Absolute risk of pregnancy-associated venous thromboembolism (VTE) varied depending on the type of thrombophilia among women with a family history of VTE, a systematic review and meta-analysis found.
While all thrombophilias increased the risk of pregnancy-associated VTE, those with the highest absolute risk were antithrombin deficiency, protein C deficiency, protein S deficiency and homozygous factor V Leiden, reported F. Nanne Croles, MD, of Erasmus University Medical Centre in the Netherlands, and colleagues.
But absolute risks of pregnancy-associated VTE were much lower for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations, the authors wrote in The BMJ.
They noted that the 2012 American College of Chest Physicians (ACCP) guidelines about absolute risk estimates of pregnancy-associated VTE in women with inherited thrombophilia “are based on a limited number of cohort studies” and an estimated baseline incidence of VTE multiplied by odds ratios found in prior research. But they added that “no systematic review or meta-analysis of absolute risk of pregnancy-associated VTE for women with thrombophilia has been published.”
Researchers examined 36 observational studies reporting on pregnancies without the use of anticoagulants, as well as the outcome of first VTE for women with thrombophilia. Venous thromboembolism was defined by the condition being “confirmed by objective means” or if the patient received “a full course of a full dose anticoagulant treatment without objective testing.”
Antithrombin deficiency had the highest absolute risk of both antepartum (7.3%, 95% CI 1.8%-15.6%) and post-partum (11.1%, 95% CI 3.7%-21.0%) pregnancy-associated VTE — albeit with wide confidence intervals. Thrombophilias with the smallest absolute combined risk (heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, and compound heterozygous factor V Leiden and prothrombin G20210A mutations) were all below 3%, the authors said.
Croles and colleagues noted that, compared against the ACCP guidelines, their meta-analysis found “markedly higher” absolute risk estimates for women with antithrombin and protein C deficiency (antepartum: 3.2%, 95% CI 0.6%-8.2%; postpartum: 5.4%, 0.9%-13.8%) and “more conservative” for protein S deficiency (antepartum 0.9%, 95% CI 0.0%-3.7%; postpartum: 4.2%, 95% CI 0.7%-9.4%).
They also noted that absolute risk estimates for heterozygous factor V Leiden and heterozygous prothrombin G20210A mutation “were lower compared with ACCP guidelines.”
Croles and colleagues concluded that while “further research for more precise estimates is needed,” women with antithrombin or protein C or protein S deficiencies and family history of venous thromboembolism, and all women with homozygous factor V Leiden mutation should be considered for routine thrombosis prophylaxis. But both the risk estimates and chosen thresholds for treatment do not support routine use of this treatment for women with heterozygous factor V Leiden or heterozygous prothrombin G20210A mutations or compound heterozygous factor V Leiden and prothrombin G20210A mutation, they added.
Croles disclosed no conflicts of interest.
Other co-authors disclosed support from Ferring Pharmaceuticals, Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Bayer Nederland, Pfizer Nederland, Baxter, Sanquin, Bristol-Myers Squibb, Uniqure, Shire, Novonordisk, CSL Behring, Baxalta (Shire) and Roche.