New Study on Aging, VWF Levels and Bleeding Risk
Investigators from the Hemophilia Center of Western Pennsylvania (HCWP) recently looked at the effect of aging on von Willebrand factor (VWF) levels in patients with type 1 von Willebrand disease (VWD). The authors of the article were Craig D. Seaman, MD, MS and Margaret V. Ragni, MD, MPH. Seaman is Assistant Professor of Medicine, Division of Hematology/Oncology at HCWP. Ragni is Professor of Medicine and Clinical Translational Science, Department of Medicine, Division of Hematology/Oncology University of Pittsburgh Medical Center. She is also the Director of HCWP.
Ragni and Seaman looked to establish whether VWF levels increase as patients with VWD age, and if so, whether this can be associated with lower risk for bleeding. A retrospective chart review was therefore conducted of type 1 VWD patients who went for regularly scheduled clinic visits at HCWP. The authors culled data based on clinical history and laboratory tests that measured VWF levels and functioning. A condensed version of the “Molecular and Clinical Markers for the Diagnosis and Management of Type 1 (MCMDM-1) VWD Bleeding Assessment Tool (BAT),” was employed to identify patients with normal vs. abnormal bleeding symptoms and to determine bleeding severity.
The review included 39 patients (32 female, 7 male) with type 1 VWD with regularly scheduled clinic visits between February 2016 and January 2017. The mean age of patient participants was 41.8 years. Eighteen patients were 45 years of age or older, including 7 who were 60 years or older. 34% of female participants were taking hormonal therapy. After data analysis, it was determined that aging was associated with a decrease in bleeding symptoms in type 1 VWD patients. They did not however establish a link between aging and increased VWF levels. Ragni and Seaman recognized that this conclusion runs up against previous studies suggesting that despite increasing VWF levels, bleeding symptoms do not decrease in aging type 1 VWD patients. The authors sought to account for the disparate findings.
“One issue is the method of BAT administration. The BATs allow a detailed and objective bleeding history to discriminate between patients with and without VWD and gauge the severity of VWD. Previous studies determined the bleeding score based on lifetime bleeding symptoms; however, this may not accurately reflect current bleeding risk,” explained the authors. “For example, a patient may have had a significant number of bleeding symptoms in early adulthood corresponding to a high bleeding score; however, even if bleeding manifestations lessen, or completely resolve, with aging, the bleeding score will remain unchanged. This prevents a proper assessment of the patient’s current bleeding phenotype.”
The authors go on to acknowledge several study limitations such as a small patient sample size and the potential skewing effect of hormonal therapy on increasing VWF levels in female participants. Ragni and Seamen also noted that while they did find an “inverse association” between aging and bleeding symptoms, they caution against drawing a direct causal link. Instead, they note that further studies are necessary. In fact, they are planning a multicenter, cross-sectional study to investigate the association of aging with VWF levels and bleeding risk in patients with type 1 VWD. Findings from further studies could help inform clinical management and avoid the unnecessary overuse of therapies such as VWF concentrates or the synthetic hormone DDAVP (1-Desamino-8d-Arginine Vasopressin).
“Administering DDAVP or VWF concentrate to older patients with type 1 VWD having normalized VWF levels may be harmful, placing patients at risk of thrombosis, electrolyte disturbance, and other adverse effects, concluded the authors. “Additionally, such therapy is costly and represents a considerable waste of health-care dollars if its use is not warranted. For these reasons, investigation into the effect of aging on VWF levels and bleeding risk in patients with VWD is sorely needed.”
Seaman C, Ragni M. The Association of Aging with von Willebrand Factor Levels and Bleeding Risk in Type 1 Von Willebrand Disease. Clinical and Applied Thrombosis/Hemostasis. 2018 April; 24(3): 434-438.