Research finds bleeding severity varies widely in type 2 VWD
Understanding variants' effect on disease manifestations aids diagnosis, treatment
The severity of bleeding in type 2 von Willebrand disease (VWD) can vary widely between subtypes and even among patients who carry the same genetic change or variant, with women and adults generally having more severe symptoms, a study finds.
“Understanding how specific VWF genetic variants determine or influence the clinical [disease manifestations] in different subtypes of type 2 VWD is crucial for accurate diagnosis, personalized treatment, and improved prognosis,” its researchers wrote. The study, “Genetic determinants of clinical variability in type 2 von Willebrand disease: bridging genotype and phenotype,” was published in Haematologica.
Type 2 VWD occurs when von Willebrand factor (VWF), a protein that helps blood to clot, doesn’t function correctly due to certain genetic variants. There are four disease subtypes, depending on how VWF is altered. In type 2A, VWF can’t properly connect to other VWF molecules and form large multimers, or multimers are broken down too rapidly. In type 2B, VWF binds too strongly to a protein on platelets even in the absence of an injury, while in type 2M it doesn’t correctly bind to proteins on platelets. In type 2N, VWF fails to properly interact with factor VIII, another clotting protein.
While the clinical and genetic features of type 2 VWD are known, it’s still unclear how specific variants affect bleeding severity. This led researchers to explore the relationship between VWF variants and bleeding severity in type 2 VWD patients to seek to explain why some patients bleed more than others.
Differences in bleeding in type 2 VWD
The study included 371 patients with genetically diagnosed type 2 VWD. Bleeding severity was measured using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT), a questionnaire that scores symptoms, such as heavy periods, nosebleeds, and easy bruising.
The ISTH-BAT “helps predict clinical outcomes by quantifying bleeding severity,” the researchers wrote. “Higher scores have been linked to an increased need for intensive on-demand therapy and may help to identify patients who might benefit from regular [preventive therapy].”
Scores were available for 274 patients (192 adults, 82 children). Among these, 83 had type 2A VWD, 69 had type 2B, 106 had type 2M, and 16 had type 2N. Median bleeding scores were highest in those with type 2A (7 points), followed by those with type 2B (5 points). Type 2M and 2N scored 4 points each. Women scored higher than men (6 vs. 4 points) and adults scored higher than children (6 vs. 3).
A total of 67 different genetic variants were identified. Interestingly, bleeding severity varied widely among patients with the same VWD subtype or those carrying the same genetic variant. This shows other factors besides genetic makeup may influence bleeding.
Certain symptoms, such as heavy periods (62%), nosebleeds (61%), and bleeding into the skin (59%), were common across all type 2 VWD subtypes. Bleeding in the mouth (55%) and after childbirth or postpartum (55%) were also common.
The study did find subtype-specific differences in bleeding patterns, however.
Type 2A had the highest rates of bleeding into the skin (69%), nosebleeds (67%), heavy periods (69%), and postpartum bleeds (62%). Type 2B had a similar pattern with slightly lower rates. In type 2M, nosebleeds were most common (61%), followed by heavy periods (57%) and postpartum bleeds (53%). Type 2N was different, with more joint and muscle bleeds.
Overall, “the study highlights significant variations in bleeding manifestations and severity across the different subtypes, as well as the impact of genetic variants on clinical outcomes,” the researchers wrote, noting that “several key factors” may explain why symptoms and their severity vary widely in VWD.
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