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Hemostatic System (hemostatic + system)
Selected AbstractsThe 894 G > T variant of endothelial nitric oxide synthase (eNOS) increases the risk of recurrent venous thrombosis through interaction with elevated homocysteine levelsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2004S. G. Heil Summary.,Background: Venous thrombosis is a multicausal disease involving both genetic as well as acquired risk factors. Hyperhomocysteinemia is associated with a 2-fold increased risk of recurrent venous thrombosis (RVT). Recently, the 894 G > T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia. Objectives: We hypothesized an interrelation of hyperhomocysteinemia, the eNOS 894 G > T variant and RVT risk. Methods: The eNOS 894 G > T variant was studied in 170 cases with a history of RVT and 433 controls from the general population. Results: The eNOS 894 TT genotype may increase RVT risk [odds ratio (OR) 1.3 (0.7,2.6)], but no association of the eNOS 894 G > T variant with elevated homocysteine was found in controls. Interestingly, in RVT cases the coexistence of both the 894 TT genotype and elevated tHcy levels (> 90th percentile) was more frequently present than in controls, which led to a substantially increased risk of recurrent venous thrombosis [fasting tHcy OR 5.3 (1.1,24.1), postload tHcy OR 6.5 (1.6,29.5)]. Conclusion: The results of the present study demonstrate that the eNOS 894 G > T variation interacts with elevated tHcy levels, leading to an increased risk of recurrent thrombotic events. This interaction points in the direction of S-nitrosation as a mechanism by which homocysteine exerts its detrimental effects on the hemostatic system. [source] An updated view of hemostasis: mechanisms of hemostatic dysfuntion associated with sepsisJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2005DACVECC, Kate Hopper BVSc Abstract Objective: To review the current understanding of mechanisms involved in normal hemostasis and to describe the changes associated with pro-inflammatory disease processes such as sepsis. Data sources: Original research articles and scientific reviews. Human data synthesis: Organ damage caused by sepsis is created in part by the interdependent relationship between hemostasis and inflammation. Markers of coagulation have been found to have prognostic value in human patients with sepsis and there are both experimental and clinical investigations of the therapeutic potential of modulating the hemostatic system in sepsis. Improvement of 28-day all-cause mortality in severe sepsis by treatment with recombinant human activated Protein C strongly supports the interdependence of hemostasis and inflammation in the pathophysiology of sepsis. Veterinary data synthesis: Publications reporting clinical evaluation of the hemostatic changes occurring in septic dogs or cats are minimal. Experimental animal models of sepsis reveal significant similarity between human and animal sepsis and may provide relevance to clinical veterinary medicine until prospective clinical evaluations are published. Conclusions: It is now apparent that inflammation and the coagulation system are intimately connected. Understanding this relationship provides some insight into the pathogenesis of the hemostatic changes associated with sepsis. This new updated view of hemostasis may lead to the development of novel therapeutic approaches to sepsis and disseminated intravascular coagulation in veterinary medicine. [source] Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effectLIVER TRANSPLANTATION, Issue 10 2001I. Quintus Molenaar Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation (fibrinogen level, activated partial thromboplastin time [aPTT], prothrombin time, and platelet count) and fibrinolytic variables (tissue-type plasminogen activator [tPA] antigen and activity, plasminogen activator inhibitor activity, and D-dimer), as well as thromboelastography (reaction time [r], clot formation time, and maximum amplitude) in 27 patients administered either high-dose aprotinin (2 × 106 kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 × 106 KIU/h, and 1 × 106 KIU before reperfusion; n = 10), regular-dose aprotinin (2 × 106 KIU at induction and continuous infusion of 0.5 × 106 KIU/h; n = 8), or placebo (n = 9) during OLT. Blood samples were drawn at seven standardized intraoperative times. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dimer and tPA antigen levels) was significantly lower in aprotinin-treated patients compared with the placebo group. Interestingly, coagulation times (aPTT and r) were significantly more prolonged in aprotinin-treated patients than the placebo group. No difference was seen in the incidence of perioperative thrombotic complications in the entire study population (n = 137). Aprotinin has an anticoagulant rather than a procoagulant effect. Its blood-sparing (prohemostatic) effect appears to be the overall result of a strong antifibrinolytic and a weaker anticoagulant effect. These findings argue against a prothrombotic effect of aprotinin in patients undergoing OLT. [source] Development of a Severe von Willebrand Factor/ADAMTS13 Dysbalance During Orthotopic Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009I. T. A. Pereboom Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications. [source] Prolonged low-dose thrombolytic therapy: A novel adjunctive strategy in the management of an infected right atrial thrombusCLINICAL CARDIOLOGY, Issue 7 2002Sheila Chuang M.D. Abstract An 81-year-old man presented with a large, infected right atrial thrombus that was refractory to anticoagulants and several courses of antibiotics. The risk of surgical removal of the thrombus, which was associated with a pacemaker electrode, was considered prohibitive. The patient was treated for 7 days with low-dose (40 mg/day) tissue-type plasminogen activator (t-PA). Hemostatic monitoring during infusion revealed (1) aplasma t-PA antigen that was approximately 5% of that achieved during short-course t-PA for acute myocardial infarction, (2) biochemical evidence of prolonged clot lysis, and (3) no significant depletion of fibrinogen or plas-minogen. Nearly complete dissolution of the thrombus was observed. His bacteremia was eradicated by intravenous penicillin despite the presence of the pacemaker lead. This case highlights the benefits of combined antibiotic and thrombolytic therapy and documents for the first time the response of the human hemostatic system to prolonged t-PA infusion and the plasma t-PA levels attained when thrombolytic therapy is administered in this manner. Prolonged courses of fibrinolytic agents may be a good alternative to surgical intervention in selected patients with infected, right-sided intracardiac thrombi. [source] | ||||||||||