Background: Acquired von Willebrand syndrome (AVWS) is an underdiagnosed bleeding disorder that can be associated with hematological malignancies, such as chronic lymphocytic leukemia (CLL). The management of AVWS remains empirical and relies heavily on dissemination of clinical experiences.

Aims: We present an elderly male with asymptomatic CLL who developed AVWS. Our objective is to highlight the importance of treating the underlying cause despite the lack of other guideline-driven treatment indications.

Methods: Case report. 

Results: A 92-year-old male presented with recurrent epistaxis requiring hospitalization. In the preceding 18-month period, he had 16 visits to hospital with mucocutaneous bleeding, primarily epistaxis, without prior personal or family history of bleeding. Two years prior to this presentation, he was diagnosed with asymptomatic, Rai stage 0, CLL. Laboratory testing showed a low VWF antigen (VWF:Ag; 0.06 U/mL; N:0.40-1.75), undetectable VWF activity (< 0.1 U/mL, N:0.45-1.80), low factor VIII level (FVIII; 0.13 U/mL, N:0.50-1.49), a significantly elevated VWF propeptide to antigen ratio (VWFpp/VWF:Ag) of 17.0 (N:0.9-1.45), and weakly positive anti-VWF total IgG antibodies. Daily infusions of plasma-derived VWF concentrate helped control his bleeding temporarily. The patient failed a trial of corticosteroids and IVIG. Therefore, the clinical decision was to treat his CLL with Obinutuzumab and Chlorambucil for 6 cycles, which resolved his bleeding symptoms and lymphocytosis. Upon treatment completion, testing showed normalization in VWF:Ag (1.14 U/mL), VWF activity (1.33 U/mL), FVIII (1.50 U/mL), and VWFpp/VWF:Ag ratio (0.9). Twenty-two months after therapy, he remains in remission without evidence of AVWS or lymphocytosis.

Graphic representation of FVIII (IU/mL), von Willebrand factor antigen (VWF:Ag; IU/mL), and von Willebrand factor activity (VWF:Act; IU/mL) in association with the absolute lymphocyte count (LYMPH; x 109/L) and Obinutuzumab and Chlorambucil (G-Clb) chemoimmunotherapy treatment.

Conclusions: This is the first report demonstrating remission induction in both AVWS and CLL following therapy with Obinutuzumab and Chlorambucil. We suspect Obinutuzumab played a particular role in inducing remission compared to corticosteroids and IVIG. In the setting of asymptomatic hematologic malignancies, the benefit of treating AVWS with chemoimmunotherapy may outweigh the risks as it can reduce significant bleeding-related morbidity.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/to-treat-or-not-remission-induction-of-acquired-von-willebrand-syndrome-secondary-to-chronic-lymphocytic-leukemia-a-case-report/