Toward a Standard Practice to Quantify von Willebrand Factor Degradation During Left Ventricular Assist Device Support

Background. Continuous-flow left ventricular assist devices (LVADs) cause degradation of von Willebrand factor (VWF) multimers and bleeding. Multiple techniques exist to characterize VWF deficiency. However, a standard methodology has not been established in LVAD patients. Toward this goal, we evaluated 4 methods to quantify VWF multimers. Methods. We collected paired blood samples from patients (n = 48) before and after 1 week of LVAD support. After 652 +/- 59 days of support, patients were classified as bleeders (>= 1 bleeding episode) or nonbleeders. VWF mul- timers were resolved with electrophoresis and immuno-blotting, the gold-standard to evaluate VWF multimers. We evaluated 4 quantification methods. Results. Each method demonstrated significant VWF degradation during LVAD support vs a paired, pre-LVAD sample (method 1, VWF length: 48 of 48 patients, -10% +/- 1%, P < .0001; method 2, VWF density: 40 of 48, -34% (interquartile range, -46% to -8%), P < .0001; method 3, pre-LVAD to LVAD ratio: 46 of 48, 17 +/- 5: 10 +/- 1, P < .0001; method 4, LVAD/pre-LVAD index: 46 of 48, 57% (inter-quartile range, 50% to 73%), P < .0001). Bleeding occurred in 27 of 48 patients. Method 1 demonstrated significantly fewer VWF multimers in bleeders compared with non-bleeders (-11% +/- 1% vs -8% +/- 1%; P = .01). Other methods did not demonstrate this potentially important clinical relationship. Conclusions. A standardized methodology is needed to quantify VWF multimer degradation with mechanical circulatory support devices. Novel method 1 successfully quantified the patient-specific change in VWF multimer length during LVAD support and demonstrated a difference in VWF multimers between bleeders and non-bleeders. Adoption of consensus methodology will assist to standardize patient-specific bleeding risk, inform anticoagulation and antiplatelet therapy, and evaluate LVAD hemocompatibility. (C) 2021 by The Society of Thoracic Surgeons