Von Willebrand disease (vWD) is the most common inherited bleeding disorder worldwide, caused by the missing or defective von Willebrand factor (vWF), a blood-clotting protein. vWF is a multimeric protein that interacts with platelets to form the initial platelet aggregate, a primary hemostasis. Referred to as a “biological sensor of blood flow,” vFW can be stretched open under high shear stress and bind to platelets. In various cardiovascular conditions, vWF is degraded by shear stress, which results in a loss of high molecular weight multimers. This correlates strongly with a pressure gradient in cardiovascular conditions, such as obstructive hypertrophic cardiomyopathy (HC), which suggests that vWF testing could reflect the natural history of progression in HC and could accurately reflect responses to medical treatment and possibly predict prognosis.
In a recent study published in the American Journal of Cardiology, Mayo Clinic researchers examined the relation of peak pressure gradient to vWF function before and after discrete treatment interventions in hypertrophic cardiomyopathy and compared this data with results seen with the standard HC biomarker brain natriuretic peptide (or B-type natriuretic peptide, BNP). Additionally, researchers compared the severity of vWF disruption with other cardiac disorders in which vWF abnormalities are known to be associated with bleeding from acquired von Willebrand disease.
“In analyzing HC closer, it was discovered that new biomarkers were needed to accurately reflect the severity of HC and to predict therapeutic response in HC. Since shear stress is directly related to the severity of HC and other cardiovascular conditions, vWF became a very good candidate for our study,” said Dong Chen, M.D., Ph.D. a Consultant in the Hematopathology Laboratory at Mayo Clinic and senior author on this paper.
In the study, BNP and vWF indexes were strikingly increased in patients with HC compared to normal controls. This suggests the potential utility of these biomarkers as interim screening tools in addition to annual electrocardiography procedures in patients suspected of having the HC phenotype. According to the article, these patients could include first-degree relatives of patients with HC or people at risk who are participating in competitive athletics.
The study results also suggest that the severity of the vWF high molecular multi-user loss is correlated with HC severity. When HC is corrected by surgery, vWF abnormalities are also restored.
“Based on our results, vWF activity, antigen, and multi-user testing could provide an objective assessment of a patient’s HC severity,” said Dr. Chen. “Its recovery to a normal state suggests that it can also be used to assess the successfulness of the surgery.”
In conclusion, vWF can be used in clinical management of HC and post-surgical assessment of patients with HC.
For more information about von Willebrand factor, view the Mayo Medical Laboratories Hot Topic video series and testing resources.