Association of Blood Type with Von Willebrand Disease Severity Among Patients at an Academic Hemophilia Treatment Center

Introduction: ABO blood group is an important determinant of von Willebrand factor (VWF) synthesis, function, and metabolism. Blood type O is associated with reductions in VWF antigen and activity, often in a pattern that mimics mild Type 1 von Willebrand disease (VWD). While inherited VWF gene mutations are common in moderate to severe VWD, they are less frequent in mild disease (VWF antigen or activity 30-50%, previously “Low VWF”), and ABO blood type may be a determinant of VWF levels in these patients. Given this relationship, we hypothesized that patients with blood type O will be more likely than non-type O patients to have a diagnosis of mild rather than moderate/severe VWD. Additionally, we aimed to determine the impact of family history on VWD severity, specifically whether those without a family history of VWD are more likely to have mild disease than patients with a positive family history.

Methods: We conducted a retrospective chart review of patients evaluated at Cardeza Foundation Hemophilia & Thrombosis Center – a Hemophilia Treatment Center (HTC) affiliated with a large academic hospital – for possible or confirmed VWD from January 1, 2017, through December 31, 2023. Patients without a definitive VWD diagnosis, ABO blood type on file, or those with VWF activity > 50% were excluded. Demographic, historical, and laboratory values were collected for eligible patients, including ABO blood type, nadir VWF activity, VWF antigen, factor VIII activity, and presence or absence of VWD family history by patient report and documentation in the electronic health record. Logistic regression was used for analysis.

Results: Data was collected for 124 eligible patients, among whom 89% were female and 81% had blood type O. In patients diagnosed as having VWD with VWF activity < 50%, individuals with type O blood were not significantly more likely to have mild disease, relative to those with non-O blood types (69% vs 50%, adjusted OR 2.32 [95% CI 0.87-6.22], P=.094). However, among patients classified as having Type 1 VWD (N = 79), those with type O blood were significantly more likely to have mild disease than non-O patients (80% vs 50%, adjusted OR 6.39 [95% CI 1.35-30.22], P=.019). In patients with Type 2 VWD (N = 18), though, there was no association between blood type and likelihood of mild disease (20% in type O vs 31% in non-O). Lastly, we did not find a significant association between family history of VWD and presence of mild vs moderate/severe disease; 69% of patients without a family history had mild disease compared to 56% with a family history (adjusted OR 2.00 [95% CI 0.85-4.67], P=.113).

Conclusion: Our observational study of VWD patients at an academic HTC found that among all patients, there was no significant association between type O blood and mild VWD, though the magnitude of the ORs for both variables is suggestive of an association. But, among patients diagnosed with Type 1 VWD, those with type O blood were significantly more likely to have mild disease than non-O patients, while there was no association in Type 2 VWD, though the latter group was small. This is clinically relevant, as most patients with reduced VWF levels due to type O blood have a Type 1 VWD pattern. Overall, the small size of our study and lack of readily available genetic testing data limit the conclusions that can be drawn. However, our results highlight the importance of considering ABO blood type in the diagnosis of VWD, and larger studies incorporating genetic testing and scoring of bleeding severity with a validated assessment tool will be helpful to differentiate mild Type 1 VWD from Low VWF in type O patients.