The Effect of Eltrombopag on the Expression of Platelet Collagen Receptor GPVI in Pediatric ITP.

Summary

Using eltronmobag as an alternative pathway, which depend on stimulation of thrombocyte synthesis, in chronic and persistent immune thrombocytopenia may be more promising treatment than the classic type, not only by increasing platelets count but also through enhancing of the platelets activation and upregulation of GPVI expression on platelet surface. This study will include 40 pediatric patients with chronic or persistent ITP, recruited from the Hematology clinic of pediatric hospital Ain Shams University, aiming to investigate the efficacy, \& the safety and tolerability of eltrombopag therapy for children as well as the ability of eltrombopag to enhance the platelet activation through the up-regulation of glycoprotein VI (GPVI) receptor expression in comparison with other lines of treatment. Patients will be divided into 2 groups : Group 1 on eltrombopag ; Group 2 : receiving other lines of therapy . All Patients will be subjected to : 1. bleeding score assessment ( baseline \&every month ) and Health related quality of life based on Kids' ITP Tools (KIT) questionnaires( baseline and week 24 ) 2. Baseline and at week 24 bone marrow examination with reticulin stain 3. clinical examination every 2 weeks and complete blood counts. 4. Assessment of soluble form of glycoprotein VI using sandwich enzyme-linked immunosorbent assay (ELISA) as well as assessment of platelet activation by GPVI using flowcytometry (Gardiner, etal.,2010 ) at baseline and at the end of 6 months treatment period

Timeline

Start

2018-08-01

Primary completion

2021-09-01

Completion

2021-09-01

Publications

• Background Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. doi: 10.1182/blood-2005-12-015222. Epub 2006 Oct 31.
• Results Buchanan GR. Overview of ITP treatment modalities in children. Blut. 1989 Jul;59(1):96-104. doi: 10.1007/BF00320257.
• Results Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, Lambert MP, Marcello LM, Iyengar M, Chan GW, Chagin KD, Theodore D, Bailey CK, Bakshi KK. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015 Aug;2(8):e315-25. doi: 10.1016/S2352-3026(15)00114-3. Epub 2015 Jul 28.
• Results Chiou TJ, Chang YF, Wang MC, Kao CW, Lin HY, Chen TY, Hsueh EJ, Lan YJ, Sung YC, Lin SF, Bai LY, Chen CG. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura. Transl Res. 2015 Dec;166(6):750-761.e4. doi: 10.1016/j.trsl.2015.09.005. Epub 2015 Sep 30.
• Results Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28;346(13):995-1008. doi: 10.1056/NEJMra010501. No abstract available.
• Results Ehrlich LA, Kwitkowski VE, Reaman G, Ko CW, Nie L, Pazdur R, Farrell AT. U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia. Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26657. Epub 2017 Jun 19.
• Results Gardiner EE, Andrews RK. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI. Transfus Med Rev. 2014 Apr;28(2):56-60. doi: 10.1016/j.tmrv.2014.03.001. Epub 2014 Mar 12.
• Results Gardiner EE, Thom JY, Al-Tamimi M, Hughes A, Berndt MC, Andrews RK, Baker RI. Restored platelet function after romiplostim treatment in a patient with immune thrombocytopenic purpura. Br J Haematol. 2010 May;149(4):625-8. doi: 10.1111/j.1365-2141.2010.08092.x. Epub 2010 Feb 8. No abstract available.
• Results Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. doi: 10.1016/S0140-6736(15)61107-2. Epub 2015 Jul 28.
• Results Holmes ML, Bartle N, Eisbacher M, Chong BH. Cloning and analysis of the thrombopoietin-induced megakaryocyte-specific glycoprotein VI promoter and its regulation by GATA-1, Fli-1, and Sp1. J Biol Chem. 2002 Dec 13;277(50):48333-41. doi: 10.1074/jbc.M206127200. Epub 2002 Sep 30.
• Results Klaassen RJ, Blanchette VS, Barnard D, Wakefield CD, Curtis C, Bradley CS, Neufeld EJ, Buchanan GR, Silva MP, Chan AK, Young NL. Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools. J Pediatr. 2007 May;150(5):510-5, 515.e1. doi: 10.1016/j.jpeds.2007.01.037.
• Results Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, Cines DB, Cooper N, Godeau B, Greinacher A, Imbach P, Khellaf M, Klaassen RJ, Kuhne T, Liebman H, Mazzucconi MG, Newland A, Pabinger I, Tosetto A, Stasi R. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013 Apr 4;121(14):2596-606. doi: 10.1182/blood-2012-07-442392. Epub 2013 Jan 29.
• Results Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
• Results Yun SH, Sim EH, Goh RY, Park JI, Han JY. Platelet Activation: The Mechanisms and Potential Biomarkers. Biomed Res Int. 2016;2016:9060143. doi: 10.1155/2016/9060143. Epub 2016 Jun 15.
• Results Meletis J, Katsandris A, Raptis SD, Mantzourani M. Successful treatment of Immune Thrombocytopenic Purpura (ITP) with the thrombopoietin-mimetic romiplostim. Med Sci Monit. 2010 Aug;16(8):CS100-2.

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