Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase
(Btk) that has proven to be an effective therapeutic agent for multiple B-cell
mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased
bleeding risk compared to standard chemotherapy. Bleeding events range from
minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part
to the effects of ibrutinib on several distinct platelet signaling pathways.
There is currently minimal data to guide clinicians regarding the use of
ibrutinib in patients at high risk for bleeding or on anticoagulant or
antiplatelet therapy. In addition, the potential cardiovascular protective
effects of ibrutinib monotherapy in patients at risk for vascular disease is
unknown. Patients should be cautioned against using nonsteroidal
anti-inflammatory drugs, fish oils, vitamin E, and aspirin-containing products,
and consider replacing ibrutinib with a different agent if dual antiplatelet
therapy is indicated. Patients should not take vitamin K antagonists
concurrently with ibrutinib; direct oral anticoagulant should be used if
extended anticoagulation is strongly indicated. In this review, we describe the
pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction
strategies for common clinical scenarios associated with ibrutinib.