Gustavsen Alice, Skattum Lillemor, Bergseth Grethe, Lorentzen Bjorg, Floisand Yngvar, Bosnes Vidar, Mollnes Tom Eirik, Barratt-Due Andreas
Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Oslo, Norway. Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University and Clinical Immunology and Transfusion Medicine, Region Skane, Lund, Sweden Research Laboratory, Nordland Hospital Bodø, and K.G. Jebsen TREC, University of Tromsø Department of Obstetrics Department of Haematology Department of Immunology, Section of Medical Immunology, Oslo University Hospital, Oslo Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Medicine (Baltimore). 2017 Mar;96(11):e6338. doi: 10.1097/MD.0000000000006338.
Antiphospholipid syndrome (APS) in pregnancy may trigger the life-threatening catastrophic antiphospholipid syndrome (CAPS). Complement activation is implicated in the pathogenesis, and inhibition of complement factor C5 is suggested as an additional treatment option.
PATIENT CONCERNS, DIAGNOSIS AND INTERVENTIONS: We present a pregnant patient treated with the C5-inhibitor eculizumab due to high risk of developing devastating APS-related complications. The complement inhibitory effects of the treatment were examined both in the patient and the premature infant.
Complement activity in the mother recovered considerably faster than anticipated; however, no new thrombosis or CAPS developed during the last week of pregnancy or postpartum. Blood sampling from the umbilical vein and artery, and from the infant after delivery showed low complement activity; however, only 0.3% of the eculizumab concentration detected in the mother, consistent with low placental passage of eculizumab.
The data underscore the importance of close monitoring of complement inhibition and individualizing dosage regimens in pregnant patients receiving eculizumab. We document how traditional functional complement activity tests cannot assess the effect of eculizumab in premature infants due to the very low levels of complement factors detected in this infant born in gestational week 33. Only trace amounts of eculizumab passed the placenta. In conclusion, complement C5 inhibition might be a safe candidate treatment option for APS during pregnancy and delivery, and additionally, enables prolongation of pregnancy with important weeks.
妊娠期抗磷脂综合征(APS)可能引发危及生命的灾难性抗磷脂综合征(CAPS)。补体激活与发病机制有关,抑制补体因子C5被认为是一种额外的治疗选择。
患者情况、诊断与干预措施:我们报告了一名因有发生严重APS相关并发症的高风险而接受C5抑制剂依库珠单抗治疗的孕妇。对该患者及其早产儿的治疗的补体抑制作用进行了检测。
母亲体内的补体活性恢复速度比预期快得多;然而,在妊娠最后一周或产后未出现新的血栓形成或CAPS。从脐静脉和动脉以及分娩后的婴儿采集的血样显示补体活性较低;然而,婴儿体内检测到的依库珠单抗浓度仅为母亲体内的0.3%,这与依库珠单抗的胎盘通过率低一致。
这些数据强调了在接受依库珠单抗治疗的孕妇中密切监测补体抑制情况并个体化给药方案的重要性。我们记录了由于在孕33周出生的这名婴儿中检测到的补体因子水平极低,传统的功能性补体活性测试无法评估依库珠单抗对早产儿的效果。只有微量的依库珠单抗通过了胎盘。总之,补体C5抑制可能是妊娠期和分娩期APS的一种安全的候选治疗选择,此外,还能延长孕周。