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
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.