von Willebrand disease combined with other hemostasis disorders: an overlooked clinical entity

von Willebrand disease (VWD) is common, affecting ∼1% of the general population. Due to this relatively high prevalence, it can co-occur with other coagulation disorders. However, combined defects are often underrecognized in clinical practice. Diagnostic anchoring, overlapping symptoms, and limited access to comprehensive hemostatic and genetic testing contribute to these missed diagnoses. A growing number of case reports, case series, and cohort studies have documented the coinheritance of VWD with hemophilia A or B, rare coagulation factor deficiencies, and platelet function disorders. In some cohorts, up to one-third of cases with mild VWD had an additional hemostatic defect. Emerging genomic data also suggest that multiple low-frequency variants affecting hemostasis can co-occur in the same individual, particularly in populations with founder effects or high rates of consanguinity. Combined defects can alter bleeding severity, complicate diagnosis, and affect treatment decisions. Broader awareness and multidisciplinary evaluation are critical for addressing this underappreciated aspect of inherited bleeding disorders.

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Publication Details

Journal
Research and Practice in Thrombosis and Haemostasis
Published
2025-11-01
DOI
https://doi.org/10.1016/j.rpth.2025.103259
Primary Topic
Platelet Disorders and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

von Willebrand disease combined with other hemostasis disorders: an overlooked clinical entity

Omid Seidizadeh, Flora Peyvandi, Pier Mannuccio Mannucci
Research and Practice in Thrombosis and Haemostasis
Platelet Disorders and Treatments
article

von Willebrand disease combined with other hemostasis disorders: an overlooked clinical entity

Omid Seidizadeh, Flora Peyvandi, Pier Mannuccio Mannucci
article en

Abstract

von Willebrand disease (VWD) is common, affecting ∼1% of the general population. Due to this relatively high prevalence, it can co-occur with other coagulation disorders. However, combined defects are often underrecognized in clinical practice. Diagnostic anchoring, overlapping symptoms, and limited access to comprehensive hemostatic and genetic testing contribute to these missed diagnoses. A growing number of case reports, case series, and cohort studies have documented the coinheritance of VWD with hemophilia A or B, rare coagulation factor deficiencies, and platelet function disorders. In some cohorts, up to one-third of cases with mild VWD had an additional hemostatic defect. Emerging genomic data also suggest that multiple low-frequency variants affecting hemostasis can co-occur in the same individual, particularly in populations with founder effects or high rates of consanguinity. Combined defects can alter bleeding severity, complicate diagnosis, and affect treatment decisions. Broader awareness and multidisciplinary evaluation are critical for addressing this underappreciated aspect of inherited bleeding disorders.

Research and Practice in Thrombosis and HaemostasisVol. 9(8)
University of Milan (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
Università degli Studi di Milano, Dipartimenti di Eccellenza, European Commission, Ministero della Salute, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Third Health Programme
Openalex Percentile: Top 54%
Platelet Disorders and Treatments
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