Heterozygous inheritance of factor V Leiden is the most common heritable thrombophilia. Found in 3 to 15 percent of select European populations and 3 percent of African Americans, it is virtually absent in African blacks and Asians (Lockwood, 2012). One theory for its relatively high prevalence suggests that the heterozygous state may confer a survival advantage, possibly because of reduced bleeding with childbirth or trauma (MacCallum, 2014).
Women who are heterozygous for factor V Leiden account for approximately 40 percent of VTE cases during pregnancy. However, the actual risk among pregnant women who are heterozygous and who do not have a personal history or a irstdegree relative with a thrombotic episode before age 50 years is 5 to 12 events per 1000 gravidas (see Table 52-2). In contrast, this risk rises to at least 10 percent among pregnant women with a personal or family history. Pregnant women who are homozygous without a personal or family history have a 1-to 4-percent risk for VTE, whereas those with such a history have an approximately 17 -percent risk (American College of Obste tricians and Gynecologists, 2017c).
Diagnosis during pregnancy is performed by DNA analy sis for the mutant factor V gene. Bioassay is not used because of the normal resistance that develops after early pregnancy (Walker, 1997). Of note, activated protein C resistance can also be caused by anti phospholipid syndrome, which is described on page 1008 and also detailed in Chapter 59 (p. 1143).
To assess the prognostic signiicance of maternal factor V
Leiden mutation during pregnancy, Kjellberg and colleagues (2010) compared the outcomes of 491 carriers with those of 1055 controls. All three of the thromboembolic events occurred among the carriers. But, preterm birth rates, birthweights, or hypertensive complication rates did not difer between the two groups. In a prospective observational study of approximately 5000 women conducted by the Maternal-Fetal Medicine Units
Network, the heterozygous mutant gene incidence was 2.7 percent (Dizon-Townson, 2005). Of three pulmonary emboli and one deep-vein thrombosis cases-a rate of 0.8 per 1000 pregnancies-none were among these carriers. Moreover, in the heterozygous women, the risks of preeclampsia, placental abruption, fetal-growth restriction, or pregnancy loss were not elevated. he investigators concluded that universal prenatal screening for the Leiden mutation and prophylaxis for carriers without a prior VTE is not indicated.
his missense mutation in the prothrombin gene leads to excessive accumulation of prothrombin, which then may be converted to thrombin. Prothrombin levels are increased approximately 30 percent in heterozygotes and 70 percent in homozygotes (MacCallum, 2014). As with factor V Leiden, a personal or family history of VTE in a irst-degree relative before age 50 years raises the risk of VTE during pregnancy (see Table 52-2). For a heterozygous carrier with such a history, the risk exceeds 10 percent. Without such a history, heterozygous carriers of the mutation have less than a I-percent risk of VTE during pregnancy (American College of Obstetricians and Gynecologists, 2017 c).