Characterization of Von Willebrand Factor Multimer Structure in Patients With Severe Aortic Stenosis

Abstract

Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N ¼ 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used.

Differences in von Willebrand factor function in type 2A von Willebrand disease and left ventricular assist device‐induced acquired von Willebrand syndrome

“…As a consequence, VWF multimer analysis is the gold standard to detect aVWS in these patients 5, 19. Comparable findings were obtained for aortic stenosis patients, in which aVWS has also been frequently detected 20, 21. As multimer analysis is a time‐consuming technique, an ELISA‐based method was proposed as an alternative to detect VWF proteolysis 7.…”

“…5,19 Comparable findings were obtained for aortic stenosis patients, in which aVWS has also been frequently detected. 20,21 As multimer analysis is a time-consuming technique, an ELISA-based method was proposed as an alternative to detect VWF proteolysis. 7 We also determined if there was a correlation between the ratios of VWF parameters or the loss of HMW VWF multimers and the occurrence of bleeding, but no relationship was found.…”

Acquired Von Willebrand Deficiency in Adults With Aortic Stenosis: A Systematic Review

“…It concludes that AVWS in AS patients is not similar to those in Type 2A. Therefore, further studies are required to support the evidence and prevent misclassification [ 4 ].This study suggests against Type 2A, however, it still confirms the presence of Acquired Von Willebrand deficiency (AVWS).…”

“…However, Kellermair et al, in their study on 31 AS, argued that the multimeric pattern of Acquired Von Willebrand Syndrome (AVWS) in severe AS is not identical to that seen in acquired Von Willebrand syndrome (AVWS) type 2A or VWD type 2A. The article suggests that a lack of electrophoretic standardization and misclassifications contributed to this, and cites more extensive research and analysis for further conclusions [ 4 ].…”

“…When conformational changes occur in ultra-large VWF, they are cleaved by the enzymes [ 3 ]. High molecular weight multimer deficiency - caused by increased shear stress due to the stenosed valve - is believed to contribute to VWF deficiency in AS [ 4 ]. Due to conflicting evidence within previous literature and limited awareness amongst the general population and physicians, it is important to review the association between the above [ 5 ].…”