High Risk of Pregnancy Related Venous Thromboembolism in Women with a Hereditary Deficiency of Antithrombin, Protein C or Protein S in Concomitance of Other Thrombophilic Defects: A Retrospective Cohort Study.

Abstract

Venous thromboembolism (VTE)during pregnancy is still an important cause of maternal morbidity and mortality in the Western world. The risk VTE in pregnant women is five times higher than in non-pregnant women of the same age. This risk is increased by thrombophilic defects. In a family cohort study we assessed the risk of VTE during pregnancy/puerperium and the contribution of concomitant thrombophilic defects in women with hereditary antithrombin, protein C or protein S deficiencies.Women were recruited from a previous large family cohort study, which was designed to estimate the risk of VTE in first degree relatives from probands with documented VTE and a deficiency of antithrombin, protein C or protein S. Probands were excluded from analysis. Blood samples of female relatives were tested on the index deficiencies and prothrombin G20210A, factor V Leiden, hyperhomocysteinemia and increased levels of VIII:C, IX:C and XI:C. Observation time was defined as the fertile period (from age 15–45 years), or until the first VTE, or until end of study period.The cohort contained 222 female relatives, of whom 101 women were deficient and 121 non-deficient. The absolute risk of venous thromboembolism in deficient women was 1.76 per 100 person-years versus 0.19 per 100 person-years in non-deficient women (Relative Risk (RR) 9.2; 95% CI 3.8–26.7). Concomitance of none, one and more than one thrombophilic defect increased the risk in deficient (1.55, 2.14 and 2.92 per 100 person-years, respectively) and non-deficient women (0.16, 0.09 and 0.54 per 100 person -years, respectively). Annual incidences (AI) were lower in ever pregnant than never pregnant deficient women, 1.37 per 100 person-years versus 2.96 per 100 person-years (RR 0.5; 95% CI 0.2–0.99)(Table). These were 0.09 per 100 person-years versus 0.70 per 100 person-years in non-deficient women (RR 0.1; 95% CI 0.02–0.9). In ever pregnant deficient women 71% of VTE episodes were pregnancy related. A majority (75%) of never pregnant deficient women revealed VTE associated with oral contraceptives.Women with hereditary antithrombin, protein C or protein S deficiencies are at high risk of VTE. Concomitance of other thrombophilic defects increased this risk. In fertile women most episodes of VTE are associated with either pregnancy or oral contraceptives.DeficientNon-deficientEver pregnant (n=54)Never Pregnant (n=47)Ever pregnant (n=79)Never pregnant (n=42)Women with VTE, n171223Observation period, yr12414052169430AI, % (95% CI)1.37 (0.80–2.19)2.96 (1.53–5.18)0.09 (0.01–0.33)0.70 (0.14–2.04)RR (95% CI)0.5 (0.2–0.99) P=0.050.1 (0.02–0.9) P=0.04Pregnancy related VTE, n (%)12 (71)01 (50)0Oral contraceptive related VTE, n (%)2 (12)9 (75)03 (100)