Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Br J Haematol. 2018 Oct;183(2):267-275. doi: 10.1111/bjh.15530. Epub 2018 Aug 23.
Acquired von Willebrand syndrome (AVWS) is reported in high-flow high-shear congenital cardiac disorders. We hypothesized that the narrowed pulmonary vasculature in idiopathic pulmonary arterial hypertension (IPAH) may induce AVWS. We conducted a cross-sectional evaluation of children with IPAH. Patients with bleeding symptoms and/or laboratory abnormalities (thrombocytopenia, anomalies in coagulation screening tests) were tested in-depth for haemostatic defects. Fourteen children were followed with IPAH of which 8 were eligible. Four children exhibited abnormal bleeding scores (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool: 3-5). All 8 patients showed very prolonged platelet function analyser (PFA)-100 closure times. Six children demonstrated either mild thrombocytopenia or low-normal von Willebrand factor (VWF) antigen (VWF:Ag) or VWF activity [mean (range), in iu/dl: VWF:Ag: 70 (61-91); VWF activity: 57 (34-70)]. Average VWF collagen binding capacity (VWF:CB) was 64 iu/dl (range: 53-123 iu/dl), with low-normal VWF activity/VWF:Ag or VWF:CB/VWF:Ag ratios occurring in five patients. All children had normal multimers distribution patterns. One patient underwent a lung transplantation, with normalization of haemostatic abnormalities post-surgery. Overall, 8 out of 14 children with IPAH had mild to moderate bleeding symptoms and/or laboratory abnormalities in keeping with AVWS. Normalization of the haemostatic defects following lung transplantation and lack of family history of bleeding attests to the acquired nature of their defects.
获得性血管性血友病综合征 (AVWS) 见于高流量高切变先天性心脏疾病。我们假设特发性肺动脉高压 (IPAH) 中狭窄的肺血管可能会引起 AVWS。我们对患有 IPAH 的儿童进行了横断面评估。有出血症状和/或实验室异常(血小板减少、凝血筛选试验异常)的患者进行了深入的止血缺陷检测。对 14 名患有 IPAH 的儿童进行了随访,其中 8 名符合条件。4 名儿童出现异常出血评分(国际血栓与止血学会出血评估工具:3-5)。所有 8 名患者的血小板功能分析仪 (PFA)-100 闭合时间均明显延长。6 名儿童表现为轻度血小板减少症或低正常血管性血友病因子 (VWF) 抗原(VWF:Ag)或 VWF 活性[平均值(范围),iu/dl:VWF:Ag:70(61-91);VWF 活性:57(34-70)]。平均 VWF 胶原结合能力 (VWF:CB) 为 64 iu/dl(范围:53-123 iu/dl),5 名患者的 VWF 活性/VWF:Ag 或 VWF:CB/VWF:Ag 比值较低。所有儿童的多聚体分布模式均正常。1 名患者接受了肺移植,术后止血异常正常化。总体而言,14 名 IPAH 儿童中有 8 名存在轻度至中度出血症状和/或实验室异常,符合 AVWS 的特征。肺移植后止血缺陷的正常化以及无家族出血史证实了其缺陷的获得性。