A Scoring System to Predict the Likelihood of Acquired Von Willebrand Syndrome (AVWS) in Patients with Cardiovascular Diseases
Authors: Duello Katherine M. , Colleen Thomas S , Chen Dong , Blackshear Joseph L 
Published: October 2019

Abstract
Abstract 3377

Background
Bleeding from AVWS may occur in aortic stenosis (AS), hypertrophic cardiomyopathy (HCM), mitral regurgitation (MR), and prosthetic valve dysfunction (PVD) due to loss of von Willebrand factor (VWF) high molecular weight multimers caused by shear stress. Traditional laboratory testing for AVWS, including VWF antigen (VWF:Ag) and ristocetin cofactor activity lack sensitivity in this setting, and VWF multimer analysis, a costly and time-consuming test, must be used for confirmative diagnosis. The goal of this study is to develop a clinical and laboratory approach to predict the likelihood of AVWS, and consequently obviate the need for multimer analysis.

Methods
160 patients with or without a bleeding history were prospectively enrolled with mild, moderate, or severe AS (n=65), HCM (n=32), MR (n=25), or with heart valve replacement (n=38). These patients were investigated at the time of clinically indicated echocardiography with VWF latex immunoturbidic activity (VWF:Ltx), VWF:Ag, (abnormal versus normal cutoff of VWF:Ltx/VWF:Ag is <0.80) platelet function analyzer 100 collagen ADP (PFA-CADP) and VWF multimer analysis. Single variable logistic regression analysis was performed to estimate clinical or laboratory variables that were strongly associated with the probability of abnormal multimers, including results of echocardiographic peak velocity and PFA-CADP. Associations with abnormal multimers were summarized with estimated relative risk (RR) and 95% CI. A scoring system was then created to evaluate the risk of abnormal multimers among cardiac patients.

Results
Overall, 50% of patients had abnormal multimers, indicating likely AVWS. The estimated probability of abnormal multimers showed a significant association between peak velocity, PFA-CADP and VWF:Lx/Ag (Table 1).
Logistic regression analysis using forward selection identified only peak velocity (p<0.001) and PFA-CADP (p=0.033) as the factors showing the strongest evidence of association with abnormal multimers. VWF:Lx/Ag was no longer significant after adjusting for these two variables. Estimated relative risk of abnormal multimers for values of peak velocity and PFA-CADP were then derived (Table 2).
From these relative risks a scoring algorithm was created in order to determine who should be screened for abnormal multimers. A value of 1 was subtracted from each relative risk and rounded to the nearest integer to obtain a score for peak velocity (<3 m/sec=0, 3.0–3.9 m/sec=3, 4.0–4.9 m/sec=5, >5.0 m/sec=7), and for PFA-CADP (≤120 sec=0, 121–180 sec=2, > 180 sec=3). The score from each of the two variables was added to obtain a total score ranging from 0 to 10. The risk score was categorized into four levels, which are 0, 2–3, 5–7, and 8–10, as shown in Table 3.

Conclusion
Both hemodynamic severity and PFA-CADP testing results could be incorporated into a scoring system to identify potential AVWS due to loss of HMWM in patients with various cardiovascular conditions. Further studies are needed to validate such a scoring system in a separate set of patients.

Disclosures:
No relevant conflicts of interest to declare.