Thrombosis research
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There is now compelling evidence that use of oral contraceptives and postmenopausal hormonal therapies containing various estrogens is associated with a weak, but clinically relevant risk of both arterial and venous thrombosis. The increased risk is related to type and dose of both estrogen and combined progestagen and mode of delivery. Treatment induces mainly subtle changes in individual components of the coagulation and fibrinolytic systems, but the overall effect is the induction of a prothrombotic phenotype. This brief review summarizes some of the mechanisms responsible the prothrombotic effects of such treatment.
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Thrombosis research · Dec 2012
ReviewSystematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter?
Prothrombin complex concentrates are used for rapid reversal of vitamin K antagonists in patients with bleeding or those requiring surgery or invasive procedures. Current guidelines suggest 4-factor products are preferred over 3-factor prothrombin complex concentrates. ⋯ More reliable correction of the international normalized ratio was seen with 4-factor compared to 3-factor prothrombin complex concentrates which may have clinical implications since 4-factor products are unavailable in some countries.
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Thrombosis research · Oct 2012
ReviewMicroparticles in vascular disorders: how tissue factor-exposing vesicles contribute to pathology and physiology.
Coagulation is initiated by tissue factor (TF). Coagulant TF is constitutively expressed by extravascular cells, but there is increasing evidence that TF can also be present within the blood, in particular during pathological conditions. ⋯ Remarkably, high levels of coagulant TF-exposing vesicles are present in other body fluids such as saliva and urine of healthy persons, suggesting that these vesicles play a physiological role. We postulate that the presence of TF-exposing vesicles in body fluids as saliva and urine provides an additional source of coagulant TF that promotes coagulation, thereby reducing blood loss and contributing to host defence by reducing the risk of microorganisms entering the "milieu intérieur".
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Orally active direct inhibitors of thrombin and factor Xa have now been approved for treatment or prevention of deep vein thrombosis,and stroke associated with atrial fibrillation. The factor Xa inhibitor, rivaroxaban, has shown promising results in the treatment of acute coronary syndrome but is not yet approved for that indication. ⋯ These agents have fewer drug interactions than warfarin, have a predictable clearance, and hence do not require monitoring. Patients with renal insufficiency have delayed clearance and hence may have elevated levels of the drug leading to increased risk of bleeding.
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Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. ⋯ Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.