(P-HC-6) A Rare Case of Type 1-like Acquired von Willebrand Disease in a Patient with Hyperviscosity Syndrome Due to Hypergammaglobulinemia Responsive to Therapeutic Plasma Exchange

Acquired von Willebrand Disease (AvWD) is an uncommon complication of hypergammaglobulinemia associated with plasma cell and lymphoid neoplasm. Most forms of cancer-associated AvWD are caused by selective loss of high molecular weight multimers (HMWMs), resulting in a type 2-like vWD from a clinical and laboratory perspective. Herein, we report a rare case of hyperviscosity and bleeding associated with AvWD that uniquely manifested as a type 1-like AvWD which was responsive to therapeutic plasma exchange (TPE).


Study

Design/Methods:

Clinical/laboratory data were extracted via chart review. Coagulation testing consisted of von Willebrand Factor (vWF) measurement via automated latex-enhanced immunoassay and activity testing (Werfen, Orangeburg, NY), a one stage PTT-based assay for FVIII activity (Werfen, Orangeburg, NY), and multimer analysis (agarose gel electrophoresis).


Results/Findings:

A 79-year-old male with past medical history of lymphoplasmacytic lymphoma presented with gastrointestinal bleeding and anemia [Hematocrit (Hct) and hemoglobin (Hb) were 23.7 (normal: 38.5-50%) and 7.2 (normal: 13.2-17.1 g/dl)]. Additional testing showed an IgM level >5850 (normal: 40-230 g/dl) and viscosity of 5.1 (normal: 1.5-1.9 cP). vWF activity level was 46% (normal: 58-163%) with vWF antigen 59% (normal: 62-175%), FVIII activity of 39.9% (66-143%) and PTT of 30.5 (normal: 22.5-32 sec). Multimer analysis showed decreased concentration with normal distribution of vWF HMWMs, a ‘type 1’ pattern (Figure A). The clinical picture was interpreted as bleeding caused by AvWD with a type 1-like phenotype (the patient had no prior history of vWD). The apheresis service was consulted for TPE to treat the hyperviscosity and AvWD, with the first procedure done using 3000 mL 5% albumin, as well as 1000 mL plasma to replete reduced vWF/FVIII. Following TPE #1, IgM dropped to 3098 g/dl and viscosity to 2.0 cP. The following morning, Hct and Hb increased to 28.3% and 8.9 g/dL, respectively. There was, however, a rebound increase in IgM to 4207 g/dl; therefore, and in anticipation of immediate cytoreductive therapy, a second TPE was performed with ~3500ml of 5% albumin-only replacement. Follow-up IgM level was 2607 g/dl and no additional TPE was performed. Repeat vWF studies were within normal limits on serial follow-up tests performed days after completion of TPE #2 (vWF antigen: 98% and 127%, vWF activity: 94% and 106%, FVIII activity: 70.8% and 75.6%). The patient reported no bleeding after TPE #2.


Conclusions:

AvWD occurring secondary to hyperviscosity presenting with the rare type 1-like form can be effectively managed in the acute phase by TPE.