Perioperative diagnosis and impact of acquired von Willebrand syndrome in infants with congenital heart disease

Abstract

AVWS (acquired von Willebrand syndrome) has been reported in patients with congenital heart diseases (CHD) associated with shear stress caused by significant blood flow gradients. Its etiology and impact on intraoperative bleeding during pediatric cardiac surgery have not been systematically studied. This single-center, prospective, observational study investigated appropriate diagnostic tools of aVWS compared to multimer analysis as diagnostic gold standard and aimed to clarify the role of aVWS in intraoperative hemorrhage. A total of 65 newborns and infants aged 0-12 months scheduled for cardiac surgery at our tertiary referral center during 03/18 to 07/19 were included in the analysis. The GPIbM/VWF:Ag ratio provided the best predictability of aVWS (area under the curve (AUC) 0.81[0.75-0.86]), followed by VWF:CB/VWF:Ag ratio (AUC 0.70[0.63-0.77]) and peak systolic echocardiographic gradients (AUC 0.69[0.62-0.76]). A cutoff value of 0.83 was proposed for the GPIbM/VWF:Ag ratio. Intraoperative high molecular weight multimer (HMWM) ratios were inversely correlated with cardiopulmonary bypass (CPB) time (r=-0.57) and aortic cross clamp (ACC) time (r=-0.54). Patients with intraoperative aVWS received significantly more fresh frozen plasma (FFP) (p=0.016) and fibrinogen concentrate (FIB) (p=0.011) compared to those without. The amounts of other administered blood components and chest closure times did not differ significantly. CPB appears to trigger aVWS in pediatric cardiac surgery. The GPIbM/VWF:Ag ratio is a reliable test that can be included in routine intraoperative laboratory workup. Our data provide the basis for further studies in larger patient cohorts to achieve definitive clarification of the effects of aVWS and its potential treatment on intraoperative bleeding.

Acquired von Willebrand Syndrome in a Patient Undergoing Extracorporeal Membrane Oxygenation: A Case Report

“…Some assays use ristocetin to trigger vWF-GPIb (vWF:GPIbR) binding and others rely on the spontaneous binding of a gain-of-function recombinant GPIbα fragment that can bind to vWF in the absence of ristocetin (vWF:GPIbM). A recent study reported that measuring the vWF:GPIbM/vWF:Ag ratio is promising as it has a high positive predictive value [15].…”

Acquired von Willebrand syndrome is common in infants with systemic-to-pulmonary shunts: Retrospective case-series

“…Hunt et al described lower postoperative levels of ADAMTS13 in the perioperative period of neonates and infants with CHD ( 33 ), which should be taken into account when considering VWF concentrate supplementation. In this context, the introduction of additional routine laboratory parameters such as the VWF:GPIbM/VWF:Ag ratio is a promising possibility for a timely aVWS diagnosis in the perioperative course of paediatric CHD patients ( 34 ). In our opinion, implementation of methods for rapid aVWS detection is necessary and should be available in centers performing neonatal cardiac surgery and providing extracorporeal support.…”

The Role of the von Willebrand Factor Collagen-Binding Assay (VWF:CB) in the Diagnosis and Treatment of von Willebrand Disease (VWD) and Way Beyond: A Comprehensive 36-Year History

“…Kalbhenn et al 318 included the VWF:CB in their study of COVID-19 patients. Icheva et al 319 included the VWF:CB in their study of AVWS in infants with congenital heart disease. Van Den Helm et al 320 included the VWF:CB in their study on pediatric ECMO, reporting changes in VWF multimers, VWF:Ag, and activity; in summary, VWF:Ag increased and HMWM, VWF:RCo/Ag, and VWF:CB/Ag ratios all decreased while patients were on ECMO, compared with baseline pre-ECMO samples and healthy children.…”