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Response to Treatment With Rituximab in a Patient With Acquired von Willebrand Disease

Response to Treatment With Rituximab in a Patient With Acquired von Willebrand Disease

The patient is a 58-year-old woman (AA genotype) who was found to have a prolonged activated partial thromboplastin time (aPTT) of 65.7 seconds during a preoperative evaluation for spinal stenosis surgery and mild rectal bleeding. Her aPTT test repeatedly remained abnormally prolonged. The patient had an aPTT mixing study that did not correct immediately or at 2 hours (56.4 seconds vs control 29.7 seconds). Her bleeding time was also abnormally prolonged at 11 minutes.

The patient’s factor VIII level was 10%, her von Willebrand factor (vWF) antigen level was 13%, and her vWF ristocetin level was 13% with extremely low levels of vW multimers, indicating acquired von Willebrand disease (type III or severe type I) with an accompanying factor VIII deficiency.

The patient’s dilute Russell’s viper venom test (DRVVT) was normal. Circulating anticoagulant was presumed to be associated with the monoclonal immunoglobulin (Ig)G-lambda (1,800 mg/dL) discovered on a serum protein electrophoresis and immunoprecipitation studies. The patient had a bone marrow biopsy that showed 10% plasma cells and confirmed diagnosis of monoclonal gammopathy of undetermined significance (MGUS). Because of the planned surgical procedures, the patient was treated with corticosteroids. She failed to respond to prednisone at 1 mg/kg for 2 weeks and IV immunoglobulin (1 g/kg/d × 2 infusion) treatment. In light of recent reports of successful treatment of autoimmune diseases refractory to standard therapy, such as immune thrombocytopenic purpura, with rituximab (Rituxan), we tried the following regimen on this patient: rituximab at 375 mg/m² IV administered weekly for 4 weeks for two cycles. After treatment, the patient’s aPTT, bleeding time, and factor VIII levels normalized; however, she relapsed and was successfully re-treated. Pre- and posttreatment levels are provided in the following table:

CONCLUSION: To the best of our knowledge, this is the first time rituximab has been used to treat acquired von Willebrand disease secondary to autoantibodies. The response stopped the patient’s clinical bleeding. She had a partial response in her laboratory measurements, with correction of bleeding time and improved but still prolonged aPTT, while her von Willebrand parameters remained low. She relapsed after a year and a second response was observed by re-treatment with rituximab.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

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