Trębacz Oksana, Szafarz Katarzyna, Zdziarska Joanna, Podlewski Jacek, Weryński Piotr, Tarała Wojciech, Iwaniec Teresa
Department of Pediatrics and Pediatric Gastroenterology with Pediatric Cardiology Subdivision, St. Jadwiga the Queen Clinical Regional Hospital No. 2, Rzeszow, Poland.
Department of Neurobiology, Maj Institute of Pharmacology Polish Academy of Science, Krakow, Poland.
Res Pract Thromb Haemost. 2025 Aug 7;9(5):102995. doi: 10.1016/j.rpth.2025.102995. eCollection 2025 Jul.
Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder due to a deficiency of von Willebrand factor (VWF). High shear stress causes stretching and rupture of VWF multimers, leading to functional loss and increased proteolysis. This occurs in cardiovascular diseases, reducing high-molecular-weight multimers (HMWMs). Patent ductus arteriosus (PDA) and ventricular septal defect (VSD) cause blood shunting between systemic and pulmonary circulation, increasing shear stress, and may contribute to AVWS.
To investigate whether children with PDA and VSD experience disturbances in platelet-related activity that cause HMWM loss and an AVWS-like phenotype.
The study involved 54 children with PDA and VSD. Patients who met the screening criteria, including a ristocetin cofactor activity to VWF antigen ratio (VWF:RCo/VWF:Ag) and/or collagen binding to VWF:Ag ratio (VWF:CB/VWF:Ag) <0.8, underwent VWF multimer analysis, and the VWF large multimer index (VWF-LMI) was calculated.
Of the 54 patients, 26 (48.1%) underwent multimer analysis, and an AVWS-like phenotype was found in 13 (24.1%). These patients had significantly lower percentage of HMWMs and lower VWF-LMI (27.3 ± 2.9% vs 38.8 ± 5.5% and 75.5 ± 7.3 vs 108.1 ± 14.7, respectively, < .001). A VWF-LMI <0.8 effectively predicted an AVWS-like phenotype with a sensitivity of 1.0 and a specificity of 0.87, followed by the VWF:CB/VWF:Ag ratio, with a sensitivity of 0.57 and specificity of 0.80 at the same threshold.
Nearly a quarter (25%) of children with VSD and PDA exhibit an AVWS-like phenotype. In addition to, VWF multimer analysis and VWF-LMI assessment, the VWF: CB/VWF:Ag ratio is suitable for screening in this group.
获得性血管性血友病综合征（AVWS）是一种由于血管性血友病因子（VWF）缺乏引起的罕见出血性疾病。高剪切应力导致VWF多聚体伸展和断裂，导致功能丧失和蛋白水解增加。这在心血管疾病中发生，导致高分子量多聚体（HMWMs）减少。动脉导管未闭（PDA）和室间隔缺损（VSD）导致体循环和肺循环之间的血液分流，增加剪切应力，可能导致AVWS。
研究患有PDA和VSD的儿童是否经历血小板相关活性紊乱，从而导致HMWM丢失和类似AVWS的表型。
该研究纳入了54例患有PDA和VSD的儿童。符合筛查标准的患者，包括瑞斯托霉素辅因子活性与VWF抗原比值（VWF:RCo/VWF:Ag）和/或胶原蛋白与VWF:Ag比值（VWF:CB/VWF:Ag）<0.8，进行VWF多聚体分析，并计算VWF大多聚体指数（VWF-LMI）。
54例患者中，26例（48.1%）进行了多聚体分析，13例（24.1%）发现了类似AVWS的表型。这些患者的HMWMs百分比和VWF-LMI显著降低（分别为27.3±2.9%对38.8±5.5%和75.5±7.3对108.1±14.7，P<0.001）。VWF-LMI<0.8有效地预测了类似AVWS的表型，敏感性为1.0，特异性为0.87，其次是VWF:CB/VWF:Ag比值，在相同阈值下敏感性为0.57，特异性为0.80。
近四分之一（25%）患有VSD和PDA的儿童表现出类似AVWS的表型。除了VWF多聚体分析和VWF-LMI评估外，VWF:CB/VWF:Ag比值适用于该组的筛查。
