Seminars in vascular medicine
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The number of patients anticoagulated with warfarin has rapidly increased over the last decade. Approximately 1% of these patients experience serious bleeding and 0.5% die annually from bleeding. ⋯ For life-threatening bleeding, the use of clotting factor concentrates is essential for immediate anticoagulation reversal, whereas for less severe bleeding intravenous vitamin K is the treatment of choice. Vitamin K (by the intravenous or oral route) should also be used in overanticoagulated patients who are not actively bleeding but who are at high risk of doing so if their anticoagulation is not, at least partially, corrected.
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Progressive atherosclerosis followed by plaque rupture is the leading cause of acute cardiovascular events. Inhibition of platelet aggregation by acetylsalicylic acid (aspirin) reduces recurrent cardiovascular events in secondary prevention trials. By extracting data from available randomized trials that examined aspirin prevention in persons without previously known cardiovascular disease, we evaluated the use of aspirin as a primary prevention measure. ⋯ In healthy men above 45 years of age, men with an increased cardiovascular risk profile, and persons with diabetes mellitus or hypertension, the use of aspirin reduces the incidence of myocardial infarction and has a neutral effect on cerebrovascular events. The protective effect of aspirin is apparently most prominent in those persons with an increased risk of manifest atherosclerotic vascular disease. Notwithstanding these results, for each patient it remains essential to balance the cardiovascular risk profile against the small increased risk of bleeding complications when prescribing aspirin.
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This article focuses on the role of the tissue factor (TF)-thrombin pathway in cardiac ischemia-reperfusion (I/R) injury. We and others have used rabbit models of cardiac I/R injury to show that anti-TF therapy prevents the transient decrease in regional myocardial blood flow, reduces platelet and fibrin(ogen) accumulation, and reduces infarct size. At present, the mechanism by which TF-initiated coagulation contributes to myocardial injury is not established. ⋯ In contrast, inhibition of thrombin reduced infarct size to a similar extent as anti-TF therapy. We propose that the TF-thrombin pathway may contribute to myocardial injury by an additional mechanism that is not dependent on fibrin deposition but involves activation of protease activated receptor 1 (PAR-1) on vascular endothelial cells and cardiac myocytes. Anti-TF therapy would inhibit both thrombin-dependent fibrin deposition and thrombin-dependent PAR-1 signaling.
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Inherited thrombophilia has been reported to be associated with an increased risk for complications of pregnancy, including venous thromboembolism (VTE) as well as preeclampsia (PEC), fetal loss (FL), fetal growth retardation (FGR), and abruptio placentae (AP), the latter probably due to inadequate placental perfusion. The estimate of risk largely depends on the kind of thrombophilia and on the criteria applied for the selection of the patients, producing in some cases contradictory results. Convincing evidence is available that deficiency of antithrombin III (AT), protein C (PC), and protein S (PS) is a risk factor for VTE and late FL. ⋯ However, the absolute risk for VTE during pregnancy and puerperium is between 1 and 3%, in comparison with the baseline risk of 0.08%. Antithrombotic prophylaxis with subcutaneous heparin is warranted during puerperium in all women with thrombophilia and throughout all pregnancy in women at higher risk (AT deficiency, homozygosity for factor VLeiden, and perhaps PC and PS deficiencies); treatment with subcutaneous heparin for prevention of FL among women with thombophilia is under investigation. Presence of inherited thrombophilia increases the risk for VTE due to oral contraceptives up to an absolute risk of 3 per 1000 person-years, in comparison with the baseline risk of 3 to 6 per 10000 person-years; the risk is further increased by first usage, the use of preparations containing third-generation progestins, and thrombophilia due to AT, PC, and PS deficiency as well as homozygous factor V (Leiden) and combined defects.
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Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. ⋯ For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.