood pressure (pconcentration of endothelin-1 patients with hypertension were characterized by hyperreactivity of nitricoxidergic system, augmented lability of endothelin producing system, and impaired athrombogenecity of vascular endothelium. Complex assessment of vasomotor function of vascular endothelium by sequential vasoactive tests characterizes functional and metabolic activity of cerebral and peripheral vessels and can be used for improvement of risk stratification and monitoring of efficacy of treatment of patients with hypertension. PMID:15111971

  12. Robustness of nanofiltration for increasing the viral safety margin of biological products.

    Science.gov (United States)

    Caballero, Santiago; Diez, José M; Belda, Francisco J; Otegui, Magdalena; Herring, Steven; Roth, Nathan J; Lee, Douglas; Gajardo, Rodrigo; Jorquera, Juan I

    2014-03-01

    In this study, the virus-removal capacity of nanofiltration was assessed using validated laboratory scale models on a wide range of viruses (pseudorabies virus; human immunodeficiency virus; bovine viral diarrhea virus; West Nile virus; hepatitis A virus; murine encephalomyocarditis virus; and porcine parvovirus) with sizes from 18 nm to 200 nm and applying the different process conditions existing in a number of Grifols' plasma-derived manufacturing processes (thrombin, α1-proteinase inhibitor, Factor IX, antithrombin, plasmin, intravenous immunoglobulin, and fibrinogen). Spiking experiments (n = 133) were performed in process intermediate products, and removal was subsequently determined by infectivity titration. Reduction Factor (RF) was calculated by comparing the virus load before and after nanofiltration under each product purification condition. In all experiments, the RFs were close to or greater than 4 log10 (>99.99% of virus elimination). RF values were not significantly affected by the process conditions within the limits assayed (pH, ionic strength, temperature, filtration ratio, and protein concentration). The virus-removal capacity of nanofiltration correlated only with the size of the removed agent. In conclusion, nanofiltration, as used in the manufacturing of several Grifols' products, is consistent, robust, and not significantly affected by process conditions. PMID:24485384

  13. NCO-sP(EO-stat-PO Coatings on Gold Sensors—a QCM Study of Hemocompatibility

    Directory of Open Access Journals (Sweden)

    Frank K. Gehring

    2011-05-01

    Full Text Available The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide—polypropylene oxide co-polymers NCO-sP(EO-stat-PO when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM sensors were coated with ultrathin NCO-sP(EO-stat-PO films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP, followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP. Thrombin antithrombin-III complex (TAT, β-thromboglobulin (β-TG and platelet factor 4 (PF4 were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules.

  14. Surface treatment of biomaterials by gamma and swift heavy ions grafting

    International Nuclear Information System (INIS)

    To date, the successful substitution of small diameter arteries by vascular grafts has not been achieved in humans. In order to reduce their thrombogenicity which remains the major obstacle, polymeric materials endowed with a specific affinity for Antithrombin III (ATIII) and thus able to catalyse the inhibition of thrombin by ATIII, as heparin does, were devised. Sulfonate and sulfonamide groups were introduced on phenyl rings belonging to styrene residues which were radiation grafted (swift heavy ions and gamma radiation) onto poly(vinylene difluoride) (PVDF) and poly(hexafluoropropylene vinylidene fluoride) (P(VDF-HFP)). Contrary to gamma radiation grafting, with swift heavy ions grafting, only small regions are modified; thus, the properties of the initial substrate are preserved. A characterization of surface topography was carried out by Scanning Electron Microscopy and Atomic Force Microscopy. The efficacy of the surface modification was monitored with respect to the total amount of bound 'heparin-like' molecules measured by a toluidine blue assay, and the anticoagulant potential estimated by the thrombin time test

  15. Effects of carboxymethyl chitosan on the blood system of rats

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Dawei [College of Marine Life Sciences, Ocean University of China, Qingdao 266003 (China); Han, Baoqin, E-mail: baoqinh@ouc.edu.cn [College of Marine Life Sciences, Ocean University of China, Qingdao 266003 (China); Dong, Wen; Yang, Zhao; Lv, You; Liu, Wanshun [College of Marine Life Sciences, Ocean University of China, Qingdao 266003 (China)

    2011-04-29

    Highlights: {yields} We report, for the first time, the safety of carboxymethyl chitosan in blood system. {yields} CM-Chitosan has no significant effects on coagulation function of rats. {yields} CM-Chitosan has no significant effects on anticoagulation performance of rats. {yields} CM-Chitosan has no significant effects on fibrinolytic function of rats. {yields} CM-Chitosan has no significant effects on hemorheology of rats. -- Abstract: Carboxymethyl chitosan (CM-chitosan), a derivative of chitosan, was extensively studied in the biomedical materials field for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CM-chitosan in the blood system are lacking. In this study CM-chitosan was implanted into the abdominal cavity of rats to determine blood indexes at different times and to evaluate the effects of CM-chitosan on the blood system of rats. Coagulation function was reflected by thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4) indexes; anti-coagulation performance was assessed by the index of antithrombinIII (ATIII); fibrinolytic function was reflected by plasminogen (PLG) and fibrin degradation product (FDP) indexes; and blood viscosity (BV) and plasma viscosity (PV) indexes reflected hemorheology. Results showed that CM-chitosan has no significant effects on the blood system of rats, and provides experimental basis for CM-chitosan to be applied in the field of biomedical materials.

  16. Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas.

    Science.gov (United States)

    Kuang, S Q; Hasham, S; Phillips, M D; Wolf, D; Wan, Y; Thiagarajan, P; Milewicz, D M

    2001-03-15

    A large east Texas family with autosomal dominant inheritance of a novel bleeding disorder has been identified. The disorder is characterized clinically by easy bruising, life-threatening bleeding with trauma or surgery, and menorrhagia in affected women. Laboratory studies demonstrated prolongation of the prothrombin time and activated partial thromboplastin time in affected individuals. Paradoxically, assays of known coagulation factors are all within normal limits. To determine the molecular basis of this disease, a candidate gene linkage analysis in this kindred was done. Initially it was hypothesized that the cause of the disease in this family could be an antithrombin III (AT3) mutation that resulted in a constitutively active AT3 in the absence of heparin binding. Linkage studies using DNA from the family and an intragenic polymorphic marker within the AT3 gene showed that the disease mapped to this locus. The coding region and intron/exon junctions of AT3 were sequenced using the proband's DNA, but this analysis failed to identify a mutation. Additional family members were recruited for the study, and 16 polymorphic markers around the AT3 gene were analyzed. Using 2 recombinants, the critical interval for the defective gene was narrowed to approximately 1.5 Mb, centromeric to AT3. The factor V (FV) gene was mapped into the disease interval and sequenced; there were no mutations found. Elucidation of the genetic defect causing the bleeding disorder in this family may reveal a novel protein involved in the coagulation cascade. PMID:11238089

  17. [Aneurysm of the abdominal aorta and preoperative disseminated intravascular coagulation].

    Science.gov (United States)

    Chauvet, V; Bussac, J J; Jullian, H; Juhan-Vague, I; Branchereau, A

    1991-01-01

    A case of abdominal aortic aneurysm associated with preoperative signs of disseminated intravascular coagulation is reported. The 69-year-old female patient presented with spontaneously appearing petechiae and bruising. She had 0.95 g.l-1 fibrinogen, 105 G.l-1 platelets, and 100 micrograms.ml-1 fibrin and fibrinogen degradation products. Investigations revealed an 80 mm diameter aneurysm of the abdominal aorta, extending from the coeliac trunk to the iliac arteries. Heparin 7,000 IU.day-1 resulted in a biological improvement for a week only. At that time, levels of coagulation factors were: 92% factor II, 88% factor V, 100% factors VII and X, 100% antithrombin III. Surgical cure of the aneurysm was nevertheless carried out. Twenty standard units of platelets, 8 g fibrinogen, four units of fresh frozen plasma, five homologous and two autologous red cell units were transfused during the procedure. No coagulation factors were necessary during the postoperative course, which was uneventful. The management of coagulation factor infusions, before or after aortic cross-clamping, is discussed. PMID:2058833

  18. Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

    Directory of Open Access Journals (Sweden)

    PAVÃO MAURO S. G.

    2002-01-01

    Full Text Available Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75% and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25% disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin.

  19. Solute removal capacity of high cut-off membrane plasma separators.

    Science.gov (United States)

    Ohkubo, Atsushi; Kurashima, Naoki; Nakamura, Ayako; Miyamoto, Satoko; Iimori, Soichiro; Rai, Tatemitsu

    2013-10-01

    In vitro blood filtration was performed by a closed circuit using high cut-off membrane plasma separators, EVACURE EC-2A10 (EC-2A) and EVACURE EC-4A10 (EC-4A). Samples were obtained from sampling sites before the plasma separator, after each plasma separator, and from the ultrafiltrate of each separator. The sieving coefficient (S.C.) of total protein (TP), albumin (Alb), IgG, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), fibrinogen (Fib), antithrombin III (AT-III), and coagulation factor XIII (FXIII) were calculated. The S.C. of each solute using EC-2A and EC-A4 were as follows; TP: 0.25 and 0.56, Alb: 0.32 and 0.73, IgG: 0.16 and 0.50, IL-6:0.73 and 0.95, IL-8:0.85 and 0.82, TNF-α: 1.07 and 0.99, Fib: 0 and 0, FXIII: 0.07 and 0.17, respectively. When compared with the conventional type of membrane plasma separators, EVACURE could efficiently remove cytokines while retaining coagulation factors such as fibrinogen. Moreover, EC-2A prevented protein loss, whereas EC-4A could remove approximately 50% of IgG. PMID:24107276

  20. Clinical Presentation, Management, and Outcomes of Deep Vein Thrombosis Based on Doppler Ultrasonography Examination.

    Science.gov (United States)

    Al-Thani, Hassan; El-Menyar, Ayman; Asim, Mohammad; Kiliyanni, Abdul Salim

    2016-07-01

    We studied the frequency, clinical presentation, and outcomes of deep vein thrombosis (DVT). Serial Doppler ultrasonography was performed between 2008 and 2013 for 6420 patients with suspected DVT. Diagnosis was confirmed in 662 (10.3%) participants (mean age: 50 ± 17 years; 51% females). Obesity, diabetes mellitus, and malignancy were reported in 47%, 28%, and 16%, respectively. Abnormal protein C, protein S, factor V Leiden, or antithrombin III were found in 9%, 7%, 3.8%, and 4%, respectively. Left, right, and both legs were involved in 55%, 37%, and 8%, respectively. Common femoral, popliteal, and posterior tibial veins were affected in 48.5%, 72%, and 71%, respectively. Postthrombotic syndrome, pulmonary embolism, and death were reported in 50%, 12.2%, and 15% of cases, respectively. Kaplan-Meier survival curves and Cox regression analysis showed that gender had no impact on mortality during follow-up; however, age (>50 years) was associated with greater risk of death (hazard ratio: 6.54; 95% confidence interval: 3.2-13.3). These findings will improve our understanding of the various risk factors and help develop institutional guidelines for the management of patients with DVT. PMID:26345414

  1. Effects of Erwinia-asparaginase on the coagulation system.

    Science.gov (United States)

    Carlsson, H; Stockelberg, D; Tengborn, L; Braide, I; Carneskog, J; Kutti, J

    1995-11-01

    L-Asparaginase treatment during induction therapy in acute lymphoblastic leukaemia (ALL) is known to be frequently complicated by thromboembolic events. It was recently suggested that L-asparaginase derived from Erwinia chrysanthemi alters the coagulation system less severely than does Escherichia coli asparaginase. In a series of 11 adult patients with ALL, we investigated some parameters of the coagulation system during treatment with Erwinia asparaginase. The doses employed were rather high; all patients below the age of 60 years received 15,000 U/m2 daily over 14 days. In accordance with what is known from treatment with E. coli asparaginase, we observed significant lowering of antithrombin as well as of fibrinogen. However, as to fibrinogen indeed a significant decrease had occurred prior to the institution of Erwinia asparaginase treatment. The most striking observation in the present study was that the levels of prothrombin complex, reflecting the function of K-vitamin dependent coagulation factors II, VII and X, remained within normal ranges during treatment. This indicates that these coagulation factors were not affected by Erwinia asparaginase, an observation at variance with several reports where E. coli asparaginase was investigated. This latter observation was the only finding which could lend support to the view that Erwinia asparaginase affects the coagulation system less than E. coli asparaginase. Finally, one of our patients developed a sinus thrombosis, a severe thrombotic complication. PMID:7493674

  2. Blood peptidome-degradome profile of breast cancer.

    Directory of Open Access Journals (Sweden)

    Yufeng Shen

    Full Text Available BACKGROUND: Cancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients. METHODOLOGY AND PRINCIPAL FINDINGS: The peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP and age, race, and menopausal status matched control healthy persons (HP were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins. CONCLUSIONS: Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.

  3. Macrophage Matrix Metalloproteinase-12 Dampens Inflammation and Neutrophil Influx in Arthritis

    Directory of Open Access Journals (Sweden)

    Caroline L. Bellac

    2014-10-01

    Full Text Available Resolution of inflammation reduces pathological tissue destruction and restores tissue homeostasis. Here, we used a proteomic protease substrate discovery approach, terminal amine isotopic labeling of substrates (TAILS, to analyze the role of the macrophage-specific matrix metalloproteinase-12 (MMP12 in inflammation. In murine peritonitis, MMP12 inactivates antithrombin and activates prothrombin, prolonging the activated partial thromboplastin time. Furthermore, MMP12 inactivates complement C3 to reduce complement activation and inactivates the chemoattractant anaphylatoxins C3a and C5a, whereas iC3b and C3b opsonin cleavage increases phagocytosis. Loss of these anti-inflammatory activities in collagen-induced arthritis in Mmp12−/− mice leads to unresolved synovitis and extensive articular inflammation. Deep articular cartilage loss is associated with massive neutrophil infiltration and abnormal DNA neutrophil extracellular traps (NETs. The NETs are rich in fibrin and extracellular actin, which TAILS identified as MMP12 substrates. Thus, macrophage MMP12 in arthritis has multiple protective roles in countering neutrophil infiltration, clearing NETs, and dampening inflammatory pathways to prepare for the resolution of inflammation.

  4. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    Directory of Open Access Journals (Sweden)

    Sinuhe eHahn

    2015-02-01

    Full Text Available It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia be accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture which relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in angiogenic growth factors, complement activation, reduced levels of placenta protein 13 or excessive neutrophil activation evident in preeclampsia.

  5. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

  6. Preeclampsia - will orphan drug status facilitate innovative biological therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

  7. [Effects of intravenous injection of sulphated galactomannan on anticoagulant activity of rat plasma].

    Science.gov (United States)

    Drozd, N N; Makarov, V A; Tolstenkov, A S; Lapikova, E S; Miftakhova, N T; Mestechkina, N M; Shcherbukhin, V D; Il'ina, A V; Varlamov, V P

    2008-01-01

    We studied anticoagulant activity in vitro and in vivo of sulfate depolymerisation galactomannan guar with the following characteristics: Man:Gal 1.64, molecular mass 127 kDa, sulfation degree 1.46. We found the ability of galactomannan-HSO3Na (GM) to increase the time of blood coagulation in the test aPTT with an increase of its concentration and to decrease velocity of chromogenic substrate on the factor Xa hydrolysis. Specific antithrombin and anti-factor Xa activities of GM were 35.8 +/- 1.8 IU/mg and 6.6 +/- 0.5 IU/mg, respectively. In biospecific electrophoresis complexes arise between GM and protamine sulfate. Intravenous injection of GM to rats prolonged plasma coagulation time in the aPTT test with dose reduction from 1 to 3 mg/kg. In rat thrombosis model a dose of 3 Mg/kg produced a 100% inhibition of blood clot. PMID:18946908

  8. [Effect on low-molecular-weight heparin obtained using a chitinolytic complex on the anticoagulant activity of plasma in rabbits and rats].

    Science.gov (United States)

    Drozd, N N; Tolstenkov, A S; Makarov, V A; Miftakhova, N T; Bannikova, G E; Sukhanova, P P; Varlamov, V P; Vikhoreva, G E

    2007-01-01

    The anticoagulant activity of low-molecular-weight heparin with an average molecular weight of 4.7 kD (LMWH-4.7) has been studied. This derivative was prepared from unfractionated heparin with the help of chitinolytic enzyme complex from Streptomyces kurssanovii. The antithrombin activity of LMWH-4.7 (aIla activity) was 72 +/- 9 IU/mg and the activity with respect to the blood coagulation factor Xa (aXa activity) was 200 +/- 33 IU/mg, which corresponded to an aXa/aIIa ratio of 2.8 (necessary for effective antithrombotic drugs). The aIIa and aXa activity exhibited a dose-dependent variation upon intravenous and subcutaneous injections in rabbits, so that a high aIIa/aXa ratio was retained: 5 min after the intravenous injection of a minimum dose (0.3 mg/kg), this ratio was 2, 7, and for a greater dose (3.0 mg/kg) it reached 3.8. Subcutaneous injections were followed by slow elimination of the anticoagulant within 24 h. LMWH-4.7 upon intraperitoneal injections produced a dose-dependent inhibition of a model thrombosis in rats. Complete inhibition was observed for a dose of 3 mg/kg. Thus, it is possible to obtain active LMW heparin with the help of chitinases. PMID:17523450

  9. Sulodexide: implicazioni cliniche ed economiche

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2005-06-01

    Full Text Available Sulodexide is a highly purified glycosaminoglycan approved for leg ulcers treatment. It contains two principal components: heparan sulfate, a fast-moving heparin fraction, (80% and dermatan sulfate (20%. Sulodexide is available as an oral agent and as an injectable preparation. Its pharmacological action is obtained by dose-dependent coagulation factors inhibition: dermatan sulfate upgrades the physiological action of a selective thrombin inhibitor, heparin cofactor II, and heparan sulfate depresses activated factor X, via an increase of antithrombin III action. The antithrombotic action is enhanced by platelet aggregation inhibition and by the activation of the fibrinolytic system. This paper summarizes the results of some of the main trials that evaluated sulodexide in the treatment of peripheral occlusive arterial disease and venous leg ulcers; a trial on prevention of recurrent deep venous thrombosis with sulodexide is also reviewed. We analyzed data about the clinical and economical impact of chronic venous insufficiency with a particular attention to the cost of medication, hospitalization and management of leg ulcers. The hypothetical savings correlated to the reduction of leg ulcers incidence and healing time attainable with sulodexide have been estimated. A comparison between the different acquisition costs of the drugs frequently used to treat leg ulcers is also provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease and its treatments on the patient are assessed.

  10. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph.

    Science.gov (United States)

    Monroe, Dougald M; Jenny, Richard J; Van Cott, Kevin E; Buhay, Shelly; Saward, Laura L

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  11. Characterization of IXINITY® (Trenonacog Alfa, a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    Directory of Open Access Journals (Sweden)

    Dougald M. Monroe

    2016-01-01

    Full Text Available The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148 polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant]. Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX both with and without factor VIIIa (FVIIIa and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed 97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa; once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX.

  12. Effects of carboxymethyl chitosan on the blood system of rats

    International Nuclear Information System (INIS)

    Highlights: → We report, for the first time, the safety of carboxymethyl chitosan in blood system. → CM-Chitosan has no significant effects on coagulation function of rats. → CM-Chitosan has no significant effects on anticoagulation performance of rats. → CM-Chitosan has no significant effects on fibrinolytic function of rats. → CM-Chitosan has no significant effects on hemorheology of rats. -- Abstract: Carboxymethyl chitosan (CM-chitosan), a derivative of chitosan, was extensively studied in the biomedical materials field for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CM-chitosan in the blood system are lacking. In this study CM-chitosan was implanted into the abdominal cavity of rats to determine blood indexes at different times and to evaluate the effects of CM-chitosan on the blood system of rats. Coagulation function was reflected by thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4) indexes; anti-coagulation performance was assessed by the index of antithrombinIII (ATIII); fibrinolytic function was reflected by plasminogen (PLG) and fibrin degradation product (FDP) indexes; and blood viscosity (BV) and plasma viscosity (PV) indexes reflected hemorheology. Results showed that CM-chitosan has no significant effects on the blood system of rats, and provides experimental basis for CM-chitosan to be applied in the field of biomedical materials.

  13. [Interaction of hypoxia and haemostasis--hypoxia as a prothrombotic factor at high altitude?].

    Science.gov (United States)

    Schobersberger, Wolfgang; Hoffmann, Georg; Gunga, Hanns-Christian

    2005-04-01

    For an extended period of time various research projects have been conducted on the relationship of hypoxia and haemostasis. The enclosed article contains the conclusion to which extent lack of oxygen can activate the coagulation system and induce a prothrombotic state. The majority of studies proved a shortening of coagulation times during acute exposure to hypoxia, whereas activated parameters of coagulation and fibrinolysis like prothrombin fragment F1+2 as well as thrombin-antithrombin III complexes and D-dimer remained mostly unmodified. It is suggested that a prolonged sojourn at high altitudes could lead to activation of the coagulation system through an increase of haematocrit and blood viscosity. Recently it was proven that people living at high altitudes show an enhanced risk of stroke incidents. The significance of the change in haemostasis on that outcome has not yet been part of the research. However, it has been proven that the activity of the coagulation system does not play a pathophysiological part in the development of acute mountain sickness and high altitude pulmonary edema. Recent studies also demonstrated that moderate hypoxia during long haul flights may not be the main trigger in inducing deep vein thrombosis in passengers. PMID:15966261

  14. Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis.

    Science.gov (United States)

    Xu, Xinsen; Zhou, Yanyan; Miao, Runchen; Chen, Wei; Qu, Kai; Pang, Qing; Liu, Chang

    2016-06-01

    We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis. PMID:27052251

  15. The role of biochemical risk factors in the etiology of AIS in children and adults.

    Science.gov (United States)

    Kopyta, Ilona; Zimny, Mikołaj; Sarecka-Hujar, Beata

    2015-01-01

    Stroke is an abrupt onset of both focal and global neurological deficits secondary to a vascular event lasting more than 24 h and with a vascular background as its only cause. It can be triggered by a rupture of a blood vessel, aneurysm (hemorrhagic stroke, HS), thrombosis or embolisms (ischemic stroke, IS). In developed countries, it is the third most common cause of death in the adult population. Stroke in children is a rare disorder with a reported frequency of about 3 cases per 100,000 children per year. The history of acute brain ischemia is burdened with neurological complications such as motor impairment, speech impairment and intellectual delay. Moreover, in children after AIS seizures and epilepsy are also quite common. Stroke is a heterogeneous disorder; its risk factors in adults are well known, however, in pediatrics, in more than 20% cases, the cause of stroke is impossible to determine. Due to the fact that stroke usually arises as a consequence of the cerebral thrombosis, many of the mechanisms responsible for its occurrence can be considered as risk factors. We have reviewed the recent case-control studies conducted on pediatric patients regarding biochemical risk factors such as elevated levels of homocysteine, fibrinogen, protein C, protein S, antithrombin III, lipoprotein(a), cholesterol and its fractions, and compared them with the results obtained from adult patients. PMID:25428197

  16. Biopolymer-modified graphite oxide nanocomposite films based on benzalkonium chloride-heparin intercalated in graphite oxide

    Energy Technology Data Exchange (ETDEWEB)

    Meng Na; Zhou Ninglin; Shen Jian [Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing Normal University, Nanjing 210046 (China); Zhang Shuangquan, E-mail: zhouninglin@njnu.edu.cn, E-mail: jshen@njnu.edu.cn, E-mail: shuangquanz@yahoo.com [Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing 210046 (China)

    2010-05-07

    Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clots. In the present work, poly(dimethylsiloxane)(PDMS)/graphite oxide-benzalkonium chloride-heparin (PDMS/modified graphite oxide) nanocomposite films were obtained by the solution intercalation technique as a possible drug delivery system. The heparin-benzalkonium chloride (BAC-HEP) was intercalated into graphite oxide (GO) layers to form GO-BAC-HEP (modified graphite oxide). Nanocomposite films were characterized by XRD, SEM, TEM, ATR-FTIR and TGA. The modified graphite oxide was observed to be homogeneously dispersed throughout the PDMS matrix. The effect of modified graphite oxide on the mechanical properties of the nanocomposite film was investigated. When the modified graphite oxide content was lower than 0.2 wt%, the nanocomposites showed excellent mechanical properties. Furthermore, nanocomposite films become delivery systems that release heparin slowly to make the nanocomposite films blood compatible. The in vitro studies included hemocompatibility testing for effects on platelet adhesion, platelet activation, plasma recalcification profiles, and hemolysis. Results from these studies showed that the anticoagulation properties of PDMS/GO-BCA-HEP nanocomposite films were greatly superior to those for no treated PDMS. Cell culture assay indicated that PDMS/GO-BCA-HEP nanocomposite films showed enhanced cell adhesion.

  17. Studies on contact activation: effects of surface and inhibitors.

    Science.gov (United States)

    Cameron, C L; Fisslthaler, B; Sherman, A; Reddigari, S; Silverberg, M

    1989-01-01

    Contact activation is initiated when the plasma proteins, Hageman factor (factor XII), prekallikrein and high molecular weight kininogen interact with negatively charged materials. The activation of the intrinsic pathway of blood coagulation and the production of bradykinin are among the sequelae of contact activation. The kinetics of the activation of the contact system are modified by plasma inhibitors, C1 inhibitor being quantitatively the most important. We propose that the activation of the system requires that the stimulus provided by the surface must be greater than a threshold value to overcome the effects of the inhibitors. We show in this paper that the amount of surface required for activation is much reduced in the absence of C1 inhibitor (Hereditary Angioedema) or in the cold where the inhibitor loses much of its effectiveness. Antithrombin III inhibition of activated Hageman factor is augmented by heparin which is also an activator of Hageman factor. The rate constants for inhibition remain much lower than for C1 inhibitor, however. PMID:2530427

  18. The Hemostatic System and Angiogenesis in Malignancy

    Directory of Open Access Journals (Sweden)

    Marek Z. Wojtukiewicz

    2001-01-01

    Full Text Available Coagulopathy and angiogenesis are among the most consistent host responses associated with cancer. These two respective processes, hitherto viewed as distinct, may in fact be functionally inseparable as blood coagulation and fibrinolysis, in their own right, influence tumor angiogenesis and thereby contribute to malignant growth. In addition, tumor angiogenesis appears to be controlled through both standard and non-standard functions of such elements of the hemostatic system as tissue factor, thrombin, fibrin, plasminogen activators, plasminogen, and platelets. “Cryptic” domains can be released from hemostatic proteins through proteolytic cleavage, and act systemically as angiogenesis inhibitors (e.g., angiostatin, antiangiogenic antithrombin III aaATIII. Various components of the hemostatic system either promote or inhibit angiogenesis and likely act by changing the net angiogenic balance. However, their complex influences are far from being fully understood. Targeted pharmacological and/ or genetic inhibition of pro-angiogenic activities of the hemostatic system and exploitation of endogenous angiogenesis inhibitors of the angiostatin and aaATIII variety are under study as prospective anti-cancer treatments.

  19. Spectroscopic and Electrochemical Detection of Thrombin/5'-SH or 3'-SH Aptamer Immobilized on (porous) Gold Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Park, Buem Jin; Sa, Young Seung; Kim, Yong Hwan; Kim, Young Hun [Kwangwoon University, Seoul (Korea, Republic of)

    2012-01-15

    Thrombin is a serine protease that catalyzes the conversion of soluble fibrinogen to insoluble fibrin, and thus induces physiological and pathological blood coagulation. Therefore, it is important to detect thrombin in blood serum for purposes of diagnosis. To achieve this goal, it has been suggested that a 15-mer aptamer strongly binds with thrombin to form a G-quartet structure of the aptamer. Generally, 5'-end thiol-functionalized aptamer has been used as an anti-thrombin binder. Herein, we evaluate the possibility of utilizing a 3'-SH aptasensor for thrombin detection using SPR spectroscopy, and compare the enhancement of the electrochemical signal of the thrombin-aptamer bound on a porous gold substrate. Although the two aptamers have similar configurations, in SPR analysis, the 3'-SH aptamer was a effective aptasensor as well as 5'-SH aptamer. Results from electrochemical analysis showed that the porous gold substrate acted as a good substrate for an aptasensor and demonstrated 5-fold enhancement of current change, as compared to gold thin film.

  20. Thrombophilia

    Directory of Open Access Journals (Sweden)

    Maurizio Zangari

    2008-01-01

    Full Text Available Thrombophilia or hypercoagulable state is a clinical condition characterized by a tendency to develop venous (less frequently arterial thrombosis. The development of a venous thromboembolic episode (VTE is the result of environmental risk factors such as age, male sex, obesity, the exposure to “risk periods” of immobilization, trauma, cancer, pregnancy or the use of exogenous hormones or antineoplastic medications often on a background of a congenital procoagulant state. Table 1 summarizes the most frequently inherited and acquired thrombophilic conditions in a population of patients with a first episode of VTE.In patients with venous thrombosis before the early nineties a biologic cause of thrombophilia was detectable in only 5% to 15% of cases and was confined to deficiencies of antithrombin, protein C, and protein S. The discovery of two prothrombotic mutations prevalent in white populations, the factor V-Arg506Gln mutation (factor V Leiden and the prothrombin G20210A mutation has significantly increased the number of patients with recognizable hereditary risk factor. The antiphospholipid antibody syndrome and elevated plasma homocysteine levels are also frequently identifiable risk factors in patients presenting with venous as well as arterial thrombosis.

  1. Syntenic assignment of human chromosome 1 homologous loci in the bovine.

    Science.gov (United States)

    Threadgill, D S; Threadgill, D W; Moll, Y D; Weiss, J A; Zhang, N; Davey, H W; Wildeman, A G; Womack, J E

    1994-08-01

    Three mouse chromosomes (MMU 1, 3, and 4) carry homologs of human chromosome 1 (HSA 1) genes. A similar situation is found in the bovine, where five bovine chromosomes (BTA 2, 3, 5, 16, and unassigned syntenic group U25) contain homologs of HSA 1 loci. To evaluate further the syntenic relationship of HSA 1 homologs in cattle, 10 loci have been physically mapped through segregation analysis in bovine-rodent hybrid somatic cells. These loci, chosen for their location on HSA 1, are antithrombin 3 (AT3), renin (REN), complement component receptor 2 (CR2), phosphofructokinase muscle type (PFKM), Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR), alpha fucosidase (FUCA1), G-protein beta 1 subunit (GNB1), alpha 1A amylase, (AMY1), the neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), and alpha skeletal actin (ACTA1). AT3, REN, CR2, and GNB1 mapped to BTA 16, PFKM to BTA 5, AMY1A and NRAS to BTA 3, FGR and FUCA1 to BTA 2, and ACTA1 to BTA 28. PMID:8001974

  2. Complications of bariatric surgery: Presentation and emergency management.

    Science.gov (United States)

    Kassir, Radwan; Debs, Tarek; Blanc, Pierre; Gugenheim, Jean; Ben Amor, Imed; Boutet, Claire; Tiffet, Olivier

    2016-03-01

    The epidemic in obesity has led to an increase in number of so called bariatric procedures. Doctors are less comfortable managing an obese patient after bariatric surgery. Peri-operative mortality is less than 1%. The specific feature in the obese patient is that the classical signs of peritoneal irritation are never present as there is no abdominal wall and therefore no guarding or rigidity. Simple post-operative tachycardia in obese patients should be taken seriously as it is a WARNING SIGNAL. The most common complication after surgery is peritonitis due to anastomotic fistula formation. This occurs typically as an early complication within the first 10 days post-operatively and has an incidence of 1-6% after gastric bypass and 3-7% after sleeve gastrectomy. Post-operative malnutrition is extremely rare after restrictive surgery (ring, sleeve gastrectomy) although may occur after malabsorbative surgery (bypass, biliary pancreatic shunt) and is due to the restriction and change in absorption. Prophylactic cholecystectomy is not routinely carried out during the same procedure as the bypass. Superior mesenteric vein thrombosis after bariatric surgery is a diagnosis which should be considered in the presence of any postoperative abdominal pain. Initially a first etiological assessment is performed (measurement of antithrombin III and of protein C and protein S, testing for activated protein C resistance). If the least doubt is present, a medical or surgical consultation should be requested with a specialist practitioner in the management of obese patients as death rates increase with delayed diagnosis. PMID:26808323

  3. Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation [v1; ref status: indexed, http://f1000r.es/3ah

    Directory of Open Access Journals (Sweden)

    Freeha Arshad

    2014-05-01

    Full Text Available Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF. Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor.  Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part be responsible for the increased risk for vascular disease seen in liver transplant recipients.

  4. Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold.

    Science.gov (United States)

    Hilberg, Thomas; Gläser, Doreen; Reckhart, Carsten; Prasa, Dagmar; Stürzebecher, Jörg; Gabriel, Holger H W

    2003-11-01

    For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60-120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTP(ex+in)) and endogenous (ETP(ex+in)) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTP(ex+in) were increased ( PIAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and alpha(2)-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD). PMID:12883904

  5. Relationship between manic state after presenile onset and silent cerebral infarction

    International Nuclear Information System (INIS)

    Magnetic resonance (MR) imaging was performed in 12 patients who incurred manic state after the age of 50 (manic group). Twelve other age- and sex-matched patients who incurred emotional disturbance at the young age served as controls. Patients with a history of cerebral stroke and local neurologic symptoms were excluded. Silent cerebral infarction (SCI) were concomitantly seen on MR images in 66.7% in the manic group, which was significantly higher than the control group (16.7%). Approximately half of the patients in the manic group seemed to be in the parenchymal manic state associated with SCI. Patients in the manic state associated with SCI was at a risk for developing cerebral stroke. Therefore, the treatment such as antithrombin therapy for cerebrovascular disorder was considered important, from the viewpoint of early treatment of cerebral infarction. Since lesions were frequently observed in the right frontal lobe and basal nucleus in manic patients with the associated SCI, these sites may be in part involved in the occurrence of manic state. (N.K.)

  6. Platelet-derived microparticles associate with fibrin during thrombosis.

    Science.gov (United States)

    Siljander, P; Carpen, O; Lassila, R

    1996-06-01

    Platelet-derived microparticles (MP) are reported to express both pro- and anticoagulant activities. Nevertheless, their functional significance has remained unresolved. The present study monitored the generation and fate of MP in an experimental model of thrombosis with costimulation of platelets by collagen and thrombin. When minimally anticoagulated (0.5 micromol/L PPACK) blood was perfused over immobilized fibrillar type I collagen in a flow chamber at a low shear rate (300 s(-1)), endogenous thrombin was generated, as evidenced by thrombin-antithrombin III complex. In contrast to full anticoagulation 150 micromol/L PPACK) and the absence of collagen, large platelet aggregates and fibrin ensued during perfusions over collagen in the presence of thrombin. In these thrombi, MP, defined as GPIIbIIIa- and P-selectin-positive vesicles (<1 micron), were found to align fibrin in immunofluorescence and scanning immunoelectron microscopy. Moreover, in sections of embolectomized thromboemboli from patients GPIIbIIIa- and P-selectin-positive material compatible with MP was detected in a fibrin strand-like pattern. In vitro binding studies showed that MP bound to fibrin and acted there as procoagulants. In summary, we show that MP generated during thrombus formation associate with local fibrin. This adhesive function fibrin could imply a sustained modulatory role for MP in evolving thrombi. PMID:8639834

  7. Analytical and statistical comparability of generic enoxaparins from the US market with the originator product.

    Science.gov (United States)

    Mourier, Pierre A J; Agut, Christophe; Souaifi-Amara, Hajer; Herman, Fréderic; Viskov, Christian

    2015-11-10

    Low-molecular-weight heparins (LMWHs) are complex anticoagulant drugs, made from heparin porcine mucosa starting material. Enoxaparin sodium manufactured by Sanofi is one of the most widely prescribed LMWHs and has been used since 1993 in the USA. In 2010, US Food and Drug Administration approval for supplying generic enoxaparin was granted to Sandoz and subsequently to Amphastar. Little is known, however, of the differences in composition of these preparations. In this study, samples from several batches of generic enoxaparins were purchased on the US market and analyzed with state of the art methodologies, including disaccharide building blocks quantification, nuclear magnetic resonance (NMR), and a combination of orthogonal separation techniques. Direct high-performance liquid chromatography analysis of the different enoxaparin batches revealed distinct process fingerprints associated with each manufacturer. Disaccharide building block analysis showed differences in the degree of sulfation, the presence of glycoserine derivatives, as well as in proportions of disaccharides. Results were compared by statistical approaches using multivariate analysis with a partial least squares discriminant analysis methodology. The variations were statistically significant and allowed a clear distinction to be made between the enoxaparin batches according to their manufacturer. These results were further confirmed by orthogonal analytical techniques, including NMR, which revealed compositional differences of oligosaccharides both in low- and high-affinity antithrombin fractions of enoxaparin. PMID:26280926

  8. Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Esther K. Wolthuis

    2012-01-01

    Full Text Available Preventing tissue-factor-(TF- mediated systemic coagulopathy improves outcome in models of sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate ventilator-induced lung injury (VILI. We investigated the effect of relative TF deficiency on pulmonary coagulopathy and inflammation in a murine model of VILI. Heterozygous TF knockout (TF+/− mice and their wild-type (TF+/+ littermates were sedated (controls or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours. Mechanical ventilation resulted in pulmonary coagulopathy and inflammation, with more injury after mechanical ventilation with higher tidal volumes. Compared with TF+/+ mice, TF+/− mice demonstrated significantly lower pulmonary thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in lung wet-to-dry ratio, BALF total protein levels, neutrophil influx, and lung histopathology scores between TF+/− and TF+/+ mice. Notably, pulmonary levels of cytokines were significantly higher in TF+/− as compared to TF+/+ mice. Systemic levels of cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.

  9. Preventive Efficacy of Fucoidan in Rats Exposed to γ-Rays

    International Nuclear Information System (INIS)

    Fucoidan (FDN); β-1,3-glucan is a natural polysaccharide extracted from brown seaweeds, with a wide variety of biological properties, especially the anti-inflammatory, anti-coagulation and anti-oxidative effects. The objective of this work was to evaluate the radioprotective effect of FDN. The study was performed on Sprague-Dawley rats that were administered during 10 days FDN (100 mg/ kg body wt), rats exposed to 5 Gy γ-rays, rats administered FDN + γ-rays comparing with control animals. The haemostatic parameters (protein-C, antithrombin-III and tissue-plasminogen activators activities), the haematological parameters: count of blood elements (total leukocytes, neutrophils, lymphocytes) and bone marrow cells (erythroid, lymphoid and myeloid cells) and biochemical parameters: thiobarbituric acid-reactive substances (TBARS) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSPx) were evaluated. Results showed that γ-rays provoked marked changes in haemostatic markers, haematological parameters and anti oxidative enzymes as well as TBARS level. FDN ameliorated the alteration in all tested parameters and markers induced due to exposure to γ-rays. These data demonstrate that FDN might be viewed as a non-toxic potent agent for preventing γ-rays induced cellular hazards. Conclusion, the results may facilitate the development of a new radio protective agent with low toxicity.

  10. Diagnostic uses of snake venom.

    Science.gov (United States)

    Marsh, N A

    2001-01-01

    Snake venom toxins are invaluable for the assay of coagulation factors and for the study of haemostasis generally. Thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assays as well as detecting dysfibrinogenaemias. Since SVTLE are not inhibited by heparin, they can be used for assaying antithrombin III in samples containing heparin. Snake venom prothrombin activators are utilised in prothrombin assays, whilst Russell's viper venom (RVV) can be used to assay clotting factors V, VII, X and lupus anticoagulants (LA). Activators from the taipan, Australian brown snake and saw-scaled viper have also been used to assay LA. Protein C (PC) and activated PC (APC) resistance can be measured by means of RVV, Protac (from Southern copperhead snake venom) and STA-Staclot (from Crotalus viridis helleri) whilst von Willebrand factor can be studied with Botrocetin (Bothrops jararaca). Finally, snake venom C-type lectins and metalloproteinase disintegrins are being used to study platelet glycoprotein receptors and show great potential for use in the routine coagulation laboratory. PMID:11910187

  11. A comparison of haemocoagulation tests in the experimental endotoxin model DIC and in rats whole-body irradiated by 250 Gy

    International Nuclear Information System (INIS)

    A comparison of results of tests performed with the endotoxin model of disseminated intravascular coagulation (DIC) and with irradiated groups of rats led to the conclusion that after whole-body irradiation with the high dose of 250 Gy, DIC occurs, in spite of the fact that the first stage, the hypercoagulation condition, can hardly be observed. In the experimental endotoxin model, an increase of activated partial thromboplastin test (APTT) values and prolongation of the thrombin time was observed up to 24 hours for two endotoxin doses. After both endotoxin doses, the fibrinogen level was transiently decreased with a subsequent increase. The fibrin monomers correspond to a decrease in the fibrinogen level. After the first dose, they were positive between the 3rd and 12th hours, and after the second dose, positivity was observed 6 hours after the application. The antithrombin III level was decreased after 12 hours for both endotoxin doses. The thrombocyte count was considerably reduced already from the 6th hour after administering endotoxin to the end of the experiment. Considerable changes in thrombocyte aggregation were observed only 3 hours after administering the second dose. When comparing the resulting values of these tests with values observed in irradiated animals, a certain agreement was found in the nature of the changes after exposure to 250 Gy. The fibrinogen level was transiently decreased 3 hours after irradiation, when considerable changes in the thrombocyte aggregation also occurred. (author) 5 figs., 17 refs

  12. Hemothorax under thrombolytic therapy with recombinant tissue: plasminogen activator (rt-PA) in a 16-year-old girl.

    Science.gov (United States)

    Varnholt, V; Ringe, H; Nietsch, L; Gaedicke, G

    1999-12-01

    We present the case of a 16-year-old girl with an extended thrombosis of the femoral and iliac vein and the inferior vena cava during pleuropneumonia; predisposing risk factors for thrombophilia were: use of contraceptives, nicotine abuse and congenital deficiency of antithrombin III (not previously diagnosed). Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA; initial dose: 0.08 mg/kg/h) was started. 2 days later--after diagnosis of an extended hemothorax: 1500 ml blood were obtained after thoracocentesis, transfusion of packed red blood cells was necessary--rt-PA was stopped, with only heparin (400 U/kg/d) being administered. 36 h later--the thrombosis had not yet changed--the thrombolytic therapy with rt-PA was continued in a markedly reduced dose (0.015 mg/kg/d) with no further bleeding complications. 8 days later--after successful thrombolysis--t-PA was stopped, heparin was given for another 10 days, then cumarin was administered orally. PMID:10650854

  13. [Adult-onset rare diseases].

    Science.gov (United States)

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-01

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.). PMID:24566697

  14. Comparison of three different anti-Xa assays in major orthopedic surgery patients treated with fondaparinux.

    Science.gov (United States)

    Ikejiri, Makoto; Wada, Hideo; Yamaguchi, Toshio; Miyazaki, Shinichi; Hasegawa, Masahiro; Wakabayashi, Hiroki; Asanuma, Kunihiro; Sakaguchi, Akane; Matsumoto, Takeshi; Ohishi, Kohshi; Fujimoto, Naoki; Yamada, Norikazu; Ito, Masaaki; Katayama, Naoyuki; Sudo, Akihiro

    2016-05-01

    Anti-Xa assays are useful for monitoring the effects of selective anti-Xa drugs, such as fondaparinux, in the prophylaxis of deep vein thrombosis. In the present study, anti-Xa activity was measured using three different assays, Testzym(®) Heparin S, STA(®)-Liquid Anti-Xa and HemosIL(®) Liquid Heparin. Anti-Xa activity in each assay gradually increased from day one after administration to day eight, and still remained on day 15. Although there were significant differences in anti-Xa activity among the three assays, the activity showed significant correlation across assays. There were no significant differences in the anti-Xa activity between patients with and without DVT or between patients with and without massive bleeding on day one before and after administration, day four, day eight and day 15. Anti-Xa activity in each assay was weakly correlated with antithrombin (AT) activity. The AT activity in patients were significantly higher on days four, eight and 15 compared with day one before and after administration, suggesting that AT activity increases following the administration of fondaparinux. The three anti-Xa assay kits tested are useful for monitoring fondaparinux treatment in orthopedic surgery patients. PMID:26922193

  15. A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients

    DEFF Research Database (Denmark)

    Robinson, Sian; Zincuk, Aleksander; Larsen, Ulla Lei; Ekstrom, Claus; Nybo, Mads; Rasmussen, Leif Bjarne; Toft, Palle

    2013-01-01

    24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter. RESULTS: Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n= 20) and 40 mg BID (n=19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU...... critically ill patients weighing 50 - 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40mg BID, or 1mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and....../ml respectively. A dose of 30 mg BID (n= 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n=19) achieved near steady state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40...

  16. Coagulant and anticoagulant activities of Bothrops lanceolatus (Fer de lance) venom.

    Science.gov (United States)

    Lôbo de Araújo, A; Kamiguti, A; Bon, C

    2001-01-01

    Bothrops lanceolatus venom contains caseinolytic, phospholipase, esterase and haemorrhagic activities. We have investigated the coagulant and anticoagulant actions of B. lanceolatus venom on human citrated plasma and on purified plasma components. Although B. lanceolatus venom up to 50 microg/ml was unable to clot citrated plasma, at concentrations > or = 5 microg/ml the venom dose-dependently clotted purified human fibrinogen, indicating the presence of a thrombin-like enzyme. Human plasma (final concentration > or = 12.5%) dose-dependently inhibited the venom-induced fibrinogen clotting. This finding suggested that endogenous plasma protease inhibitors can affect the venom's action on fibrinogen. To investigate this possibility, B. lanceolatus venom was incubated with different plasma protease inhibitors and the activity on fibrinogen tested. alpha(2)-Macroglobulin and alpha(1)-antitrypsin did not interfere with the coagulant activity of the venom whereas the antithrombin-III/heparin complex partially inhibited this activity. A non-toxic, acidic phospholipase A(2) purified from B. lanceolatus venom prolonged the activated partial thromboplastin time in human plasma from 39.7+/-0.5 s (control with saline) to 60.2+/-0.9 s with 50 microg of PLA(2) (p<0.001), suggesting an anticoagulant activity associated with this enzyme. This anticoagulant activity may account for some of the effects of the venom on blood coagulation. PMID:10978756

  17. Hemocompatibility of Axial Versus Centrifugal Pump Technology in Mechanical Circulatory Support Devices.

    Science.gov (United States)

    Schibilsky, David; Lenglinger, Matthias; Avci-Adali, Meltem; Haller, Christoph; Walker, Tobias; Wendel, Hans Peter; Schlensak, Christian

    2015-08-01

    The hemocompatible properties of rotary blood pumps commonly used in mechanical circulatory support (MCS) are widely unknown regarding specific biocompatibility profiles of different pump technologies. Therefore, we analyzed the hemocompatibility indicating markers of an axial flow and a magnetically levitated centrifugal device within an in vitro mock loop. The HeartMate II (HM II; n = 3) device and a CentriMag (CM; n = 3) adult pump were investigated in a human whole blood mock loop for 360 min using the MCS devices as a driving component. Blood samples were analyzed by enzyme-linked immunosorbent assay for markers of coagulation, complement system, and inflammatory response. There was a time-dependent activation of the coagulation (thrombin-antithrombin complexes [TAT]), complement (SC5b-9), and inflammation system (polymorphonuclear [PMN] elastase) in both groups. The mean value of TAT (CM: 4.0 μg/L vs. 29.4 μg/L, P centrifugal CM device showed significantly lower activation of coagulation and inflammation than that of the HM II axial flow pump. Both HM II and CM have demonstrated an acceptable hemocompatibility profile in patients. However, there is a great opportunity to gain a clinical benefit by developing techniques to lower the blood surface interaction within both pump technologies and a magnetically levitated centrifugal pump design might be superior. PMID:26234452

  18. Vegetarians and cardiovascular risk factors: hemostasis, inflammatory markers and plasma homocysteine.

    Science.gov (United States)

    Mezzano, D; Muñoz, X; Martínez, C; Cuevas, A; Panes, O; Aranda, E; Guasch, V; Strobel, P; Muñoz, B; Rodríguez, S; Pereira, J; Leighton, F

    1999-06-01

    We studied hemostatic and inflammatory cardiovascular risk factors (CVRF), and total plasma homocysteine (tHcy) in 26 vegetarians (23 lacto- or ovolactovegetarians and 3 vegans), matched by age, sex and socioeconomic status with omnivorous controls. Vegetarians had significantly lower proportion of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma lipids, significantly shortened bleeding time, and increased blood platelet count and in vitro platelet function (aggregation and secretion). Plasma levels of all coagulation or fibrinolytic factors and natural inhibitors synthesized in the liver were lower in vegetarians than in controls. Whereas for some factors this decrease was statistically significant (fibrinogen, factor VIIc, antithrombin III, protein S, plasminogen) for the remaining (factors VIIIc, Vc, prothrombin, protein C) a trend in the same direction was found. For hemostatic proteins of predominantly extrahepatic origin (von Willebrand factor. tPA, PAI-1) this tendency was not present. No significant differences in inflammatory proteins (C-reactive protein and alpha1-protease inhibitor) were detected in both groups. tHcy was significantly increased in vegetarians, and correlated only with cobalamin levels. The increased platelet function and tHcy found in vegetarians may counteract the known cardiovascular health benefits of vegetarian diet (VD). PMID:10404767

  19. Venous thromboembolism: The intricacies

    Directory of Open Access Journals (Sweden)

    Dutta T

    2009-01-01

    Full Text Available Venous thromboembolism (VTE has been a subject of great interest of late. Since Rudolph Virchow described the famous Virchow′s triad in 1856, there have been rapid strides in the understanding of the pathogenesis and factors responsible for it. Discovery of various thrombophilic factors, both primary and acquired, in the last 40 years has revolutionized prognostication and management of this potentially life-threatening condition due to its associated complication of pulmonary thromboembolism. Detailed genetic mapping and linkage analyses have been underlining the fact that VTE is a multifactorial disorder and a complex one. There are many gene-gene and gene-environment interactions that alter and magnify the clinical picture in this disorder. Point in case is pregnancy, where the risk of VTE is 100-150 times increased in the presence of Factor V Leiden, prothrombin mutation (Prothrombin 20210A and antithrombin deficiency. Risk of VTE associated with long-haul air flight has now been well recognized. Thrombotic events associated with antiphospholipid syndrome (APS are 70% venous and 30% arterial. Deep venous thrombosis and pulmonary embolism are the most common venous events, though unusual cases of catastrophes due to central vein thrombosis like renal vein thrombosis and Budd-Chiari syndrome (catastrophic APS may occur.

  20. Pulmonary embolism and deep venous thrombosis after spinal surgery

    International Nuclear Information System (INIS)

    The incidence of pulmonary embolism (PE) and deep venous thrombosis (DVT) in 36 patients after lumbar spinal surgery was investigated. Anterior spinal fusion (ASF) had been performed in 6 cases, fenestration in 20 cases, and posterior interbody fusion (PLIF) in 10 cases. Fenestration and PLIF were performed in the prone position. PE was diagnosed by lung perfusion scans, and DVT on the basis of clinical signs. The blood gas analysis data and serum thrombin anti-thrombin III complex (TAT) and D-dimer levels were examined following surgery. PE and symptomatic DVT had occurred in each 2 cases (5.6%). Although PE cases were asymptomatic, the PaO2 level decreased 20% on postoperative day 7, and D-dimer was significant increased on postoperative day 14. It should be noted that PE and DVT are not very rare after spinal surgery, and it is important to diagnose them earlier and to prevent them. Blood gas analysis and determination of D-dimer levels after spinal surgery are useful for early detection of PE. (author)

  1. Emerging antithrombotic drugs: A review

    Directory of Open Access Journals (Sweden)

    P Sikka

    2011-01-01

    Full Text Available Thromboembolic disorders are one of the disorders for which the researchers are still in search for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows the researchers′ inefficiency in searching efficacious and safe antithrombotic drugs. The researchers have reached to the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, they can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, the researchers are using clopedogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide. Warfarin is an old antithrombotic drug, which is still being used but due to various side effects and drug interactions, they are bound to use newer drugs. Newer antiplatelet drugs include prasugrel, ticagrelor, cangrelor and elinogrel whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban and edoxaban are also newer entry in this category as Factor Xa inhibitors. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are going on.

  2. Logic gates and antisense DNA devices operating on a translator nucleic Acid scaffold.

    Science.gov (United States)

    Shlyahovsky, Bella; Li, Yang; Lioubashevski, Oleg; Elbaz, Johann; Willner, Itamar

    2009-07-28

    A series of logic gates, "AND", "OR", and "XOR", are designed using a DNA scaffold that includes four "footholds" on which the logic operations are activated. Two of the footholds represent input-recognition strands, and these are blocked by complementary nucleic acids, whereas the other two footholds are blocked by nucleic acids that include the horseradish peroxidase (HRP)-mimicking DNAzyme sequence. The logic gates are activated by either nucleic acid inputs that hybridize to the respective "footholds", or by low-molecular-weight inputs (adenosine monophosphate or cocaine) that yield the respective aptamer-substrate complexes. This results in the respective translocation of the blocking nucleic acids to the footholds carrying the HRP-mimicking DNAzyme sequence, and the concomitant release of the respective DNAzyme. The released product-strands then self-assemble into the hemin/G-quadruplex-HRP-mimicking DNAzyme that biocatalyzes the formation of a colored product and provides an output signal for the different logic gates. The principle of the logic operation is, then, implemented as a possible paradigm for future nanomedicine. The nucleic acid inputs that bind to the blocked footholds result in the translocation of the blocking nucleic acids to the respective footholds carrying the antithrombin aptamer. The released aptamer inhibits, then, the hydrolytic activity of thrombin. The system demonstrates the regulation of a biocatalytic reaction by a translator system activated on a DNA scaffold. PMID:19507821

  3. Chemiluminescence and chemiluminescence resonance energy transfer (CRET) aptamer sensors using catalytic hemin/G-quadruplexes.

    Science.gov (United States)

    Liu, Xiaoqing; Freeman, Ronit; Golub, Eyal; Willner, Itamar

    2011-09-27

    The incorporation of hemin into the thrombin/G-quadruplex aptamer assembly or into the ATP/G-quadruplex nanostructure yields active DNAzymes that catalyze the generation of chemiluminescence. These catalytic processes enable the detection of thrombin and ATP with detection limits corresponding to 200 pM and 10 μM, respectively. The conjugation of the antithrombin or anti-ATP aptamers to CdSe/ZnS semiconductor quantum dots (QDs) allowed the detection of thrombin or ATP through the luminescence of the QDs that is powered by a chemiluminescence resonance energy-transfer (CRET) process stimulated by the hemin/G-quadruplex/thrombin complex or the hemin/G-quadruplex/ATP nanostructure, in the presence of luminol/H(2)O(2). The advantages of applying the CRET process for the detection of thrombin or ATP, by the resulting hemin/G-quadruplex DNAzyme structures, are reflected by low background signals and the possibility to develop multiplexed aptasensor assays using different sized QDs. PMID:21866963

  4. Kontrazeption & Thrombophilie - Eine Stellungnahme der Deutschen Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin (DGGEF e. V. und des Berufsverbands für Frauenärzte (BVF e.V.

    Directory of Open Access Journals (Sweden)

    Rabe T

    2012-01-01

    Full Text Available Mehr als eine halbe Million Menschen sterben jährlich in der EU an venösen Thromboembolien (VTE, meist in höherem Alter oder im Zusammenhang mit Operationen, aber auch junge Frauen im reproduktiven Alter unter Anwendung hormonaler Kontrazeptiva. In einigen Teilen der Bevölkerung sind angeborene Störungen im Gerinnungssystem (Faktor-V-Leiden, Prothrombin-Mutation G20210A, Protein C-, Protein S- und Antithrombin-Mangel für ein erhöhtes VTE-Risiko verantwortlich. Das VTE-Risiko wird durch folgende Faktoren beeinflusst: Langstreckenreisen, Immobilisierung, Lebensalter, Zigarettenrauchen, hoher Body Mass Index, Operationen, Krebserkrankungen, Flüssigkeitsverlust, Schwangerschaft, orale hormonale Kontrazeptiva, Hormonersatztherapie. Ein generelles Laborscreening für Thrombophilie vor Verordnung oraler Kontrazeptiva (OC wird nicht empfohlen. Es sollte nur bei positiver Familienanamnese und/oder Eigenanamnese hinsichtlich VTE oder kardiovaskulärer Verschlusserkrankungen durchgeführt werden. Faktor-V-Leiden-Mutation ist die häufigste kongenitale Thrombophilie. Eine heterozygote Faktor-V-Leiden-Mutation (VTE-Risiko ca. 5-fach erhöht findet man bei 3–13 %, eine homozygote (VTE-Risiko ca. 10-fach erhöht bei 0,2–1 % der europäischen Bevölkerung. Prothrombin-Mutation G20210A: Autosomal dominant vererbte Mutation (ca. 2 % der Europäer führt zu einem ca. 3-fachen Anstieg des VTE-Risikos. Das VTE-Risiko ist deutlich erhöht, wenn einer oder mehrere zusätzliche Risikofaktoren, wie Faktor- V-Leiden, Protein C-, Protein S- und Antithrombin- Mangel, vorliegen. Protein-C- und Protein-S-Mangel: Das Risiko venöser Thrombosen wird durch einen Protein C- oder Protein S-Mangel erhöht (Odds Ratio 3–15 bzw. 5–11. Antithrombin-Mangel führt in Abhängigkeit vom Typ des Antithrombin-Mangels zu einem 4–50-fach erhöhten VTE-Risiko. Orale hormonale Kontrazeptiva für Frauen enthalten meist Gestagene in Kombination mit oder ohne synthetische

  5. [Nephrotic syndrome revealed by pulmonary embolism: about four cases].

    Science.gov (United States)

    Chaudesaygues, E; Grasse, M; Marchand, L; Villar, E; Aupetit, J-F

    2014-11-01

    Nephrotic syndrom is an association of proteinuria>3g/d or 50mg/kg/d, an hypoalbuminemiadiabetes, high blood pressure and amyloidosis. We present four cases about nephrotic syndrome after thromboembolic disease. In every case, patients show a pulmonary embolism symptomatic of a nephrotic syndrom, whose diagnostic could be delayed up to six months after first pulmonary symptoms. This raised the problem of renal biopsy in these patients who need anticoagulation. In minimal change nephrosis, without hematuria, high blood pressure or renal dysfonction, a corticosteroid therapy test could be done assuming that is corticosensitive minimal glomerular injury. In every case, anticoagulation course must be completed and maintained in case of patent nephrotic syndrom with an albuminemia under 20g/L. In case of pulmonary embolism or deep vein thrombosis, idiopathic-looking, a nephrotic syndrome must be sought-after. The two diagnosis ways are the proteinuria on the urine dipstick and the hypoproteinemia on usual biology. The main mechanism is the coagulation factor leak, side effect of the nephrotic syndrom, notably because of the antithrombin III. PMID:25281996

  6. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.

    Science.gov (United States)

    Verespy Iii, Stephen; Mehta, Akul Y; Afosah, Daniel; Al-Horani, Rami A; Desai, Umesh R

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80-100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  7. Avaliação de anticoagulantes naturais e de fatores da coagulação em pacientes com distúrbios congênitos de glicosilação (DCG tipo I An evaluation of natural anticoagulants and coagulation factors in patients with congenital disorders of glycosylation type I

    Directory of Open Access Journals (Sweden)

    Anna Letícia Soares

    2010-01-01

    with neurologic symptoms that include psychomotor retardation, ataxia, hypotonia and stroke-like episodes. Many haemostatic system proteins only present biological activity after glycosylation. The aim of this study was to evaluate coagulation inhibitors (free protein S, protein C and antithrombin and coagulation factors (VIII, IX and XI in CDG type I patients. Eleven patients with CDG type I (three males and eight females with a mean age of 5.6 years old, and eight patients without CDG (four males and four females with a mean age of 4.5 years old (control group were evaluated. The diagnoses of CDG type I were confirmed by isoelectric focusing of serum transferrin. When coagulation inhibitors were evaluated, decreased activity of free protein S and protein C, and a pronounced reduction of antithrombin were observed compared to the control group. There was no significant difference for coagulation factors VIII and IX but a markedly decrease in factor XI. The present results suggest that a combined deficiency of coagulation inhibitors is responsible for the pro-thrombotic state observed in CDG patients. We recommend that a haemostatic analysis should be performed in CDG patients with clinical haemostatic manifestations before invasive procedures are performed.

  8. Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women Efeitos da terapia de reposição hormonal estroprogestativa sobre o sistema de coagulação e de fibrinólise em mulheres na pós-menopausa

    Directory of Open Access Journals (Sweden)

    Claudio E Bonduki

    2007-01-01

    Full Text Available OBJECTIVE: To evaluate antithrombin III (AT, thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT] generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE, 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP, or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0 and after 3 (T3, 6 (T6 and 12 (T12 months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.OBJETIVO: Avaliar os marcadores antitrombina III (AT, fragmento 1 + 2 da trombina (F1+2 e complexo trombina-antitrombina (TAT, bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE 0,625 mg/dia, isoladamente ou

  9. Anticoagulant profile of iopamidol and meglumine amidotrizoate and their lack of thrombin generation: an in vitro study

    International Nuclear Information System (INIS)

    The aim of this in vitro study was to sketch the subtle anticoagulant profile of iopamidol 300 mg l/ml (low osmolality non ionic contrast medium) and meglumine amidotrizoate 370 mg l/ml (high osmolality ionic contrast medium) in situations where variable amounts of clotting factors are observed and to check whether thrombin-generation significantly occurred in non anti-coagulated blood-contrast materials mixtures. In the first experiment, mixtures of deficient plasmas with a routine plasma pool provided different ranges with a variable amounts of clotting factor II, V, VIII, X, XI and XII. For each clotting factor level studied within these ranges, an activated partial thromboplastin time was determined with either contrast material loaded thromboplastin (5% v/v) used as a control. In the second experiment fibrino-peptide A (FpA) or modified anti-thrombin III (ATM) assays were performed in either (9:1) non anti-coagulated blood contrast materials mixtures or blood-glucose mixtures (control). Differing aPTT prolongation profiles were observed when clotting factors V, VIII, XI and XII were lowered in the plasma. However, neither iopamidol not amidotrizoate induced an aPTT prolongation with decreasing clotting factor II. In the second experiment no significant thrombin generation was observed as both blood - contrast materials mixtures showed significantly lower FpA and ATM levels (p < 0.001) than glucose control after 5 minutes and 10 minutes incubation at room temperature. These findings provide evidence that the use of iopamidol in angiographic procedures does not increase risk of clotting or hemorrhage. (author)

  10. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

    Science.gov (United States)

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    Background Schistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. Methodology/Principal Findings Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. Conclusion/Significance This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID:26267788

  11. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni.

    Directory of Open Access Journals (Sweden)

    Luiz Arthur Calheiros Leite

    Full Text Available Schistosomiasis mansoni is a chronic liver disease, in which some patients (5-10% progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients.Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55. Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X, protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1.This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status.

  12. Topical thrombin preparations and their use in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Brianne L Dunn

    2009-10-01

    Full Text Available Brianne L Dunn1, Walter E Uber1, John S Ikonomidis21Department of Pharmacy Services and 2Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USAAbstract: Coagulopathic bleeding may lead to increased morbidity and mortality after cardiac surgery. Topical bovine thrombin has been used to promote hemostasis after surgical procedures for over 60 years and is used frequently as a topical hemostatic agent in cardiac surgery. Recently, use of bovine thrombin has been reported to be associated with increased risk for anaphylaxis, thrombosis, and immune-mediated coagulopathy thought secondary to the production of antifactor V and antithrombin antibodies. In patients who develop bovine thrombin-induced immune-mediated coagulopathy, clinical manifestations may range from asymptomatic alterations in coagulation tests to severe hemorrhage and death. Patients undergoing cardiac surgical procedures may be at increased risk for development of antibodies to bovine thrombin products and associated complications. This adverse immunologic profile has led to the development of alternative preparations including a human and a recombinant thrombin which have been shown to be equally efficacious to bovine thrombin and have reduced antigenicity. However, the potential benefit associated with reduced antigenicity is not truly known secondary to the lack of long-term experience with these products. Given the potentially higher margin of safety and less stringent storage concerns compared to human thrombin, recombinant thrombin may be the most reasonable approach in cardiac surgery.Keywords: bovine thrombin, human thrombin, recombinant thrombin, immune-mediated coagulopathy, topical hemostatic agents, thrombin 

  13. Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: A cell-adhesive and plasmin-degradable biosynthetic material for tissue repair

    Science.gov (United States)

    Halstenberg, Sven

    2002-01-01

    The goal of the research presented in this dissertation was to create a biomimetic artificial material that exhibits functions of extracellular matrix relevant for improved nerve regeneration. Neural adhesion peptides were photoimmobilized on highly crosslinked poly(ethylene glycol)-based substrates that were otherwise non-adhesive. Neurons adhered in two-dimensional patterns for eleven hours, but no neurites extended. To enable neurite extension and nerve regeneration in three dimensions, and to address the need for specifically cell adhesive and cell degradable materials for clinical applications in tissue repair in general, an artificial protein was recombinantly expressed and purified that consisted of a repeating amino acid sequence based on fibrinogen and anti-thrombin III. The recombinant protein contained integrin-binding RGD sites, plasmin degradation sites, heparin binding sites, and six thiol-containing cysteine residues as grafting sites for poly(ethylene glycol) diacrylate via Michael-type conjugate addition. The resulting protein-graft-poly(ethylene glycol)acrylates were crosslinked by photopolymerization to form hydrogels. Although three-dimensional, RGD mediated and serine protease-dependent ingrowth of human fibroblasts into protein-graft-poly(ethylene glycol) hydrogels occurred, only surface neurite outgrowth was observed from chick dorsal root ganglia. Axonal outgrowth depended on the concentration of matrix-bound heparin, suggesting that improved mechanical strength of the hydrogels and possible immobilization of neuroactive factors due to the presence of heparin promoted neurite outgrowth. Together, the above results show that specific biological functions can be harnessed by protein-graft-poly(ethylene glycol) hydrogels to serve as matrices for tissue repair and regeneration. In particular, the two design objectives, specific cell adhesion and degradability by cell-associated proteases, were fulfilled by the material. In the future, this and

  14. MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity.

    Science.gov (United States)

    Dobó, József; Harmat, Veronika; Beinrohr, László; Sebestyén, Edina; Závodszky, Péter; Gál, Péter

    2009-07-15

    Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 is an abundant component of the lectin pathway of complement. The related enzyme, MASP-2 is capable of activating the complement cascade alone. Though the concentration of MASP-1 far exceeds that of MASP-2, only a supporting role of MASP-1 has been identified regarding lectin pathway activation. Several non-complement substrates, like fibrinogen and factor XIII, have also been reported. MASP-1 belongs to the C1r/C1s/MASP family of modular serine proteases; however, its serine protease domain is evolutionary different. We have determined the crystal structure of the catalytic region of active MASP-1 and refined it to 2.55 A resolution. Unusual features of the structure are an internal salt bridge (similar to one in factor D) between the S1 Asp189 and Arg224, and a very long 60-loop. The functional and evolutionary differences between MASP-1 and the other members of the C1r/C1s/MASP family are reflected in the crystal structure. Structural comparison of the protease domains revealed that the substrate binding groove of MASP-1 is wide and resembles that of trypsin rather than early complement proteases explaining its relaxed specificity. Also, MASP-1's multifunctional behavior as both a complement and a coagulation enzyme is in accordance with our observation that antithrombin in the presence of heparin is a more potent inhibitor of MASP-1 than C1 inhibitor. Overall, MASP-1 behaves as a promiscuous protease. The structure shows that its substrate binding groove is accessible; however, its reactivity could be modulated by an unusually large 60-loop and an internal salt bridge involving the S1 Asp. PMID:19564340

  15. N-[3H]acetyl-labeling, a convenient method for radiolabeling of glycosaminoglycans

    International Nuclear Information System (INIS)

    A method for the introduction of N-[3H]acetyl groups into glycosaminoglycans is described. The procedure is based on [3H]acetylation of N-unsubstituted hexosamine residues by treating the polysaccharides with [3H]acetic anhydride. Preparations of heparin and heparin sulfate were found to contain significant numbers of N-unsubstituted hexosamine residues, as isolates. In contrast, such units could not be detected in chondroitin sulfate, dermatan sulfate, or hyaluronic acid. These polysaccharides were therefore subjected to partial N-deacetylation by reaction with hydrazine in the presence of hydrazine sulfate. After treatment with [3H]acetic anhydride, the specific activities of the resulting labeled polysaccharide preparations ranged between 0.1 X 106 and 0.6 X 106 cpm 3H/μg of uronic acid. The 3H-labeled polysaccharide preparations did not differ significantly from the corresponding unlabeled starting materials with regard to polyanion properties (chromatography on DEAE-cellulose) or polymer chain size (gel chromatography). Further, the radiolabeled polysaccharide derivatives were susceptible to specific enzymatic degradation (chondroitinase ABC and mammalian heparitinase) and retained their ability to interact specifically with certain proteins - for example, [3H]heparin with antithrombin [3H]hyaluronic acid oligosaccharides with chondroitin sulfate proteoglycan. These findings indicate that the labeling procedures did not induce any major structural derangement of the polysaccharide molecules. The method developed should be useful in providing labeled glycosaminoglycans for metabolic and enzymatic experiments as well as for studies on the interacion between glycosaminoglycans and other bilogical macromolecules

  16. N-(/sup 3/H)acetyl-labeling, a convenient method for radiolabeling of glycosaminoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Hook, M.; Riesenfeld, J.; Lindahl, U.

    1982-01-15

    A method for the introduction of N-(/sup 3/H)acetyl groups into glycosaminoglycans is described. The procedure is based on (/sup 3/H)acetylation of N-unsubstituted hexosamine residues by treating the polysaccharides with (/sup 3/H)acetic anhydride. Preparations of heparin and heparin sulfate were found to contain significant numbers of N-unsubstituted hexosamine residues, as isolates. In contrast, such units could not be detected in chondroitin sulfate, dermatan sulfate, or hyaluronic acid. These polysaccharides were therefore subjected to partial N-deacetylation by reaction with hydrazine in the presence of hydrazine sulfate. After treatment with (/sup 3/H)acetic anhydride, the specific activities of the resulting labeled polysaccharide preparations ranged between 0.1 X 10/sup 6/ and 0.6 X 10/sup 6/ cpm /sup 3/H/..mu..g of uronic acid. The /sup 3/H-labeled polysaccharide preparations did not differ significantly from the corresponding unlabeled starting materials with regard to polyanion properties (chromatography on DEAE-cellulose) or polymer chain size (gel chromatography). Further, the radiolabeled polysaccharide derivatives were susceptible to specific enzymatic degradation (chondroitinase ABC and mammalian heparitinase) and retained their ability to interact specifically with certain proteins - for example, (/sup 3/H)heparin with antithrombin (/sup 3/H)hyaluronic acid oligosaccharides with chondroitin sulfate proteoglycan. These findings indicate that the labeling procedures did not induce any major structural derangement of the polysaccharide molecules. The method developed should be useful in providing labeled glycosaminoglycans for metabolic and enzymatic experiments as well as for studies on the interacion between glycosaminoglycans and other bilogical macromolecules.

  17. Structural and functional characterization of cleavage and inactivation of human serine protease inhibitors by the bacterial SPATE protease EspPα from enterohemorrhagic E. coli.

    Directory of Open Access Journals (Sweden)

    André Weiss

    Full Text Available EspPα and EspI are serine protease autotransporters found in enterohemorrhagic Escherichia coli. They both belong to the SPATE autotransporter family and are believed to contribute to pathogenicity via proteolytic cleavage and inactivation of different key host proteins during infection. Here, we describe the specific cleavage and functional inactivation of serine protease inhibitors (serpins by EspPα and compare this activity with the related SPATE EspI. Serpins are structurally related proteins that regulate vital protease cascades, such as blood coagulation and inflammatory host response. For the rapid determination of serpin cleavage sites, we applied direct MALDI-TOF-MS or ESI-FTMS analysis of coincubations of serpins and SPATE proteases and confirmed observed cleavage positions using in-gel-digest of SDS-PAGE-separated degradation products. Activities of both serpin and SPATE protease were assessed in a newly developed photometrical assay using chromogenic peptide substrates. EspPα cleaved the serpins α1-protease inhibitor (α1-PI, α1-antichymotrypsin, angiotensinogen, and α2-antiplasmin. Serpin cleavage led to loss of inhibitory function as demonstrated for α1-PI while EspPα activity was not affected. Notably, EspPα showed pronounced specificity and cleaved procoagulatory serpins such as α2-antiplasmin while the anticoagulatory antithrombin III was not affected. Together with recently published research, this underlines the interference of EspPα with hemostasis or inflammatory responses during infection, while the observed interaction of EspI with serpins is likely to be not physiologically relevant. EspPα-mediated serpin cleavage occurred always in flexible loops, indicating that this structural motif might be required for substrate recognition.

  18. Potential Risk Factors Associated With Vascular Diseases in Patients Receiving Treatment for Hypertension

    Science.gov (United States)

    Kim, Hyunjung; Park, Joonhong; Chae, Hyojin; Lee, Gun Dong; Lee, Sang Yoon; Lee, Jong Min; Oh, Yong-Seog

    2016-01-01

    Background Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. Methods A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. Results All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. Conclusions The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them. PMID:26915609

  19. Cellular folding pathway of a metastable serpin.

    Science.gov (United States)

    Chandrasekhar, Kshama; Ke, Haiping; Wang, Ning; Goodwin, Theresa; Gierasch, Lila M; Gershenson, Anne; Hebert, Daniel N

    2016-06-01

    Although proteins generally fold to their thermodynamically most stable state, some metastable proteins populate higher free energy states. Conformational changes from metastable higher free energy states to lower free energy states with greater stability can then generate the work required to perform physiologically important functions. However, how metastable proteins fold to these higher free energy states in the cell and avoid more stable but inactive conformations is poorly understood. The serpin family of metastable protease inhibitors uses large conformational changes that are downhill in free energy to inhibit target proteases by pulling apart the protease active site. The serpin antithrombin III (ATIII) targets thrombin and other proteases involved in blood coagulation, and ATIII misfolding can thus lead to thrombosis and other diseases. ATIII has three disulfide bonds, two near the N terminus and one near the C terminus. Our studies of ATIII in-cell folding reveal a surprising, biased order of disulfide bond formation, with early formation of the C-terminal disulfide, before formation of the N-terminal disulfides, critical for folding to the active, metastable state. Early folding of the predominantly β-sheet ATIII domain in this two-domain protein constrains the reactive center loop (RCL), which contains the protease-binding site, ensuring that the RCL remains accessible. N-linked glycans and carbohydrate-binding molecular chaperones contribute to the efficient folding and secretion of functional ATIII. The inability of a number of disease-associated ATIII variants to navigate the folding reaction helps to explain their disease phenotypes. PMID:27222580

  20. Evaluation of bone marrow with particular consideration of the megakaryocyte lineage and coagulation profile in the pregnant fallow deer (Dama dama).

    Science.gov (United States)

    Snarska, A; Sobiech, P

    2016-01-01

    The aim of the study was to evaluate the megakaryocyte lineage of bone marrow and coagulation parameters in fallow deer during the last month of pregnancy. The animals were managed in the barn-feeding system. Twenty female fallow deer, aged 2-3 years, divided into 2 groups were used in the study. Group 1 comprised the females in the last month of pregnancy, and the non-pregnant females were used as the control. All the animals were clinically healthy. Coagulation parameters were measured in all the deer: thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma concentrations of fibrinogen, D-dimer, and antithrombin III. A quantitative assessment of bone marrow was carried out for the erythroblastic, myeloid, lymphoid, monocyte-macrophage, and megakaryopoietic cell lines. A detailed analysis of megakaryocyte lineage was performed after whole blood and platelet count. There were no significant differences in the erythroblast, granulocyte, monocyte-macrophage and lymphoid systems between the animal groups. Thrombocyte count in the pregnant deer was lower than that found in the control group. Bone marrow smears revealed a slightly decreased megakaryocyte count, while the megakaryoblast and promegakaryocyte counts were unchanged. The analysis of coagulation parameters showed increased levels of fibrinogen, thrombin time, prothrombin time and activated partial thromboplastin time in the pregnant animals. The study suggested a hyperactivation of the coagulation system with a slight reduction in the megakaryocyte count in bone marrow, and a reduction in platelet count in peripheral blood at the end of pregnancy. PMID:27487510

  1. Evaluation of serum asymmetric dimethylarginine levels in patients with psoriasis vulgaris

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    Recep Bilgiç

    2015-12-01

    Full Text Available Background and Design: In this study, we aimed to evaluate the serum asymmetric dimethylarginine (ADMA levels and investigate the relationship between the severity of the disease and other cardiovascular risk factors in patients with psoriasis. Materials and Methods: This is a prospective, single-center, and controlled clinical study. Forty male patients with psoriasis and forty healthy male volunteers were included in the study. The psoriasis area severity index (PASI was used for evaluating the disease severity. Results: Forty consecutive male patients with psoriasis aged between 20 and 41 years (mean: 26.03±6.55 as study group and forty healthy male volunteers aged between 20 and 32 years (mean: 23.40±3.57 as control group were included in the study. There was no statistically significant difference in ADMA, homocysteine, vitamin B12, high density lipoprotein (HDL, and antithrombin III levels between the study and control groups. In psoriatic group, a mean 1.19-fold increase was observed in the serum ADMA levels in association with increased severity of PASI scores but it was not statistically significant. In the patient group, waist circumference (p=0.03, total cholesterol (p=0.007, low density lipoprotein (LDL cholesterol (p=0.014 and fibrinogen (p=0.049 levels were higher and folic acid (p=0.04 levels were lower than in the control group. In terms of laboratory parameters, a significant negative relationship between ADMA and HDL (p=0.045, and LDL (p=0.04 and total cholesterol (p=0.01 was found only in the control group. Conclusion: It seems that psoriasis with concomitant atherogenic dyslipidemia, enflammation and tendency to obesity is an independent risk factor for cardiovascular diseases and this risk seems to be present since earlier ages in correlation with disease severity. Extensive studies are needed to clearly demonstrate the relationship between this situation and serum ADMA levels in patients with psoriasis

  2. Perioperative changes in coagulative and fibrinolytic function during surgical treatment of abdominal aortic aneurysm and arteriosclerosis obliterans.

    Science.gov (United States)

    Aramoto, H; Shigematsu, H; Muto, T

    1994-12-01

    To determine the factors which influence perioperative coagulative and fibrinolytic function, we studied 41 patients who underwent surgical repair of unruptured abdominal aortic aneurysm (AAA) and 30 patients who underwent arterial reconstruction for arteriosclerosis obliterans (ASO). In patients with AAA, the levels of fibrin/fibrinogen degradation products (FDP) (11.4 +/- 20.1 micrograms/ml), thrombin-antithrombin III complex (TAT) (22.0 +/- 21.8 micrograms/l), plasmin-alpha 2 plasmin inhibitor complex (PIC) (2.6 +/- 2.9 micrograms/ml) and d-dimer of cross-linked fibrin degradation products (D-D) (8.4 +/- 10.8 micrograms/ml) were elevated, particularly when the AAAs had a large mural thrombus surface area or were accompanied by aneurysm of the iliac or femoral artery. In arterial aneurysms, blood coagulability and secondary fibrinolytic activity were believed to be enhanced. In patients with ASO, the level of TAT (17.2 +/- 24.8 micrograms/l) was so elevated that they were considered to show chronic hypercoagulability. Among the ASO patients with aorto-iliac lesions, those with concomitant graft occlusion or anastomotic aneurysm had significantly elevated levels of TAT. Proximal arterial occlusion or accompanying aneurysm in the ASO patients was associated with increased levels of PIC and D-D. Postoperative fluctuations in conventional hematological variables did not differ significantly among the surgical procedures. Conventional markers showed a transient decrease due to consumption during surgery, and a subsequent recovery or an actual increase within several days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7737753

  3. Edoxaban: a focused review of its clinical pharmacology.

    Science.gov (United States)

    Lip, Gregory Y H; Agnelli, Giancarlo

    2014-07-21

    Long-term anticoagulation treatment with warfarin has been associated with a number of limitations in clinical practice and there is a need for more convenient long-term anticoagulation treatment. One of the non-vitamin K oral anticoagulants in development is edoxaban, a factor Xa inhibitor that is administered once daily. The pharmacological properties of edoxaban have various advantages in anticoagulant therapy. Edoxaban quickly reaches peak plasma concentrations in 1.5 h, has a half-life of 10-14 h, has relatively high bioavailability of 62% and exhibits highly selective, competitive, concentration-dependent inhibition of human factor Xa. The plasma concentrations of edoxaban are also closely correlated with suppression of thrombin generation and a range of platelet activation parameters (fragment 1+2, thrombin-antithrombin complex, and β-thromboglobulin), which edoxaban has been shown to rapidly inhibit. The anticoagulant activity of edoxaban is not affected by food intake or ethnicity and a number of drug-drug interaction studies have been performed. Co-administration of edoxaban with strong P-glycoprotein inhibitors, such as dronedarone, quinidine, and verapamil requires edoxaban dose-reduction by 50% to avoid the risk of over-exposure. The exposure of edoxaban may also increase in patients with a body weight ≤60 kg and moderate renal impairment. This meant a dose-reduction strategy in patients at risk of over-exposure was utilized in Phase III clinical studies. In conclusion, the pharmacological properties of edoxaban provide rapid and specific inhibition of factor Xa, which is closely related to plasma concentrations. Given the limitations with long-term warfarin therapy, once-daily edoxaban may provide a convenient long-term alternative for patients. PMID:24810388

  4. Biochemical and enzymatic characterization of human kallikrein 5 (hK5), a novel serine protease potentially involved in cancer progression.

    Science.gov (United States)

    Michael, Iacovos P; Sotiropoulou, Georgia; Pampalakis, Georgios; Magklara, Angeliki; Ghosh, Manik; Wasney, Greg; Diamandis, Eleftherios P

    2005-04-15

    Human kallikrein 5 (KLK5) is a member of the human kallikrein gene family of serine proteases. Preliminary results indicate that the protein, hK5, may be a potential serological marker for breast and ovarian cancer. Other studies implicate hK5 with skin desquamation and skin diseases. To gain further insights on hK5 physiological functions, we studied its substrate specificity, the regulation of its activity by various inhibitors, and identified candidate physiological substrates. After producing and purifying recombinant hK5 in yeast, we determined the k(cat)/K(m) ratio of the fluorogenic substrates Gly-Pro-Arg-AMC and Gly-Pro-Lys-AMC, and showed that it has trypsin-like activity with strong preference for Arg over Lys in the P1 position. The serpins alpha(2)-antiplasmin and antithrombin were able to inhibit hK5 with an inhibition constant (k(+2)/K(i)) of 1.0 x 10(-) (2)and 4.2 x 10(-4) m(-1) min(-1), respectively. No inhibition was observed with the serpins alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, although alpha(2)-macroglobulin partially inhibited hK5 at high concentrations. We also demonstrated that hK5 can efficiently digest the extracellular matrix components, collagens type I, II, III, and IV, fibronectin, and laminin. Furthermore, our results suggest that hK5 can potentially release (a) angiostatin 4.5 from plasminogen, (b) "cystatin-like domain 3" from low molecular weight kininogen, and (c) fibrinopeptide B and peptide beta15-42 from the Bbeta chain of fibrinogen. hK5 could also play a role in the regulation of the binding of plasminogen activator inhibitor 1 to vitronectin. Our findings suggest that hK5 may be implicated in tumor progression, particularly in invasion and angiogenesis, and may represent a novel therapeutic target. PMID:15713679

  5. Predicting perioperative venous thromboembolism in Japanese gynecological patients.

    Directory of Open Access Journals (Sweden)

    Masae Ikeda

    Full Text Available OBJECTIVE: To develop a convenient screening method that can predict perioperative venous thromboembolism (VTE and identify patients at risk of fatal perioperative pulmonary embolism (PE. METHODS: Patients hospitalized for gynecological abdominal surgery (n = 183 underwent hematology tests and multidetector computed tomography (MDCT to detect VTE. All statistical analyses were carried out using the SPSS software program (PASWV19.0J. RESULTS: The following risk factors for VTE were identified by univariate analysis: plasmin-alpha2-plasmin inhibitor complex (PIC, thrombin-antithrombin III complex (TAT, and prolonged immobility (all p<0.001; age, neoadjuvant chemotherapy (NAC, malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01; and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all p<0.05. Multivariate analysis using these factors revealed that PIC, age, and transverse tumor diameter were significant independent determinants of the risk of VTE. We then calculated the incidence rate of perioperative VTE using PIC and transverse tumor diameter in patient groups stratified by age. In patients aged ≤40 years, PIC ≥1.3 µg/mL and a transverse tumor diameter ≥10 cm identified the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50 s, PIC ≥1.3 µg/mL identified a high risk of VTE with an accuracy of 78.2%. In patients aged ≥60 years, a transverse tumor diameter ≥15 cm (irrespective of PIC or PIC ≥1.3 µg/mL identified the high-risk group with an accuracy of 82.4%. CONCLUSIONS: We propose new screening criteria for VTE risk that are based on PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of these criteria for predicting the risk of perioperative VTE and for identifying patients with a high risk of fatal perioperative PE.

  6. Natural coagulation inhibitors and active protein c resistance in preeclampsia

    Directory of Open Access Journals (Sweden)

    Cengiz Demir

    2010-01-01

    Full Text Available INTRODUCTION: The etiology of preeclampsia is not fully established. A few studies have shown a relationship between natural coagulation inhibitors and preeclampsia. OBJECTIVES: The purpose of this study was to investigate the status of natural coagulation inhibitors and active protein C resistance (APC-R in preeclampsia. PATIENTS AND METHODS: We studied 70 women with preeclampsia recruited consecutively and 70 healthy pregnant and 70 nonpregnant women as controls. Plasma protein C (PC, free protein S (fPS, antithrombin III (ATIII and APC-R were evaluated. RESULTS: ATIII values were found to be significantly lower in preeclamptic patients than in the control groups (p< 0.001. Nevertheless, there was no significant difference between the healthy pregnant and nonpregnant women groups (p=0.141. The fPS values of the preeclamptic and healthy pregnant groups were lower than that of the nonpregnant group (p< 0.001, and the fPS value of the preeclamptic pregnant women was lower than that of healthy pregnant women (p<0.001. The PC value of the preeclamptic pregnant women was lower than that of the control groups (p< 0.001. The PC value of the healthy pregnant women was lower than that of the nonpregnant women (p< 0.001. The mean APC activity values were lower in the preeclamptic patients than that of the control groups (p< 0.001, p< 0.001. The APC-R positivity rates of the preeclamptic groups were higher than that of the control groups (p<0.001. CONCLUSIONS: This study demonstrated that ATIII, fPS, PC values and APC resistance were lower and APC-R positivity was higher in preeclamptic women than in normal pregnant and nonpregnant women.

  7. Honeybee Venom Proteome Profile of Queens and Winter Bees as Determined by a Mass Spectrometric Approach

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    Ellen L. Danneels

    2015-10-01

    Full Text Available Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS. Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings.

  8. Honeybee venom proteome profile of queens and winter bees as determined by a mass spectrometric approach.

    Science.gov (United States)

    Danneels, Ellen L; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C

    2015-11-01

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings. PMID:26529016

  9. New developments in the management of moderate-to-severe hemophilia B.

    Science.gov (United States)

    Nazeef, Moniba; Sheehan, John P

    2016-01-01

    Hemophilia B is an X-linked genetic deficiency of coagulation factor IX (FIX) activity associated with recurrent deep tissue and joint bleeding that may lead to long-term disability. FIX replacement therapy using plasma-derived protein or recombinant protein has significantly reduced bleeding and disability from hemophilia B, particularly when used in a prophylactic fashion. Although modern factor replacement has excellent efficacy and safety, barriers to the broader use of prophylaxis remain, including the need for intravenous (IV) access, frequent dosing, variability in individual pharmacokinetics, and cost. To overcome the requirement for frequent factor dosing, novel forms of recombinant FIX have been developed that possess extended terminal half-lives. Two of these products (FIXFc and rIX-FP) represent fusion proteins with the immunoglobulin G1 (IgG1) Fc domain and albumin, respectively, resulting in proteins that are recycled in vivo by the neonatal Fc receptor. The third product has undergone site-specific PEGylation on the activation peptide of FIX, similarly resulting in a long-lived FIX form. Clinical trials in previously treated hemophilia B patients have demonstrated excellent efficacy and confirmed less-frequent dosing requirements for the extended half-life forms. However, gaps in knowledge remain with regard to the risk of inhibitor formation and allergic reactions in previously untreated patient populations, safety in elderly patients with hemophilia, effects on in vivo FIX distribution, and cost-effectiveness. Additional strategies designed to rebalance hemostasis in hemophilia patients include monoclonal-antibody-mediated inhibition of tissue factor pathway inhibitor activity and siRNA-mediated reduction in antithrombin expression by the liver. Both of these approaches are long acting and potentially involve subcutaneous administration of the drug. In this review, we will discuss the biology of FIX, the evolution of FIX replacement therapy, the

  10. The role of autolysis loop in determining the specificity of coagulation proteases

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    L. Yang

    2007-08-01

    Full Text Available We recently demonstrated that the substitution of the autolysis loop (residues 143 to 154 in the chymotrypsin numbering system of activated protein C (APC with the corresponding loop of factor Xa (fXa renders the APC mutant (APC/fX143-154 susceptible to inhibition by antithrombin (AT in the presence of pentasaccharide. Our recent results further indicated, that in addition to an improvement in the reactivity of APC/fX143-154 with AT, both the amidolytic and anti-factor Va activities of the mutant APC have also been significantly increased. Since the autolysis loop of APC is five residues longer than the autolysis loop of fXa, it could not be ascertained whether this loop in the mutant APC specifically interacts with the activated conformation of AT or if a shorter autolysis loop is responsible for a global improvement in the catalytic activity of the mutant protease. To answer this question, we prepared another APC mutant in which the autolysis loop of the protease was replaced with the corresponding loop of trypsin (APC/Tryp143-154. Unlike an ~500-fold improvement in the reactivity of APC/fX143-154 with AT in the presence of pentasaccharide, the reactivity of APC/Tryp143-154 with the serpin was improved ~10-fold. These results suggest that both the length and structure of residues of the autolysis loop are critical for the specificity of the coagulation protease interaction with AT. Further factor Va inactivation studies with the APC mutants revealed a similar role for the autolysis loop of APC in the interaction with its natural substrate.

  11. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    International Nuclear Information System (INIS)

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI had

  12. [Countermeasure for obstetric hemorrhage].

    Science.gov (United States)

    Ishikawa, Gen

    2010-03-01

    Although the number of maternal death in Japan has decreased especially since 1990's and its total number has reached the level of developed countries, obstetric hemorrhage is still equally important as obstetric embolism and hypertension in pregnancy as a cause of maternal death. Intrapartum abnormal bleeding is defined as hemorrhage which amounts to more than 500 ml during intrapartum period by Japan Society of Obstetrics and Gynecology (JSOG). However, according to the official register of peripartum data in Japan, the upper normal limit (mean + 1.5 SD) of the amount of hemorrhage during intrapartum period was 900 g at vaginal singleton delivery, 1600 g at singleton cesarean delivery, 1900 g at multifetal vaginal delivery and 2600 g at multifetal cesarean delivery. Thus, upper normal limit is varied depending on mode of deliveries and fetal number. The character of obstetric DIC is marked consumptive coagulopathy and increased fibrinolytic system. Principal strategy for treatment of obstetric DIC is compensation of expended coagulating factors. Thus, the most important strategy is to administer FFP However, it is necessary to be unfreezed for administration of FFP, and it is time-consuming. Prompt and firm decision for administration of FFP is important. Priority of administration of platelet concentrate is not high. Rather the use of antithrombin should be considered. Guideline of response to obstetric critical hemorrhage has been tentatively constructed by Japanese Society of Anesthesiologists, JSOG and other related academic societies. According to the guideline, recommended medical intervention depends on the shock index. At the extremely severe clinical state like placenta previa with accreta and placental abruption, multidisciplinary and prompt approach fulfills very important role to bring through. Strategy of treatment for obstetric DIC and the guideline of response to obstetric critical hemorrhage are also important at such state. Level 1 and other

  13. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

    Science.gov (United States)

    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4). PMID:26214580

  14. Gold nanoparticles doped conducting polymer nanorod electrodes: ferrocene catalyzed aptamer-based thrombin immunosensor.

    Science.gov (United States)

    Rahman, Md Aminur; Son, Jung Ik; Won, Mi-Sook; Shim, Yoon-Bo

    2009-08-15

    Au nanoparticles-doped conducting polymer nanorods electrodes (AuNPs/CPNEs) were prepared by coating Au nanorods (AuNRs) with a conducting polymer layer. The AuNRs were prepared through an electroless deposition method using the polycarbonate membrane (pore diameter, 50 nm, pore density, 6 x 10(8) pores/cm(2)) as a template. The AuNPs/CPNEs combining catalytic activity of ferrocene to ascorbic acid were used for the fabrication of an ultrasensitive aptamer sensor for thrombin detection. The AuNPs/3D-CPNEs were characterized employing cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Sandwiched immunoassay for alpha-human thrombin with NH(2)-functionalized-thrombin binding aptamer (Apt) immobilized on AuNPs/3D-CPNEs was studied through the electrocatalytic oxidation of ascorbic acid by the ferrocene moiety that was bound with an antithrombin antibody and attached with the Apt/3D-CPNEs probe through target binding. Various experimental parameters affecting thrombin detection were optimized, and the performance of the thrombin aptamer sensor was examined. The Apt/AuNPs/3D-CPNEs based thrombin sensor exhibited a wide dynamic range of 5-2000 ng L(-1) and a low detection limit of 5 ng L(-1) (0.14 pM). The selectivity and the stability of the proposed thrombin aptamer sensor were excellent, and it was tested in a real human serum sample for the detection of spiked concentrations of thrombin. PMID:20337374

  15. Efficient expression and secretion of recombinant hirudin III in E. coli using the L-asparaginase II signal sequence.

    Science.gov (United States)

    Tan, Shuhua; Wu, Wutong; Liu, Jingjing; Kong, Yi; Pu, Yinghui; Yuan, Riying

    2002-08-01

    One of the hirudin variants HV3 was efficiently expressed in Escherichia coli using the L-asparaginase II signal sequence and the product was secreted into the culture medium. For the secretory manufacture of HV3, the L-asparaginase II signal sequence containing a single NheI restriction site at its 3' end was designed using the degenerate codons and PCR-amplified from E. coli chromosomal DNA. The synthetic HV3 coding sequence was fused to the signal sequence in-frame by its 5' NheI restriction site. The above signal-HV3 fusion gene was inserted into an expression vector pTA, which was derived from pkk223-3 such that its expression was under the control of the tac promotor. The resulting HV3 secretion expression vector pTASH thus constructed was introduced into an E. coli host cell AS1.357 with high L-asparaginase II producing level. After inducing with IPTG, the expression product was efficiently secreted into the culture medium and shake-flask culturing gave a yield of approximately 5 x 10(5)ATU/L (approximately 60mg/L). The secreted HV3 was easily purified from culture supernatant using ultrafiltration, ion-exchange column chromatography, and FPLC reverse-phase chromatography. The purified rHV3 from the culture supernatant had the expected N-terminal amino sequence and strong antithrombin activity, suggesting that the signal sequence was completely removed and the product was processed accurately during the secretion process. PMID:12182823

  16. Etiology and portal vein thrombosis in Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    Oguz Uskudar; Meral Akdogan; Nurgul Sasmaz; Sevinc Yilmaz; Muharrem Tola; Burhan Sahin

    2008-01-01

    AIM: To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome (BCS)patients prospectively.METHODS: A total of 75 patients (40 female, 35 male) who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively.Findings from on physical examination, ultrasonography,duplex ultrasonography and venography were analyzed.Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance,and anticardiolipin antibodies, antinuclear antibodies,and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit.RESULTS: At least one etiological factor was determined in 54 (72%) of the patients. The etiology could not be defined in 21 (28%) patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient.The most common cause was the web (16%), the second was Hydatid disease (11%), the third was Behcet's disease (9%). Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them (82%).CONCLUSION: Behcet's disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal vein thrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.

  17. Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.

    Science.gov (United States)

    Cugno, Massimo; Mari, Daniela; Meroni, Pier Luigi; Gronda, Edoardo; Vicari, Francesco; Frigerio, Maria; Coppola, Raffaella; Bottasso, Bianca; Borghi, Maria Orietta; Gregorini, Luisa

    2004-07-01

    Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF. PMID:15198737

  18. The human HDL proteome displays high inter-individual variability and is altered dynamically in response to angioplasty-induced atheroma plaque rupture.

    Science.gov (United States)

    Jorge, Inmaculada; Burillo, Elena; Mesa, Raquel; Baila-Rueda, Lucía; Moreno, Margoth; Trevisan-Herraz, Marco; Silla-Castro, Juan Carlos; Camafeita, Emilio; Ortega-Muñoz, Mariano; Bonzon-Kulichenko, Elena; Calvo, Isabel; Cenarro, Ana; Civeira, Fernando; Vázquez, Jesús

    2014-06-25

    Recent findings support potential roles for HDL in cardiovascular pathophysiology not related to lipid metabolism. We address whether HDL proteome is dynamically altered in atheroma plaque rupture. We used immunoaffinity purification of HDL samples from coronary artery disease patients before and after percutaneous transluminal coronary angioplasty (PTCA), a model of atheroma plaque disruption. Samples were analyzed by quantitative proteomics using stable isotope labeling and results were subjected to statistical analysis of protein variance using a novel algorithm. We observed high protein variability in HDL composition between individuals, indicating that HDL protein composition is highly patient-specific. However, intra-individual protein variances remained at low levels, confirming the reproducibility of the method used for HDL isolation and protein quantification. A systems biology analysis of HDL protein alterations induced by PTCA revealed an increase in two protein clusters that included several apolipoproteins, fibrinogen-like protein 1 and other intracellular proteins, and a decrease in antithrombin-III, annexin A1 and several immunoglobulins. Our results support the concept of HDL as dynamic platforms that donate and receive a variety of molecules and provide an improved methodology to use HDL proteome for the systematic analysis of differences among individuals and the search for cardiovascular biomarkers. Biological significance The HDL proteome is an interesting model of clinical relevance and has been previously described to be dynamically altered in response to pathophysiological conditions and cardiovascular diseases. Our study suggests that interindividual variability of HDL proteome is higher than previously thought and provided the detection of a set of proteins that changed their abundance in response to plaque rupture, supporting the concept of HDL as dynamic platforms that donate and receive a variety of molecules. PMID:24747125

  19. [Ph1 positive acute lymphoblastic leukemia with DIC after operation of colon and lung cancer].

    Science.gov (United States)

    Yashige, H; Fujii, H

    1989-07-01

    We reported a rare case of triple cancers with acute lymphoblastic leukemia (ALL) associated with disseminated intravascular coagulopathy (DIC) after the operations of colon cancer and primary lung cancer. A 78-year-old Japanese male, who had been operated upon for colon cancer (adenocarcinoma) on March 1981, metastatic brain tumor (adenocarcinoma) on December 1986, and primary lung cancer (squamous cell carcinoma) on February 1987, was admitted to our hospital because of severe general malaise on December 6 1987. On admission, he had mild hepatosplenomegaly and hemorrhage diathesis such as purpura. Serum LDH increased to 2,515 mU/ml. The white blood cell count was 6,210/microliters with 53% leukemia cells, and the platelet count was 12,000/microliters. A bone marrow was infiltrated with 96.0% leukemia cells. The leukemia cells stained positively for PAS and negatively for peroxidase. Immunological examination of leukemia cells showed that HLA-DR, TdT, B1 and J5 were positive and cytoplasmic Igmu and surface Ig were negative, indicating common ALL. The coagulation studies revealed that the activated partial thromboplastin time was prolonged to 42.0 seconds, FDP increased to 79.9 micrograms/ml, and antithrombin-III decreased to 62%. Chromosome analysis showed a 48, XY, +2, +21q-, t(9;22) karyotype. He was diagnosed as having Ph1 positive ALL associated with DIC. He was treated with vindesine, prednisolone, L-asparaginase, and adriamycin and complete remission (CR) was achieved after two months. But on August 1988, 8 months after CR, ALL and brain tumor relapsed and he died of pneumonia on September 19, 1988. PMID:2810793

  20. Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice.

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    Garabet G Toby

    Full Text Available Hemophilia B is an inherited X chromosome-linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX fused to the Fc region of IgG (rFIXFc with an extended half-life in animals and humans.Procoagulant properties of rFIXFc and rFIX (BENEFIX® were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models.The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice.

  1. The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant.

    Science.gov (United States)

    Bos, Ineke G A; Lubbers, Yvonne T P; Roem, Dorina; Abrahams, Jan Pieter; Hack, C Erik; Eldering, Eric

    2003-08-01

    C1-inhibitor (C1-Inh) is a serine protease inhibitor (serpin) with a unique, non-conserved N-terminal domain of unknown function. Genetic deficiency of C1-Inh causes hereditary angioedema. A novel type of mutation (Delta 3) in exon 3 of the C1-Inh gene, resulting in deletion of Asp62-Thr116 in this unique domain, was encountered in a hereditary angioedema pedigree. Because the domain is supposedly not essential for inhibitory activity, the unexpected loss-of-function of this deletion mutant was further investigated. The Delta 3 mutant and three additional mutants starting at Pro76, Gly98, and Ser115, lacking increasing parts of the N-terminal domain, were produced recombinantly. C1-Inh76 and C1-Inh98 retained normal conformation and interaction kinetics with target proteases. In contrast, C1-Inh115 and Delta 3, which both lack the connection between the serpin and the non-serpin domain via two disulfide bridges, were completely non-functional because of a complex-like and multimeric conformation, as demonstrated by several criteria. The Delta 3 mutant also circulated in multimeric form in plasma from affected family members. The C1-Inh mutant reported here is unique in that deletion of an entire amino acid stretch from a domain not shared by other serpins leads to a loss-of-function. The deletion in the unique N-terminal domain results in a "multimerization phenotype" of C1-Inh, because of diminished stability of the central beta-sheet. This phenotype, as well as the location of the disulfide bridges between the serpin and the non-serpin domain of C1-Inh, suggests that the function of the N-terminal region may be similar to one of the effects of heparin in antithrombin III, maintenance of the metastable serpin conformation. PMID:12773530

  2. COOH-terminal substitutions in the serpin C1 inhibitor that cause loop overinsertion and subsequent multimerization.

    Science.gov (United States)

    Eldering, E; Verpy, E; Roem, D; Meo, T; Tosi, M

    1995-02-10

    The region COOH-terminal to the reactive center loop is highly conserved in the serine protease inhibitor (serpin) family. We have studied the structural consequences of three substitutions (Val451-->Met, Phe455-->Ser, and Pro476-->Ser) found in this region of C1 inhibitor in patients suffering from hereditary angioedema. Equivalent substitutions have been described in alpha 1-antitrypsin and antithrombin III. The mutant C1 inhibitor proteins were only partially secreted upon transient transfection into COS-7 cells and were found to be dysfunctional. Immunoprecipitation of conditioned media demonstrated that in the intact, uncleaved form they all bind to a monoclonal antibody which recognizes specifically the protease-complexed or reactive center-cleaved normal C1 inhibitor. A second indication for an intrinsic conformational change was the increased thermostability compared to the normal protein. Furthermore, gel filtration studies showed that the Val451-->Met and Pro476-->Ser mutant proteins, and to a lesser extent Phe455-->Ser, were prone to spontaneous multimerization. Finally, a reduced susceptibility to reactive center cleavage by trypsin was observed for all three mutants, and the cleaved Val451-->Met and Pro476-->Ser mutants failed to adopt the conformation recognized by a cleavage-specific monoclonal antibody. Investigation of plasmas of patients with the Val451-->Met or Pro476-->Ser substitutions showed that these dysfunctional proteins circulate at low levels and are recognized by the complex-specific antibody. These results strongly indicate a conformational change as a result of these carboxylterminal substitutions, such that anchoring of the reactive center loop at the COOH-terminal side is not achieved properly. We propose that this results in overinsertion of the loop into beta-sheet A, which subsequently leads to multimerization. PMID:7852321

  3. Republication: Two Premature Neonates of Congenital Syphilis with Severe Clinical Manifestations.

    Science.gov (United States)

    Akahira-Azuma, Moe; Kubota, Mai; Hosokawa, Shinichi; Kaneshige, Masao; Yasuda, Noriko; Sato, Noriko; Matsushita, Takeji

    2015-09-01

    Congenital syphilis (CS) is a public health burden in both developing and developed countries. We report two cases of CS in premature neonates with severe clinical manifestations; Patient 1 (gestational age 31 weeks, birth weight 1423 g) had disseminated idiopathic coagulation (DIC) while Patient 2 (gestational age 34 weeks and 6 days, birth weight 2299 g) had refractory syphilitic meningitis. Their mothers were single and had neither received antenatal care nor undergone syphilis screening. Both neonates were delivered via an emergency cesarean section and had birth asphyxia and transient tachypnea of newborn. Physical examination revealed massive hepatosplenomegaly. Laboratory testing of maternal and neonatal blood showed increased rapid plasma reagin (RPR) titer and positive Treponema pallidum hemagglutination assay. Diagnosis of CS was further supported by a positive IgM fluorescent treponemal antibody absorption test and large amounts of T. pallidum spirochetes detected in the placenta. Each neonate was initially treated with ampicillin and cefotaxime for early bacterial sepsis/meningitis that coexisted with CS. Patient 1 received fresh frozen plasma and antithrombin III to treat DIC. Patient 2 experienced a relapse of CS during initial antibiotic treatment, necessitating parenteral penicillin G. Treatment was effective in both neonates, as shown by reductions in RPR. Monitoring of growth and neurological development through to age 4 showed no evidence of apparent delay or complications. Without adequate antenatal care and maternal screening tests for infection, CS is difficult for non-specialists to diagnose at birth, because the clinical manifestations are similar to those of neonatal sepsis and meningitis. Ampicillin was insufficient for treating CS and penicillin G was necessary. PMID:26543391

  4. Heparin Resistance and Anticoagulation Failure in a Challenging Case of Cerebral Venous Sinus Thrombosis.

    Science.gov (United States)

    King, Adam B; O'Duffy, Anne E; Kumar, Avinash B

    2016-07-01

    We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance. PMID:27366296

  5. Thrombin-anti-thrombin levels and patency of arterio-venous fistula in patients undergoing haemodialysis compared to healthy volunteers: a prospective analysis.

    Directory of Open Access Journals (Sweden)

    James A Milburn

    Full Text Available BACKGROUND: Patients on haemodialysis (HD are at an increased risk of sustaining thrombotic events especially to their vascular access which is essential for maintenance of HD. OBJECTIVES: To assess whether 1 markers of coagulation, fibrinolysis or endothelial activation are increased in patients on HD compared to controls and 2 if measurement of any of these factors could help to identify patients at increased risk of arteriovenous (AVF access occlusion. PATIENTS/METHODS: Venous blood samples were taken from 70 patients immediately before a session of HD and from 78 resting healthy volunteers. Thrombin-antithrombin (TAT, D-dimer, von Willebrand factor (vWF, plasminogen activator inhibitor-1 antigen (PAI-1 and soluble p-selectin were measured by ELISA. C-reactive protein (hsCRP was measured by an immunonephelometric kinetic assay. Determination of the patency of the AVF was based upon international standards and was prospectively followed up for a minimum of four years or until the AVF was non-functioning. RESULTS: A total of 70 patients were studied with a median follow-up of 740 days (range 72-1788 days. TAT, D-dimer, vWF, p-selectin and hsCRP were elevated in patients on HD compared with controls. At one year follow-up, primary patency was 66% (46 patients. In multivariate analysis TAT was inversely associated with primary assisted patency (r = -0.250, p = 0.044 and secondary patency (r = -0.267, p= 0.031. CONCLUSIONS: The novel finding of this study is that in patients on haemodialysis, TAT levels were increased and inversely correlated with primary assisted patency and secondary patency. Further evaluation is required into the possible role of TAT as a biomarker of AVF occlusion.

  6. Trypanosoma brucei modifies the tsetse salivary composition, altering the fly feeding behavior that favors parasite transmission.

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    Jan Van Den Abbeele

    Full Text Available Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent. Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. Therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. As an obligate blood feeder, tsetse flies rely on their complex salivary potion to inhibit host haemostatic reactions ensuring an efficient feeding. The results of this experimental study suggest that the parasite might promote its transmission through manipulation of the tsetse feeding behavior by modifying the saliva composition. Indeed, salivary gland Trypanosoma brucei-infected flies display a significantly prolonged feeding time, thereby enhancing the likelihood of infecting multiple hosts during the process of a single blood meal cycle. Comparison of the two major anti-haemostatic activities i.e. anti-platelet aggregation and anti-coagulation activity in these flies versus non-infected tsetse flies demonstrates a significant suppression of these activities as a result of the trypanosome-infection status. This effect was mainly related to the parasite-induced reduction in salivary gland gene transcription, resulting in a strong decrease in protein content and related biological activities. Additionally, the anti-thrombin activity and inhibition of thrombin-induced coagulation was even more severely hampered as a result of the trypanosome infection. Indeed, while naive tsetse saliva strongly inhibited human thrombin activity and thrombin-induced blood coagulation, saliva from T. brucei-infected flies showed a significantly enhanced thrombinase activity resulting in a far less potent anti-coagulation activity. These data clearly provide evidence for a trypanosome-mediated modification of the tsetse

  7. Haemostatic Parameters in Patients with Behçet’s Disease

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    Juma K. Alkaabi

    2014-05-01

    Full Text Available Objectives: This study aimed to evaluate the cause of thrombosis in Behçet’s disease (BD patients, since abnormalities in coagulation and fibrinolytic parameters have shown contradictory results. Methods: Haemostatic parameters were retrospectively evaluated in BD patients treated between January 2007 and January 2011 at Sultan Qaboos University Hospital, Oman. The blood samples of 35 Omani BD patients and 30 healthy controls were analysed for factor VIII:C levels, activated protein C resistance (APCR, von Willebrand factor (vWF antigens (Ag, collagen binding and ristocetin co-factor activity (RiCoF, antithrombin (AT, protein C (chromogenic and clotting, protein S, homocysteine, tissue plasminogen activator, plasminogen activator inhibitor, plasminogen, alpha 2-antiplasmin, lupus anticoagulant and anticardiolipin and beta2-glycoprotein-1 antibodies. Results: The mean values of factor VIII:C, vWF Ag, AT and protein S were significantly higher in the patient group (P = 0.01, 0.006, 0.04 and 0.01, respectively. There was no deficiency in protein C. Screening for APCR, anticardiolipin antibodies, anti-beta2-glycoprotein-1 antibodies and lupus anticoagulant was negative and there were no differences in homocysteine levels, nor were there differences between patients with and without thrombosis. Six patients had elevated factor VIII:C levels (>150 IU/dL, P <0.02 which normalised on repeat measurements after three months. Conclusion: The elevation of factors VIII:C, vWF Ag and AT most likely represent an acute phase phenomenon. In this study, thrombophilic factors did not seem to explain thrombotic tendency. Therefore, further mechanistic studies in a larger group of patients are needed to elucidate the basis for thrombosis in BD. We hypothesise that active BD causes vasculitic endothelial perturbation with dysfunction, leading to the observed increased propensity for thrombosis.

  8. Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia.

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    Ted Wun

    Full Text Available BACKGROUND: Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease. METHODS: We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions. RESULTS: The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied. CONCLUSIONS: GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM, leukocyte activation (MAC-1, LFA-1, PM aggregates and the coagulation cascade (tissue factor, thrombin-antithrombin complexes. Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00911495.

  9. Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

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    J.B. Rezende-Neto

    2010-12-01

    Full Text Available Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals and hypotensive resuscitation at 60% of baseline MAP (10 animals. Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg. Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%, sham (95 ± 2.8 vs 59 ± 4.1%, and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%. Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

  10. Endogenous angiogenesis inhibitors and their therapeutic implications.

    Science.gov (United States)

    Cao, Y

    2001-04-01

    A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and

  11. ²H-NMR and ¹³C-NMR study of the hydration behavior of poly(2-methoxyethyl acrylate), poly(2-hydroxyethyl methacrylate) and poly(tetrahydrofurfuryl acrylate) in relation to their blood compatibility as biomaterials.

    Science.gov (United States)

    Miwa, Yuko; Ishida, Hiroyuki; Tanaka, Masaru; Mochizuki, Akira

    2010-01-01

    We recorded ²H-NMR spectra of (deuterated) water in the presence of poly(2-methoxyethyl acrylate) (PMEA), poly(2-hydroxyethyl methacrylate) (PHMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA). The observed ²H-NMR peak intensities varied substantially with water content and temperature, depending upon either strong binding to polymer surface or suppressed peaks due to freezing. Indeed, ²H-NMR signals in the presence of PHEMA were strongly dependent upon its water content, while those of hydrated PMEA and PTHFA remained unchanged even at -30°C and -20°C. The latter were considerably broadened at -50°C and -30°C, respectively, due to freezing water from the super-cooled state. As a result, the states of the water molecules in PMEA and PTHFA can be classified into three types; free, freezing bound and non-freezing water molecules. The states of the water in PHEMA depend on the water content, and the water can be classified into two types, free and non-freezing water, which exhibit rapid fluctuation and restricted mobility because of the presence of macromolecules, respectively. A kind of freezing bound water, however, should exist in PHEMA. This is also consistent with the substantially decreased ²H spin-lattice relaxation times of hydrated PHEMA as compared with those of PMEA or PTHFA. It is also interesting to note that the flexibility of bound water or polymer (PMEA > PTHFA > PHEMA) is related to a characteristic parameter for biocompatibility such as the production of TAT (thrombin-antithrombin III complex) as a marker of activation of the coagulation system. Therefore, it is naturally recognized that such differential polymer dynamics might be responsible for concomitant changes in structure and dynamics of surrounding water molecules in the vicinity of constituent polymer network. PMID:20573319

  12. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

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    A. A. Arshinov

    2005-04-01

    Full Text Available Objective. To assess coagulation parameters and activity indices in pts with systemic lupus erythematosus (SLE. Material and methods . 86 pts with SLE (83 female and 3 male were examined. 12 of them had antiphospholipid syndrome. Mean age was 35,9±1,5 years (from 18 to 58 years, mean disease duration was 9,8+1,4 years. Control group consisted of 60 healthy volunteers with mean age 37,1+4,1 years. SLE activity assessment was performed with SLAM, SLEDAI and ECLAM indices. Results. SLE pts showed 5-fold (p<0,01 increase of spontaneous platelets aggregation and more than 3-fold increase of factor von Willebrand antigen (FWA concentration. Platelet activation in pts was accompanied by decrease of platelet aggregation with collagen (on 27%, p<0,01. Characteristic sign of coagulation hemostasis activation was significant increase of soluble fibrin-monomer complexes (SFMC concentration on 81 % (p<0,01 so as increase D-dimers level in 53,3% of pts. Fibrinogen concentration was increased on 29%, spontaneous fibrinolysis parameters were decreased on 20%, antithrombin (AT 111 - on 21% in comparison with control. Direct correlation between activity indiccs and SFMC(ECLAM, r=0,5, fibrinogen concentration (SLAM, r=0,34, D- dimers level (ECLAM, r=0,5, spontaneous platelet aggregation (ECLAM, r=0,5 so as inverse correlation with AT III activity (SLEDAI, r-0,73 was revealed. Conclusion. Changes of hemostasis parameters in SLE may serve as predictors of thrombotic disorders development and indication to drug correction of blood coagulation disorders. Direct correlation between blood coagulation system activity and indices of SLE activity.

  13. Practical applications of snake venom toxins in haemostasis.

    Science.gov (United States)

    Marsh, Neville; Williams, Vaughan

    2005-06-15

    Snake venom toxins affecting haemostasis have facilitated extensively the routine assays of haemostatic parameters in the coagulation laboratory. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen/fibrinogen breakdown product assay and for the detection of fibrinogen dysfunction. SVTLE are not inhibited by heparin and can thus can be used for assaying antithrombin III and other haemostatic variables in heparin-containing samples. Snake venoms are a rich source of prothrombin activators and these are utilised in prothrombin assays, for studying dysprothrombinaemias and for preparing meizothrombin and non-enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains toxins which have been used to assay blood clotting factors V, VII, X, platelet factor 3 and, importantly, lupus anticoagulants (LA). Other prothrombin activators (from the taipan, Australian brown snake and saw-scaled viper) have now been used to assay LA. Protein C and activated protein C resistance can be measured by means of RVV and Protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing snake venom proteins, show potential for studying platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib. Snake venom toxins affecting haemostasis are also used in the therapeutic setting: Ancrod (from the Malayan pit viper, Calloselasma rhodostoma), in particular, has been used as an anticoagulant to achieve 'therapeutic defibrination'. Other snake venom proteins show promise in the treatment of a range of haemostatic disorders. PMID:15922782

  14. Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain

    International Nuclear Information System (INIS)

    We correlated coagulation and fibrinolytic parameters with small-vessel disease revealed by magnetic resonance imaging (MRI) of the brain. One hundred and eleven patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study; 57 males and 54 females with an average age of 66.6±9.6, age range 40 to 85, years old. Among them, 76 patients had a history of symptomatic cerebral infarction; 38 patients hypertension; and 24 patients diabetes mellitus. Patients with large cortical infarction, cerebral hemorrhage, demyelinating disease or mass lesions were excluded from the present study. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The small infarction was defined as a lesion less than 10 mm in diameter. The activity of von Willebrand factor (vWF) correlated significantly with the grade of caps at the anterior and posterior horns of the lateral ventricle, and the number of small infarctions in the subcortical white matter and basal ganglia, suggesting vWF could be a predictor for these small-vessel disease. The grade of caps at posterior horn of the lateral ventricle and the number of small infarctions in the subcortical white matter were associated significantly with the concentration of plasma fibrinogen and reversely with the activity of antithrombin III, an inhibitory factor in coagulation system. These results indicate that hypercoagulable state may causatively relate with small-vessel disease in the territory of medullary artery branching from cortical artery. On the contrary, these coagulation parameters did not correlate significantly with small ischemic lesions in the territory of perforating artery. No correlation was observed between the level of marker proteins for platelet activation and the degree of small-vessel disease, indicating the activation of platelet could not associate with the etiology of small-vessel disease. (author)

  15. Serine Protease Inhibitors as Good Predictors of Meat Tenderness: Which Are They and What Are Their Functions?

    Science.gov (United States)

    Boudida, Yasmine; Gagaoua, Mohammed; Becila, Samira; Picard, Brigitte; Boudjellal, Abdelghani; Herrera-Mendez, Carlos H; Sentandreu, Miguel; Ouali, Ahmed

    2016-04-25

    Since years, serine proteases and their inhibitors were an enigma to meat scientists. They were indeed considered to be extracellular and to play no role in postmortem muscle proteolysis. In the 1990's, we observed that protease inhibitors levels in muscles are a better predictor of meat tenderness than their target enzymes. From a practical point of view, we therefore choose to look for serine protease inhibitors rather than their target enzymes, i.e. serine proteases and the purpose of this report was to overview the findings obtained. Fractionation of a muscle crude extract by gel filtration revealed three major trypsin inhibitory fractions designed as F1 (Mr:50-70 kDa), F2 (Mr:40-60 kDa) and F3 (Mr:10-15kD) which were analyzed separately. Besides antithrombin III, an heparin dependent thrombin inhibitor, F1 and F2 comprised a large set of closely related trypsin inhibitors encoded by at least 8 genes bovSERPINA3-1 to A3-8 and able to inhibit also strongly initiator and effector caspases. They all belong to the serpin superfamily, known to form covalent complexes with their target enzymes, were located within muscle cells and found in all tissues and fluids examined irrespective of the animal species. Potential biological functions in living and postmortem muscle were proposed for all of them. In contrast to F1 and F2 which have been more extensively investigated only preliminary findings were provided for F3. Taken together, these results tend to ascertain the onset of apoptosis in postmortem muscle. However, the exact mechanisms driving the cell towards apoptosis and how apoptosis, an energy dependent process, can be completed postmortem remain still unclear. PMID:25085261

  16. Role of serine proteases in the regulation of interleukin-877 during the development of bronchopulmonary dysplasia in preterm ventilated infants.

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    Mallinath Chakraborty

    Full Text Available The chemokine interleukin-8 is implicated in the development of bronchopulmonary dysplasia in preterm infants. The 77-amino acid isoform of interleukin-8 (interleukin-877 is a less potent chemoattractant than other shorter isoforms. Although interleukin-877 is abundant in the preterm circulation, its regulation in the preterm lung is unknown.To study expression and processing of pulmonary interleukin-877 in preterm infants who did and did not develop bronchopulmonary dysplasia.Total interleukin-8 and interleukin-877 were measured in bronchoalveolar lavage fluid from preterm infants by immunoassay. Neutrophil serine proteases were used to assess processing. Neutrophil chemotaxis assays and degranulation of neutrophil matrix metalloproteinase-9 were used to assess interleukin-8 function.Peak total interleukin-8 and interleukin-877 concentrations were increased in infants who developed bronchopulmonary dysplasia compared to those who did not. Shorter forms of interleukin-8 predominated in the preterm lung (96.3% No-bronchopulmonary dysplasia vs 97.1% bronchopulmonary dysplasia, p>0.05. Preterm bronchoalveolar lavage fluid significantly converted exogenously added interleukin-877 to shorter isoforms (p<0.001. Conversion was greater in bronchopulmonary dysplasia infants (p<0.05. This conversion was inhibited by α-1 antitrypsin and antithrombin III (p<0.01. Purified neutrophil serine proteases efficiently converted interleukin-877 to shorter isoforms in a time- and dose-dependent fashion; shorter interleukin-8 isoforms were primarily responsible for neutrophil chemotaxis (p<0.001. Conversion by proteinase-3 resulted in significantly increased interleukin-8 activity in vitro (p<0.01.Shorter, potent, isoforms interleukin-8 predominate in the preterm lung, and are increased in infants developing bronchopulmonary dysplasia, due to conversion of interleukin-877 by neutrophil serine proteases and thrombin. Processing of interleukin-8 provides an attractive

  17. Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study.

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    Heiko Rühl

    Full Text Available The increased thrombotic risk of oral contraceptives (OC has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC. To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use.Blood samples were collected prospectively from healthy women (n = 21 before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA technology. Thrombin generation markers and other hemostasis parameters were measured additionally.All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003. Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur.In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk.

  18. In vivo antithrombotic properties of a heparin from the oocyte test cells of the sea squirt Styela plicata(Chordata-Tunicata

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    L. Cardilo-Reis

    2006-11-01

    Full Text Available In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10% of mammalian heparin and about 5% as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porcine heparin in rat models of venous thrombosis and blood loss. Intravenous administration of the oocyte test cell heparin to Wistar rats (both sexes, weighing ~300 g, N = 4 in each group at a dose of 5.0 mg/kg body weight, which produced a 1.8-fold increase in plasma activated partial thromboplastin time, inhibited thrombosis by 45 ± 13.5% (mean ± SD without any bleeding effect. The same dose of porcine heparin inhibited thrombosis by 100 ± 1.4%, but produced a blood loss three times greater than that of the saline-treated control. However, 10-fold reduction of the dose of porcine heparin to 0.5 mg/kg body weight, which produced a 5-fold increase in plasma-activated partial thromboplastin time, inhibited thrombosis by 70 ± 13% without any bleeding effect. The antithrombotic properties of a new heparin isolated from test cells of the sea squirt S. plicata, reported here for the first time, indicate that, although sea squirt oocyte test cell heparin was a poor anticoagulant compared to porcine heparin, it had a significant antithrombotic effect without causing bleeding.

  19. Activation of blood clotting and fibrinolysis in angiocardiography with ionic and non-ionic contrast medium; Aktivierung von Blutgerinnung und Fibrinolyse nach Angiokardiographie mit ionischem und nichtionischem Kontrastmittel

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, U.H. [Gerinnungsphysiologisches Lab., Zentrum fuer Frauenheilkunde, Universitaetsklinikum Essen (Germany); Park, J.W. [Herz-Zentrum Kaiser-Wilhelm-Krankenhaus, Duisburg (Germany); Weber, S. [Schering AG, Geschaeftsbereich Deutschland, Berlin (Germany); Kothe, A. [Gerinnungsphysiologisches Lab., Zentrum fuer Frauenheilkunde, Universitaetsklinikum Essen (Germany); Schnitker, J. [Inst. fuer Angewandte Statistik GmbH, Bielefeld (Germany); Behrends-Steins, B. [Schering AG, Geschaeftsbereich Deutschland, Berlin (Germany); Albring, M. [Schering AG, Geschaeftsbereich Deutschland, Berlin (Germany)

    1997-06-01

    Blutgerinnung gemessen. Ergebnisse: Unter dem Einfluss von Amidotrizoat waren die Bildung der Prothrombinfragmente 1 und 2 sowie als Ausdruck der Thrombinaktivitaet der Thrombin-Antithrombin-III-Komplex (TAT) merklich hoeher als unter Iopromid, erreicht aber keine statistische Signifikanz (p<0,15). Die Plasmainaktivitaet, ausgedrueckt durch den Plasmin-Antiplasmin-Komplex (PAP), war nach der Angiokardiographie erhoeht. Dieser Effekt war deutlicher ausgepraegt bei Patienten, die das ionische Amidotrizoat erhalten hatten (p<0,05). Die D-dimeren Spaltprodukte und Fibrinabbauprodukte waren unter dem Einfluss von Amidotrizoat gegenueber Iopromid deutlich erhoeht (p<0,01). Die Erhoehung von Fibrinabbauprodukten und D-Dimeren sind ein direktes Mass fuer einen gesteigerten Fibrinabbau und somit indirekt auch fuer eine gesteigerte Bildung von Fibrin. Schlussfolgerung: Die Ergebnisse der hier vorgestellten Studie sind ein Hinweis dafuer, dass antikoagulatorische, die Fibrin-Polymerisierung inhibierende Effekte von ionischem Roentgenkontrastmittel, die in vitro beschrieben wurden, auf die In-vivo-Situation im haemostatischen System nicht uebertragbar sind. (orig.)

  20. Radioimmunoassay of protein C system

    International Nuclear Information System (INIS)

    Protein C system is an anticoagulation pathway which consists of protein C (PC), protein S (PS), thrombomodulator (TM) and protein C inhibitor (PCI). Using the McAb SZ-57, the authors have established SZ-57-Sepharose CL-6B affinity chromatography to purify human urinary TM. A procedure for isolation and purification of PC, PS and PCI from albumin-free human plasma by rivanol precipitation was also established. The isolation steps include adsorption onto and elution from barium, PEG precipitation, ion-exchange chromatography and preparative isoelectric focusing and so on. The molecular weight, isoelectric points, amino acid contents and the functional activity of these proteins were consistent with other previous reports. Four radioimmunoassays (RIAs) of PC, PS, TM and PCI were established using the equilibrium method. 125I-PC and 125I-PS were prepared using the chloramine-T method. 125I-PCI was prepared by iodogen method and 125I-TM by Bolton-Hunter method. Their sensitivities were 3.94 μg/L, 9.87 μg/L, 6.16 μg/L and 2.58 μg/L, respectively. The recovery rates were 104.28%, 94.30%, 105.22% and 101.89. Some antiserum provided a linear response from 6.25 to 1024 μg/L for PC, 21 to 700 μg/L for PS, 8.1 to 560 μg/L for TM and 4.8 to 1024 μg/L for PCI. The intra- and inter-assay CV were 4.4% and 9.68% for PC RIA, respectively, 4.99% and 13.14% for PS RIA, 5.10% and 10.94% for TM RIA, 2.73% and 8.62% for PCI RIA. The cross reactivity with factor II, thrombin, and antithrombin III was negligible. These methods can be used as effective tools especially for diagnosis of thrombosis and basic or clinical studies of protein C system. (20 refs., 8 figs., 6 tabs.)

  1. Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

    Science.gov (United States)

    Laine, Outi K; Koskela, Sirpa M; Outinen, Tuula K; Joutsi-Korhonen, Lotta; Huhtala, Heini; Vaheri, Antti; Hurme, Mikko A; Jylhävä, Juulia; Mäkelä, Satu M; Mustonen, Jukka T

    2014-09-01

    Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection. PMID:24751477

  2. Heparin enhances the catalytic activity of des-ETW-thrombin.

    Science.gov (United States)

    Goodwin, C A; Deadman, J J; Le Bonniec, B F; Elgendy, S; Kakkar, V V; Scully, M F

    1996-04-01

    The thrombin mutant, des-ETW-thrombin, lacking Glu(146), Thr(147), and Trp(148) within a unique insertion loop located at the extreme end of the primary specificity pocket, has been shown previously to exhibit reduced catalytic activity with respect to macromolecular and synthetic thrombin substrates and reduced or enhanced susceptibility to inhibition. Investigation of the hydrolysis of peptidyl p-nitroanilide substrates by des-ETW-thrombin showed increased activity in the presence of heparin and other sulphated glycosaminoglycans. No effect was observed upon the activity of wild-type thrombin. Heparin was found to decrease the K(m) for cleavage of four thrombin-specific substrates by des-ETW-thrombin by 3-4-fold. Similarly, pentosan polysulphate (PPS) decreased the K(m) with these substrates by 8-10-fold. Heparin also increased the rate of inhibition of des-ETW-thrombin by antithrombin III and D-phenylalanyl-prolyl-arginylchloromethane (PPACK). The inhibition of des-ETW-thrombin by a number of thrombin-specific peptide boronic acids also showed significant reduction in the final K(i) in the presence of heparin, due to reduction in the off-rate. A peptide analogue of a sequence of hirudin which binds thrombin tightly to exosite I (fibrinogen recognition site) potentiated the activity of des-ETW-thrombin against peptide p-nitroanilide substrates in a manner similar to heparin. The K(i) for the inhibition of des-ETW-thrombin by p-aminobenzamidine was decreased by these ligands from 9.7 mM to 7.5 mM, 5.1 mM, and 2.5 mM in the presence of heparin, hirudin peptide and PPS respectively, suggesting the increased catalytic activity is due to enhanced access to the primary specificity pocket. The positive influence of these ligands on des-ETW-thrombin was reversed in the presence of ATP or ADP; the latter has previously been shown to inhibit thrombin activity by blocking initial interaction with fibrinogen at exosite 1. Because the effect of heparin and PPS is similar to

  3. Anticoagulation after anterior myocardial infarction and the risk of stroke.

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    Jacob A Udell

    MI there was no benefit from the use of warfarin up to 90 days post-MI to prevent ischemic stroke. Our data suggests that routine anticoagulation of patients with anterior-wall MI may not be indicated. Prospective randomized trials are needed to determine the optimal antithrombin strategy for preventing this common and serious adverse outcome.

  4. Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

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    Luiz Arthur Calheiros Leite

    Full Text Available BACKGROUND: Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55 correlate with the severity of their periportal fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR. The blood coagulation factors (II, VII, VIII, IX and X, protein C and antithrombin IIa (ATIIa, plasminogen activator inhibitor 1 (PAI-1 and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29, including raised serum transaminases (p<0.001 and lower levels of albumin (p = 0.0156. Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001 and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001. Additionally, patients with more advanced fibrosis (n = 38 had lower levels of protein C compared to those with only central fibrosis (p = 0.0124. The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001, and D-dimer levels 2.2 times higher (p<0.001 with 13 of the 55 patients having levels above the cut-off. CONCLUSION/SIGNIFICANCE: This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and

  5. Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

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    Benjamin M Scott

    Full Text Available In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1 yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3 was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1 as a serpin amenable to phage display and suggest the utility of this approach for the selection

  6. inherited thrombophilia and recurrent pregnancy loss Trombofilias heredadas y pérdida gestacional recurrente

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    Angela Patricia Cadavid Jaramillo

    2002-03-01

    Full Text Available One of the causes of recurrent pregnancy loss is thrombophilia, defined as a tendency to thrombosis or hypercoagulability, with various clinical manifestations dependent on the vascular region affected by the absence of blood flow. Thrombophilias can be classified as inherited or acquired, according to the nature of their cause. The former are factor V Leiden, the prothrombin G20210A, the methilenetetrahydrofolate reductase C677T, deficiencies of the natural anticoagulants antithrombin III, protein C and protein S, dysfibrinogens and homocystinuria. The group of acquired thrombophilias includes antiphospholipid syndrome, activated protein C resistance without alterations in the gene of factor V and mild or moderate hyperhomocysteinemia. This article reviews several recent studies looking for association between different thrombophilias and recurrent pregnancy loss. Also diagnostic, prophylactic and therapeutic recommendations are included, for women with thrombophilia and pregnancy loss Una de las causas de pérdida gestacional recurrente es la trombofilia, que se define como una tendencia a la trombosis o hipercoagulabilidad, con variabilidad en las manifestaciones clínicas dependiente de la región vascular afectada por la ausencia de flujo sanguíneo. Las trombofilias se pueden clasificar como heredadas y adquiridas de acuerdo con la naturaleza de su causa. Entre las trombofilias heredadas están el factor V Leiden, la protrombina G20210A, la metilentetrahidrofolato reductasa C677T, las deficiencias de los anticoagulantes naturales antitrombina III, proteína C y proteína S, las disfibrinogenemias y la homocistinuria. En el grupo de las trombofilias adquiridas se encuentran el síndrome antifosfolípido, la resistencia a la proteína C activada sin alteraciones en el gen del factor V y la hiperhomocisteinemia leve o moderada. Este artículo es una revisión de la literatura de estudios recientes que han buscado la asociación entre las

  7. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.

    Science.gov (United States)

    Gaussem, Pascale; Alhenc-Gelas, Martine; Thomas, Jean-Louis; Bachelot-Loza, Christilla; Remones, Veronique; Ali, Fouad Dali; Aiach, Martine; Scarabin, Pierre-Yves

    2011-03-01

    Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this. PMID:21225090

  8. An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

    Science.gov (United States)

    Schenauer, Matthew R.; Leary, Julie A.

    2009-10-01

    In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non

  9. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    Science.gov (United States)

    2009-01-01

    Background Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors

  10. New developments in the management of moderate-to-severe hemophilia B

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    Nazeef M

    2016-04-01

    Full Text Available Moniba Nazeef,1,2 John P Sheehan1,2 1Department of Medicine, Division of Hematology/Oncology, 2UW Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Hemophilia B is an X-linked genetic deficiency of coagulation factor IX (FIX activity associated with recurrent deep tissue and joint bleeding that may lead to long-term disability. FIX replacement therapy using plasma-derived protein or recombinant protein has significantly reduced bleeding and disability from hemophilia B, particularly when used in a prophylactic fashion. Although modern factor replacement has excellent efficacy and safety, barriers to the broader use of prophylaxis remain, including the need for intravenous (IV access, frequent dosing, variability in individual pharmacokinetics, and cost. To overcome the requirement for frequent factor dosing, novel forms of recombinant FIX have been developed that possess extended terminal half-lives. Two of these products (FIXFc and rIX-FP represent fusion proteins with the immunoglobulin G1 (IgG1 Fc domain and albumin, respectively, resulting in proteins that are recycled in vivo by the neonatal Fc receptor. The third product has undergone site-specific PEGylation on the activation peptide of FIX, similarly resulting in a long-lived FIX form. Clinical trials in previously treated hemophilia B patients have demonstrated excellent efficacy and confirmed less-frequent dosing requirements for the extended half-life forms. However, gaps in knowledge remain with regard to the risk of inhibitor formation and allergic reactions in previously untreated patient populations, safety in elderly patients with hemophilia, effects on in vivo FIX distribution, and cost-effectiveness. Additional strategies designed to rebalance hemostasis in hemophilia patients include monoclonal-antibody-mediated inhibition of tissue factor pathway inhibitor activity and siRNA-mediated reduction in antithrombin

  11. Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats.

    Science.gov (United States)

    Asakura, H; Asamura, R; Ontachi, Y; Hayashi, T; Yamazaki, M; Morishita, E; Miyamoto, K-I; Nakao, S

    2005-05-01

    We examined the role of nitric oxide (NO) produced by an inducible isoform of NO synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) and investigated changes in organ function, plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS-induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the 8-h LPS group died, and we examined blood samples from five rats in this group. None of the other rats died. The LPS-induced elevation of creatinine, alanine aminotransferase, glomerular fibrin deposition and plasminogen activator inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL did not affect the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that reflect the lysis of cross-linked fibrin were significantly increased by L-NIL coadministration in the LPS-induced DIC model. Plasma levels of NOX and endothelin were obviously increased by LPS infusion. However, both levels were significantly suppressed in the LPS + L-NIL group, when compared with the LPS group. Although mean arterial pressure (MAP) was significantly decreased between 2 and 8 h compared with the control in the LPS group, this depression was significantly attenuated in the LPS + L-NIL group. Our results suggest that NO induced by iNOS contributes to hypotension (depressed MAP), the progression of hepatic and renal dysfunction, microthrombus deposition and elevated endothelin levels in the rat model of LPS-induced DIC. PMID:15869603

  12. Reperfusionsstrategien beim Myokardinfarkt: Stellenwert der interventionellen Kardiologie

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    Huber K

    2006-01-01

    , wie z. B. der Plättcheninhibitor Prasugrel (TRITON-TIMI-38-Studie oder das direkte Antithrombin Bivalirudin (HORIZON-Studie werden derzeit in klinischen Studien getestet. Es laufen derzeit auch Studien zur Untersuchung der Wertigkeit von Substanzen, die – während der PPCI verabreicht – in der Lage sein sollen, "Reperfusionsschäden" zu vermeiden (APEXAMI, DELTA-MI.

  13. Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes.

    Science.gov (United States)

    Oberbach, Andreas; Blüher, Matthias; Wirth, Henry; Till, Holger; Kovacs, Peter; Kullnick, Yvonne; Schlichting, Nadine; Tomm, Janina M; Rolle-Kampczyk, Ulrike; Murugaiyan, Jayaseelan; Binder, Hans; Dietrich, Arne; von Bergen, Martin

    2011-10-01

    Obesity is associated with multiple adverse health effects and a high risk of developing metabolic and cardiovascular diseases. Therefore, there is a great need to identify circulating parameters that link changes in body fat mass with obesity. This study combines proteomic and metabolomic approaches to identify circulating molecules that discriminate healthy lean from healthy obese individuals in an exploratory study design. To correct for variations in physical activity, study participants performed a one hour exercise bout to exhaustion. Subsequently, circulating factors differing between lean and obese individuals, independent of physical activity, were identified. The DIGE approach yielded 126 differentially abundant spots representing 39 unique proteins. Differential abundance of proteins was confirmed by ELISA for antithrombin-III, clusterin, complement C3 and complement C3b, pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP4), serum amyloid P (SAP), and vitamin-D binding protein (VDBP). Targeted serum metabolomics of 163 metabolites identified 12 metabolites significantly related to obesity. Among those, glycine (GLY), glutamine (GLN), and glycero-phosphatidylcholine 42:0 (PCaa 42:0) serum concentrations were higher, whereas PCaa 32:0, PCaa 32:1, and PCaa 40:5 were decreased in obese compared to lean individuals. The integrated bioinformatic evaluation of proteome and metabolome data yielded an improved group separation score of 2.65 in contrast to 2.02 and 2.16 for the single-type use of proteomic or metabolomics data, respectively. The identified circulating parameters were further investigated in an extended set of 30 volunteers and in the context of two intervention studies. Those included 14 obese patients who had undergone sleeve gastrectomy and 12 patients on a hypocaloric diet. For determining the long-term adaptation process the samples were taken six months after the treatment. In multivariate regression analyses, SAP, CLU

  14. The role of ventilation-perfusion lung scintigraphy in the diagnosis of pulmonary embolism in nephrotic syndrome patients

    International Nuclear Information System (INIS)

    Purpose: Patients with nephrotic syndrome (NS) have a high risk to develop thrombosis and even to progress to pulmonary embolism (PE). This study was performed to investigate the possible role of ventilafion-perfusion (V/Q) lung scans to evaluate PE in NS patients. Methods: 194 patients with NS (8 cases of minimal change NS (MCNS), 33 of mesangial proliferative (MsPGN), 19 of Mesangiocapillary glomerulonephritis (MCGN), 69 of membranous nephropathy, 56 of focal and segmental glomerular sclerosis (FSGS), and 9 of NS induced from purpura, SLE, diabetes mellitus or amyloidosis) were studied. In all patients, the development probability of PE was assessed based on the results of V/Q lung scans (Technegas for ventilation and Tc-99m MAA for perfusion imaging). The findings of V/Q lung scans were interrupted into high, intermediate, low or no probability of PE. The patients' clinical symptoms and signs were observed. Additional examinations included chest radiography, and serum biochemical tests such as albumin, blood urea nitrogen (BUN), creatinine (Cr), plasma fibrinogen (Fg), antithrombin III (AT III), prothrombin time (PT), and activated partial thromboplastin time (APTT). Results: Based on the findings of V/Q lung scans, 39 (20%) of the patients were categorized as having a high probability of PE and 56 (29%) as intermediate or low probability of PE. The occurrence of PE in patients with membranous nephropathy (23 cases, 33%) was significantly higher than that in those other pathological types. In the 86 patients with severe hypoalbuminemia (serum albumin concentration = 20g/L. The Fg and AT III levels were found to be correlated with the occurrence of PE. The clinical symptoms and signs, chest radiograph results and values of BUN, Cr, PT and APTT were not consistent with the occurrence of PE. Conclusion: Though usually clinically silent, PE is not a rare complication in patients with NS, especially in those with membranous nephropathy. In this study, the occurrence

  15. Hematologic risk factors for stroke in Saudi children

    International Nuclear Information System (INIS)

    Objective was to explore the hematologic risk factors for stroke in cohort of Saudi children. We evaluated children at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Investigations for suspected cases included neuroimaging, transcranial Dopppler (TCD) for cases of sickle cell diseases (SCD), and Duplex scan. Hemostatic assays included coagulation screening tests, tests of thrombin generation and fibrinolysis, coagulation inhibitors, and activated protein C resistance. During the study period, 104 Saudi children (aged one month to 12 years) with stroke were seen. The mean age of the cohort was 27.1 months (SD=39.3 months) and median was 6 months. Ischemic strokes accounted for the majority of cases (76%). A major risk factor was identified in 93 of 104 cases of stroke (89.4%). Hematologic disorders were the most common (46.2%), followed by prothrombic disorders (31.7%); microcystic hypochromic anemia (26%); sickle cell disease (SCD), or SCB-thalassemia, (11.5%), and factor IX deficiency (2.9%). Raised anticardiolipin antibodies (13/49, 26.5%) was the most frequent abnormality. Deficiencies of the natural anticoagulants (protein S, protein C and antithrombin III) were as follows: protein S (15/70, 21.4%); protein C (15/70,21.4%) and combined deficiency of 2 or more inhibitors (9/70, 12.9%). Activated protein C resistance has not been detected. Contrary to the findings of previous studies from Saudi Arabia, SCD is a common risk factor and is severe, as it resulted in multiple strokes. Moyamoya syndrome was diagnosed in 2 patients with SCD, one of whom had revascularization surgery (encephaldoduroarteriosynangiosis). Assessment of children with SCD at a risk of stroke was helped by the introduction of TCD followed by neuroimaging, using MRI and magnetic resonanceangiography

  16. Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden.

    Science.gov (United States)

    Eichinger, S; Weltermann, A; Philipp, K; Hafner, E; Kaider, A; Kittl, E M; Brenner, B; Mannhalter, C; Lechner, K; Kyrle, P A

    1999-10-01

    Normal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma's potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2. TAT, D-Dimer and the ETP at the 12th, 22nd and 34th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both

  17. Etiology of hypercoagulable state in women with recurrent fetal loss without other causes of miscarriage from Southern Italy: new clinical target for antithrombotic therapy

    Directory of Open Access Journals (Sweden)

    Maristella D’Uva

    2008-10-01

    Full Text Available Maristella D’Uva1, Pierpaolo Di Micco2, Ida Strina1, Antonio Ranieri1, Carlo Alviggi1, Antonio Mollo1, Francesca Fabozzi1, Lucia Cacciapuoti1, Maria Teresa Scotto di Frega1, Mariateresa Iannuzzo2, Giuseppe De Placido11Dipartimento Universitario di Scienze Ostetriche Ginecologiche e Medicina della Riproduzione, Area Funzionale di Medicina della Riproduzione ed Endoscopia Ginecologica, Università degli Studi di Napoli Federico II, via Pansini 5 Building 9, 80131, Naples, Italy; 2Internal Medicine Division, Fatebenefratelli Hospital of Naples, Naples, ItalyBackground: Recurrent fetal loss (RPL is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL.Patients and methods: Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M.Results: Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data.Conclusion: After a thorough evaluation of

  18. Heparin Versus Bivalirudin in Acute Myocardial Infarction: Unfractionated Heparin Monotherapy Elevated to Primary Treatment in Contemporary Percutaneous Coronary Intervention.

    Science.gov (United States)

    Centurión, Osmar Antonio

    2016-01-01

    Bivalirudin, a direct thrombin inhibitor, was developed as an antithrombin agent for patients undergoing percutaneous coronary interventions (PCI) with the hypothesis that it would reduce bleeding complications without compromising the rate of ischemic events compared to heparin plus GP IIb/IIIa inhibitors. Although the cumulative evidence makes a strong argument for the use of bivalirudin rather than heparin plus systematic GP IIb/IIIa inhibitors for the great majority of patients with acute myocardial infarction (AMI) undergoing PCI, the benefit observed with bivalirudin was achieved because of the major bleeding complications with the use of heparin plus GP IIb/IIIa inhibitors. When bivalirudin was compared with unfractionated heparin alone there was no benefit in ischemic complications with a decrease in major bleeding. However, in a recent large randomized controlled trial comparing bivalirudin with unfractionated heparin alone in AMI patients undergoing primary PCI, bivalirudin did not reduce bleeding complications and was associated with higher rates of stent thrombosis, myocardial reinfarction, and repeat revascularization compared with heparin. Moreover, a very recent meta-analysis shed more insights on the utilization of bivalirudin versus heparin regimens during PCI. Findings from this meta-analysis suggest that routine use of bivalirudin offers little advantage over heparin among PCI patients. In a detailed analysis of some randomized trials and observational studies with bivalirudin in AMI patients done by myself and published almost five years ago in this journal, I rendered some reflections on the future widespread use of bivalirudin. "In the setting of PCI in AMI patients, and in the absence of GP IIb/IIIa inhibitors, bivalirudin did not offer any beneficial effect in the incidence of the composite end points when compared with heparin alone. For now, in real world practice, one would probably choose a well known cheaper drug that has already passed

  19. Imbalance of pro- vs. anti-coagulation factors in Chinese patients with Budd-Chiari syndrome and non-cirrhotic portal vein thrombosis.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available The coagulation abnormalities in non-cirrhotic Budd-Chiari syndrome (NC-BCS and non-cirrhotic portal vein thrombosis (NC-PVT are unclear. We conducted this case-control study to investigate the coagulation profile of NC-BCS and NC-PVT in Chinese patients.We measured the levels of factors II, V, VII, VIII, IX, X, XI, XII, protein C (PC, protein S (PS and antithrombin (AT in blood samples from 37 NC-BCS patients, 74 NC-PVT patients, and 100 healthy controls. The levels and ratios of pro- and anti-coagulation factors were compared between patients with NC-BCS and healthy controls, between different types of NC-BCS and between NC-PVT and healthy controls.In patients with NC-BCS, factor VIII (P<0.001 was significantly elevated; factor V (P<0.001, VII (P<0.001, IX (P = 0.003, X (P<0.001, XI (P<0.001, XII (P<0.001, PC (P<0.001 and AT (P<0.001 were significantly decreased; and no difference was observed for factor II (P = 0.088 and PS (P = 0.199 compared with healthy controls. Factor VIII-to-PC (P = 0.008, factor VIII-to-PS (P = 0.037 and factor VIII-to-AT (P = 0.001 were significantly increased; other ratios were significantly reduced or did not show any difference. No differences were observed between different types of NC-BCS for individual pro- and anti-coagulation factors or the ratios between them. Among patients with NC-PVT, factor VIII (P<0.001 was significantly elevated and other factors were significantly decreased. Factor II-to-PC (P<0.001, factor VIII-to-PC (P<0.001, factor IX-to-PC (P<0.001, factor VIII-to-PS (P<0.001, factor II-to-AT (P<0.001, factor VIII-to-AT (P<0.001 and factor IX-to-AT (P<0.001 were significantly increased; all other ratios for NC-PVT were significantly reduced or did not show any significant difference.NC-BCS and NC-PVT are associated with elevated levels of factor VIII and the decreased levels of PC and AT were probably the most significant features of coagulation imbalance. Additionally, NC-PVT was associated with

  20. Structural and functional properties of heparin analogues obtained by chemical sulphation of Escherichia coli K5 capsular polysaccharide.

    Science.gov (United States)

    Razi, N; Feyzi, E; Björk, I; Naggi, A; Casu, B; Lindahl, U

    1995-07-15

    Capsular polysaccharide from Escherichia coli K5, with the basic structure (GlcA beta 1-4GlcNAc alpha 1-4)n, was chemically modified through N-deacetylation, N-sulphation and O-sulphation [Casu, Grazioli, Razi, Guerrini, Naggi, Torri, Oreste, Tursi, Zoppetti and Lindahl (1994) Carbohydr. Res. 263, 271-284]. Depending on the reaction conditions, the products showed different proportions of components with high affinity for antithrombin (AT). A high-affinity subfraction, M(r) approx. 36,000, was shown by near-UV CD, UV-absorption difference spectroscopy and fluorescence to cause conformational changes in the AT molecule very similar to those induced by high-affinity heparin. Fluorescence titrations demonstrated about two AT-binding sites per polysaccharide chain, each with a Kd of approx. 200 nM. The anti-(Factor Xa) activity was 170 units/mg, similar to that of the IIId international heparin standard and markedly higher than activities of previously described heparin analogues. Another preparation, M(r) approx. 13,000, of higher overall O-sulphate content, exhibited a single binding site per chain, with Kd approx. 1 microM, and an anti-(Factor Xa) activity of 70 units/mg. Compositional analysis of polysaccharide fractions revealed a correlation between the contents of -GlcA-GlcNSO3(3,6-di-OSO3)- disaccharide units and affinity for AT; the 3-O-sulphated GlcN unit has previously been identified as a marker component of the AT-binding pentasaccharide sequence in heparin. The abundance of the implicated disaccharide unit approximately equalled that of AT-binding sites in the 36,000-M(r) polysaccharide fraction, and approached one per high-affinity oligosaccharide (predominantly 10-12 monosaccharide units) isolated after partial depolymerization of AT-binding polysaccharide. These findings suggest that the modified bacterial polysaccharide interacts with AT and promotes its anticoagulant action in a manner similar to that of heparin. PMID:7626010

  1. Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    HU Bao-Yu

    2006-02-01

    Full Text Available Abstract Background Thrombocytopenia is commonly observed in severe leptospirosis. However, previous studies on coagulation alterations during leptospirosis resulted in inconsistent conclusions. Some findings showed that the prominent levels of thrombocytopenia observed in severe leptospirosis did not reflect the occurrence of disseminated intravascular coagulation (DIC syndrome, while the others reached the conclusion that the hemorrhages observed in leptospirosis were due to DIC. The aim of this study is to elucidate whether DIC is an important feature of leptospirosis. Methods The leptospirosis model of guinea pig was established by intraperitoneal inoculation of Leptospira interrogans strain Lai. Hematoxylin and eosin (HE staining, electron microscopy and immunohistochemistry staining were used to detect the pathologic changes. Platelet thrombus or fibrin thrombus was detected by HE, Martius Scarlet Blue (MSB staining and electron microscopy. Hemostatic molecular markers such as 11-dehydrogenate thromboxane B2 (11-DH-TXB2, thrombomodulin (TM, thrombin-antithrombin III complex (TAT, D-Dimer and fibrin (ogen degradation products (FDPs in the plasma were examined by quantitative enzyme-linked immunosorbent assay (ELISA to evaluate the hematological coagulative alterations in leptospirosis models. Results Pulmonary hemorrhage appeared in the model guinea pig 24 hours after leptospires intraperitoneal inoculation, progressing to a peak at 96 hours after the infection. Leptospires were detected 24 hours post-inoculation in the liver, 48 hours in the lung and 72 hours in the kidney by immunohistochemistry staining. Spiral form of the bacteria was initially observed in the liver, lung and kidney suggestive of intact leptospires, granular form of leptospires was seen as the severity increased. Platelet aggregation in hepatic sinusoid as well as phagocytosis of erythrocytes and platelets by Kupffer cells were both observed. Neither platelet thrombus

  2. Modifications de la coagulation sanguine dans la fièvre jaune

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    J. Vellard

    1929-01-01

    Full Text Available L'étude des modifications de la coagulation sanguine à l'aide de la technique BRAZIL-VELLARD, réalisée chez 25 malades atteints de formes diverses, mortelles, graves, et bénignes, entre le lléme et le XIIIéme jour de maladie, et chez 12 convalescents, a permis d'arriver aux conclusions suivantes: 1º. Les variations du pouvoir coagulant du serum sont très irrégulières et peu différentes des celles observées chez de sujets normaux. 2º. La coagulabilité du plasma, dès le IIème jour de la maladie, présente une diminution marquée, constante chez tous les malades, atteignant son chiffre le plus bas entre le VIIème et le IXème jour et revenant progressivement á la normale pendant la convalescence. 3º. Cette diminution de la coagulabilité est due principalement á l'apparition de grandes quantités d'antithrombines dans la circulation; la diminution du fibrinogène observée dans quelques cas, est toujours peu accusée. 4º. La diminution de la coagulabilité du plasma, qui n'a jusqu'ici été observée avec cette intensité que dans la fièvre jaune, peut être d'un certain secours pour le diagnostic précoce de cette affection; elle n'a jamais été vérifiée chez des malades atteints d'autres affections fébriles. 5º. Au point de vue du pronostic, la diminution précoce et très accentuée de la coagulabilité est un symptôme grave, indiquant une lésion profonde de la cellule hépatique. 6º. Dans la fièvre jaune expérimentale du Macacus rhesus, les altérations de la coagulation sanguine sont de même nature, mais paraissent plus tardives et moins accusées que chez l'homme.

  3. Value of the first post-transplant biopsy for predicting long-term cardiac allograft vasculopathy (CAV and graft failure in heart transplant patients.

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    Carlos A Labarrere

    Full Text Available BACKGROUND: Cardiac allograft vasculopathy (CAV is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA] and endothelial activation (intercellular adhesion molecule-1 in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years. Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00-374.77; and 3.99, p = 0.005, 95% CI = 1.53-10.40 and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08-3.03; and 1.31, p = 0.001, 95% CI = 1.12-1.55. First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years. CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively

  4. Enfermedad tromboembólica venosa y cirrosis hepática Venous thromboembolism and liver cirrhosis

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    M. J. García-Fuster

    2008-05-01

    , thrombosis characteristics, and treatment complications. Results and conclusions: approximately 0.8% of all hospitalized patients with cirrhosis had a non-portal VTE despite the elevated INR and low platelet count. We found low serum albumin, acquired antithrombin III, protein C and protein S deficiency, presence of antiphospholipid antibodies, and hyperhomocisteinemia in blood tests. Many patients had hemorragic complications during anticoagulation therapy, and 35% needed blood transfusions.

  5. Factor Xa generation by computational modeling: an additional discriminator to thrombin generation evaluation.

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    Kathleen E Brummel-Ziedins

    Full Text Available Factor (fXa is a critical enzyme in blood coagulation that is responsible for the initiation and propagation of thrombin generation. Previously we have shown that analysis of computationally generated thrombin profiles is a tool to investigate hemostasis in various populations. In this study, we evaluate the potential of computationally derived time courses of fXa generation as another approach for investigating thrombotic risk. Utilizing the case (n = 473 and control (n = 426 population from the Leiden Thrombophilia Study and each individual's plasma protein factor composition for fII, fV, fVII, fVIII, fIX, fX, antithrombin and tissue factor pathway inhibitor, tissue factor-initiated total active fXa generation was assessed using a mathematical model. FXa generation was evaluated by the area under the curve (AUC, the maximum rate (MaxR and level (MaxL and the time to reach these, TMaxR and TMaxL, respectively. FXa generation was analyzed in the entire populations and in defined subgroups (by sex, age, body mass index, oral contraceptive use. The maximum rates and levels of fXa generation occur over a 10- to 12- fold range in both cases and controls. This variation is larger than that observed with thrombin (3-6 fold in the same population. The greatest risk association was obtained using either MaxR or MaxL of fXa generation; with an ∼2.2 fold increased risk for individuals exceeding the 90(th percentile. This risk was similar to that of thrombin generation(MaxR OR 2.6. Grouping defined by oral contraceptive (OC use in the control population showed the biggest differences in fXa generation; a >60% increase in the MaxR upon OC use. FXa generation can distinguish between a subset of individuals characterized by overlapping thrombin generation profiles. Analysis of fXa generation is a phenotypic characteristic which may prove to be a more sensitive discriminator than thrombin generation among all individuals.

  6. Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

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    Ashis K Mukherjee

    Full Text Available BACKGROUND: The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia. PRINCIPAL FINDINGS: By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation. CONCLUSION/SIGNIFICANCE: In order to develop peptide

  7. Increased PADI4 expression in blood and tissues of patients with malignant tumors

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    Zhao Yan

    2009-01-01

    Full Text Available Abstract Background Peptidylarginine deiminase type 4 (PAD4/PADI4 post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673 as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT were investigated in the blood of patients with various tumors by ELISA (n = 1121. Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with

  8. Peculiarities of coagulation hemostasis disorders in patients with chronic obstructive pulmonary disease

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    Yakovlieva V.H.

    2015-09-01

    Full Text Available The violation of blood coagulation properties is observed in many diseases of the respiratory system, including chronic obstructive pulmonary disease (COPD. It is known that in a stable COPD phase release of proinflammatory cytokines in blood is observed, it leads to disturbance of hemostasis parameters toward hypercoagulation. The aim of our study was to determine possibility of coagulation disorders formation in patients with COPD in a stable phase of pathological process at different stages of disease course and identify relationship between coagulation parameters levels and degree of violation of ventilation lung function. Materials and methods. We examined 30 patients with COPD in a stable disease phase, included in the main group (FEV1 =49,5±15,5% of the due, there were 27 men (90.0%, 3 (30.0% women, mean age was 61,8±7,9 years, level of pack /years index - 34,2±15,3. The control group consisted of 10 healthy subjects matched with the patients of the main group by age and sex. All patients were divided into 2 subgroups. Subgroup 1 included 16 patients with moderate COPD, that is the level of FEV1>50% (61,8±7,4% of predicted, and subgroup 2 - 14 COPD patients with severe COPD, that is the level of FEV1 <50% (35,3±8,2% of predicted. Patients received standard treatment according to the disease stage. Main indicators of coagulation levels: prothrombin index (PI, prothrombin ratio (PR, international normalized ratio (INR, activated partial thromboplastin time (APTT, thrombin time (TT and antithrombin III (AT III were identified in all patients. Results. The levels of PI, PR and INR in the subgroup 1 differed significantly from those of in the subgroup 2, control group (p<0,05 and pointed at hypercoagulation, whereas in the subgroup 2 all indicators were absolutely identical with control group. Correlation link between the level of INR levels and FEV1 (r=-0,73; p<0.01 in patients of the main group was determined. Levels of APTT, TT and AT

  9. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    International Nuclear Information System (INIS)

    Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients

  10. Perinatal stroke in Saudi children: clinical features and risk factors

    International Nuclear Information System (INIS)

    To describe the clinical features and presentations of perinatal stroke in a prospective and retrospective cohort of Saudi children and ascertain the risk factors. Patients with perinatal stroke were identified from within a cohort of 104 Saudi children who were evaluated at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia from July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Neuroimaging for suspected cases of stroke consisted of cranial CT, MRI, or both. During the study period, 23 (22%) of 104 children (aged one months to 12 years) were diagnosed to have had perinatal stroke. The male: female ratio was 1.6:1. Ten (67%) of the 15 children who had unilateral ischemic involvement had their lesion in the left hemisphere. The presentation of the ischemic result was within 24-72 hours of life in 13 (57%) patients, and in 6 children (26%), motor impairment was recognized at or after the age of 4 months. Nine children (39%) had seizures at presentation. Pregnancy, labor, and delivery risk factors were ascertained in 18 (78%) cases. The most common of these included emergency cesarean section in 5 cases, and instrumental delivery in other 5. Screening for prothrombotic risk factors detected abnormalities in 6 (26%) patients on at least one test carried out between 2 months and 9 years of age. Four children (17%) had low protein C, which was associated low protein S and raised anticardiolipin antibodies (ACA) in one patient, and low antithrombin III in another. Low proteins S was detected in a 42-month-old boy. The abnormality in the sixth child was confined to raised ACA. The present study highlights the non-specific features by which stroke presents during the neonatal period. The data are in keeping with the potential role for inherited and acquired thrombophilia as being the underlying cause. However, the high prevalence of

  11. Neonatal arterial iliac thrombosis in type-I protein C deficiency: a case report

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    Capretti Maria G

    2010-03-01

    Full Text Available Abstract A male infant born by caesarean section at 38 weeks of gestational age (B.W. 4055 g; Apgar 9-10, in the first two hours of life his right leg became hypovascularizated. Normal values of leukocities, red cells, haematocrit, hemoglobin, platelets. C-Reactive Protein negative. Electrolytes and coagulation tests were normal. Normal vitamin K coagulation proteins levels. Serological tests for TORCH (IgM and Parvovirus (IgG and IgM were negative. Sonography showed a reduced blood flow in the iliac artery and reported a 1 cm long vessel thrombosis. From 8 hours of life we administred an intravenous infusion of unfractionated heparin (UFH 75 UI/Kg for the first 10 minutes then 28 UI/Kg/h. On the 2nd day tests were performed to assess absence of inhibiting-clot factors. The dosage of homocysteine, protein S and antithrombin was normal. FV Leiden and antiphospholipid antibodies were negative. The mapping of G20210A prothrombin's gene resulted normal, whereas the concentration of Protein C was lower than normal: activity 46% (68-150%, antigen 35% (70-150%. The same deficiency was also found in the father. The mother showed normal concentrations. No episodies of thrombosis events were documentated in the family. The intravenous unfractionated heparin (UFH therapy was replaced after 64 hours by subcutaneous nadroparin 600 UI twice/day, which was stopped 5 days later when the vessel sonografic images were completely normal. During the hospitalization the infant didn't show bleeding. The child was followed-up yearly until 4 years of age: he was well and had a normal body and mental development. The final diagnosis is likely to be of a permanent protein C deficiency in heterozygous form. Our case is interesting because the first manifestation was an important thrombosis of large vessel that occurred within a few hours of life in absence of perinatal risk factors, as if it was a homozygous disease, but the patient had a heterozygotic form. In literature

  12. 儿童重症肺炎凝血指标与降钙素原变化及分析%The change of coagulation indicators and procalcitonin in children with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    黄彩芝; 莫丽亚; 李爱国; 杨娟; 邓永超

    2015-01-01

    Objective To explore the changes in the levels of coagulation indicators and procalcitonin (PCT) in children with severe pneumonia. Methods A total of 76 children with severe pneumonia were selected and were divided into two groups according to the level of PCT, PCT<2.00 ng/ml group and PCT≥2.00 ng/ml group. Thirty healthy children were selected as normal controls. The levels of PCT, platelet counts (PLT), antithrombin-Ⅲ(AT-Ⅲ) activity and D-dimer (DD) were measured and compared among groups. Results Compared with control group, PCT, PLT and DD levels were signiifcantly higher and AT- Ⅲactivity was signiifcantly lower in severe pneumonia group (P<0.05). AT- Ⅲactivity and PLT were signiifcantly lower and DD level was signiifcantly higher in PCT≥2.00 ng/ml group than those in PCT<2.00 ng/ml group (P<0.05). The incidence of disseminated intravascular coagulation (DIC) in PCT≥2.00ng/ml group was signiifcantly higher than that in PCT<2.00ng/ml group (33.33%vs. 9.09%, correctedχ2=5.02, P=0.025). Conclusions There is dysfunction of coagulation in children with severe pneumonia. The higher level of PCT is, more obvious coagulation dysfunction is. The severe pneumonia children with high level of PCT are more likely to be complicated with disseminated inravascular coagulation.%目的:探讨重症肺炎患儿凝血指标与降钙素原(PCT)的变化。方法选取重症肺炎患儿76例,根据PCT升高的程度分为2组,PCT<2.00 ng/ml组和PCT≥2.00 ng/ml组;另选择30例健康儿童作为正常对照组。检测并分析比较各组的PCT、血小板计数(PLT)、抗凝血酶Ⅲ(AT-Ⅲ)活性和D-二聚体(DD)水平。结果与对照组比较,重症肺炎组PCT、PLT、DD水平明显升高,AT-Ⅲ活性明显降低,差异均有统计学意义(P<0.05);PCT≥2.00 ng/ml组的AT-Ⅲ活性和PLT水平相比PCT<2.00 ng/ml组更低,而DD水平更高,差异均有统计学意义(P<0.05);PCT≥2.00 ng/ml组的DIC发生率(33.33%)高于PCT<2.00 ng

  13. The specificity of interactions between proteins and sulfated polysaccharides

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    Barbara Mulloy

    2005-12-01

    Full Text Available Sulfated polysaccharides are capable of binding with proteins at several levels of specificity. As highly acidic macromolecules, they can bind non-specifically to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically significant. On the other hand, several systems have been identified in which very specific substructures of sulfated polysaccharides confer high affinity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affinity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fine structure of dermatan sulfate (DS to its interaction with heparin cofactor II (HCII, and the involvement of sea urchin egg-jelly fucans in species specific fertilization. A third, intermediate, kind of specific interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS, in which patterns of sulfate substitution can show differential affinities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them.Os polissacarídeos sulfatados são capazes de se ligar às proteínas com diferentes níveis de especificidade. São macromoléculas altamente ácidas que podem se ligar de forma inespecífica a qualquer domínio básico da superfície de uma proteína em soluções com baixa força iônica, contudo tais interações não parecem ser fisiologicamente significativas. Por outro lado, foram identificados vários sistemas nos quais componentes estruturais muito específicos dos polissacarídeos sulfatados conferem alta afinidade para algumas proteínas. O exemplo mais conhecido é o pentassacarídeo da heparina com alta afinidade pela antitrombina. Outros exemplos podem ser

  14. Prevalência dos fatores trombofílicos em mulheres com infertilidade Prevalence of thrombophilic factors in infertile women

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    Adriana de Góes e Silva Soligo

    2007-05-01

    disease were evaluated. Infertility is defined as one year of unprotected sexual intercourse without conception. The acquired and/or inherited thrombophilic factors investigated were: anticardiolipin antibody (aCL, lupus anticoagulant (LA, protein C deficiency (PCD, protein S deficiency (PSD, antithrombin III deficiency (ATD, presence of the factor V Leiden, mutation G20 210A in the prothrombin gene, and C677T mutation of methylene tetrahydrofolate reductase (MTHFR. RESULTS: the prevalence values obtained for aCL and LA were 2%. The prevalence of the hereditary thrombophilic factors were: PCD=4%, PSD=6%, ATD=5%, factor V Leiden=3%, prothrombin mutation=3%, MTHFR mutation=57%. Conclusions: of the 144 patients selected, 105 women (72.9% presented at least one thrombophilic factor. This reinforces the importance and justifies the need of investigation in this group.

  15. Interaction of peptide-bound beads with lipopolysaccharide and lipoproteins.

    Science.gov (United States)

    Suzuki, Masatsugu M; Matsumoto, Megumi; Omi, Hiroyuki; Kobayashi, Tomomi; Nakamura, Akio; Kishi, Hiroko; Kobayashi, Sei; Takagi, Takashi

    2014-05-01

    We previously reported the generation of lipopolysaccharide (LPS)-binding peptides by phage display and chemical modification. Among them, a dodecapeptide designated Li5-025 (K'YSSSISSIRAC'; K' and C' denote d-lysine and d-cysteine, respectively) showed a high binding affinity for LPS and was resistant to protease digestion (Suzuki et al., 2010). In the current study, Li5-025-bound silica beads, hereafter referred to as P-beads, were generated and found to be devoid of LPS-neutralizing activity. Thus, LPS bound to the P-beads could be directly used in the Limulus amebocyte lysate (LAL) assay. P-beads bound LPS dissolved in solutions of ethanol, pH4, pH10, and 0.5M NaCl and LPS bound to the P-beads was quantitatively assayed. The sensitivity of this assay was observed to be approximately 0.1pg/mL LPS. P-beads bound LPS dissolved in antithrombin III (AT III) solution which is a strong inhibitor of activated factors C and B as well as the clotting enzyme in the LAL assay; the inhibitory effect of AT III was completely reversed upon washing the P-beads with 25% acetonitrile. This was employed as the first step for the detection of free LPS in plasma using the LAL assay. LPS added to human plasma at 0°C followed by application to the P-beads and subsequent washing with 25% acetonitrile resulted in low LPS activity as detected by the LAL assay. However, further washing of the P-beads with 0.1% Triton X100 in 25% acetonitrile resulted in high LPS activity. This is the first instance of quantitative detection of free LPS in plasma using the LAL assay, and the sensitivity of this method was observed to be 1pg/mL of LPS. The proteins eluted in the 0.1% Triton X-100 wash were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Two protein bands of 28kDa and 18kDa were predominantly observed. Mass spectrometry analysis revealed that the 28kDa and 18kDa bands corresponded to apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), respectively. Apo

  16. Angiotensin converting enzyme (ACE DD genotype: relationship with venous thrombosis Genótipo DD da enzima conversora de angiotensina (ECA: relação com trombose venosa

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    Terezinha P. Munhoz

    2005-06-01

    Full Text Available Venous thromboembolism is a common multifactorial disease associated with acquired and inherited predisposing factors. Several polymorphisms, e.g. factor V Leiden, factor II G20210A and deficiency of antithrombin, protein C and protein S, have been associated with venous thromboembolism. Angiotensin converting-enzyme affects hemostasis by decreasing fibrinolysis. Angiotensin converting-enzyme gene polymorphism, a 287 pb insertion/deletion at introns 16, is related to variations in enzyme serum levels. The DD genotype has been associated with increased risk for venous thrombosis. This study examined the frequency of the angiotensin converting-enzyme alleles I and D and their association with venous thrombosis in a group of individuals from the south of Brazil. Seventy-one patients with deep venous thrombosis and/or pulmonary thromboembolism and 71 healthy individuals were analysed in a case-control study. The angiotensin converting-enzyme ID genotyping was performed by polymerase chain reaction. The frequencies of the D allele and DD genotype were, respectively, 51.4% and 22.5% for patients, and 64.7% and 45.0% for controls. The Odds Ratio for the dominant hypothesis (DD+ID versus II genotypes was 0. 75 (CI 95%; 0.29-1.93 and the Odds Ratio for recessive hypothesis (DD versus ID+II was 0.35 (CI 95%; 0.16-0.78. In conclusion, our results indicate a protective effect of the angiotensin converting-enzyme DD genotype on venous thromboembolism.O troemboembolismo venoso (TEV é uma doença multifatorial associada com fatores de risco adquiridos e hereditários. Vários polimorfismos, tais como fator V de Leiden, mutação G20210A da protrombina e as deficiências de proteína C, proteína S e anti-trombina são considerados fatores de risco para TEV. A enzima conversora da angiotensina (ECA afeta a hemostasia diminuindo a fibrinólise. O polimorfismo no gene da ECA, caracterizado pela inserção/deleção de um fragmento de 287 pb no intron16, est

  17. Distúrbios de coagulação em pacientes com osteonecrose da cabeça femoral Coagulation disorders in patients with femoral head osteonecrosis

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    Flávio Luís Garcia

    2013-02-01

    Full Text Available OBJETIVO: Comparar a ocorrência de trombofilias em pacientes com osteonecrose idiopática da cabeça femoral em relação aos pacientes com osteonecrose secundária da cabeça femoral. MÉTODOS: Um total de 24 pacientes consecutivos foram avaliados, sendo oito portadores de osteonecrose idiopática e 16 de osteonecrose secundária. Os exames realizados na detecção de trombofilias foram as dosagens de proteína C, proteína S e antitrombina e as pesquisas de mutações nos genes da protrombina e do fator V. Comparamos estatisticamente os resultados através do cálculo da razão de chances ou odds ratio das diferentes trombofilias entre os dois grupos. RESULTADOS: O odds ratio para a deficiência da proteína S e deficiência da proteína C entre os grupos idiopático e secundário foram respectivamente 5 e 2,14. Desta maneira, um indivíduo com osteonecrose idiopática possui uma chance 5 vezes maior de apresentar deficiência da proteína S e 2,14 vezes maior de apresentar deficiência da proteína C do que um indivíduo com osteonecrose secundária. CONCLUSÃO: Pacientes com osteonecrose idiopática têm maiores chances de apresentar trombofilias do que aqueles com osteonecrose secundária, sugerindo que estes distúrbios de coagulação podem desempenhar um papel importante na patogênese dos casos de osteonecrose onde não há inicialmente nenhum fator de risco identificável. Nível de Evidência III, Estudo de Caso-Controle.OBJECTIVE: To compare the occurrence of thrombophilic disorders in patients with idiopathic osteonecrosis of the femoral head and patients with secondary osteonecrosis of the femoral head. METHODS: Twenty-four consecutive patients were enrolled, with eight of them presenting idiopathic osteonecrosis and 16 presenting secondary osteonecrosis. The tests for detection of thrombophilic disorders were measurements of protein C, protein S and antithrombin levels and detection of prothrombin and factor V gene mutations. We

  18. An unusual cause of acute abdominal pain – A case presentation

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    Hunt Trevor M

    2006-04-01

    Full Text Available Abstract Background In 1983, Graham Hughes described a condition of Antiphospholipid Syndrome in which there was a danger of thrombosis. The condition is readily detectable by blood tests and, once diagnosed; the risk of further thrombosis can be significantly reduced by anticoagulation treatments. Affected groups of patients can be distinguished by a specific blood test – the detection of antiphospholipid antibody (Ref-1. Patients with Hughes syndrome have hypercoaguable state with a markedly increased risk of both arterial and venous thrombosis and there is temporal persistence of antibody positivity. Case presentation A 44-year-old woman was admitted under the acute surgical "take" with left sided abdominal pain radiating to her back. She had a history of borderline thyrotoxicosis in the early 1990s. She was on etonogestrel-releasing implants for contraception and there was no history of previous deep venous thrombosis. She was very tender, locally, over the left side of the abdomen. Investigations showed haemoglobin of 13.2 g/dl, white cell count of 19.9 10*9/L, and platelets 214 10*9/L with neutrophilia. Amylase and renal function tests were found to be normal. Liver function tests were deranged with Gamma GT 244 u/l (twice normal. An abdominal Ultrasound Scan suggested a possible splenic infarction, which was confirmed by a CT scan of her abdomen. Tests were carried out to investigate the possibility of a post thrombotic state. Coagulation risk factors for thrombosis were within the normal limits; Protein S 67 %(60–140, Protein C 103 % (72–146, Antithrombin 3 110 %(80–120 and Activated P C Resistance was 1.9(2.0–4.3. The Hams test was negative but the Anticardiolipin antibody test was positive. IgM level was 52 (normal is up to 10 and IgG was 18.8 (normal is up to 10. She also had border line APC Sensitivity 1.9 (2 to 4.3. Kaolin time 49 sec (70–120 Ktmix 64 sec (70–120, thyroid function test revealed TSH 0.32 mu/L, fT4 20

  19. 彩超诊断小腿肌间静脉血栓对骨科手术诊疗的应用价值%The application value of color Doppler ultrasonography in diagnosis of venous plexus thrombosis of calf muscle for orthopedic operation treatment

    Institute of Scientific and Technical Information of China (English)

    张宇明; 张文云; 邓荷萍; 房勤茂; 甄景琴; 封彦凤

    2012-01-01

    thrombosis before surgery. Hypertension and hyperlipidemia were detected in 32 patients( 59. 3% ) whose age was over 50 years. After anticoagulation and thrombolytic therapy, CDFI characters were changed gradually from no blood flow to part of the blood flow visible in lumina or fluent blood flow. As respect of biochemical indicators, plasma antithrombin Ⅲ activity and prothrombin time index were increased, however, D-dimer, fibrinogen and thrombin activity index were decreased gradually. No pulmonary embolism was observed during orthopedic surgery after anticoagulation and thrombolytic treatment for 2 weeks. Conclusion Color Doppler ultrasonography is an useful method to diagnose calf muscle vein thrombosis, so as to prevent deep vein thrombosis effectively, which is valuable for diagnosis and treatment of surgical patients in clinic in order to minimize the incidence of pulmonary embolism.

  20. Estudo de fatores pró-trombóticos e pró-inflamatórios na cardiomiopatia chagásica Study of pro-thrombotic and pro-inflammatory factors in chagas cardiomyopathy

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    Leila Maria Magalhães Pessoa de Melo

    2010-10-01

    Full Text Available FUNDAMENTO: A relação entre atividade inflamatória e pró-trombótica na cardiomiopatia chagásica e em outras etiologias é obscura. OBJETIVO: Estudar o perfil de marcadores pró-trombóticos e pró-inflamatórios em pacientes com insuficiência cardíaca chagásica e compará-los com os de etiologia não chagásica. MÉTODOS: Coorte transversal. Critérios de inclusão: fração de ejeção do VE (FEVE um mês. Os pacientes foram divididos em dois grupos: grupo 1 (G1 - sorologias positivas para Chagas - e grupo 2 (G2 - sorologias negativas para Chagas. Fator pró-inflamatório: PCR ultrassensível. Fatores pró-trombóticos: fator trombina-antitrombina, fibrinogênio, antígeno do fator de von Willebrand, P-selectina plasmática e tromboelastograma. Amostra calculada para poder de 80%, assumindo-se diferença de 1/3 de desvio-padrão; p significativo se BACKGROUND: The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear. OBJECTIVE: To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology. METHODS: Cross-sectional cohort. Inclusion criteria: left ventricle ejection fraction (LVEF one month. The patients were divided into two groups: group 1 (G1 - seropositive for Chagas - and group 2 (G2 - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is < 0.05. Statistical analysis: Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables. RESULTS: Between January and June 2008, 150 patients were included, 80 in G1

  1. 2型糖尿病患者凝血状态研究%The study of blood coagulation status in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    穆志静; 王立

    2013-01-01

    目的 探讨2型糖尿病患者合并血管病变对凝血状态的影响.方法 纳入2型糖尿病住院患者311例,依据有无大血管并发症分为3组,即单纯糖尿病组130例,糖尿病合并高血压组151例,糖尿病合并冠心病组30例,同时选择我院同期健康体检者30例作为健康对照组.检测抗凝血酶-III(AT-III)、蛋白C(PC)、蛋白S(PS)、活化部分凝血活酶时间(APTT)、血浆凝血酶原时间(PT)、血浆纤维蛋白原(Fib)、血浆凝血酶时间(TT))水平评价凝血功能.结果 与健康对照组相比较,糖尿病组AT-III、PC、PS活性明显降低,凝血四项中APTT、PT降低、Fib升高,2组比较差异有统计学意义(P<0.05).糖尿病合并冠心病组与单纯糖尿病组相比,PC、PS差异有统计学意义(P<0.05).糖尿病合并冠心病组Fib及PLT升高较单纯糖尿病组更为明显,差异有统计学意义(P<0.05).结论 糖尿病患者抗凝血功能紊乱,处于血栓前状态,合并心血管并发症患者尤为明显.AT-III、PC、PS及凝血四项的测定可能有利于糖尿病患者凝血状态的评估,有利于血管并发症的早期干预.%Objective To explore the changes and clinical significance in coagulation anti-coagulation and fibrinolysis system in patients with type 2 diabetes mellitus ( DM ). Methods To measure thrombin time ( TT ), activated partial thrombo-plastin time ( APTT ), prothrombin time ( PT ), and fibrinogen ( Fib ), anti-thrombin Ⅲ ( AT-Ⅲ ), protein C ( PC ), protein S ( PS ) in 311 patients with type 2 diabetes mellitus from 2010 to 2011. These patients were categorized as single DM group, DM with hypertension group, DM with coronary heart disease group. At the same time, 30 health)' people were selected as contrast group. SPSS software was used for statistic analysis. Results The activity of AT-Ⅲ,PC,PS of type 2 diabetes melli-tus were progressively lower than those of control group. There was a significant difference between single DM

  2. MANEJO DE LA EMBARAZADA CON TROMBOFILIA HEREDITARIA

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    Jorge Hasbún H.

    2003-01-01

    evaluation of secondary profilaxis with Low Molecular Weight Heparin in the next gestation, was the proposal of this study in an observational prospective design. Patients and methods: eleven patients with recent thrombosis sent for specialized control were studied for thrombophilia Antithrombin III deficiency, protein S Deficiency, Factor V Leyden, Methylentetrahydrofolate reductase Mutation GenC677T, Hiperhomocysteinemia, Protrombin G20210A Mutation and Antiphospholipid syndrome (anticardiolipin antibodies and lupus anticoagulant plasmatic determinations of coagulation factors. During the next pregnancy, they were treated with Dalteparine 2500-5000 U each day during gestation and two month after delivery, with strict clinical, ultrasound and hemostatic controls. Results: Thrombophilia was proved in all cases. Eight cases with isolated form: three protein S Deficiency, two protein C Deficiency, two FactorV Leyden and one case of Hypehomocysteinemia. Three patients had a combined form: one with Protrombin G20210A mutation + Def protein C + Mutation Gen C677T and two cases with Factor V Leyden + Mutation Gen C677T. There were eleven healthy and term pregnancy without obstetrical or hemostatic complications and three espontaneous abortion. We discuss clinical events, the trombotic risk and we wake considerations about the detection and meaning of treatment. In conclusion, the detection of thrombophilias is very important in high risk women and Dalteparine is safe in thrombosis prophilaxis during pregnancy

  3. Effects of Danshensu on maternal syndrome in phosphatidyleserine/ phosphatidylcholine micro vesicle induced-mouse model: is it a candidate for preeclampsia remedy?

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    SHEN Yang; HU Ya-li; ZHANG Yan; WANG Jing-mei

    2010-01-01

    Backgroud Up to date, there is few satisfactory pharmacotherapy, except for aspirin and heparin, to stop the preeclampsia progression. Although the mechanism of preeclampsia is poorly understood, it has been proven to be associated with coagulation activation. Researches on prophylactic and therapeutic application of anticoagulants may benefit the clinical aspects of preeclampsia individuals. This study aimed to evaluate the effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine (PS/PC) microvesicle induced-mouse model. Methods Sixty-six preeclampsia-like pregnant mice, induced by PS/PC microvesicle administration, were randomly divided into six groups. From days 5.5 to 16.5 of pregnancy, each group was respectively treated as follows: a) mice in group C (n=12, control group) were injected with 100 μl of filtered phosphate-buffered saline into the tail vein every day; b) group PE (n=15, preeclampsia model group) were injected in the same way with 100 μl of filtered PS/PC vesicle suspension; c) group H (n=9, group treated with heparin) were injected with 1 unit heparin together with PS/PC vesicle suspension; d) group A (n=10, group treated with aspirin) were injected with 20 μg/g aspirin-DL lysine as well; e) group LD (n=10, group treated with low-dose Danshensu) were injected with 10 μg/g Danshensu; and f) group HD (n=10, group treated with high-dose Danshensu) were injected with 30 μg/g Danshensu. Systolic blood pressure, total urinary protein levels, blood tests for some hemostatic function parameters (mean platelet counts, plasma antithrombin III activity (AT-Ⅲ), D-D dimmer levels, and thrombin time), fibrin deposition by phosphotungstic acid hematoxylin staining, and thrombomodulin expression by immunohistochemistry staining in placentas were examined as indices for maternal syndrome. Results Heparin showed significant effects on maternal syndrome of preeclampsia such as hypertension and proteinuria, and different doses of

  4. Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte New anticoagulants for the prophylaxis of venous thromboembolism

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    Ricardo de Alvarenga Yoshida

    2011-06-01

    novos inibidores diretos do fator Xa e inibidores do fator IIa.After about 50 years of experience with heparin and vitamin K antagonists (VKA, research and clinical studies of new anticoagulants have recently evolved . Although traditional anticoagulants have proven to be clinically useful, they have important limitations in terms of laboratory control, complications, side effects and interactions with medications and food. .Unfractionated heparin interacts with plasma proteins and the vascular wall, may trigger thrombocytopenia, can only be administered parenterally, requires control by the laboratory test of partial thromboplastin time, may cause osteoporosis and alopecia when used for long periods and it is produced from biological sources. VKA have the advantage of being administered orally, but the control (made by the international normalized ratio can be difficult in some cases, since they have delayed onset of action and metabolism and a narrow therapeutic window. They also interact with foods and with a large number of medications, can cause skin necrosis in patients with antithrombin and protein C and S deficiencies and may induce fetal changes when prescribed in pregnancy. In the 1980´s the low-molecular-weight heparins were developed and proved to be an evolution over unfractionated heparin, because of their greater bio-availability, fixed dose per body weight, no need for laboratory control, subcutaneous administration, lower risk of heparin-induced thrombocytopenia, and efficacy and safety similar to unfractionated heparin. Over the last decade, a series of new anticoagulants have appeared in the market and shown promising results in several situations of venous thromboembolism prophylaxis and treatment. In the present review, the new low-molecular-weight heparins, ultra-low molecular weight heparin, pentasaccharides and the new direct inhibitors of factor Xa and factor IIa.are addressed.

  5. Revisão sobre alterações hemostáticas na doença hipertensiva específica da gravidez (DHEG Hemostatic changes revision in preeclampsia

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    Luci Maria Sant'Ana Dusse

    2001-01-01

    determinação de marcadores de tromboembolismo, como um parâmetro para o planejamento de futuras gestações, uma vez que a recorrência da DHEG é da ordem de 20%.Preeclampsia (PE characterises by development of hypertension, proteinuria and swelling in pregnant women around 20th pregnancy week. The hemodynamic changes observed in the normal pregnancy comprising renal and cardiovascular adaptations that did not occur in PE. The most important feature of this disease is a pronounced arteriolar vasoconstriction leading to a increase of the peripheral vascular resistance responsable to high blood pressure. Evidences of platelet consumption and endothelial cell disfunction have been observed in PE. Conflicting opinions related to the fibrinolytic system have been raised on the literature including increase, decrease or even no changes in this system preeclamptic compared to normal pregnant women. Efforts have been carried out in order to define hemostatic parameters with diagnostic and prognostic value, considering that PE diagnosis is essentially based on clinical data and often hard to be established. In this way, platelet count, thrombomodulin, thrombin-antithrombin complex and plasminogen activator inhibitor type 2 measurement were performed as helpful parameters for PE diagnosis. However, it remains to be established the usefulness of all these laboratory markers. Recently, it was suggested an association between the occurence of pregnancy complication, including PE, and the presence of genetic mutations which favors the development of thromboembolic events. It has been proposed a hemostatic the assessment in preeclamptic women, even if there was no previous thromboembolic episody, by using thrombotic markers as an useful parameter for planning future pregnancies, once PE recurrence is about 20%.

  6. Changing characteristics of commonly used indicators in different liver diseases and the Correlation with clotting mecha-nism%肝病常用指标在不同肝病中的变化特点及与凝血机制相关性分析

    Institute of Scientific and Technical Information of China (English)

    陈静; 段钟平; 童新元; 丛玉隆

    2014-01-01

    Objective To study the changing characteristics of coagulation factors and fibrinogen degradation products in different liver disease,liver disease,blood clotting and bleeding balance between relations,to explore the balance between coagulation and bleeding of hepatic diseases.Methods Coagulation factor Ⅱ,Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ activity was detected by one-stages clotting method.Coagulogram such as APTT,TT,PT and Fig were measured by solidification method.Antithrombin Ⅲ (AT-Ⅲ),protein C (PC)activity were measured by chromogen-ic substrate assay.FDP concentration was detected using immunoturbidimetry.Results Except for FⅧ,coagulation factors and anticoagulant proteins synthesized by the liver decreased,coagulogram extended,FDP and D-D concen-tration increased in blood.Conclusion With the progression of liver diseases,the procoagulation and anti-coagulation elements synthesized by liver were parallelly reduced.Fibrinolysis activity was enhanced,which led to the imbalance between blood clotting and anti-clotting .This might be an important cause for bleeding in the end-stage of liver dis-ease patients.%目的:研究由肝脏合成的促抗凝因子、纤维蛋白原降解产物等成分在不同肝病中的变化特点,探讨肝脏疾病凝血与出血之间的平衡关系。方法(1)凝血因子活性检测(F:C):包括 FⅡ:C、FⅤ:C、FⅦ:C、FⅧ:C、FⅨ:C、FⅩ:C、FⅪ:C、FⅫ:C 均采用一期凝固法,试剂来自德国 Simens 公司,所用仪器为美国 ACL advance;(2)活化部分凝血酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(Fig)测定采用凝固法,仪器为美国Backman 公司 ALT TOP,试剂与仪器配套;(3)蛋白 C(PC)、抗凝血酶Ⅲ(AT-Ⅲ)活性测定采用发色底物法,仪器均为法国 stago 公司的 sta-R,试剂与仪器配套;(4)纤维蛋白原降解产物(FDP)含量检测采用免疫比浊法

  7. 冠心病患者肥胖与血栓前状态相关性的研究%Correlation between obesity and prethrombotic state in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    郭佳佳; 胡松; 王丽娜; 毛拥军; 王仁萍

    2015-01-01

    Objective:To explore the correlation among overweight ,obesity and markers of prethrombotic state in patients with coronary heart disease (CHD) .Methods:A total of 288 patients to hospital from 2013 to 2014 and di-agnosed as CHD by coronary angiography were selected .According to body mass index (BMI) ,they were divided into CHD control group (n= 106) ,overweight group (n= 121) and obesity group (n= 61) .Levels of fibrinogen (Fg) ,plasma D dimmer (D-D) ,von Willebrand factor (vWF) ,antithrombin Ⅲ (AT-Ⅲ) and plasminogen activator inhibitor (PAI)-1 were compared among three groups ,then received correlation analysis . Results:Compared with CHD control group ,there were significant rise in levels of triglyceride ,total cholesterol ,fasting blood glucose and mean arterial pressure ,morbidity rates of hypertension and diabetes mellitus in overweight group and obesity group , P<0.05 or <0.01. Compared with CHD control group ,there were significant rise in levels of Fg [ (2.89 ± 0.60) g/L vs .(3.54 ± 0.63) g/L vs .(3.92 ± 0.94) g/L] ,D-D [ (282.13 ± 73.15) ng/ml vs .(390.04 ± 73.54) ng/ml vs . (471.92 ± 80.38) ng/ml] ,vWF [ (108.62 ± 24.66)% vs .(138.45 ± 25.96)% vs .(161.20 ± 29.39)% ] and PAI-1 [ (6.97 ± 1.28) ng/ml vs .(9.60 ± 1.73) ng/ml vs .(12.33 ± 2.16) ng/ml] in overweight group and obesity group , P<0.01 all ,and those of obesity group were significantly higher than those of overweight group , P<0.01 or <0.05 ;AT-Ⅲ level [ (89.94 ± 17.99)% vs .(69.89 ± 20.22)% ] significantly reduced in obesity group (P<0.05) . Pearson correlation analysis indicated that BMI was positively correlated with markers of prethrombotic state [Fg:r=0.536 ,P<0.001 ;D-D:r= 0.250 , P< 0.001 ;vWF :r= 0.611 , P< 0.001 ;PAI-1:r=0.788 , P< 0.001) . Conclusion:BMI is positively correlated with markers of prothrombotic state in CHD patients .%目的:探讨冠心病患者超重、肥胖与血栓前状态标志物之间的相关性。方法:选择2013~2014年来院就诊