A LinkedIn note by Shadi Tabibian, 2nd. Laboratory Hematologist and Director, Iranian Comprehensive Hemophilia Care Center; Deputy of Research, Blood Diseases Research Center, Iran University of Medical Sciences:
Can a “normal” VWF activity-to-antigen ratio rule out Type 2 von Willebrand disease? Not always. One of the most interesting diagnostic lessons from this recent review is the heterogeneity of Type 2M VWD. Some patients may have a normal VWF:GPIbB/VWF:Ag ratio (≥0.7) while still having a clinically relevant qualitative defect in VWF function—particularly involving collagen binding. In such cases, relying solely on the conventional screening panel may lead to a missed diagnosis. The addition of VWF collagen-binding (VWF:CB) testing can reveal abnormalities that would otherwise remain hidden and can help characterize different Type 2M phenotypes. A valuable reminder that in VWD diagnostics, “normal” does not always mean “excluded.” Sometimes, the diagnostic clue lies not in the absolute values—but in which function of VWF we actually measured.
Click here for a comprehensive discussion of VWD subtype 2M in the open-access review: Favaloro EJ, Pasalic L, Curnow J. 100 years of von Willebrand disease: the journey to contemporary diagnostic pathways–an illustrative case-based narrative review. Semin Thromb Hemost. 2026. doi: 10.1055/a-2834-5520. PMID: 41881049.
Review Abstract
von Willebrand disease (VWD) is the most commonly inherited bleeding disorder, with a prevalence surpassing hemophilia A. Unfortunately, VWD may be variously underdiagnosed, overdiagnosed, or misdiagnosed, depending on the expertise of the managing clinician and testing laboratories. Diagnostic challenges are due to the heterogeneity of VWD and the complexities surrounding laboratory assessment, including reactive influences on VWF levels. At least six types of VWD can be identified, with these classified according to the functional defect and/or level of deficiency in the plasma protein von Willebrand factor (VWF). The VWF protein has several functions, most of which can be assessed by laboratory testing; however, this increases the diagnostic complexity, and clinicians/laboratory staff may not understand the differences in these tests and what they assess. Thus, a battery of laboratory tests is required to enable an effective diagnosis or exclusion of VWD, as well as its type classification. VWD was first identified in a young female patient by Erik von Willebrand in 1924, with a seminal publication on his findings appearing in the literature in 1926. This year, 2026, represents 100 years of VWD. We review some of the history of VWD, as well as outlining the contemporary diagnostic pathway for VWD, assisted by several illustrative case examples.
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