Homozygous carriers of factor V Leiden have an approximately 80-fold increased 
risk of venous thrombosis. Also double heterozygous carriers of both the factor 
V Leiden and the prothrombin gene mutations are at high thrombotic risk. The 
magnitude of the risk of venous thrombosis in pregnant women with the two severe 
thrombophilic conditions has not been estimated so far. We performed a 
multicenter retrospective family study in women with homozygous factor V Leiden, 
double heterozygous factor V Leiden and the prothrombin gene mutation, and women 
with normal coagulation. Only relatives of index patients with thrombosis formed 
the study cohort. Fifteen homozygous and 39 double heterozygous women were 
compared to 182 women with normal coagulation. Venous thrombosis occurred in 3 
of 19, 2 of 50 and 1 of 221 pregnancies, respectively. One thrombotic episode 
occurred in the third trimester, the remaining 5 in the postpartum. The 
prevalence of venous thrombosis was 15.8% (95% CI 3.4-39.6) for homozygotes. 
4.0% (95% CI 0.5-13.7) for double heterozygotes and 0.5% for women with normal 
coagulation. The relative risk of pregnancy-related venous thrombosis was 41.3 
(95% CI 4.1-419.7) for homozygous and 9.2 (95% CI 0.8-103.2) for double 
heterozygous carriers. In conclusion, homozygous carriers of factor V Leiden 
and, to a lesser extent, double heterozygous carriers of factor V Leiden and of 
the prothrombin mutation have an increased risk of venous thrombosis during 
pregnancy, particularly high during the postpartum period. On the basis of these 
findings we recommend that these women receive anticoagulant prophylaxis at 
least in the postpartum, that should perhaps be extended to the whole pregnancy 
in homozygous carriers.