Von Willebrand factor multimer quantitation for assessment of cardiac lesion severity and bleeding risk

Essentials VWF multimers have an established association with valvular heart disease. Significant interlaboratory variation exists in VWF multimeric analysis. We describe a method to normalize VWF multimers for assessment of cardiac lesion severity and clinical bleeding. Normalized VWF multimer ratios improved the diagnostic capabilities of the assay. Background: von Willebrand factor (VWF) multimer quantitation has been utilized in the assessment of valvular heart disease, however, there is no standardized method for quantitation. We compared three methods of assessment which utilized a normal plasma control. Methods: We analyzed 476 samples and their control plasma from 368 patients with valvular heart disease, hypertrophic cardiomyopathy, or LVAD therapy, and 27 normal subjects. VWF multimers were assessed as normalized VWF multimer ratios (NMR) of gel bands >15/2-15 (NMR15) or gel bands >10/2-10 (NMR10). Associations of VWF laboratory and multimeric assessments with cardiac lesion severity and acquired bleeding were investigated. Results: Abnormal multimers were present in 78% of patients with moderate to severe hemodynamic abnormalities compared to 19% of patients with normal or mildly abnormal hemodynamics. NMR showed strong association with severe cardiac lesions (NMR15: OR 15.29, CI 9.04-27.18; NMR10: OR 14.18, CI 8.88-23.21). PFA-CADP was strongly associated with moderate to severe cardiac lesions (OR 14.91, CI 9.08-24.50). PFA-CADP and NMR15 showed excellent ability to discriminate ≥moderate (AUC 0.86, CI 0.83-0.89 and 0.83, CI 0.79-0.87 respectively) and severe cardiac lesions (AUC 0.84, CI 0.81-0.88 and 0.85, CI 0.81-0.88 respectively). NMR was less strongly associated with bleeding (OR 4.01 for NMR10, CI 2.49-6.58). Conclusion: Quantification of VWF multimers may provide clinical utility in circumstances where clinical estimation of cardiac lesion severity is challenging, such as with dysfunctional prosthetic valves. The presence of abnormal VWF multimers is associated with bleeding, however further quantitation provided only modest improvement in risk stratification.