Acquired Von Willebrand Disease – To Treat Or Not To Treat The Inhibitor?

Acquired von Willebrand disease is a relatively rare but possibly under diagnosed bleeding disorder. The etiology is multifactorial, including underlying malignancy, drugs, valvular heart disease, mechanical cardiac assist devices, autoimmune diseases and infections. The disorder is characterized by mucocutaneous bleeding presenting in adulthood with no prior history or family history of bleeding tendency.

A retrospective chart review was performed on patients with a diagnosis of acquired von Willebrand disease over a period of 15 years. We identified 10 patients with this diagnosis in the absence of valvular heart disease or the presence of a mechanical cardiac assist device. The initial presentation along with demographic features, co-morbidities, laboratory values at the time of initial presentation and subsequent follow up, treatment of bleeding episodes and cause of death were noted.

The mean age at diagnosis was 56.5 years with range of 39-75 years. Males and females were equally affected. One patient each had aortic valve stenosis and hypothyroidism, both of which were treated and not felt to be responsible for the diagnosis of acquired von Willebrand disease. Six of ten patients had an underlying myelo / lymphoproliferative disorder while two had a remote history of cured high grade colon cancer. Most of the patients presented with mucocutneous bleeding including easy bruising, epistaxis, gingival bleeding, and GI bleeding. Post procedural urinary tract bleeding was the presenting sign in two patients and one patient presented with spontaneous intracranial hemorrhage. All but two patients presented with ristocetin cofactor activity of <10% and factor VIII and von Willebrand antigen levels in the range of 4-31% and 10-23% respectively. Multimer patterns were either severely reduced high molecular weight multimers or decreased multimers with normal distribution. For all patients, the presenting lab values remained unchanged at follow up even over several years (up to 12 in our series), including in those who received treatment for the underlying myelo / lyphoproliferative disorder. Treatment to control bleeding included DDAVP, IVIg, factor VIII/VWF concentrates, rituximab, plasma exchange, and recombinant factor VIIa, all with varying degrees of success. Six of ten patients did experience recurrent bleeding episodes and two ultimately died of uncontrolled GI bleeding.

Acquired von Willebrand disease is a rare entity, typically presenting with severely decreased factor levels, and often associated with significant morbidity and potential mortality. Although some patients experience recurrent and refractory bleeding, others may survive for more than 10 years without major complications with this condition. As reported previously in literature, most of the cases in our series were also associated with underlying myelo / lymphoproliferative disorders. In two of our patients the development of acquired von Willebrand disease preceded the diagnosis of a lymphoproliferative disorder by 3-4 years, suggesting that close monitoring for future development of these disorders is warranted. In contrast to previous reports, treatment of the underlying myelo / lymphoprolifertive disorder did not lead to improvement in the bleeding episodes or lab values in any of our patients that were treated (5/6). In acquired hemophilia, approximately 80% of patients experience significant bleeding, and mortality has been quoted in the range of 8-22%. Thus, treatment usually includes an attempt to eradicate the inhibitor with immune suppression. In our series, 60% of the patients experienced recurrent and refractory bleeding, and mortality was also 20%, suggesting that a similar approach should be considered in those with acquired von Willebrand disease.

No relevant conflicts of interest to declare.