Abstract：
BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome.
METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396.
RESULTS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030).
CONCLUSIONS: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies.
BACKGROUND: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.
METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396.
RESULTS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030).
CONCLUSIONS: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies.
BACKGROUND: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.
摘要：
背景：对于患有抗磷脂综合征的妇女，没有关于妊娠和产后血栓性和严重出血并发症风险的前瞻性数据。我们旨在评估抗磷脂综合征孕妇前瞻性队列中的血栓形成和出血事件。
方法：这个多中心，prospective,在法国的76个中心进行了观察性研究.为了有资格参加这项研究，女性必须诊断出抗磷脂综合征;在2020年4月17日前受孕;持续妊娠已达到妊娠12周;并在妊娠18周前纳入研究.排除标准为活动性系统性红斑狼疮肾病,或者多胎妊娠.严重出血被定义为由于出血或侵入性手术而需要红细胞输血或产妇重症监护病房。定义为介入放射学或外科手术，控制出血.GR2研究已在ClinicalTrials.gov注册，NCT02450396。
结果：2014年5月26日至2020年4月17日期间，27个中心的168例妊娠符合研究纳入标准。168例女性中有89例(53%)有血栓形成病史。纳入时的中位期限为妊娠8周。168名女性中有16名（10%）（95CI5-15）有血栓形成（6名[4%]女性；95%CI1-8）或严重出血事件（12名[7%]女性；95%CI4-12）。研究期间没有死亡。血栓形成事件的主要危险因素是纳入时的狼疮抗凝阳性（6名血栓形成妇女中的6名[100％]与152名无血栓形成妇女中的78名[51％]；p=0·030）和胎盘功能不全（6名妇女中的4名[67％]与162名妇女中的28名[17％]；p=0·013）。严重出血事件的主要危险因素是预先存在的孕产妇高血压（12名妇女中有4名[33%]，156名妇女中有11名[7%]；p=0.014），纳入时的狼疮抗凝阳性（12名女性中的12[100％]对146名女性中的72[49％]；p<0·0001）和抗磷脂病史期间（12名女性中的12[100％]对156名女性中的104[67％]；p=0·019），三重抗磷脂抗体阳性（12名女性中有8名[67%]，147名女性中有36名[24%]；p=0·0040），胎盘功能不全（12名女性中有5名[42%]，156名女性中有27名[17%]；p=0·038），以及34周或更早的早产（11名妇女中有5名[45％]，145名妇女中有12名[8％]；p=0·0030）。
结论：尽管治疗遵循国际建议，一部分抗磷脂综合征女性出现了与妊娠相关的血栓性或严重出血并发症,最常见的是产后。狼疮抗凝和胎盘功能不全是这些危及生命的并发症的危险因素。这些并发症很难预防，但对产前与产前特征相关的知识应提高认识,并帮助医生管理这些高危妊娠.
背景：法国狼疮，法国安全协会，协会GougerotSjögren，法语国家协会，AFM-Telethon,法国内科和风湿病学会，科钦医院,法国卫生部,FOREUM,协会大奖赛VeroniqueRoualet,UCB。
方法：这个多中心，prospective,在法国的76个中心进行了观察性研究.为了有资格参加这项研究，女性必须诊断出抗磷脂综合征;在2020年4月17日前受孕;持续妊娠已达到妊娠12周;并在妊娠18周前纳入研究.排除标准为活动性系统性红斑狼疮肾病,或者多胎妊娠.严重出血被定义为由于出血或侵入性手术而需要红细胞输血或产妇重症监护病房。定义为介入放射学或外科手术，控制出血.GR2研究已在ClinicalTrials.gov注册，NCT02450396。
结果：2014年5月26日至2020年4月17日期间，27个中心的168例妊娠符合研究纳入标准。168例女性中有89例(53%)有血栓形成病史。纳入时的中位期限为妊娠8周。168名女性中有16名（10%）（95CI5-15）有血栓形成（6名[4%]女性；95%CI1-8）或严重出血事件（12名[7%]女性；95%CI4-12）。研究期间没有死亡。血栓形成事件的主要危险因素是纳入时的狼疮抗凝阳性（6名血栓形成妇女中的6名[100％]与152名无血栓形成妇女中的78名[51％]；p=0·030）和胎盘功能不全（6名妇女中的4名[67％]与162名妇女中的28名[17％]；p=0·013）。严重出血事件的主要危险因素是预先存在的孕产妇高血压（12名妇女中有4名[33%]，156名妇女中有11名[7%]；p=0.014），纳入时的狼疮抗凝阳性（12名女性中的12[100％]对146名女性中的72[49％]；p<0·0001）和抗磷脂病史期间（12名女性中的12[100％]对156名女性中的104[67％]；p=0·019），三重抗磷脂抗体阳性（12名女性中有8名[67%]，147名女性中有36名[24%]；p=0·0040），胎盘功能不全（12名女性中有5名[42%]，156名女性中有27名[17%]；p=0·038），以及34周或更早的早产（11名妇女中有5名[45％]，145名妇女中有12名[8％]；p=0·0030）。
结论：尽管治疗遵循国际建议，一部分抗磷脂综合征女性出现了与妊娠相关的血栓性或严重出血并发症,最常见的是产后。狼疮抗凝和胎盘功能不全是这些危及生命的并发症的危险因素。这些并发症很难预防，但对产前与产前特征相关的知识应提高认识,并帮助医生管理这些高危妊娠.
背景：法国狼疮，法国安全协会，协会GougerotSjögren，法语国家协会，AFM-Telethon,法国内科和风湿病学会，科钦医院,法国卫生部,FOREUM,协会大奖赛VeroniqueRoualet,UCB。
