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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.

Author information

1
Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
2
Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
3
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
4
Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK.
5
Department of Medicine III, Paracelsus Medical University, Salzburg, Austria.
6
Klinikum Schwabing, Academic Teaching Hospital of the University of Munich, Munich, Germany.
7
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
8
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Abstract

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.

PMID:
27909342
PMCID:
PMC5338745
DOI:
10.1038/leu.2016.316
[Indexed for MEDLINE]
Free PMC Article

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