A Pilot Study on Probing of Imatinib Induced Platelet Dysfunction in Patients with Chronic Myeloid Leukemia-Chronic Phas
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A Pilot Study on Probing of Imatinib Induced Platelet Dysfunction in Patients with Chronic Myeloid Leukemia-Chronic Phase and Absence of Associated Bleeding Manifestation: Trying to Solve an Enigma Rajib De1 • Ranjini Chowdhury2 • Tuphan Kanti Dolai1 • Biswajit Bhar3 Mohammad Mirazul Islam4 • Prantar Chakrabarty5 • Suryyani Deb6
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Received: 28 April 2020 / Accepted: 28 October 2020 Ó Indian Society of Hematology and Blood Transfusion 2020
Abstract Imatinib, the first Tyrosine Kinase Inhibitor (TKI) used for the treatment of chronic myeloid leukaemia (CML) has revolutionized the management by inhibiting BCR-ABL tyrosine kinase. According to earlier reports there are concerns regarding the adverse effect of imatinib on haemostasis by causing platelet dysfunction. Here we studied platelet function using platelet aggregometry, in 19 CML chronic phase (CML-CP) patients on imatinib therapy, in complete haematologic response (CHR). The median duration of imatinib therapy before performing the test was 154 days. This study reveals that there are large
Rajib De and Ranjini Chowdhury have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12288-020-01376-8) contains supplementary material, which is available to authorized users. & Suryyani Deb [email protected] 1
Department of Haematology, NRS Medical College, 138 AJC Bose Road, Kolkata 700014, India
2
Department of Biochemistry, University of Calcutta, Kolkata 700019, India
3
Institute of Haematology and Transfusion Medicine, Medical College, MCH 3rd Floor, 88 College Street, Kolkata 700073, India
4
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford St, Boston, MA 02114, USA
5
Vivekananda Institute of Medical Sciences, 99 Sarat Bose Road, Kolkata 700026, India
6
Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, Kolkata, West Bengal 741249, India
inter-individual variations in platelet functions among imatinib treated patients and different levels of variability have been seen for different agonists. Most common aggregation abnormality (\ 50% aggregation) was seen with low dose collagen (1 lg/ml) in 31.57% patients. Despite in-vitro platelet aggregation defects, none of the patients showed any bleeding symptoms. This enigma can possibly be explained by the fact that platelet specific agonists, epinephrine and collagen act in synergy for platelet aggregation compared against individual low dose agonists, supported by ex-vivo experiments in normal healthy control group (n = 5) (p value \ 0.0004 for epinephrine, p value \ 0.0001 for collagen). This experiment was also confirmed in a CML-CP patient. In future, more studies are needed to find out the exact mechanism of this inhibition. Keywords Platelet aggregation Chronic myeloid leukemia Imatinib therapy Inter-patient variability Collagen epinephrine synergy Abbreviations CML Chronic Myeloid Leukemia CML-CP Chronic Myeloid Leukem
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