Platelet functions of CLL and MCL patients treated with Imbruvica (ibrutinib). (A) Clinical and biological data were collected before initiation of the treatment (day 0) and after 2 to 4 weeks of treatment (days 15-30). Platelet aggregation induced by collagen (3.3 µg/mL), adenosine 5′-diphosphate (5 µM), or U46619 (5 µM) on PRP was assessed as in Figure 1 at day 0 and days 15 to 30 and expressed as means ± SEM. It is noteworthy that platelet aggregation induced by collagen at day 0 was slightly reduced in the patients group compared with healthy donors (88 ± 6% for healthy donors and 69 ± 7% for patients, P < .01, n = 19 healthy donors). Of note, in the nonbleeding group at days 15 to 30, patients 06 and 10 had a strong reduction of aggregation. Importantly, patient 06 ($) experienced a severe metrorrhagia at day 50. Platelet adhesion on VWF matrix was assessed for 6 patients (01, 02, 03, 07, 08, and 14) as in Figure 1 and expressed as the surface coverage. Results are presented as means ± SEM. (B) Example of a patient (01) showing platelet dysfunction and bleeding symptoms on ibrutinib treatment. (C) Example of a patient (08) with normal platelet responses and no hemostasis-related adverse effect on ibrutinib treatment. Hyperleukocytosis was not correlated to ex vivo platelet dysfunction. *P < .05 and **P < .01. D0, day 0; D15, day 15.