Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation Patients: A Single Institution’s Experience*

Abstract

Objectives: 1) Describe the prevalence of acquired von Willebrand syndrome in pediatric patients undergoing extracorporeal membrane oxygenation deemed to be at increased risk for the disease in our institution, 2) discuss the challenges of testing for acquired von Willebrand syndrome diagnosis, 3) describe the characteristics of the patient population found to have acquired von Willebrand syndrome and their outcomes, and 4) discuss the potential implications of acquired von Willebrand syndrome on bleeding complications. Design: Retrospective chart review. Setting: PICU and cardiovascular ICU in a single institution. Patients: All PICU and cardiovascular ICU extracorporeal membrane oxygenation patients 0–18 years old who underwent screening for acquired von Willebrand syndrome between January 2014 and December 2016. Interventions: Humate P administration to a small subset of acquired von Willebrand syndrome positive subjects. Measurements and Main Results: Laboratory data of identified patients were analyzed. The diagnosis of acquired von Willebrand syndrome was made based on decreased ristocetin cofactor activity to von Willebrand factor antigen ratio and/or abnormal multimer analysis. Clinical data were extracted from the chart and through the Pediatric Extracorporeal Membrane Oxygenation Outcome Registry to describe the demographics, comorbidities, and outcomes of this patient population. In the 2 years, 29 patients had laboratory testing performed for surveillance and in cases of clinical bleeding. Of these, 23 (79%) were positive by criteria. No significant difference in mortality rate was found between patients with acquired von Willebrand syndrome versus without. We also did not find a significant difference in the blood product utilization or bleeding complications between patients with acquired von Willebrand syndrome versus without. Humate P was administered in 39% of patients (9/23) who were positive for acquired von Willebrand syndrome, but no significant difference was seen in blood product utilization or bleeding complications between acquired von Willebrand syndrome patients receiving Humate P versus those who did not. Conclusions: Acquired von Willebrand syndrome is a common but under recognized disorder in pediatric extracorporeal membrane oxygenation patients. The clinical implications of this disorder on bleeding and its potential treatments are still unclear.

Hemostasis in neonatal ECMO

“…Shear stress determines disruption of high molecular weight vWf multimers, causing the "acquired von Willebrand syndrome" (AVWS), which consists of a functional defect in vWf, associated with bleeding (12, 35,45,46). This condition is well described in patients with mechanical valves and ventricular assist devices (VADs) (47). However, literature on pediatric patients is scarce, despite evidence suggesting this phenomenon is common during ECMO (47,48).…”

“…This condition is well described in patients with mechanical valves and ventricular assist devices (VADs) (47). However, literature on pediatric patients is scarce, despite evidence suggesting this phenomenon is common during ECMO (47,48). Acquired von Willebrand syndrome might occur in 100% of the patients under ECMO support, and it is reversible at the weaning (47).…”

“…However, literature on pediatric patients is scarce, despite evidence suggesting this phenomenon is common during ECMO (47,48). Acquired von Willebrand syndrome might occur in 100% of the patients under ECMO support, and it is reversible at the weaning (47). Due to the pivotal role of highweight vWf multimers in neonatal primary hemostasis, AVWS might be more pronounced in newborns than adults as they counterbalance platelet hyporeactivity (46).…”

Pediatric Mechanical Circulatory Support: Pathophysiology of Pediatric Hemostasis and Available Options

“…Instead, cleavage and consumption of the HMWM bound to platelets and collagen can trigger acquired von Willebrand syndrome (AVWS) with potential risk for bleeding. There are few available studies suggesting that AVWS is a common and underdiagnosed clinical feature in pediatric MCS (17)(18)(19)(20). Optimization of VAD pump designs has been proven to improve hemocompatibility and lower adverse event occurrence.…”

More to Learn About Acquired Von Willebrand Syndrome

“…As they note, emerging data has highlighted the development of acquired von Willebrand syndrome (AVWS) in both adult and pediatric ECMO patients. [1][2][3][4] The loss of high molecular weight multimers (HMWM) secondary to shear stress from the extracorporeal circuit may lead to impaired platelet activation and therefore increase the risk of bleeding.…”