Inherited thrombophilias: implications for pregnancy-associated venous thromboembolism and obstetric complications

Abstract

Pregnancy may unmask an unrecognized thrombophilia with the development of venous thromboembolism (VTE) or obstetric complications associated with placental insufficiency. The surge of interest in thrombophilias in pregnancy has led to a marked increase in screening despite considerable gaps in current knowledge and uncertainty as to the clinical implications. Currently, restraint should be exercised to avoid indiscriminate testing for inherited thrombophilias in the general obstetric population. Studies reporting the prevalence of underlying inherited thrombophilias in women with pregnancy-associated VTE are summarized. Among women with VTE, factor V Leiden was identified in 28.2% (pooled OR, 10.1; 95% CI, 6.6-15.7), prothrombin G20210A was identified in 18.1% (pooled OR, 11.4; 95% CI, 6.0-21.4), and MTHFR C677T was identified in 12.8% (pooled OR, 1.1; 95% CI, 0.7-1.7). Although inherited thrombophilias predispose to thrombus formation, many additional factors, such as a personal history of VTE, may be more important determinants of a future VTE. No large randomized trials exist on which to base thromboprophylaxis management in pregnancy. An approach to pregnancy thromboprophylaxis is proposed, which utilizes estimated risks of antepartum or postpartum VTE in each thrombophilia and is adjusted for personal history, family history, or no history of VTE. Acquired risk factors, such as caesarean section, should also be taken into consideration. The prevalence of each thrombophilia in women with recurrent early or late fetal losses, placental abruption, preeclampsia, and fetal growth restriction is summarized. Whether women with adverse obstetric outcomes should be screened for inherited thrombophilias depends on the type of complication and the specific thrombophilia. The significance of finding a thrombophilia following obstetric complications is largely unknown. Further research is required to determine whether the presence of a thrombophilia in this context modifies a woman's risk of recurrent obstetric complications or pregnancy-associated VTE and whether treatment improves her next pregnancy outcome.