BACKGROUND Inherited quantitative (type I) deficiency of plasma antithrombin is associated with a high risk of venous thromboembolism, which further increases in pregnancy. Inherited thrombophilia also increases the risk of obstetrical complications, but data on maternal and fetal outcomes in women with antithrombin deficiency are scarce. The aim of this study was to evaluate the risk of pregnancy-associated venous thromboembolism and obstetrical complications in women with type I antithrombin deficiency. METHODS In this single-centre, retrospective cohort study, women who had been referred to our Hemophilia and Thrombosis Centre, Milan, Italy for a thrombophilia work-up from Jan 1, 1980, to Jan 1, 2018, with type I antithrombin deficiency and who had had at least one pregnancy were included. Women with type II anthithrombin deficiency were excluded from the study. Data on pregnancy-associated venous thromboembolism, pregnancy outcomes, and the use of low-molecular-weight heparin (LMWH) were collected to evaluate the risk of pregnancy-associated venous thromboembolism and obstetrical complications with or without use of LMWH. FINDINGS 126 women had been referred to the hospital, of whom 88 (70%) had had at least one pregnancy. Eight were excluded because of referral for venous thromboembolism during pregnancy or the puerperium, resulting in 80 (63%)women evaluated for the risk of venous thromboembolism. One woman was excluded because of referral for obstetrical complications, resulting in 87 (69%) evaluated for risk of obstetrical complications. We observed three events of venous thromboembolism in 43 pregnancies in women treated with LMWH (7·0%, 95% CI 1·8-17·8), and 17 events in 146 pregnancies in women who did not receive LMWH (11·6%, 7·2-17·6; relative risk [RR] 0·6, 95% CI 0·2-1·9; p=0·57). The risk of venous thromboembolism without LMWH was 5·4% (95% CI 0·9-16·7) in women with a negative family history of venous thromboembolism, and 11·8% (6·4-19·6) in those with a positive family history of venous thromboembolism. Of the 87 women evaluated for the risk of obstetrical complications, miscarriages occurred in 6 (13%) of 45 pregnant women treated with LMWH and 32 (20%) of 161 women who did not receive LMWH (terminations excluded). Late obstetrical complications occurred in 11 (24%) of women treated with LMWH and nine (6%) in those who did not receive LMWH (RR 4·4, 95% CI 1·9-9·9; p=0·0006). INTERPRETATION Our results confirm that women with type I antithrombin deficiency have a high risk of first or recurrent venous thromboembolism during pregnancy. The risk of venous thromboembolism is highest in women with a positive family history of the condition, but still relevant in those with a negative family history, suggesting that LMWH prophylaxis should also be considered in these patients. FUNDING None.

中文翻译：

---

遗传性I型抗凝​​血酶缺乏症妇女妊娠相关静脉血栓栓塞和产科并发症的风险：一项回顾性单中心队列研究。

背景技术血浆抗凝血酶的遗传定量（I型）缺乏与静脉血栓栓塞的高风险相关，其在妊娠中进一步增加。遗传性血栓形成症也增加了产科并发症的风险，但是抗凝血酶缺乏症妇女的母婴结局数据却很少。这项研究的目的是评估I型抗凝血酶缺乏症妇女妊娠相关的静脉血栓栓塞和产科并发症的风险。方法在这项单中心，回顾性队列研究中，从1980年1月1日至2018年1月1日被转诊至意大利米兰血友病和血栓形成中心接受血友病检查的妇女，患有I型抗凝血酶缺乏症和包括至少一次怀孕的人。II型蒽蛋白缺乏的女性被排除在研究之外。收集有关妊娠相关静脉血栓栓塞，妊娠结局和使用低分子量肝素（LMWH）的数据，以评估是否使用LMWH的妊娠相关静脉血栓栓塞和产科并发症的风险。调查结果126名妇女被转诊到医院，其中88名（70％）至少有一次怀孕。由于在妊娠或产褥期转诊静脉血栓栓塞而排除了八名，因此对80名（63％）妇女进行了静脉血栓栓塞风险的评估。一名妇女因产科并发症转诊而被排除在外，导致有87名（69％）接受了产科并发症风险评估。我们在接受LMWH治疗的43例孕妇中观察到3例静脉血栓栓塞事件（7·0％，95％CI 1·8-17·8），而未接受LMWH的女性146例妊娠中有17例事件（11·6 ％，7·2-17·6；相对风险[RR] 0·6，95％CI 0·2-1·9； p = 0·57）。家族性静脉血栓栓塞史为阴性的女性，没有LMWH的静脉血栓栓塞的风险为5·4％（95％CI 0·9-16·7），而女性为11·8％（6·4-19·6）静脉血栓栓塞症家族史阳性的患者。在评估有产科并发症风险的87名妇女中，流产发生在45名接受LMWH治疗的孕妇中的6名（13％）和161名未接受LMWH治疗的妇女中的32名（20％）发生了流产（不包括终止治疗）。接受LMWH治疗的妇女中有11例（24％）发生晚期产科并发症，未接受LMWH的妇女中有9例（6％）发生（RR 4·4，95％CI 1·9-9·9；p = 0·0006）。解释我们的结果证实，患有I型抗凝血酶缺乏症的女性在怀孕期间发生首次或复发性静脉血栓栓塞的风险很高。家族病史阳性的女性发生静脉血栓栓塞的风险最高，但家族​​史阴性的女性仍具有相关性，这表明这些患者也应考虑预防LMWH。资金无。