:
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.