Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations. (9th May 2015)

• Record Type: Journal Article
• Authors: Boylan, B.; Rice, A. S.; De Staercke, C.; Eyster, M. E.; Yaish, H. M.; Knoll, C. M.; Bean, C. J.; Miller, C. H.; the Hemophilia Inhibitor Research Study Investigators; Abshire, T. C.; Dunn, A.; Kempton, C. L.; Bockenstedt, P. L.; Brettler, D. B.; Di Paola, J. A.; Radhi, M.; Lentz, S. R.; Massey, G.; Barrett, J. C.; Neff, A. T.; Shapiro, A. D.; Tarantino, M.; Wicklund, B. M.; Manco‐Johnson, M. J.; Escobar, M. A.; Gill, J. C.; Leissinger, C.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 6(2015:Jun.)
• Page Start: 1036
• Page End: 1042
• Publication Date: 2015-05-09
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12902
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12902-abs-0001"> <title>Summary</title> <sec id="jth12902-sec-0001" sec-type="section"> <title>Background</title> <p>Hemophilia A (HA) is an X‐linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis.</p> </sec> <sec id="jth12902-sec-0002" sec-type="section"> <title>Objectives</title> <p>To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and <italic>VWF</italic> genotypes.</p> </sec> <sec id="jth12902-sec-0003" sec-type="section"> <title>Patients/Methods</title> <p>Thirty‐seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable <italic>F8</italic> mutations. These patients (cases) and 73 patients with identified <italic>F8</italic> mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and <italic>VWF</italic> sequence.</p> </sec> <sec id="jth12902-sec-0004" sec-type="section"> <title>Results</title> <p>Four cases had VWF:Ag < 3 IU dL<sup>−1</sup> and <italic>VWF</italic> mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (<italic>n</italic> = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (<italic>n</italic> = 1 case). One control had VWF:Ag < 30 IU dL<sup>−1</sup> and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB.</p> </sec> <sec id="jth12902-sec-0005" sec-type="section"> <title>Conclusions</title> <p>These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy.</p> </sec> </abstract>