Concurrent treatment of chronic lymphocytic leukemia and acquired von Willebrand syndrome using a Bruton tyrosine kinase inhibitor: a case report: Treating AvWS and CLL with Acalabrutinib

Chronic lymphocytic leukemia (CLL) is frequently associated with immune dysregulation, with 20-25% of patients developing autoimmune disorders. In this context acquired coagulopathies, such as acquired von Willebrand syndrome (AvWS), occur rarely. These conditions can complicate CLL management, particularly regarding the use of Bruton tyrosine kinase inhibitors (BTKis), drugs known for their antiplatelet activity. This case report describes a rare association between CLL and AvWS, highlighting the successful use of acalabrutinib in controlling both conditions. A 74-year-old man was diagnosed with CLL in December 2021 and was initially managed with a watch-and-wait approach due to low disease burden. Disease progression occurred in 2023, characterized by marked lymphocytosis, splenomegaly, and bulky lymphadenopathy. Molecular evaluation showed unmutated IGHV, mutated NOTCH1, and absence of TP53 abnormalities. Before starting first-line treatment, the patient developed clinically relevant gastrointestinal bleeding associated with prolonged PTT. Laboratory investigations revealed acquired von Willebrand syndrome (vWF:Ag 29%, vWF:RCo 13%, FVIII 22%), without evidence of monoclonal paraproteinemia. Because of the bleeding risk, initiation of acalabrutinib was postponed and four weekly doses of rituximab were administered for AvWS. Concurrent chlorambucil therapy achieved rapid cytoreduction. However, coagulation parameters did not improve, and acalabrutinib was subsequently started in January 2024. Following treatment initiation, no further bleeding episodes occurred. The patient experienced progressive improvement of both CLL and AvWS, with normalization of vWF:Ag and vWF:RCo. At the latest follow-up in May 2026, after 28 months of treatment, the patient remained on acalabrutinib, maintaining a partial remission of CLL and complete resolution of AvWS. This case emphasizes the importance of considering rare acquired coagulation disorders in patients with CLL. It also supports treatment of the underlying malignancy as an effective strategy for managing associated autoimmune or immune-mediated complications.