Primary Hemostasis Defect Due to Acquired Von Willebrand Disease and Platelet Activation During Extracorporeal Life Support. In Vitro Correction by Purified VWF

Abstract

<h3>Purpose</h3> Acquired von Willebrand disease (aVWD) is not uncommon during long-term mechanical circulatory support. However, its development during short-term support is unknown. We aim at investigating the development of aVWD in patients under extracorporeal life support (ECLS) and its potential treatment. <h3>Methods</h3> Patients who received ECLS in our center since June 2020 were included (25). Primary hemostasis was evaluated by: VWF antigen (VWF:Ag) and activity (VWF:GPIbM) measurement (immunoturbidimetry), VWF multimers analysis (agarose-gels and immunoblotting), platelet aggregation by ristocetin (turbidimetry), platelet functional analysis (PFA-200) -collagen/epinephrine (Col/EPI) and collagen/ADP (Col/ADP) cartridges-, and platelet activation (flow cytometry analysis of P-selectin and Lisosomal antigen). Studies were performed the day after implant and 3 days after explant. T-TAS was applied in bleeding patients, using samples before and after in vitro addition of purified VWF. <h3>Results</h3> At day 1 day after implant, all patients showed increased VWF:Ag. In 15 (60%) there was an altered ratio (<0.7) between VWF:GPIbM and VWF:Ag, with loss of VWF high molecular weight multimers (HMWM). In all cases, prolonged occlusion times at the PFA with both cartridges were observed. A significant increased expression of platelet-activation antigens was detected in 5 patients (11% and 24% for P-Selectin and Lysosomal antigen, respectively, vs. control platelets). In bleeding patients, addition of purified VWF to blood samples reduced significantly (p<0.05) the occlusion time (-384s) and increased the AUW (370%) at T-TAS. All patients that survived to explant (16) showed normalization of VWF:GPIbM/VWF:Ag ratio (>0.7) and multimers, with reduction of PFA-200 values. <h3>Conclusion</h3> ECLS caused primary hemostasis alterations, leading to aVWD and platelet activation, independently of platelet counts. Hemostatic efficiency in bleeding patients can be corrected by purified VWF, as derived from the in vitro evidence. The primary hemostasis alteration observed was solved early after support removal.