Первичная иммунная тромбоцитопения. Современный взгляд на патогенез и лечение
Автор: Зотова И.И., Грицаев С.В., Бессмелъцев С.С.
Журнал: Вестник гематологии @bulletin-of-hematology
Рубрика: Обзор литературы
Статья в выпуске: 4 т.13, 2017 года.
Бесплатный доступ
В статье дано современное представление о ключевых механизмах патогенезаи методах лечения первичной иммунной тромбоцитопении. Представлена сравнительная характеристика основных методов терапии заболевания, включая оценку эффективностии безопасности лечения. Обозначена необходимость изучения индивидуальных особенностей течения заболевания и поиска предикторов ответа на терапию с целью возможного прогнозирования эффективности определенного метода лечения.
Иммунная тромбоцитопения, мегакариорцитопоэз, тромбопоэтин, линия терапии
Короткий адрес: https://sciup.org/170172521
IDR: 170172521
Список литературы Первичная иммунная тромбоцитопения. Современный взгляд на патогенез и лечение
- Rodeghiero F., Stasi R., Gernsheimer T. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009; 113:2386-2393.
- Provan D., Stasi R., Newland A. C. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010; 115:168-186.
- Stasi R., Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004; 79:504-522.
- Масчан А. А., Румянцев А. Г., Ковалева Л. Г. и др. Рекомендации российского совета экспертов по диагностике и лечению больных первичной иммунной тромбоцитопенией. Онкогематология. 2010;3:36-45.
- Neunert C., Lim W., Crowther M. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
- Меликян А. Л., Пустовая Е. И., Цветаева Н. В. и др. Национальные клинические рекомендации по диагностике и лечению первичной иммунной тромбоцитопении (идиопатической тромбоцитопенической пурпуры) у взрослых. Гематология и трансфузиология. 2015;60(1):44-56.
- Ковалева Л. Г., Сафонова Т. И., Пустовая Е. И. и др. Клинико-статистические данные и оценка различных методов терапии идиопатической тромбоцитопенической пурпуры. Терапевтический архив. 2011;4:60-65.
- Kuter D. J. Milestones in understanding platelet production: a historical overview. Br J Haematol. 2014;165(2):248-258.
- Olsson B., Andersson P. O., Jernas M. et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003 Sep;9(9):1123-1124.
- Corthay A. How do regulatory T cells work? Scand J Immunol 2009;70(4):326-336.
- Andre S., Tough D. F., Lacroix-Desmazes S. et al. Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity. Am J Pathol 2009;174(5):1575-1587.
- McMillan R., Durette C. Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood. 2004; 104:956-960.
- Лисуков И. А., МасчанА.А., ШамардинаА.В. и др. Иммунная тромбоцитопения: клинические проявления и ответ на терапию. Промежуточный анализ данных Российского регистра пациентов с первичной иммунной тромбоцитопенией и обзор литературы. Онкогематология. 2013;2:61-69.
- Cohen Y. C., Djulbegovic B., Shamai-Lubovitz O. et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med. 2000; 160:1630-1638.
- Fogarty P. F. Chronic immune thrombocytopenia in adults: epidemiology and clinical presentation. Hematol Oncol Clin North Am. 2009 Dec;23(6):1213-1221.
- Rodeghiero F., Besalduch J., Michel M. et al. Treatment practices in adults with chronic immune thrombocytopenia — a European perspective. Eur J Haematol. 2010; 84:160-168.
- Gernsheimer T. Epidemiology and pathophysiology of immune thrombocytopenic purpura. Eur J Haematol Suppl.2008 Feb;(69):3-8.
- Michel M., RauzyO.B., ThoravalF.R.etal.Characteristics and outcome of immune thrombocytopenia in elderly: results from a single center case-controlled study. Am J Hematol. 2011 Dec;86(12):980-984.
- Arnold D.M., Dentali F., Crowther M. A. et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007;146(1):25-33.
- Labarque V., Van Geet C. Clinical practice: immune thrombocytopenia in paediatrics. Eur J Pediatr. 2014 Feb;173(2):163-172.
- Neylon A.J., Saunders P. W., Howard M. R. et al. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003; 122:966-974.
- Frederiksen H., Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999; 94:909-913.
- Schoonen W. M., Kucera G., Coalson J. et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol. 2009; 145:235-244.
- Melikyan A. L., Pustovaya E. I., Volodicheva E. M. et al. Incidence of Primary Immune Thrombocytopenia (ITP) in Adults in One Region of Russia. Blood. 2016;128(22): abstract 4941;11.841.
- Portielje J. E., Westendorp R. G., Kluin-Nelemans H.C. et al. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood. 2001;97:2549-2554.
- Newland A. C., Treleaven J. G., Minchinton R. M. et al. High-dose intravenous IgG in adults with autoimmune thrombocytopenia. Lancet. 1983;1:84-87.
- Cooper N. Intravenous immunoglobulin and anti-RhD therapy in the management of immune thrombocytopenia. Hematol Oncol Clin N Am. 2009;23:1317-1327.
- Bussel J. Intravenous immune serum globulin in immune thrombocytopenia: clinical results and biochemical evaluation. Vox Sang. 1985;49 Suppl 1:44-50.
- Godeau B., LesageS., DivineM.etal.Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin. Blood. 1993 Sep 1;82(5):1415-1421.
- Cuker A., Prak E. T., Cines D. B. Can immune thrombocytopenia be cured with medical therapy? Semin Thromb Hemost. 2015 Jun;41(4):395-404.
- George J. N., Woolf S. H., Raskob G. E., et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996 Jul 1;88(1):3-40.
- Stasi R., Evangelista M. L., Stipa E. et al. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008;99(1):4-13.
- Stasi R., Brunetti M., Pagano A. et al. Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura. Blood Cells Mol Dis. 2000 Dec;26(6):582-586.
- Mazzucconi M.G., Fazi P., Bernasconi S. et al. 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):1401-1407.
- Mithoowani S., Gregory-Miller K., Goy J. et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016 0ct;3(10): e489-e496.
- Yoshida Y. Historical review. The light and shadow of Paul Kaznelson: his life and contribution to hematology. Ann Hematol. 2008;87:877-879.
- Ghanima W., Godeau B., Cines D. B. et al. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood. 2012 Aug 2;120(5):960-969.
- Kojouri K., Vesely S. K., Terrell D. R. et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004 Nov 1;104(9):2623-2634.
- Vianelli N., Galli M., de Vivo A. et al. Efficacy and safety of splenectomy in immune thrombocytopenic purpura: long-term results of 402 cases. Haematologica. 2005 Jan;90(1):72-77.
- Schwartz J., Leber M. D., Gillis S. et al. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP).Am J Hematol. 2003 Feb;72(2):94-98.
- Najean Y., Rain J. D., Billotey C. The site of destruction of autologous 111In-labelled platelets and the efficiency of splenectomy in children and adults with idiopathic thrombocytopenic purpura: a study of 578 patients with 268 splenectomies. Br J Haematol. 1997 Jun;97(3):547-550.
- Johansson E., Engervall P., Landgren O. et al. Response to splenectomy is durable after a certain point in time in adult patients with chronic immune thrombocytopenic purpura. Eur J Haematol. 2006;77:61-66.
- Keidar A., Sagi B., Szold A. Laparoscopic splenectomy for immune thrombocytopenic purpura in patients with severe refractory thrombocytopenia. Pathophysiol Haemost Thromb. 2003;33:116-119.
- Naouri A., Feghali B., Chabal J. et al. Results of splenectomy for idiopathic thrombocytopenic purpura. Review of 72 cases. Acta Haematol. 1993;89:200-203.
- Stanford E., Print F., Falconer M. et al. Immune response to pneumococcal conjugate vaccination in asplenic individuals. Hum Vaccin. 2009 Feb;5(2):85-91.
- Stasi R., Stipa E., Masi M. et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995 May;98(5):436-442.
- Pamuk G. E., Pamuk O. N., Bailar Z. et al. Overview of 321 patients with idiopathic thrombocytopenic purpura. Retrospective analysis of the clinical features and response to therapy. Ann Hematol. 2002 Aug;81(8):436-440.
- Cooper N., Evangelista M. L., Amadori S. at al. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura? Curr Opin Hematol. 2007 Nov;14(6):642-646.
- Zaja F., Battista M. L., Pirrotta M. T. et al. Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica. 2008 Jun;93(6):930-933.
- Godeau B., Porcher R., Fain O., et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood 2008;112(4):999-1004.
- Arnold D. M., Heddle N. M., Carruthers J. et al. A pilot randomized trial of adjuvant rituximab or placebo for non-splenectomized patients with immune thrombocytopenia. Blood 2012 Feb 9;119(6):1356-1362.
- Patel V. L., Mahevas M., Lee S. Y. et al. Outcomes 5 years after response to rituximab therapy in children and adults with mmune thrombocytopenia. Blood 2012;119:5989-5995.
- Cooper N., Stasi R., Cunningham Rundles S. et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol 2004;125(2): 232-239.
- Ghanima W., Elstrom R., Bussel J. B. The combination of three dexamethasone cycles and rituximab yields high response rate in previously treated immune thrombocytopenia (ITP) [abstract].Haematologica 2011;96:95. Abstract 231.
- Carson K. R., Evens A. M., Richey E. A. et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009 May 14;113(20):4834-4840.
- Provan D., Newland A. Fifty years of idiopathic thrombocytopenic purpura (ITP): management of refractory ITP in adults. Br J Haematol. 2002; 118:933-944.
- Hamidpour M., Behrendt M., Griffiths B. et al. The isolation and characterization of antiplatelet antibodies. Eur J Haematol 2006;76(4):331-338.
- Минеева Н. В., Коробинец И. И., Блинов М. Н. и др. Антигены и антитела к тромбоцитам (обзор литературы). Онкогематология. 2013;3:60-68.
- Зотиков Е. А., Бабаева А. Г., Головкина Л. Л. Тромбоциты и антитромбоцитарные антитела. М: Моно-лит,2003.128 с.
- McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol. 2000 Jul;37(3):239-248.
- Kuwana M., Ikeda Y. The role of autoreactive T-cells in the pathogenesis of idiopathic thrombocytopenic purpura. Int J Hematol 2005;81(2):106-112.
- Ji X., Zhang L., Peng J. et al. T cell immune abnormalities in immune thrombocytopenia. J Hematol Oncol. 2014 Oct 2;7:72.
- Фрейдлин И. С. Регуляторные Т-клетки: происхождение и функции. Медицинская Иммунология. 2005;7(4):347-354.
- Li S., Wang L., Zhao C. et al.CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura.Br J Haematol. 2007 Nov;139(4):605-611.
- Zufferey A., Kapur R., Semple J. W. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J Clin Med. 2017 Feb; 6(2): 16.
- AbadiU., Yarchovsky-Dolberg O., Ellis M. H. Immune thrombocytopenia: recent progress in pathophysiology and treatment. Clin Appl Thromb Hemost. 2015 Jul;21(5):397-404.
- Imbach P., Crowther M. Thrombopoietin-receptor agonists for primary immune thrombocytopenia. N Engl J Med.2011 Aug 25;365(8):734-741.
- Черешнев В. А., Юшков Б. Г., Климин В. Г. и др. Тромбоцитопоэз. М: Медицина, 2007.269 с.
- Makar R.S., Zhukov O. S., Sahud M. A. et al. Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. Am J Hematol. 2013 Dec;88(12):1041-1044.
- Nurden A. T., Viallard J. F., Nurden P. et al. New generation drags that stimulate platelet production in chronic immune thrombocytopenic purpura. Lancet. 2009;373(9674):1562-1569.
- Li J., Yang C., Xia Y. et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001; 98:3241-3248.
- Wang B., Nichol J. L., Sullivan J. T. et al. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004 Dec;76(6):628-638.
- Kuter D. J. New thrombopoietic growth factors. Blood. 2007 Jun 1;109(11):4607-4616.
- Bussel J.B., Kuter D. J., George J. N. et al. AMG 531, a thrombopoietin stimulating protein, for chronic ITP. N Engl J Med. 2006;355(16):1672-1681.
- Kaushansky K. Thrombopoietin: the primary regulator of megakaryocyte and platelet production. Thromb Haemost. 1995; 74:521-525.
- Stasi R., Evangelista M. L., Amadori S. Novel thrombopoietic agents: a review of their use in idiopathic thrombocytopenic purpura. Drugs. 2008;68(7):901-912.
- Erickson-Miller C.L,. Delorme E., Tian S. S. et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-430.
- Erickson-Miller C.L., Delorme E., Tian S. S., et al. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol. 2005 Jan;33(1):85-93.
- Инструкция по медицинскому применению препарата Энплейт (Nplate) ЛСР- 007739/09.
- Jenkins J.M., Williams D., Deng Y. et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007 Jun 1;109(11):4739-4741.
- Bussel J. B., Provan D., Shamsi T. et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic immune thrombocytopenic purpura: a randomised double-blind, placebo-controlled trial. Lancet. 2009;373(9664):641-648.
- Инструкция по медицинскому применению препарата Револейд ЛСР- 010032/09-030317.
- Kumagai Y., Fujita T., Ozaki M. et al. Pharmacodynamics and pharmacokinetics ofAMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol. 2007 Dec;47(12):1489-1497.
- Newland A., Caulier M. T., Kappers-Klunne M. et al. An open-label, unit dose-finding study ofAMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br J Haematol. 2006 Nov;135(4):547-553.
- Shirasugi Y., Ando K., HashinoS. et al. A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura. Int J Hematol. 2009 Sep;90(2):157-165.
- Kuter D. J., Bussel J. B., LyonsR. M. etal. Efficacy ofromiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403.
- Kuter D. J., Rummel M., Boccia R. et al. Romiplostim or standard of care in patients with immune thrombocytopenia.N Engl J Med. 2010 Nov 11;363(20):1889-1899.
- Bussel J. B., Kuter D. J., Pullarkat V. et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009 Mar 5;113(10):2161-2171.
- Kuter D.J., BusselJ.B., NewlandA. et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013 May;161(3):411-423.
- Bussel J.B., Cheng G., Saleh M. N. et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-2247.
- Cheng G., Saleh M. N., Marcher C. et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402.
- Saleh M. N., Bussel J. B., Cheng G. et al. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-545.
- Bussel J.B., Saleh M. N., Vasey S. Y. et al. Repeated short-term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP).Br J Haematol. 2013 Feb;160(4):538-546.
- Pullarkat V.A., Gernsheimer T. B., Wasser J. S. et al. Quantifying the reduction in immunoglobulin use over time in patients with chronic immune thrombocytopenic purpura receiving romiplostim (AMG 531).Am J Hematol. 2009 Aug;84(8):538-540.
- Wasser J., Boccia R., Lyons R. M. Use ofrituximab in a study comparing the thrombopoietin mimetic romiplostim with standard of care (SOC) in a patients with immune thrombocytopenia (ITP). Blood 2011;118(21):3282.
- Janssens A., Rodeghiero F., Anderson D. et al. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol. 2016 Jun;95(7):1077-1087.
- Brynes R.K., Orazi A., Theodore D. et al. Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: Data from the EXTEND study.Am J Hematol. 2015 Jul;90(7):598-601.
- Boiocchi L., Orazi A., Ghanima W. et al. Thrombopoietin receptor agonist therapy in primary immune thrombocytopenia is associated with bone marrow hypercellularity and mild reticulin fibrosis but no other stromal abnormalities. Mod Pathol. 2012 Jan;25(1):65-74.
- Ghanima W., Geyer J. T., Lee C. S. et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica. 2014 May;99(5):937-944.
- 100.Gernsheimer T.B., GeorgeJ.N., AledortL.M.etal.Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP).J Thromb Haemost. 2010 Jun;8(6):1372-1382.
- 101.Bussel J.B., Rodeghiero F., Lyons R. et al. Sustained hemostatic platelet counts in adults with chronic immune thrombocytopenia (ITP) following cessation of treatment with the TPO receptor agonist romiplostim: report of 9 cases. Blood (ASH Annual Meeting Abstracts). 2011;118(21): Abstract 3281.
- 102.Carpendo M., Cantoni S., Coccini V. et al. Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice. Hematol Rep. 2015;7(1):5673.
- 103.Mahevas M., Fain O., Ebbo M. et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Hematol. 2014;165(6):865-869.
- Cervinek L., Mayer J., Doubek M. Sustained remission ofchronic immune thrombocytopenia after discontinuation of treatment with thrombopoietin-receptor agonists in adults. Int J Hematol. 2015 Jul;102(1):7-11.
- 105.BusselJ.B., WangX., LopezA. etal.Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim. Hematology. 2016 May;21(4):257-262.
- 106.Gonzalez-LopezT.J., Pascual C., Alvarez-Roman M.T. et al. Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol. 2015 Mar;90(3): e40-e43.
- 107.Marshall A. L., Scarpone R., De Greef M. et al. Remissions after long-term use of romiplostim for immune thrombocytopenia. Haematologica. 2016 Dec;101(12): e476-e478.
- 108.Newland A., Godeau B., Priego V. et al. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol. 2016 Jan;172(2):262-273.
- 109.Khellaf M., Michel M., Quittet P. et al. Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program. Blood.2011;118:4338-4345.
- Птушкин В. В., Миненко С. В., Биячуев Э. Р. и др. Лечение больных с резистентной иммунной тромбо-цитопенией: обзор литературы и клинические наблюдения. Онкогематология. 2011;1:56-63.
- Зотова И. И., Абдулкадыров К. М. Опыт применения ромиплостима при хронической иммунной тромбо-цитопении, резистентной к предшествующей терапии. Гематология и трансфузиология. 2012;57(3):48-49.
- Kuter D. J., Macahiling C., Grotzinger K. M. et al. Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim. Int J Hematol. 2015,101:255263.
- Zotova I., Gritsaev S., Shilova E.et al. Thrombopoietin reсeptor agonists in the treatment of primary ITP: experience of application in clinical practice one medical center. Haematologica. 2016; 101(s1): Abstract 2091.
- Mazza P., Minoia C., Melpignano A. et al. The use of thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): a "real life" retrospective multicenter experience of the Rete Ematologica Pugliese (REP).Ann Hematol. 2016 Jan;95(2):239-244.
- Gonzalez-LopezT.J., Alvarez-RomanM.T., PascualC. et al. Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice. Eur J Haematol. 2016 Sep;97(3):297-302.
- Зотова И.И., Грицаев С. В., Шилова Е. Р. и др. Агонисты рецептора тромбопоэтина в лечении идиопати-ческой тромбоцитопенической пурпуры (первичной иммунной тромбоцитопении): эффективность и безопасность в повседневной клинической практике. Клиническая онкогематология.2017;1:93-100.