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Leukemia. 2017 May;31(5):1117-1122. doi: 10.1038/leu.2016.316. Epub 2016 Nov 2.

Ristocetin-induced platelet aggregation for monitoring of bleeding tendency in CLL treated with ibrutinib.

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Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK.
Department of Medicine III, Paracelsus Medical University, Salzburg, Austria.
Klinikum Schwabing, Academic Teaching Hospital of the University of Munich, Munich, Germany.
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.


Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0.0001). RIPA was impaired in patients receiving concomitant antiplatelet therapy or anticoagulation (14 vs 25 U, P=0.005). A gradual decline of median RIPA values was observed with increasing bleeding severity. Importantly, no CTC grade 2 or 3 bleeding were observed with RIPA values of >36 U. Sequential monitoring indicated a decrease of RIPA values from a median of 17 to 9 U within 2 weeks after initiation of treatment as well as an increase above the critical threshold of 36 U within 7 days when ibrutinib was paused. Low RIPA values were similar during treatment with another BTK inhibitor, CC292. Quantitative assessment of platelet function is a practical tool to monitor bleeding tendency under BTK-inhibitor therapy.

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