Samson Hennessy-Strahs1, Christian A Bermudez1, Michael A Acker1, Carlo R Bartoli2. 1. Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 2. Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: carlo.bartoli@uphs.upenn.edu.
Abstract
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 multimers were resolved with electrophoresis and immunoblotting, 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% (interquartile range, 50% to 73%), P < .0001). Bleeding occurred in 27 of 48 patients. Method 1 demonstrated significantly fewer VWF multimers in bleeders compared with nonbleeders (-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 nonbleeders. Adoption of consensus methodology will assist to standardize patient-specific bleeding risk, inform anticoagulation and antiplatelet therapy, and evaluate LVAD hemocompatibility.
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 multimers were resolved with electrophoresis and immunoblotting, 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% (interquartile range, 50% to 73%), P < .0001). Bleeding occurred in 27 of 48 patients. Method 1 demonstrated significantly fewer VWF multimers in bleeders compared with nonbleeders (-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 nonbleeders. Adoption of consensus methodology will assist to standardize patient-specific bleeding risk, inform anticoagulation and antiplatelet therapy, and evaluate LVAD hemocompatibility.