Abstract
Therapy with irreversible Bruton's tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is associated with bleeding. To propose the predictive markers of such bleeding, as well as mechanisms responsible for decreased bleeding at later therapy stages. We investigate platelet functional activity in 50 CLL and 16 MCL patients on ibrutinib using flow cytometry and light transmission aggregometry. Prior to treatment, both patient groups had decreased platelet counts; impaired aggregation with adenosine diphosphate (ADP); and decreased binding of CD62P, PAC1, and annexin V upon stimulation. Bleeding in patients treated with 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, platelet aggregation with ADP steadily improved, and aggregation with collagen first decreased and then increased in anticorrellation with bleeding. Bleeding in MCL was observed in 10 (62%) patients, who had decreased dense granule release before therapy. ADP and ristocetin induced platelet aggregation in ibrutinib-treated MCL patients increased on therapy, while collagen-induced aggregation evo...Continue Reading
References
Nov 1, 1991·The Journal of Clinical Investigation·A J MarcusA M Eiroa
Mar 1, 1995·The Biochemical Journal·L F MortonM J Barnes
Jun 22, 2006·Blood·Junling LiuT Kent Gartner
May 8, 2007·Journal of Translational Medicine·Dianne PulteAaron J Marcus
Jan 25, 2008·Blood·Michael HallekUNKNOWN International Workshop on Chronic Lymphocytic Leukemia
Jan 31, 2013·Blood·Francesco RodeghieroRoberto Stasi
Feb 23, 2013·Blood·Jianlin QiaoElizabeth E Gardiner
Aug 21, 2014·Leukemia·S KamelC S Tam
Oct 12, 2014·Blood·Marie LevadeBernard Payrastre
Sep 12, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Alexander P ByeJonathan M Gibbins
Oct 3, 2015·Haematologica·Andrew H LipskyAdrian Wiestner
Dec 10, 2015·Vox Sanguinis·A A IgnatovaM A Panteleev
Dec 15, 2015·American Journal of Physiology. Cell Physiology·Rachel A RiggOwen J T McCarty
Dec 3, 2016·Leukemia·L KaziankaU Jaeger
Dec 17, 2016·Haematologica·Robert H LeeWolfgang Bergmeier
Jan 21, 2017·Drugs·Emma D Deeks
Apr 5, 2017·Blood·Paul M BarrJohn C Byrd
Jan 4, 2018·Blood Advances·Alexander P ByeJonathan M Gibbins
Aug 6, 2018·Clinical Lymphoma, Myeloma & Leukemia·Joseph MockHillary Maitland
Sep 10, 2018·Thrombosis Research·A V PoletaevМ A Panteleev
Oct 5, 2018·Platelets·Anastasia A IgnatovaMikhail A Panteleev
Dec 7, 2018·British Journal of Haematology·Jennifer R BrownJan A Burger
Mar 2, 2019·Haematologica·Jennifer SeriesBernard Payrastre
Apr 16, 2019·Cancer Medicine·Peter GeorgantopoulosCharles L Bennett
May 1, 2019·Clinical Lymphoma, Myeloma & Leukemia·Marko Lucijanic, Marko Skelin
Dec 25, 2019·The Journal of Pharmacology and Experimental Therapeutics·Melissa HopperAnn Mongan
Apr 8, 2020·Cancer Management and Research·Krista Isaac, Anthony R Mato
Citations
Sep 1, 2020·Leukemia & Lymphoma·Rebecka SvanbergCarsten U Niemann
Jan 19, 2021·Journal of Thrombosis and Haemostasis : JTH·Philip Crispin, Elizabeth E Gardiner
Mar 30, 2021·Frontiers in Cell and Developmental Biology·H Yesid EstupiñánC I Edvard Smith
Apr 17, 2021·Hämostaseologie·N A PodoplelovaM A Panteleev
Aug 4, 2021·Current Oncology Reports·Maude SestierDarryl Leong
Dec 16, 2021·PloS One·Ekaterina M KoltsovaAnna N Balandina
Dec 17, 2021·Frontiers in Immunology·Leigh Naylor-AdamsonMònica Arman