Acquired von Willebrand syndrome in young children with congenital heart defects: focus on patent ductus arteriosus and ventricular septal defect

先天性心脏病患儿获得性血管性血友病:重点关注动脉导管未闭和室间隔缺损。

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Abstract

BACKGROUND: 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. OBJECTIVES: To investigate whether children with PDA and VSD experience disturbances in platelet-related activity that cause HMWM loss and an AVWS-like phenotype. METHODS: 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. RESULTS: 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, P < .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. CONCLUSION: 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.

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