Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.
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 with 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 a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal 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 anticoagulants 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.
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
J J
JJ
Shatzel
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
S R
SR
Olson
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
D L
DL
Tao
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.|Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
O J T
OJT
McCarty
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
A V
AV
Danilov
Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
T G
TG
DeLoughery
D000225:Adenine / Q000031:analogs & derivatives; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D057915:Drug Substitution; D006470:Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
D000925:Anticoagulants; D000970:Antineoplastic Agents; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
agammaglobulinemia; blood platelets; hemorrhage; ibrutinib; lymphoma