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      Pregnancy-associated thrombosis

      Hematology
      American Society of Hematology

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          Abstract

          The main reason for the increased risk of thromboembolism in pregnancy is hypercoagulability, which has likely evolved to protect women from the bleeding challenges of miscarriage and childbirth. Women are at a 4- to 5-fold increased risk of thromboembolism during pregnancy and the postpartum period compared with when they are not pregnant. Eighty percent of the thromboembolic events in pregnancy are venous, with an incidence of 0.49 to 1.72 per 1000 pregnancies. Risk factors include a history of thrombosis, inherited and acquired thrombophilia, maternal age greater than 35, certain medical conditions, and various complications of pregnancy and childbirth. Despite the increased risk of venous thromboembolism (VTE) during pregnancy and the postpartum period, most women do not require anticoagulation. Candidates include women with current VTE, a history of VTE, thrombophilia and a history of poor pregnancy outcome, or risk factors for postpartum VTE. The intensity of the anticoagulation will depend on the indication and the monitoring will depend on the intensity. At the time of delivery, anticoagulation should be manipulated to reduce the risk of bleeding complications while minimizing the risk of thrombosis. There are no large trials of anticoagulants in pregnancy, and recommendations are based on case series, extrapolations from nonpregnant patients and the opinion of experts. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women who have, or have had, VTE.

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          Most cited references37

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          Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy.

          To assess the safety and efficacy of low-molecular-weight heparins (LMWHs) for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy, a systematic review of studies to the end of 2003 was undertaken. Data on VTE recurrence and side effects were extracted and cumulative incidences of VTE and adverse effects calculated. Of 81 reports identified, 64 reporting 2777 pregnancies were included. In 15 studies (174 patients) the indication for LMWH was treatment of acute VTE, and in 61 studies (2603 pregnancies) it was thromboprophylaxis or adverse pregnancy outcome. There were no maternal deaths. VTE and arterial thrombosis (associated with anti-phospholipid syndrome) were reported in 0.86% (95% confidence interval [CI], 0.55%-1.28%) and 0.50% (95% CI, 0.28%-0.84%) of pregnancies, respectively. Significant bleeding, generally associated with primary obstetric causes, occurred in 1.98% (95% CI, 1.50%-2.57%), allergic skin reactions in 1.80% (95% CI, 1.34%-2.37%), heparin-induced thrombocytopenia in 0%, thrombocytopenia (unrelated to LMWH) in 0.11% (95% CI, 0.02%-0.32%), and osteoporotic fracture in 0.04% (95% CI, < 0.01%-0.20%) of pregnancies. Overall, live births were reported in 94.7% of pregnancies, including 85.4% in those receiving LMWH for recurrent pregnancy loss. LMWH is both safe and effective to prevent or treat VTE in pregnancy.
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            Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study.

            Venous thrombosis is one of the leading causes of maternal morbidity and mortality. In the MEGA study, we evaluated pregnancy and the postpartum period as risk factors for venous thrombosis in 285 patients and 857 control subjects. Between March 1999 and September 2004, consecutive patients with a first episode of venous thrombosis were included from six anticoagulation clinics. Partners of patients and a random digit dialing group were included as control subjects. Participants completed a questionnaire and DNA was collected. The risk of venous thrombosis was 5-fold (OR, 4.6; 95% CI, 2.7-7.8) increased during pregnancy and 60-fold (OR, 60.1; 95% CI, 26.5-135.9) increased during the first 3 months after delivery compared with non-pregnant women. A 14-fold increased risk of deep venous thrombosis of the leg was found compared with a 6-fold increased risk of pulmonary embolism. The risk was highest in the third trimester of pregnancy (OR, 8.8; 95% CI, 4.5-17.3) and during the first 6 weeks after delivery (OR, 84.0; 95% CI, 31.7-222.6). The risk of pregnancy-associated venous thrombosis was 52-fold increased in factor V Leiden carriers (OR, 52.2; 95% CI, 12.4-219.5) and 31-fold increased in carriers of the prothrombin 20210A mutation (OR, 30.7; 95% CI, 4.6-203.6) compared with non-pregnant women without the mutation. We found an increased risk of venous thrombosis during pregnancy and the postpartum period, with an especially high risk during the first 6 weeks postpartum. The risk of pregnancy-associated venous thrombosis was highly increased in carriers of factor V Leiden or the prothrombin 20210A mutation.
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              Thrombophilia in pregnancy: a systematic review.

              Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.
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                Author and article information

                Journal
                Hematology
                Hematology
                American Society of Hematology
                1520-4391
                1520-4383
                December 11 2009
                January 01 2009
                December 11 2009
                January 01 2009
                : 2009
                : 1
                : 277-285
                Article
                10.1182/asheducation-2009.1.277
                20008211
                5fd8447e-69f7-401c-a5a4-8d9002f18be3
                © 2009
                History

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