Abstract Introduction Chronic lymphocytic leukemia (CLL) is the most diagnosed leukemia in western countries. Pleural effusions rarely occur in CLL and are more often observed in advanced disease. CLL-associated malignant effusions are predominantly lymphocytic and, less commonly, chylothorax. Bruton tyrosine kinase (BTK) inhibitors, including zanubrutinib, are amongst the first line treatments for CLL. Bleeding is common with BTK inhibitors, especially first-generation, due to platelet disruption via impaired glycoprotein VI (GPVI) pathway and activation of integrin αIIbβ3. The incidence of hemorrhagic pleural effusion with second-generation BTK inhibitors is not well documented despite isolated case reports. Case Description A 78-year-old female with CLL on zanubrutinib was admitted to a Massachusetts hospital with dyspnea, weakness, and acute hypoxic respiratory failure in the setting of new large left pleural effusion. Initial bedside thoracentesis removed 1.6 L of bloody, free-flowing exudate with 151,000 red blood cells (RBCs), 2,206 white blood cells (WBCs), 41% lymphocytes, and 39% eosinophils. Flow cytometry was consistent with CLL, and culture was negative. Following discharge, she continued zanubrutinib. Four days later, she re-presented with the same symptoms in the setting of recurrent massive left pleural effusion. Pending intra-pleural catheter (IPC) placement, she developed obstructive shock due to worsening effusion with mediastinal shift requiring emergency thoracentesis with 3 L of bloody fluid drained. Following clinical stabilization, subsequent exudative fluid studies during scheduled IPC placement were similar to prior with 279,000 RBCs, 2,859 WBCs, 46% lymphocytes, 37% segmented neutrophils, 8% eosinophils, 25 mg/dL triglycerides, and no chylomicrons. There was low concern for true hemothorax as pleural fluid hematocrit was less than 50% of serum hematocrit. Given pleural eosinophilia, zanubrutinib was held for suspicion of drug-induced hemorrhage. Unfortunately, her course was complicated by empyema and septic shock, and she was eventually transitioned to comfort measures only prior to death. Discussion BTK inhibitors have known hemorrhagic side effects, although less common in second-generation drugs. Typically, bleeding involves intracranial, gastrointestinal, or urinary sources. While a case report of recurrent spontaneous hemorrhagic pleural effusion has previously been documented in a patient with CLL on zanubrutinib and simultaneous anticoagulation with apixaban, there are few published cases in patients not on therapeutic anticoagulation. In adults with hemorrhagic pleural effusion with fluid studies revealing eosinophilia, drug reaction to zanubrutinib should be considered along with discontinuation of the BTK inhibitor. This abstract is funded by: None
Bray et al. (Fri,) studied this question.