title: Ristocetin-induced platelet aggregation for monitoring of bleeding tendency in CLL treated with ibrutinib.
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.
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Kazianka
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Drucker
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Skrabs
authors.affiliation: Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK.
authors.forename: W
authors.initials: W
authors.lastname: Thomas
authors.affiliation: Department of Medicine III, Paracelsus Medical University, Salzburg, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Melchardt
authors.affiliation: Klinikum Schwabing, Academic Teaching Hospital of the University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Struve
authors.affiliation: Klinikum Schwabing, Academic Teaching Hospital of the University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: P B
authors.initials: PB
authors.lastname: Staber
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Porpaczy
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Einberger
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Heinz
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Hauswirth
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Raderer
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Thalhammer
authors.affiliation: Department of Medicine III, Paracelsus Medical University, Salzburg, Austria.
authors.forename: A
authors.identifier: 0000-0003-0648-4416
authors.initials: A
authors.lastname: Egle
authors.affiliation: Klinikum Schwabing, Academic Teaching Hospital of the University of Munich, Munich, Germany.
authors.forename: C-M
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK.
authors.forename: G
authors.initials: G
authors.lastname: Follows
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Hoermann
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Quehenberger
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Jaeger
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D010974:Platelet Aggregation / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D012310:Ristocetin / Q000494:pharmacology*
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D012310:Ristocetin; C551803:ibrutinib; D000225:Adenine