Research Update: Investigators Look at Confusing Case of VWD Misdiagnosis

Horizons in Hemophilia, December 2009

Researchers from the Medical College of Wisconsin recently looked at a puzzling case of laboratory testing for von Willebrand disease (VWD). The lead investigator of the study was Veronica Flood, MD, pediatric oncologist and assistant professor, Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee.

The type of VWD a patient has is determined by the nature of the defect in the von Willebrand factor (VWF).  If there is not enough VWF, it is a quantitative defect.  If there is enough VWF, but if the protein is defective, it is a qualitative defect.  Types I and III VWD are quantitative defects.  Type II VWD and its subtypes (2A, 2B, 2M, 2N) are qualitative.  Accurate diagnosis of the type of VWD is generally considered far more complicated than diagnosing hemophilia.

In many instances, a group of tests that measure VWF quantity and function are required to pinpoint a VWD diagnosis. Flood’s study focused on one specific case of type 2M VWD and the limitations in a particular lab test, the VWF ristocetin cofactor activity (VWF:RCo), when determining a diagnosis. VWF:RCo is a relatively simple lab test in which blood cells are separated from a patient’s plasma (the liquid part of the blood). Ristocetin, an antibiotic that prompts the binding of VWF and platelets together, is then added to the plasma. In reaction, blood with viable VWF will clot and blood with deficient VWF will not clot.      

While the patient featured in this study showed a significant decrease in VWF:RCo, the other assay tests of VWF function were normal. In addition, the patient exhibited no bleeding symptoms. Flood and colleagues discovered that while VWF:RCo tests performed outside the body registered poor VWF function, the activity of VWF inside the patient’s body did not appear to be affected. Because of this discrepancy and the lack of bleeding symptoms, investigators called the initial diagnosis of type 2M VWD into question, pointing to the likelihood of an inaccurate diagnosis.

Flood and her colleagues concluded that a correct diagnosis of VWD, regardless of type, needs to be based on not just one test but rather on a comprehensive series of tests and the patient’s symptoms.

Flood’s research was supported, in part, by a Career Development Award from the National Hemophilia Foundation. Her work was also supported by a grant from the National Institutes of Health and a Mentored Research Award from the Hemophilia and Thrombosis Research Society.

Source: Flood V, Friedman K, Gill J, et al. Limitations of the Ristocetin Cofactor Assay in Measurement of VWF Function. Journal of Thrombosis and Haemostasis. 2009; Volume 7 (Issue 11): Pages 1832 – 1839.