Abstract Number: PB0930
Meeting: ISTH 2021 Congress
Background: Interaction of VWF with collagen at sites of vascular injury supports initial platelet tethering. Defective collagen-binding may increase the bleeding risk in type 1 VWD and is a mechanism of type 2M VWD. The VWF A3 domain interacts with collagens I and III while the A1 interacts with collagens IV and VI.
Aims: Describe a single Center’s experience in diagnosis of VWF collagen IV binding defect.
Methods: Retrospective record review of a 56 y/o Caucasian female with presumptive clinical diagnosis of “Ehlers Danlos Syndrome Classic type” with history of excessive bruising, heavy menstrual bleeding, and post-operative bleeding that required RBC transfusion, suggesting additional bleeding risk factors.
Results: Testing of primary, secondary and fibrinolytic system were without evidence of abnormalities. VWF antigen, platelet-binding and multimers, as well as Factor I – XIII, platelet aggregation studies, and flow cytometry for platelets and thromboelastography (ROTEM) were within normal limits. Comprehensive bleeding disorder genetic analysis (51 genes) identified heterozygosity VWF c.4196G>A (p. Arg1399His). Subsequent VWF collagen binding profile showed decreased VWF collagen IV binding activity, with reduction of the collagen IV binding activity to VWF antigen ratio (0.58, reference interval 0.77-1.27). VWF collagen III binding, ratio of collagen III binding to VWF antigen and VWF multimers were all normal. VWF c.4196G>A (p. Arg1399His) has been shown through expression studies to have impaired binding to collagen type IV and association with a hemostatic defect in a mouse model (Slobodianuk 2019), potentially increasing bleeding score in patients with type 1 VWD (Flood 2016).
Conclusions: The interaction of VWF with collagen is physiologically important, but is uncommonly assessed in the evaluation of patients with excessive bleeding phenotype. Different VWF domains interact with collagen I/III versus collagen IV/VI. Although isolated collagen-binding defects are rare, such evaluation should be considered in patients with unexplained bleeding, as such defects may contribute to bleeding phenotype.
To cite this abstract in AMA style:Escobar M, Montanez N, Lemons J, Friedman K. Von Willebrand Factor (VWF) Collagen IV Binding Defect – A Potentially Overlooked Cause for Excessive Bleeding Phenotype [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/von-willebrand-factor-vwf-collagen-iv-binding-defect-a-potentially-overlooked-cause-for-excessive-bleeding-phenotype/. Accessed December 5, 2021.
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