Controversies in thromboembolic disease during pregnancy: a critical review

To critically appraise the body of literature concerning strategies for the prevention of thromboembolism during pregnancy.

We used the Medline data base and reference lists of articles to identify all English-language papers examining thromboembolism during pregnancy.

We identified 156 articles in the obstetric literature and 29 articles in the medical literature that referenced nonpregnant populations. Together, these articles form the primary data base on which most recommendations are based.

There are no level 1 trials (large randomized trials with definitive results) in the obstetric literature examining the efficacy of thromboembolism prophylaxis during pregnancy. There are only two level 2 trials (small randomized trials with uncertain results because of moderate to high alpha or beta error) that address prophylactic strategies in pregnant women with histories of thromboembolism or the antiphospholipid antibody syndrome. The remainder of the published trials are observational, some prospective but predominantly retrospective. Many of the recommendations from consensus panels regarding prophylactic strategies in pregnancy were based on level 1 trials in nonpregnant populations.

Although women with a history of thromboembolic disease are at appreciable risk of recurrence during pregnancy, the exact incidence is unknown and there are no adequate efficacy trials demonstrating that prophylactic regimens are effective. Heparin is the anticoagulant of choice in pregnancy; however, changes in metabolism and clearance make adequate dosing problematic. Expert consensus panels disagree over the optimal management of pregnant women at risk for thromboembolism. Randomized controlled trials during pregnancy are needed if any progress is to be made in combating this lethal disorder.