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

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 = 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.

[1]  N. Limdi,et al.  Valvular Heart Disease and Acquired Type 2A von Willebrand Syndrome: The "Hemostatic" Waring Blender Syndrome. , 2016, JAMA cardiology.

[2]  A. Undas,et al.  Increased bleeding risk in patients with aortic valvular stenosis: From new mechanisms to new therapies. , 2016, Thrombosis research.

[3]  P. Lenting,et al.  A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis , 2016, Thrombosis and Haemostasis.

[4]  J. Eikenboom,et al.  Platelet‐dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH , 2015, Journal of thrombosis and haemostasis : JTH.

[5]  O. Morel,et al.  Effects of transcutaneous aortic valve implantation on aortic valve disease-related hemostatic disorders involving von Willebrand factor. , 2015, The Canadian journal of cardiology.

[6]  K. Kuck,et al.  Treatment of acquired von Willebrand syndrome in aortic stenosis with transcatheter aortic valve replacement. , 2015, JACC. Cardiovascular interventions.

[7]  K. Tanabe,et al.  Impairment of platelet retention rate in patients with severe aortic valve stenosis. , 2013, Journal of cardiology.

[8]  Samin K. Sharma,et al.  Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with aortic stenosis undergoing valve replacement or balloon valvuloplasty , 2012, Thrombosis and Haemostasis.

[9]  G. Gerosa,et al.  von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding , 2011, Thrombosis and Haemostasis.

[10]  C. Solomon,et al.  Acquired type 2A von Willebrand syndrome caused by aortic valve disease corrects during valve surgery. , 2011, British journal of anaesthesia.

[11]  G. Golderer,et al.  Analysis of von Willebrand factor multimers by simultaneous high- and low-resolution vertical SDS-agarose gel electrophoresis and Cy5-labeled antibody high-sensitivity fluorescence detection. , 2010, American journal of clinical pathology.

[12]  A. Kaider,et al.  Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis , 2009, Thrombosis and Haemostasis.

[13]  P. Mannucci,et al.  Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor , 2006, Journal of thrombosis and haemostasis : JTH.

[14]  E. Lonn,et al.  Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. , 2003, Transfusion medicine reviews.

[15]  S. Susen,et al.  Acquired von Willebrand syndrome in aortic stenosis. , 2003, The New England journal of medicine.

[16]  R. Nagel,et al.  Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. , 1994, Blood.

[17]  J. Ware,et al.  Structure and Function of von Willebrand Factor , 1992, Thrombosis and Haemostasis.

[18]  H. Gralnick,et al.  In vitro correction of the abnormal multimeric structure of von Willebrand factor in type IIa von Willebrand's disease. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[19]  F. Hill,et al.  Analysis of the complexity of the multimeric structure of factor VIII related antigen/von Willebrand protein using a modified electrophoretic technique. , 1983, Journal of clinical pathology.

[20]  S. Rapaport.  Preoperative hemostatic evaluation: which tests, if any? , 1983, Blood.