Seminars in thrombosis and hemostasis
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During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications in connection with delivery. The most important initial factor for acute hemostasis at delivery is, however, uterine muscle contractions, which interrupt blood flow. Global tests such as Sonoclot signature, the Thromboelastogram, and a new method analyzing overall plasma hemostasis, all show changes representative of hypercoagulability during pregnancy. ⋯ Platelet count and free protein S, however, can be abnormal longer. Hemostasis should not be tested earlier than 3 months following delivery and after terminating lactation to rule out influences of pregnancy. PAI-1 and PAI-2 levels decrease fast postpartum, but PAI 2 has been detected up to 8 weeks postpartum. alpha 2 -antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be increased 6 weeks postpartum.
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Semin. Thromb. Hemost. · Dec 2002
ReviewVenous thromboembolic risk and its prevention in hospitalized medical patients.
In medical patients, the risk of venous thromboembolism (VTE) is substantially underestimated and prophylaxis is used far less than in surgical patients, reflecting the scarcity of evidence supporting antithrombotic therapy in nonsurgical settings. However, current consensus documents recommend assessment of all medical, as well as surgical, patients for thromboembolic risk and provide prophylaxis recommendations according to the risk level, determined by the presence of different clinical and molecular risk factors. Although long-term, underlying clinical and molecular risk factors also have a major impact on overall risk in medical patients; risk clearly varies with the type of medical condition. ⋯ Emerging evidence has led to a grade 1A recommendation for the use of thromboprophylaxis in these patients in the most recent consensus conference on thromboprophylaxis. Further studies, however, are required to clarify the optimal duration of prophylaxis in medical patients and to evaluate the potential role of outpatient prophylaxis. Accurate risk assessment and prompt implementation of appropriate prophylaxis, selected on the basis of evidence from well-designed controlled clinical trials, may reduce the future morbidity and mortality due to VTE in medical patients.
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Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. ⋯ Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.
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Semin. Thromb. Hemost. · Dec 2001
ReviewAnticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.
Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also attenuate inflammatory responses during sepsis. Low circulating levels of AT and protein C have been associated with poor outcome. ⋯ Experience with AT and APC in patients is promising. Data from large phase III trials of AT and APC as treatment of patients with severe sepsis will soon be available. Recombinant TFPI is currently in phase II clinical trials for severe sepsis.
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Semin. Thromb. Hemost. · Dec 2001
ReviewAdvances in the understanding of the pathogenetic pathways of disseminated intravascular coagulation result in more insight in the clinical picture and better management strategies.
Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive and ongoing activation of coagulation may result in depletion of platelets and coagulation factors, which may cause bleeding (consumption coagulopathy). ⋯ The cornerstone of the management of DIC is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation and restoration of physiological anticoagulant pathways by means of the administration of (activated) protein C concentrate or antithrombin concentrate.