Pöschl Johannes, Behnisch Wolfgang, Beedgen Bernd, Kuss Navina
Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Children's Hospital, Heidelberg, Germany.
Front Pediatr. 2021 Sep 28;9:591052. doi: 10.3389/fped.2021.591052. eCollection 2021.
Homozygous/compound heterozygous forms of congenital protein C deficiency are often associated with severe antenatal and postnatal thrombotic or hemorrhagic complications. Protein C deficiency frequently leads to severe adverse outcomes like blindness and neurodevelopmental delay in children and may even lead to death. The most widely used long-term postnatal treatment consists of oral anticoagulation with vitamin K antagonists (e.g., warfarin), which is supplemented with protein C concentrate in acute phases. Subcutaneous infusions have been described in infants mostly from 2 months of age after severe postnatal thrombosis, but not in newborns or premature infants without thromboembolism. We report the first case of a compound heterozygous protein C-deficient preterm infant, born at 31+5 weeks of gestation to parents with heterozygous protein C deficiency (protein C activity 0.9% at birth). We focus on both prenatal and perinatal management including antithrombotic treatment during pregnancy, the cesarean section, and continuous postnatal intravenous and consecutive subcutaneous therapy with protein C concentrate followed by a change of therapy to direct oral anticoagulants (DOACs) (apixaban). We report successful home treatment with subcutaneous protein C concentrate substitution overnight (target protein C activity >25%) without complication up to 12.5 years of age. We propose that early planned cesarean section at 32 or preferably 34 weeks of gestation limits potential maternal side effects of anticoagulation with vitamin K antagonists and reduces fetal thromboembolic complications during late pregnancy. Intravenously administered protein C and early switch to subcutaneous infusions (reaching about 3 kg body weight) resulted in sufficient protein C activity and has guaranteed an excellent quality of life without any history of thrombosis for 13 years now. In older children with protein C deficiency, as in our case, DOACs could be a new therapeutic option.
先天性蛋白C缺乏的纯合子/复合杂合子形式常与严重的产前和产后血栓形成或出血并发症相关。蛋白C缺乏常导致严重不良后果，如儿童失明和神经发育迟缓，甚至可能导致死亡。最广泛使用的产后长期治疗包括用维生素K拮抗剂（如华法林）进行口服抗凝，在急性期补充蛋白C浓缩物。皮下输注主要用于出生后严重血栓形成的2个月龄以上婴儿，但未用于无血栓栓塞的新生儿或早产儿。我们报告了首例复合杂合子蛋白C缺乏的早产儿病例，该婴儿在妊娠31 + 5周时出生，其父母为杂合子蛋白C缺乏（出生时蛋白C活性为0.9%）。我们重点关注产前和围产期管理，包括孕期的抗血栓治疗、剖宫产、产后持续静脉注射和随后连续皮下注射蛋白C浓缩物，之后改为直接口服抗凝剂（DOACs）（阿哌沙班）治疗。我们报告了皮下蛋白C浓缩物替代过夜的成功家庭治疗（目标蛋白C活性>25%），直至12.5岁均无并发症。我们建议在妊娠32周或最好34周时进行早期计划性剖宫产，可限制维生素K拮抗剂抗凝的潜在母体副作用，并减少妊娠晚期胎儿血栓栓塞并发症。静脉注射蛋白C并早期改为皮下输注（体重达到约3 kg时）可产生足够的蛋白C活性，并且至今已确保13年无任何血栓形成病史的优异生活质量。对于蛋白C缺乏的大龄儿童，如我们病例中的情况，DOACs可能是一种新的治疗选择。
