Hereditary risk factors for thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium.
Venous thromboembolism (VTE) is a leading cause of maternal mortality. Few studies have evaluated the individual risk of gestational VTE associated with heritable thrombophilia, and current recommendations for antenatal thromboprophylaxis in women with severe thrombophilia such as homozygous factor V Leiden mutation (FVL) depend on a positive family history of VTE. To better stratify thromboprophylaxis in pregnancy, we aimed to estimate the individual probability (absolute risk) of gestational VTE associated with thrombophilia and to see whether these risk factors are independent of a family history of VTE in first-degree relatives. We studied 243 women with the first VTE during pregnancy and the puerperium and 243 age-matched normal women. Baseline incidence of VTE of 1:483 pregnancies in women ≥35 years and 1:741 deliveries in women <35 years was assumed, according to a recent population-based study. In women ≥35 years (<35 years), the individual probability of gestational VTE was as follows: 0.7% (0.5%) for heterozygousFVL; 3.4% (2.2%) for homozygousFVL; 0.6% (0.4%) for heterozygous prothrombin G20210A; 8.2% (5.5%) for compound heterozygotes forFVLand prothrombin G20210A; 9.0% (6.1%) for antithrombin deficiency; 1.1% (0.7%) for protein C deficiency; and 1.0% (0.7%) for protein S deficiency. These results were independent of a positive family history of VTE. We provide evidence that unselected women with these thrombophilias have an increased risk of gestational VTE independent of a positive family history of VTE. In contrast to current guidelines, these data suggest that women with high-risk thrombophilia should be considered for antenatal thromboprophylaxis regardless of family history of VTE.
Blutgerinnung Ulm, Ulm, Germany.|Department of Haemostasis, Haemotherapy and Transfusion Medicine, Heinrich Heine University Medical Centre, Düsseldorf, Germany.
Andrea
A
Gerhardt
Department of Haemostasis, Haemotherapy and Transfusion Medicine, Heinrich Heine University Medical Centre, Düsseldorf, Germany.
Rüdiger E
RE
Scharf
Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom; and.
Ian A
IA
Greer
Department of Haemostasis, Haemotherapy and Transfusion Medicine, Heinrich Heine University Medical Centre, Düsseldorf, Germany.|Institute for Laboratory Medicine, Blood Coagulation and Transfusion Medicine, Düsseldorf, Germany.
Rainer B
RB
Zotz
D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D049590:Postpartum Period / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence; D011336:Probability; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics*; D054556:Venous Thromboembolism / Q000235:genetics*; D055815:Young Adult