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

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.