Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: Rapid onset and fast recovery.

BACKGROUND: Bleeding contributes to the high mortality of venovenous extracorporeal membrane oxygenation (vvECMO). The development of acquired von Willebrand syndrome (AVWS) has been identified as relevant pathology during ECMO. This study was performed to determine the onset of AVWS after implantation and the recovery of von Willebrand factor (VWF) parameters after explantation of ECMO in a large cohort of patients. METHODS: VWF parameters of 59 patients treated with vvECMO at a university ECMO center were obtained before ECMO implantation, during therapy, and after explantation. In a subgroup of patients, light transmission aggregometry of platelets and flow-cytometric quantification of platelet granule secretion were performed. RESULTS: All patients developed severe AVWS hours after implantation of vvECMO. After explantation, AVWS recovered within 3 hours in 60%, within 6 hours in 86%, and in all patients within 1 day. Aggregometry showed hypoaggregability of platelets after stimulation with ADP, ristocetin, collagen, and epinephrine. Flow-cytometric platelet analyses revealed severely reduced expression of CD62 and CD63. CONCLUSIONS: All patients during vvECMO support rapidly develop AVWS and platelet dysfunction, resulting in severe impairment of coagulation. After explantation, AVWS overwhelmingly recovers within hours, resulting in a hypercoagulative state. These findings augment the need for novel extracorporeal technologies with reduced shear stress, and shift the emphasis for intense anti-coagulation during ECMO instead to a time-point after explantation.

Early diagnosis of acquired von Willebrand Syndrome (AVWS) is elementary for clinical practice in patients treated with ECMO therapy.

AIMS: Acquired Von Willebrand syndrome (AVWS) is an acquired bleeding disorder that has been reported to aggravate bleeding complications in patients with ventricular assist devices or aortic stenosis. AVWS is characterized by the loss of the high-molecular-weight (HMW) multimers of Von Willebrand factor (VWF) with consequent impaired VWF binding to platelets and collagen. The aim of this study was to investigate the development of AVWS in patients treated with veno-venous ECMO (extracorporeal membrane oxygenation) support. METHODS: We examined the presence of AVWS in adult patients receiving ECMO support (n=18) and control subjects treated without ECMO support (n=18). The diagnosis of AVWS was made based on the ratio of collagen-binding capacity to VWF-antigen (VWF:CB/VWF:Ag) and a VWF multimeric analysis. In addition, bleeding episodes were monitored. RESULTS: All patients supported with ECMO developed AVWS. AVWS was identified in the early period after ECMO implantation, i.e. within 24 hours after ECMO implantation. In 17 patients, the VWF:CB/VWF:Ag ratio was significantly reduced and HMW multimers were severely missing, and 17 of the 18 patients developed bleeding complications and required transfusions of blood, FFP and/or platelet concentrates.In addition, nine patients without an ECMO device were investigated (prior to ECMO implantation: n=2, after ECMO explantation: n=7). CONCLUSIONS: In this study, all patients treated with ECMO support developed AVWS, and AVWS was detectable within 24 hours after ECMO implantation. However, the AVWS was reversible after ECMO explantation. Making an early diagnosis of AVWS and providing appropriate treatment may reduce the incidence of life-threatening bleeding.