Abstract Number: PB1475
Meeting: ISTH 2020 Congress
Background: Ibrutinib treatment in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is associated with bleeding at first stages, caused by action of ibrutinib on platelet signal transduction, but bleeding decreases with continued therapy.
Aims: To propose the predictive markers of bleeding on ibrutinib, as well as mechanisms responsible for decreased bleeding at later therapy stages.
Methods: Platelet functional activity was investigated in 50 CLL and 16 MCL patients on ibrutinib using flow cytometry and light transmission aggregometry. Blood was collected before ibrutinib treatment (point 0), then at 2, 4, 8 weeks (points 1-3) and 3-6 months (point 4) on treatment. The study was approved by the hospital´s Ethical Committee.
Results: Prior to treatment, both CLL and MCL patients had decreased platelet counts, impaired aggregation with ADP, and decreased binding of CD62P, PAC1, and annexin V upon stimulation. Bleeding on ibrutinib was observed in 28 (56%) CLL patients, who had decreased aggregation with ADP and platelet count before therapy. Their platelet count on therapy did not change, aggregation with ADP steadily improved, and aggregation with collagen first decreased and then increased in anticorrellation with bleeding. The only platelet function marker associated with bleeding in CLL was aggregation with ADP. Bleeding in MCL was observed in 10 (62%) patients, who had decreased dense granule release before therapy. Aggregation with ADP and ristocetin in MCL increased on therapy, while collagen-induced aggregation evolved similarly to CLL. Decreased platelet count prior to ibrutinib treatment (114±53×109/l versus 170±70×109/l) was associated with a significant risk of developing bleeding (AUC=0.71±0.07) on ibrutinib in CLL but not in MCL.
Conclusions: We show that decreased platelet count and aggregation with ADP prior to ibrutinib therapy in CLL are predictive for on-therapy bleeding. Disappearance of bleeding in the course of ibrutinib therapy is associated with improved platelet reactivity towards ADP.
To cite this abstract in AMA style:Ignatova AA, Nikitin EA, Dmitrieva EA, Vorobyev VI, Poletaev AV, Seregina EA, Polokhov DM, Maschan AA, Novichkova GA, Ptushkin VV, Panteleev MA. Bleeding Symptoms Associated with Platelet Function Abnormalities on Ibrutinib Therapy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/bleeding-symptoms-associated-with-platelet-function-abnormalities-on-ibrutinib-therapy/. Accessed May 18, 2021.
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