Journal of Blood Disorders & Transfusion

Abstract

Carfilzomib Potentiates Platelet Activation and Thrombus Growth

Fehaid Alanazi, Isaac Goncalves, Kate L. Burbury, Faith A.A. Kwa, Gasim Dobie, Fahd A. Kuriri, Ezeldine K Abdalhabib and Denise E. Jackson*

Background: Multiple Myeloma (MM) patients treated with carfilzomib are at high risk of Venous Thromboembolism (VTE), however, the underlying aetiology and mechanism remains unknown. Carfilzomib is an irreversible Proteasome Inhibitor (PI) known to have cardiac toxicity, but less is known about its thrombogenic effects. Platelets play a critical role in the pathogenesis of thrombosis; however, limited studies have reported the effects of carfilzomib on platelet function.

Objectives: To characterise the effects of carfilzomib on platelet activation and thrombus formation.

Methods: Effects of carfilzomib on platelet activation, collagen adhesion and thrombus formation are characterised using in-vitro and ex-vivo thrombosis models.

Results: Carfilzomib potentiated thrombin-induced platelet activation, demonstrated by increased P-selectin expression and integrin α_IIbβ₃ activation compared to first-generation PI, Bortezomib and control that showed no effect. The addition of dexamethasone to carfilzomib further increased thrombin-induced platelet activation compared to carfilzomib alone. Carfilzomib potentiated platelet adhesion to type-1 collagen and increased thrombus formation under arterial flow compared to Bortezomib and control that showed no effect. The increased thrombus formation under arterial flow was further enhanced when carfilzomib was combined with dexamethasone.

Conclusion: These findings suggest that carfilzomib-induced thrombosis risk in patients with multiple myeloma may be the result of enhanced platelet thrombotic function.

Published Date: 2022-09-21; Received Date: 2022-08-16