Rituximab Use in Four Patients with Acquired vonWillebrand’s Syndrome.

Treating Acquired von Willebrand’s Syndrome (AVWS) is a challenge requiring multiple therapeutic modalities to achieve success in controlling and preventing bleeding episodes. From review of the literature, clinical use of rituximab, an anti-CD20 monoclonal antibody, in AVWS has not been reported. We present our experience with four patients treated with rituximab for steroid or intravenous immunoglobulin (IVIG) refractory and/or dependent AVWS associated with IgG monoclonal gammopathy of undetermined significance. Rituximab at a dose of 375mg/m² was administered intravenously weekly for 4 consecutive weeks in the first patient. After 3 cycles of rituximab, we observed a correction of her bleeding time to normal, improvement of her prolonged aPTT, a decrease in her monoclonal IgG and cessation of her bleeding episodes for 29 months. She relapsed and was retreated with rituximab at the same dose for 3 cycles with no improvement in aPTT and bleeding time. She has had no further bleeding episodes after compliance with epsilon aminocaproic acid for one year. The second patient received rituximab intravenously at a dose of 375 mg/m² weekly for 4 weeks. Prolonged aPTT was unchanged after treatment. He was asymptomatic for 8 months and then received prophylactic IVIG and von Willebrand Factor concentrate (Humate-P) for elective hand surgery. The third patient had a concomitant worsening idiopathic neuropathy and received rituximab 375mg/m² intravenously daily for 2 consecutive days two weeks apart for his neuropathy. His neuropathy and prolonged aPTT did not improve and he developed gastrointestinal bleeding 1.5 months later. The fourth patient received rituximab 150mg/m² intravenously weekly for 4 consecutive weeks. Prolonged aPTT was unchanged after treatment. He experienced no bleeding symptoms for 38 months. Factor VIII, Ristocetin Cofactor, von Willebrand Antigen and IgG levels were not significantly affected by rituximab use in cases 2–4. Rituximab seemed to be most effective in the first and fourth cases. The dosing and number of cycles is unclear. Success in the first case with multiple cycles of therapy may be needed for response and warrants further evaluation. Additionally, it appears therapy needs to be reinforced with other agents to prevent or stop bleeding. It was well tolerated with no infectious complications in our patients. Only one patient had an infusion related reaction, which did not require stopping therapy. Further prospective studies are needed to evaluate the efficacy of rituximab and establish the dosing and treatment duration in AVWS.