The glycoprotein Ib M assay (GPIbM)/von Willebrand factor antigen (VWF:Ag) ratio can be used to reliably monitor infants with congenital heart disease (CHD) for acquired von Willebrand syndrome (VWS) during surgery, according to a study published in Blood.

Researchers conducted a single-center, prospective, observational study to investigate diagnostic tools of acquired VWS compared with multimer analysis as diagnostic criterion standard and to clarify the role of acquired VWS in intraoperative hemorrhage.

The team conducted blood sampling and echocardiographic assessment at a total of 4 time points before, during, and after surgery. They quantified postoperative bleeding by measuring chest tube secretion over the 24-hour period following surgery and evaluated different diagnostic methods for accuracy in predicting acquired VWS using receiver-operating characteristic curve analyses.

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The study included 65 newborns and infants (60% male and 40% female) scheduled for cardiac surgery at a tertiary referral center between March 2018 and July 2019. Patients had a median age of 46 days (interquartile range [IQR], 12-151) and body weight of 3.9 kg (IQR, 3.1-5.8).

The investigators found the GPIbM/VWF:Ag ratio was the best predictor of acquired VWS (area under the receiver-operating characteristic curve [AUC], 0.81; 95% confidence interval [CI], 0.75-0.86; P <.001), followed by VWF collagen binding assay/VWF:Ag ratio (AUC, 0.70; 95% CI, 0.63-0.77; P <.001) and peak systolic echocardiographic gradients (AUC, 0.69; 95% CI, 0.62-0.76; P <.001). They determined the optimal cutoff value for the GPIbM/VWF:Ag ratio was 0.83, providing a sensitivity of 73% and a specificity of 71%.

The team demonstrated that intraoperative high-molecular-weight multimer ratios were inversely correlated with cardiopulmonary bypass time (r = -0.57) and aortic cross-clamp time (r = -0.54), suggesting the procedure may trigger acquired VWS.

They reported that patients with intraoperative acquired VWS received significantly more fresh frozen plasma (59 vs 39 mL/kg; P =.016) and fibrinogen concentrate (92 vs 48 mg/kg;  P =.011) than those without the condition. The amounts of other administered blood components and chest closure times were not significantly different between those with and without acquired VWS.

“In summary, the results of this study reveal a significant incidence of [acquired] VWS among neonates and infants undergoing different types of surgical procedures for palliation or correction of [congenital heart diseases]. Because the VWF:GPIbM/VWF:Ag ratio appears to be suitable for intraoperative monitoring, it could be included in the routine intraoperative diagnostic work-up of complex neonatal surgery on [cardiopulmonary bypass],” concluded the researchers.

Limitations of the study included the difficulty quantifying intraoperative bleeding intensity and the use of a surrogate parameter, heterogeneity among patients due to different congenital heart defects and surgical procedures, the limited number of patients and inability to determine possible differences in intraoperative bleeding intensity according to acquired VWS status for standardized surgical procedures, and potential unknown confounders.


Icheva V, Ebert J, Budde U, et al. Perioperative diagnosis and impact of acquired von Willebrand syndrome in infants with congenital heart disease. Blood. 2023;141(1):102-110. doi:10.1182/blood.2022015699