High risk of pregnancy‐related venous thromboembolism in women with multiple thrombophilic defects

Abstract

SummaryPregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. This retrospective family cohort study assessed the risk of venous thromboembolism during pregnancy and puerperium, and the contribution of concomitant thrombophilic defects in families with hereditary antithrombin, protein C or protein S deficiencies. Probands were excluded. Of 222 female relatives, 101 were deficient and 121 nondeficient. Annual incidences of venous thromboembolism were 1AE76% in deficient women versus 0AE19% in non-deficient women [adjusted relative risk (RR) 11AE9; 95% confidence interval (CI), 3AE9-36AE2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1AE55% to 2AE14% and 2AE92%, and in non-deficient women from 0AE16% to 0AE09% and 0AE54% respectively. Deficient women were at lower risk (1AE37%; 0AE80-2AE19) than deficient women that had never been pregnant (2AE96%; 1AE53-5AE18); RR 0AE5 (0AE2-0AE99). This difference was due to the predominance of events related to oral contraceptives in deficient women that had never been pregnant (75%), while 71% of events in deficient women that had had at least one pregnancy were pregnancy-related. In conclusion, women with hereditary deficiencies of antithrombin, protein C or protein S are at high risk of pregnancy-related venous thromboembolism. This risk is increased by multiple additional thrombophilic defects.

VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy

“…Several observational studies have evaluated the risk of recurrent VTE with various treatment regimens [36][37][38]44,199,204,[208][209][210][211][212] (Table S18). Some of these studies stratifi ed patients according to their perceived risk of recurrence.…”

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

“…[12][13][14][15] As hyperhomocysteinemia is no longer considered an independent thrombophilic risk factor, 23,25 this defect was not taken into account, but these women were not excluded from our cohort.…”

“…12,13 We previously demonstrated that women with severe hereditary thrombophilic defects, that is, a deficiency of antithrombin, protein C, or protein S, are at very high risk during actual COC use, particularly when concomitant thrombophilic defects are present (4.6 per 100 pill-years), and the use of COCs should be strongly discouraged in these women. 14,15 As the absolute risk in women with mild thrombophilic defects is substantially lower than in women with severe thrombophilic defects, withholding COCs in women with mild hereditary thrombophilic defects might be less favorable. When discouraging COC use, an increased risk of unintended pregnancy must be taken into account as alternative nonhormonal contraception is less reliable.…”

“…Women were divided into those with no, single, or combined mild thrombophilic defects, as we recently demonstrated that aggregation of defects is often noted in thrombophilic families, and that especially the presence of multiple defects may significantly increase the absolute risk of VTE. [13][14][15] To put results into perspective, obtained absolute risks are compared with those during use of alternative contraception.…”

The evaluation of perinatal outcomes in pregnancies complicated with thrombophilias

“…Hiltunen ve ark. 'nın yaptığı preterm doğum FVL mutasyonu ilişkisinin araştırıldığı vaka kontrol çalışmasında 324 preterm doğum yapan hasta kontrol grubundaki 752 hasta ile karşılaştırıldığında FVL mutasyonu saptanan kadınlarda geç (>32 hafta) preterm doğum yapma oranı daha yüksek bulunmuştur (19) (OR: 2,9, %95 CI, 1,5-5,6). Resch ve ark.…”