Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Apr 2006
ReviewMechanism of action of factor VIIa in the treatment of coagulopathies.
Recombinant factor VIIa (rFVIIa) has been developed for treatment of bleeding in patients with hemophilia who have inhibitors against factor VIII (FVIII) or FIX, and has been found to induce hemostasis during major orthopedic surgery. The use of rFVIIa treatment for hemophilia is a new concept and is based on the low-affinity binding of FVIIa to the surface of thrombin-activated platelets. Administration of pharmacologic doses of exogenous rFVIIa enhances thrombin generation on the platelet surface at the site of injury independently of the presence of FVIII or FIX. ⋯ A tight fibrin plug will aid in resisting the overwhelming local release of fibrinolytic activity triggered by vast tissue damage occurring in extensive trauma. Local fibrinolytic activity also occurs in the gastrointestinal tract as well as during profuse postpartum bleeding. Pharmacologic doses of rFVIIa induce hemostasis in these cases also.
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In the pathogenesis of vascular disease, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. ⋯ Simultaneously, TF may bind to cellular receptors, which may affect the production and release of inflammatory mediators. There is increasing experimental evidence that TF inhibition may have beneficial effects in disease states in which the combination of coagulation and inflammation plays a prominent role.
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Semin. Thromb. Hemost. · Nov 2005
ReviewWorld Federation of Haemophilia programs in developing countries.
The World Federation of Haemophilia (WFH) is a global not-for-profit organization devoted to furthering the treatment of hemophilia and related disorders. Founded in Montreal in 1963, it has grown tremendously during the last 40 years and now has 107 National Member Organizations and has been recognized by the World Health Organization. The mission of the WFH is to introduce, improve, and maintain care for patients with hemophilia and related disorders. ⋯ The WHF launched the Global Alliance for Progress in its 40th anniversary year, establishing a partnership between the WFH and other stakeholders, including the pharmaceutical industry. The aim is to focus on 30 to 40 developing countries during the next 10 years, aiming to more than double the number of patients diagnosed with hemophilia in those countries. The WFH is also involved in fostering discussion on key issues such as safety and supply of blood products.
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Semin. Thromb. Hemost. · Apr 2005
Review Comparative StudyClopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis.
Ticlopidine and clopidogrel belong to the same chemical family of thienopyridine adenosine diphosphate (ADP)-receptor antagonists. They have shown their efficacy as platelet antiaggregant and antithrombotic agents in many animal models, both ex vivo and in vivo. Although ticlopidine was discovered more than 30 years ago, it was only recently that the mechanism of action of ADP-receptor antagonists was characterized in detail. ⋯ The clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial showed a sustained, incremental benefit when clopidogrel was added to standard therapy (including ASA) in patients with unstable angina and non-Q-wave MI. The clopidogrel for the reduction of events during observation (CREDO) trial demonstrated the benefit of continuing clopidogrel (plus ASA) for 12 months, as opposed to 1 month, after percutaneous coronary intervention. The proven efficacy of clopidogrel, coupled with its favorable safety and tolerability profile, has prompted its evaluation in an extensive, ongoing clinical trial program that will help to further characterize the benefit of clopidogrel in patients with a range of atherothrombotic profiles.
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Women experience increased thrombotic risk at pregnancy and puerperium as well as during hormonal therapy with oral contraceptives or hormone replacement therapy. Physiological and anatomical changes in pregnancy contribute to the hypercoagulable situation. ⋯ Children are at increased thrombotic risk, particularly at the neonatal period, and may express thrombosis often in association with thrombophilia. This article will focuses on the clinical association, pathogenesis, and treatment of thrombophilia-related issues in women and children.