Type 3 Von Willebrand Disease (VWD) is the most severe and least common of the three VWD types. The incidence varies by ethnicity ranging from 0.1–5.3 cases/million. 8.5% of patients develop alloantibodies to Von Willebrand Factor (VWF), becoming non-responsive to treatment or prone to life threatening reactions. Predisposing factors include extent of previous exposure to VWF and mutations causing a null-allele gene. Variability of the clinical course is attributed to different antigenic specificities and potency of the antibodies. Management of these patients during events of bleeding is challenging. We report 2 cases of girls with type 3 VWD. The first was diagnosed at birth and had her initial VWF transfusion as a neonate. The second was diagnosed at 4 years of age. Both were frequently treated with VWF and developed alloantibodies. The clinical course, severity and circumstances leading to the diagnosis were different in both cases. Life threatening anaphylactic reactions like hypotension, bronchospasm and tongue edema was noticed in the first. The second showed poor factor recovery and response to treatment with urticaria. She continued to tolerate therapy but failed tolerance induction. Peak antibody level was 84 BU compared to 3 BU in the first. Novel VWF gene mutations were detected in both. Recently the first patient was managed for profuse bleeding post extensive dental procedure. Recombinant Factor VIII infusion was administered every 3 hours with monitoring of aPTT and Factor VIII levels. Based on peak and post 3 hour levels of Factor VIII, we concluded the half life of Factor VIII could be as short as 2 hours in patients with type 3 VWD. Post infusion peak level might approach 200% in some instances. Due to persistent bleeding despite adequate correction of Factor VIII and aPTT, platelet transfusion was cautiously administered which proved to be not only effective in controlling bleed but was also safe and not associated with any anaphylactic reaction. In conclusion, patients with type 3 VWD and alloantibodies can be successfully managed with aggressive frequent therapy with recombinant Factor VIII infusions. Platelet transfusions during episodes of severe bleeding can also be safe and effective.Administration of Factor VIII by continuous infusion could be an option if high post infusion peaks are to be avoided.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.