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Ibrutinib-related bleeding

pathogenesis, clinical implications and management

Aguilar, Carlos

Blood Coagulation & Fibrinolysis: September 2018 - Volume 29 - Issue 6 - p 481–487
doi: 10.1097/MBC.0000000000000749

Ibrutinib is the first drug of a new family of Bruton's tyrosine kinases (Btk)-inhibiting agents, which have proved to be useful for the treatment of several B-cell lymphoid malignancies. This drug is associated to an increased bleeding risk from initial clinical trials especially in association with warfarin. Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib. This risk is increased by concomitant antiplatelet and anticoagulant therapy; both dual antiplatelet therapy and vitamin K antagonists are contraindicated in these patients. Potential ibrutinib users often have age-associated cardiovascular risk factors or conditions and the drug itself may trigger atrial fibrillation requiring antithrombotic therapy. Aspirin and direct oral anticoagulants can be regarded as the antithrombotic therapies of choice if required. Heparin and fondaparinux have also been used in clinical trials. Therefore, the need and duration of antithrombotic therapy must be carefully evaluated and treatment individualized according to clinical circumstances. Ibrutinib withdrawal and platelet transfusion are key for the management of major bleeding not involving the central nervous system.

Department of Haematology, Hospital General Santa Barbara, Paseo Santa Bárbara s/n, Soria, Spain

Correspondence to Carlos Aguilar, Department of Haematology, Hospital General Santa Barbara, Paseo Santa Bárbara s/n, 42004 Soria, Spain E-mail:

Received 17 March, 2018

Revised 9 June, 2018

Accepted 14 June, 2018

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