Thrombosis research
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Combined oral contraceptives (COC) are the most popular contraceptive method in developed countries. Since their introduction there have been numerous changes and modifications in its composition with the aim to improve safety and tolerability while maintaining contraceptive efficacy. ⋯ One of the adverse effects of COC is the increased risk of venous thromboembolism (VTE) in two clinical forms of presentation: deep vein thrombosis or pulmonary embolism. This review details the changes in haemostasis induced by progestin-only contraceptives and the risk of VTE in women who utilize this type of contraception; the relationship with other risk factors such as thrombophilia; the interactions of these contraceptives with anticoagulant treatment and finally the eligibility criteria for the use of hormonal contraception in women with previous VTE or thrombophilia carriers.
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Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. ⋯ This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.
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Bleeds in hemophilia are treated either on demand or prophylactically by intravenous replacement therapy with FVIII or FIX. However, there is a call for subcutaneous and less frequent drug administration, and this need may be met by administration of a suitable antibody. Pioneering studies in vitro] and in a rabbit hemophilia model suggest that blockage of tissue factor pathway inhibitor (TFPI) provides a potential alternative approach to current therapy of hemophilia patients. ⋯ Blockage of TFPI with various antagonists has been shown to effectively enhance FX activation by TF/FVIIa and improve clot formation in hemophilia blood and plasma. The monoclonal antibody, mAb 2021, is one such antagonist directed towards the Kunitz-type protease inhibitor (KPI) 2 domain of TFPI which is now being tested in preclinical and clinical trials. Using mAb 2021, we have confirmed the original findings, and further characterized the pro-haemostatic effect of this specific anti-KPI-2 mAb in preclinical studies.