Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identified main causes of inherited thrombophilia are deficiencies of antithrombin (AT), protein C, or protein S, resistance to activated protein C associated with Factor V Leiden mutation, mutant factor II, and inherited hyperhomocysteinemia. For women from symptomatic families, these defects may be associated with an increased risk of venous thrombosis during pregnancy and/or recurrent fetal loss. Inherited thrombophilia is common and appears to be a multigenic disorder. The thrombotic risk seems to be greatest for women who have AT deficiency or more than one thrombophilic defect. The abnormalities that are now recognized are only part of the genetic predisposition to thrombosis. When assessing thrombotic risk during pregnancy, acquired risk factors as well as genetic predisposition should be considered. Increasing age, obesity, immobility, and delivery by cesarean section are major acquired risk factors. Pregnancy should be planned as far as possible, and each patient should be managed individually. During pregnancy, heparin is the anticoagulant of choice, and treatment with warfarin should be avoided because of risks for the fetus. When patients receive long-term treatment with warfarin, pregnancy should be avoided or planned, and warfarin should be discontinued before conception or as soon as pregnancy is confirmed and before 6-weeks' gestation. For women who have AT deficiency, the incidence of thrombosis during pregnancy is between 20 and 40%. Adjusted-dose heparin throughout pregnancy is recommended, followed by warfarin for at least 3 months postpartum. For patients who have Factor V Leiden, mutant factor II, or a deficiency of protein C or protein S, treatment can be based on personal and family history. Thromboprophylaxis during late pregnancy and postpartum should be considered. Fetal loss may be increased for women with inherited thrombophilia. The risk appears to be greatest for women with AT deficiency and women with more than one thrombophilic defect. For women with recurrent fetal death and inherited thrombophilia, a number of case reports claim that prophylaxis with heparin during pregnancy has resulted in successful pregnancy.
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PMID:Inherited thrombophilia and pregnancy: the obstetric perspective. 984 Jun 92

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.
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PMID:Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women. 1243 Aug 99