Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case‐series

Abstract

Essentials Bleeding complications during congenital heart disease surgery in neonatal age are very common. We report the perioperative incidence of acquired von Willebrand syndrome (aVWS) in 12 infants. aVWS was detected in 8 out of 12 neonates and infants intraoperatively after cardiopulmonary bypass. Ten patients received von Willebrand factor concentrate intraoperatively and tolerated it well. SUMMARY: Background Cardiac surgery of the newborn and infant with complex congenital heart disease (CHD) is associated with a high rate of intraoperative bleeding complications. CHD-related anatomic features such as valve stenoses or patent arterial ducts can lead to enhanced shear stress in the blood stream and thus cause acquired von Willebrand syndrome (aVWS). Objective To evaluate the intraoperative incidence and impact of aVWS after cardiopulmonary bypass (CPB) in neonates and infants with complex CHD. Patients/Methods We conducted a survey of patients aged < 12 months undergoing complex cardiac surgery in our tertiary referral center. Twelve patients, whose blood samples were analyzed for aVWS before CPB and immediately after discontinuation of CPB on a routine basis, were eligible for the analysis. von Willebrand factor antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen binding activity (VWF:CB), VWF:multimers and factor VIII activity (FVIII:C) were determined. Results aVWS was diagnosed by VWF multimer analysis in 10 out of 12 patients (83%) prior to surgery and intraoperatively at the end of CPB in 8 out of 12 patients (66%). Ten patients received VWF/FVIII concentrate intraoperatively as individual treatment attempts during uncontrolled bleeding. They tolerated it well without intraoperative thrombotic events. One patient suffered a transient postoperative cerebral sinuous vein thrombosis. Conclusions aVWS is of underestimated incidence in complex CHD surgery. These data may offer a new approach to reduce the risk of severe bleedings and to achieve hemostasis during high-risk pediatric cardiac surgery by tailoring the substitution with von Willebrand factor concentrate.

Patent ductus arteriosus generates neonatal hemolytic jaundice with thrombocytopenia in Upshaw-Schulman syndrome

“…A persisting PDA in a normal newborn may result in acquired von Willebrand syndrome caused by excessive ADAMTS13-induced proteolysis of von Willebrand factor (VWF) subunits under the high shear stress conditions in the PDA, which results in a loss of highmolecular-weight VWF multimers. 19,20 This mechanism of VWF degradation leading to acquired von Willebrand syndrome is similar to the more common situation in severe aortic stenosis termed Heyde syndrome. 21 A newborn with USS who lacks any ADAMTS13 activity will typically have a first bout of unusually large VWF-induced platelet clumping with resulting thrombocytopenia and microangiopathic hemolysis with jaundice, probably triggered by the initially open DA (Figure 1B).…”

“…Note that a newborn with normal ADAMTS13 activity and persisting PDA often develops acquired von Willebrand syndrome. 19,20 BUN, blood urea nitrogen; LDH, lactate dehydrogenase; UL-VWFMs, unusually large VWF multimers. cardiomegaly (cardiothoracic ratio of 0.62 on radiograph film) was documented.…”

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

“…AVWS is characterized by the loss of high molecular weight (HMW) von Willebrand factor (VWF) multimers. 19 The exact mechanism of AVWS is unknown, but one theory suggests that it may be because of mechanical and proteolytic loss of HMW VWF. 20 In lesions that result in high shear stress, such as severe aortic stenosis, there is increased cleavage of HMW multimers by VWF cleaving protease ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) and possible mechanical destruction of VWF itself.…”

“…The efficacy of desmopressin (1-desamino-8-d-arginine vasopressin [DDAVP]) is questionable in this situation. 19,20 There is some evidence to suggest that VWF concentrates may be beneficial; however, more studies are needed. 19,20…”

Is there a role for von Willebrand factor/factor VIII concentrate supplementation in complex congenital heart surgery?

“…Icheva et al . present an interesting study that adds a relevant piece of information to this already complex pattern, introducing acquired von Willebrand syndrome (aVWS) as a possible mechanism leading to perioperative bleeding in newborns and small infants undergoing complex heart surgery.…”