The Acquired Von Willebrand Syndrome in Patients with Monoclonal IgA Proteins Is Rare but May be Clinically Severe

During the last 10 years our laboratory diagnosed and typed 5585 different patients with inherited von Willebrand disease (VWS) and acquired von Willebrand syndrome (aVWS). Out of these 21% (1217) suffered from aVWS. With 252 patients lymphoproliferative disorders were number three in frequency (21%) after cardiovascular (43%) and myeloproliferative (27%) disorders. Out of the patients with lymphoproliferative disorders patients with a monoclonal IgA protein comprised only 3.6% (9 patients). Much more abundant were monoclonal IgG´s (71%) and IgM´s (26%).

According to our data only one patient was classified as MGUS and the others suffered from myeloma. The most impressive property was the heterogeneity of their laboratory and clinical data with the exception that all patients suffered from severe bleeding complications whenever their hemostatic system was challenged by accidents or invasive procedures (even iliac crest biopsy).

The VWF:Ag ranged from 0.06 – 5.60 IU/ml and only one patient had a VWF:Ag <0.5 IU/dl. The functional test (VWF:CB) ranged from 0.06 and 5.48 IU/ml again with only one patient <0.5 IU/dl. The ratio VWF:CB / VWF:Ag was below 0.8 in three patients. Thus more than 50% of the patients would remain undetected if the VWF multimers were not included in the

diagnostic panel. Two patients displayed the whole set of multimers, while the others showed a mild (5) or severe (2) absence of the large multimers. The hallmark of the multimic pattern from patients with an IgA monoclonal protein was the presence of a lot of smeary material within the electrophoretic lanes diplayed in all patients.

In summary aVWS in the course of lymphoproliferative disorders and monoclonal IgA proteins is clinically severe, although probably not life threatening. It remains undetected with standard VWF tests and might be therefore not as rare as detected in our large patient panel.