Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Oct 2009
ReviewParticulate air pollution and cardiovascular risk: short-term and long-term effects.
It is well known that exposure to particulate air pollutants is associated with the development of adverse health effects. In particular, there is growing evidence of a close relationship between increased levels of environmental pollutants and cardiovascular disease. ⋯ Several biological mechanisms have been suggested to explain the important effect of air pollution on cardiovascular morbidity and mortality, although the exact pathways are not fully understood. The literature data on the short-term and long-term cardiovascular effects of particulate air pollutants are discussed in this review from a clinical and mechanistic point of view.
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Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both (hypodysfibrinogenemia). Most often, patients with congenital fibrinogen disorders suffer from a bleeding diathesis but paradoxically may undergo severe thrombotic episodes. Pregnancy loss is another common clinical complication. ⋯ However, the phenotype-genotype correlation is not easy to establish, and global hemostasis assays may provide a better evaluation of the patient's hemostatic state. Replacement therapy is effective in treating bleeding episodes, but it is important to tailor individual treatments because the pharmacokinetics of fibrinogen after replacement therapy is highly variable among patients. Although the number of cases studied and identified mutations are already quite substantial, the collection and comparison of molecular, biochemical, and clinical data will continue to yield valuable information on the development and course of these diseases, as well as on the choice of the most appropriate treatments.
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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.