Alloantibodies in von Willebrand disease

Abstract

The development of alloantibodies against von Willebrand factor (VWF) represents a rare but serious complication of treatment of von Willebrand disease (VWD), occurring in ∼5% to 10% of type 3 VWD patients. Affected patients can present with a range of symptoms, including lack or loss of hemostatic response to infused VWF concentrates up to anaphylactic reactions in rare cases. It is classically reported in multitransfused patients and occurs most frequently in patients with partial or complete VWF gene deletions. A positive family history of anti-VWF antibodies also appears to be a risk factor. There is a lack of standardization of laboratory methods for antibody identification and characterization. Issues of variability in laboratory approaches as well as the rarity of the complication act as a barrier to future studies. Recombinant factor VIII as well as bypassing agents and immune tolerance have been reported as effective treatments; however, aside from case reports, little exists in the literature to guide management. The imminent clinical availability of recombinant VWF has prompted a resurgence of interest in this area. Additional study is warranted to address the deficiencies in our understanding of this treatment complication.

Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease

“…23 In rare cases, alloantibody development against VWF has been observed in patients with type 3 VWD. 38 In the present study, none of the patients developed anti-VWF binding or neutralizing antibodies to VWF. Furthermore, as the initial and repeated rVWF PK results are in close agreement in this cohort of subjects with VWD, it can be concluded that there is no evidence of any inhibitory allo-antibodies that would influence the T 1/2 or other PK parameters of rVWF.…”

Skin Testing, Graded Challenge and Desensitization to Von Willebrand Factor (vWF) Products in Type III Von Willebrand Disease (VWD)

“…5 There have also been reports of patients experiencing symptoms consistent with anaphylaxis when exposed to VWF or factor VIII replacement products (some of which contain VWF). [3][4][5][6] Prior studies have identified immune complex formation and complement activation as mediators of these reactions, rather than IgE. 3 Here, we describe two VWD patients with inhibitory alloantibodies to VWF who developed VWF infusion reactions, some of which were clinically consistent with anaphylaxis given documentation of urticaria, respiratory distress and hypotension.…”

“…[3][4][5][6] Prior studies have identified immune complex formation and complement activation as mediators of these reactions, rather than IgE. 3 Here, we describe two VWD patients with inhibitory alloantibodies to VWF who developed VWF infusion reactions, some of which were clinically consistent with anaphylaxis given documentation of urticaria, respiratory distress and hypotension. Evaluation and treatment was ultimately made possible through skin prick and intradermal testing, graded challenge and/or desensitization.…”

Trial of ZMapp for Ebola Virus Infection

“…Patients with alloantibodies to von Willebrand factor 2 have safely undergone surgery with the use of recombinant factor VIII that is devoid of von Willebrand factor. 3,4 This indicates that the control of soft-tissue and surgical bleeding depends on factor VIII rather than on ristocetin cofactor levels, which remain unmeasurable in plasma throughout the postinfusion period because of the neutralizing action of alloantibodies.…”