Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Jun 2009
Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management.
Rare bleeding disorders (RBDs) are autosomal recessive diseases including the inherited deficiencies of coagulation factors such as fibrinogen, factor (F) II, FV, FV + FVIII, FVII, FX, FXI, FXIII, and multiple deficiency of vitamin K-dependent factors, with clinical manifestations ranging from mild to severe. They represent 3 to 5% of all the inherited coagulation deficiencies with a prevalence in the general population varying between 1 in 500,000 and 1 in 2 million, being higher in areas where consanguineous marriages are diffuse. Despite the progress made in past years, as a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, the actual management of bleeding episodes and particularly the prophylactic treatment in patients affected with RBDs are not well established. In this introductory article, the main features, diagnosis, available treatment options, and treatment complications of RBDs will be discussed.
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Semin. Thromb. Hemost. · Feb 2009
ReviewGene therapy for hemophilia: clinical trials and technical tribulations.
As monogenic disorders, hemophilia A and B are compelling candidates for treatment with gene therapy. In hemophilia, a therapeutic benefit achieved by gene therapy should only require a modest increase in the endogenous factor level; response to treatment can be monitored easily; and there are relevant small and large animal models. ⋯ Various viral and nonviral vectors are discussed in the context of current hurdles arising from preclinical and clinical trials. Despite disappointing clinical results to date, there are favorable indications that the near future should deliver on the long-sought promise of a cure for hemophilia.
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Semin. Thromb. Hemost. · Nov 2008
ReviewDeterminants of bleeding risk in patients on antithrombotic and antifibrinolytic drugs.
The risk of bleeding associated with antithrombotic and fibrinolytic therapy depends on factors that are specific for the drugs and the patients. In this narrative review, we describe the most important risk factors for bleeding for each class of drugs. ⋯ Knowledge of these risk factors helps to weigh the risk and benefit in the selection of therapy in individual patients. Moreover, some risk factors can be modified or avoided if they are recognized.
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Semin. Thromb. Hemost. · Oct 2008
ReviewStandardization and clinical utility of thrombin-generation assays.
Thrombin generation is a key process that determines the extent of a hemostatic plug or a thrombotic process. The ensuing thrombin burst is crucial for the formation of a stable fibrin clot. During its active life, thrombin exerts a multitude of highly regulated actions on the blood and the vessel wall, including the clotting of fibrinogen. ⋯ Thrombin-generation assays not only provide an overall assessment of hemostasis but also target potential extrahemostatic effects of the generated thrombin, a potent agonist of a multitude of cellular activation pathways. Moreover, estimation of an individual's thrombin-generation potential may correlate more closely with a hypercoagulable or hypocoagulable phenotype when compared with traditional coagulation tests. In this review, we discuss to what extent thrombin generation can be expected to reflect the clotting function of blood, the development and use of different thrombin-generation assay systems suitable for detecting changes in the kinetics of thrombin generation, and the clinical utility of thrombin generation.
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Point-of-care (POC) testing in the field of hemostasis is rapidly expanding in many countries. This includes use of global tests of hemostasis in operating theaters and especially use of POC monitors for determination of the international normalized ratio (INR) for monitoring oral anticoagulant therapy. Issues related to internal quality control and external quality assessment for these devices are reviewed. Data from external quality assessment exercises involving users of several different POC-INR devices is described, and use of split samples where a patient sample is analyzed by both a POC device and by a conventional laboratory method is described.