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Semin Thromb Hemost 2020; 46(03): 275-288
DOI: 10.1055/s-0039-1700512
Review Article

Immune Thrombocytopenia in Adults: Modern Approaches to Diagnosis and Treatment

Authors

  • Hanny Al-Samkari

    1   Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

  • David J. Kuter

    1   Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder affecting approximately 1 in 20,000 people. Patients typically present with clinically benign mucocutaneous bleeding, but morbid internal bleeding can occur. Diagnosis remains clinical, possible only after ruling out other causes of thrombocytopenia through history and laboratory testing. Many adult patients do not require treatment. For those requiring intervention, initial treatment of adult ITP is with corticosteroids, intravenous immunoglobulin, or intravenous anti-RhD immune globulin. These agents are rapid-acting but do not result in durable remissions in most patients. No corticosteroid has demonstrated superiority to others for ITP treatment. Subsequent treatment of adult ITP is typically with thrombopoietin receptor agonists (TPO-RAs; romiplostim or eltrombopag), rituximab, or splenectomy. TPO-RAs are newer agents that offer an excellent response rate but may require prolonged treatment. The choice between subsequent treatments involves consideration of operative risk, risk of asplenia, drug side-effects, quality-of-life issues, and financial costs. Given the efficacy of medical therapies and the rate of spontaneous remission in the first year after diagnosis, splenectomy is frequently deferred in modern ITP treatment algorithms. Fostamatinib (a tyrosine kinase inhibitor recently approved by the U.S. Food and Drug Administration) and several older immunosuppressive agents (azathioprine, cyclophosphamide, cyclosporine, danazol, dapsone, mycophenolate mofetil, and the Vinca alkaloids) may be useful in patients with disease unresponsive to standard therapies or in specific clinical circumstances. This comprehensive review explores diagnostic considerations and surveys new and old treatment options for adults with ITP.

Keywords

platelets - immune thrombocytopenia - diagnosis - treatment - corticosteroids - intravenous immunoglobulin - splenectomy - thrombopoietin receptor agonist - rituximab - fostamatinib

Authors' Contributions

H.A. drafted the manuscript, created the tables and figures, and contributed to the concept and design, critical revision of the intellectual content, and final approval. D.J.K. contributed to the concept and design, critical revision of the intellectual content, and final approval.




Publikationsverlauf

Publikationsdatum:
12. Dezember 2019 (online)

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med 1951; 38 (01) 1-10
    Suche in Google Scholar
  • 2 Harker LA, Finch CA. Thrombokinetics in man. J Clin Invest 1969; 48 (06) 963-974
    Suche in Google Scholar
  • 3 McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004; 103 (04) 1364-1369
    Suche in Google Scholar
  • 4 Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117 (16) 4190-4207
    Suche in Google Scholar
  • 5 Provan D, Stasi R, Newland AC. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115 (02) 168-186
    Suche in Google Scholar
  • 6 Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94 (03) 909-913
    Suche in Google Scholar
  • 7 Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. Northern Region Haematology Group. 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 (06) 966-974
    Suche in Google Scholar
  • 8 Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol 2003; 25 (08) 660-664
    Suche in Google Scholar
  • 9 Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000; 160 (11) 1630-1638
    Suche in Google Scholar
  • 10 Newton JL, Reese JA, Watson SI. et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011; 86 (05) 420-429
    Suche in Google Scholar
  • 11 Hill QA, Newland AC. Fatigue in immune thrombocytopenia. Br J Haematol 2015; 170 (02) 141-149
    Suche in Google Scholar
  • 12 Vrbensky JR, Moore JE, Arnold DM, Smith JW, Kelton JG, Nazy I. The sensitivity and specificity of platelet autoantibody testing in immune thrombocytopenia: a systematic review and meta-analysis of a diagnostic test. J Thromb Haemost 2019; 17 (05) 787-794
    Suche in Google Scholar
  • 13 Al-Samkari H, Kuter DJ. Antiplatelet antibody testing in immune thrombocytopenia and Evans syndrome: longitudinal serologic evolution and relation to clinical features [abstract]. Blood 2018; 132 (Suppl. 01) 1137
    Suche in Google Scholar
  • 14 Al-Samkari H, Kuter DJ. Thrombopoietin level predicts response to treatment with eltrombopag and romiplostim in immune thrombocytopenia. Am J Hematol 2018; 93 (12) 1501-1508
    Suche in Google Scholar
  • 15 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 (11) 2386-2393
    Suche in Google Scholar
  • 16 Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97 (09) 2549-2554
    Suche in Google Scholar
  • 17 Sailer T, Lechner K, Panzer S, Kyrle PA, Pabinger I. The course of severe autoimmune thrombocytopenia in patients not undergoing splenectomy. Haematologica 2006; 91 (08) 1041-1045
    Suche in Google Scholar
  • 18 Slichter SJ, Harker LA. Thrombocytopenia: mechanisms and management of defects in platelet production. Clin Haematol 1978; 7 (03) 523-539
    Suche in Google Scholar
  • 19 Slichter SJ, Kaufman RM, Assmann SF. et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med 2010; 362 (07) 600-613
    Suche in Google Scholar
  • 20 Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost 1977; 3 (03) 160-174
    Suche in Google Scholar
  • 21 Chantarangkul V, Clerici M, Bressi C, Tripodi A. Standardization of the endogenous thrombin potential measurement: how to minimize the effect of residual platelets in stored plasma. Br J Haematol 2004; 124 (03) 355-357
    Suche in Google Scholar
  • 22 Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 1972; 287 (04) 155-159
    Suche in Google Scholar
  • 23 Nagrebetsky A, Al-Samkari H, Davis NM, Kuter DJ, Wiener-Kronish JP. Perioperative thrombocytopenia: evidence, evaluation, and emerging therapies. Br J Anaesth 2019; 122 (01) 19-31
    Suche in Google Scholar
  • 24 Shulman NR, Weinrach RS, Libre EP, Andrews HL. The role of the reticuloendothelial system in the pathogenesis of idiopathic thrombocytopenic purpura. Trans Assoc Am Physicians 1965; 78: 374-390
    Suche in Google Scholar
  • 25 Gernsheimer T, Stratton J, Ballem PJ, Slichter SJ. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med 1989; 320 (15) 974-980
    Suche in Google Scholar
  • 26 Kitchens CS. Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit. J Clin Invest 1977; 60 (05) 1129-1134
    Suche in Google Scholar
  • 27 Kitchens CS, Weiss L. Ultrastructural changes of endothelium associated with thrombocytopenia. Blood 1975; 46 (04) 567-578
    Suche in Google Scholar
  • 28 Nakazaki K, Hosoi M, Hangaishi A, Ichikawa M, Nannya Y, Kurokawa M. Comparison between pulsed high-dose dexamethasone and daily corticosteroid therapy for adult primary immune thrombocytopenia: a retrospective study. Intern Med 2012; 51 (08) 859-863
    Suche in Google Scholar
  • 29 Bae SH, Ryoo HM, Lee WS. et al. High dose dexamethasone vs. conventional dose prednisolone for adults with immune thrombocytopenia: a prospective multicenter phase III trial [abstract]. Blood 2010; 116 (21) 3687
    Suche in Google Scholar
  • 30 Wei Y, Ji XB, Wang YW. et al. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood 2016; 127 (03) 296-302 , quiz 370
    Suche in Google Scholar
  • 31 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; 3 (10) e489-e496
    Suche in Google Scholar
  • 32 Gómez-Almaguer D, Tarín-Arzaga L, Moreno-Jaime B. et al. High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia. Eur J Haematol 2013; 90 (06) 494-500
    Suche in Google Scholar
  • 33 Gudbrandsdottir S, Birgens HS, Frederiksen H. et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 2013; 121 (11) 1976-1981
    Suche in Google Scholar
  • 34 Zaja F, Baccarani M, Mazza P. et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010; 115 (14) 2755-2762
    Suche in Google Scholar
  • 35 Chapin J, Lee CS, Zhang H, Zehnder JL, Bussel JB. Gender and duration of disease differentiate responses to rituximab-dexamethasone therapy in adults with immune thrombocytopenia. Am J Hematol 2016; 91 (09) 907-911
    Suche in Google Scholar
  • 36 Bussel JB, Lee CS, Seery C. et al. Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration. Haematologica 2014; 99 (07) 1264-1271
    Suche in Google Scholar
  • 37 Chugh S, Darvish-Kazem S, Lim W. et al. Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol 2015; 2 (02) e75-e81
    Suche in Google Scholar
  • 38 Zhang L, Zhang M, Du X, Cheng Y, Cheng G. Eltrombopag plus pulsed dexamethasone as first line therapy for subjects with immune thrombocytopenic purpura (ITP) [abstract]. Blood 2018; 132 (Suppl. 01) 733
    Suche in Google Scholar
  • 39 Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 2008; 26: 513-533
    Suche in Google Scholar
  • 40 Deng R, Balthasar JP. Pharmacokinetic/pharmacodynamic modeling of IVIG effects in a murine model of immune thrombocytopenia. J Pharm Sci 2007; 96 (06) 1625-1637
    Suche in Google Scholar
  • 41 Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura. Br J Haematol 2001; 112 (04) 1076-1078
    Suche in Google Scholar
  • 42 Tarantino MD, Young G, Bertolone SJ. et al; Acute ITP Study Group. Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children. J Pediatr 2006; 148 (04) 489-494
    Suche in Google Scholar
  • 43 Kumagai Y, Fujita T, Ozaki M. et al. Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol 2007; 47 (12) 1489-1497
    Suche in Google Scholar
  • 44 Jenkins JM, Williams D, Deng Y. et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007; 109 (11) 4739-4741
    Suche in Google Scholar
  • 45 Nomoto M, Pastino G, Rege B, Aluri J, Ferry J, Han D. Pharmacokinetics, pharmacodynamics, pharmacogenomics, safety, and tolerability of avatrombopag in healthy Japanese and white subjects. Clin Pharmacol Drug Dev 2018; 7 (02) 188-195
    Suche in Google Scholar
  • 46 Carr JM, Kruskall MS, Kaye JA, Robinson SH. Efficacy of platelet transfusions in immune thrombocytopenia. Am J Med 1986; 80 (06) 1051-1054
    Suche in Google Scholar
  • 47 Spahr JE, Rodgers GM. Treatment of immune-mediated thrombocytopenia purpura with concurrent intravenous immunoglobulin and platelet transfusion: a retrospective review of 40 patients. Am J Hematol 2008; 83 (02) 122-125
    Suche in Google Scholar
  • 48 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Thrombocytopenia in pregnancy. Number 6, September 1999. Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet 1999; 67 (02) 117-128
    Suche in Google Scholar
  • 49 Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003; 102 (13) 4306-4311
    Suche in Google Scholar
  • 50 Al-Jama FE, Rahman J, Al-Suleiman SA, Rahman MS. Outcome of pregnancy in women with idiopathic thrombocytopenic purpura. Aust N Z J Obstet Gynaecol 1998; 38 (04) 410-413
    Suche in Google Scholar
  • 51 Wyszynski DF, Carman WJ, Cantor AB. et al. Pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura. J Pregnancy 2016; 2016: 8297407
    Suche in Google Scholar
  • 52 Nicolescu A, Vladareanu AM, Voican I, Onisai M, Vladareanu R. Therapeutic options for immune thrombocytopenia (ITP) during pregnancy. Maedica (Buchar) 2013; 8 (02) 182-188
    Suche in Google Scholar
  • 53 Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood 2013; 121 (01) 38-47
    Suche in Google Scholar
  • 54 Neunert CE, Cooper N. Evidence-based management of immune thrombocytopenia: ASH guideline update. Hematology (Am Soc Hematol Educ Program) 2018; 2018 (01) 568-575
    Suche in Google Scholar
  • 55 Schwartz J, Leber MD, Gillis S, Giunta A, Eldor A, Bussel JB. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol 2003; 72 (02) 94-98
    Suche in Google Scholar
  • 56 Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood 2013; 121 (23) 4782-4790
    Suche in Google Scholar
  • 57 Morbieu C, Brunetti F, Baranès L. et al. Systematic detection of portal or splenic vein thrombosis after splenectomy for immune cytopenia. Am J Hematol 2018; 93 (07) E170-E172
    Suche in Google Scholar
  • 58 Swirski FK, Nahrendorf M, Etzrodt M. et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009; 325 (5940): 612-616
    Suche in Google Scholar
  • 59 Sun LM, Chen HJ, Jeng LB, Li TC, Wu SC, Kao CH. Splenectomy and increased subsequent cancer risk: a nationwide population-based cohort study. Am J Surg 2015; 210 (02) 243-251
    Suche in Google Scholar
  • 60 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; 172 (02) 262-273
    Suche in Google Scholar
  • 61 Marshall AL, Scarpone R, De Greef M, Bird R, Kuter DJ. Remissions after long-term use of romiplostim for immune thrombocytopenia. Haematologica 2016; 101 (12) e476-e478
    Suche in Google Scholar
  • 62 Desmond R, Townsley DM, Dumitriu B. et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 2014; 123 (12) 1818-1825
    Suche in Google Scholar
  • 63 Afdhal NH, Dusheiko GM, Giannini EG. et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014; 146 (02) 442-52.e1
    Suche in Google Scholar
  • 64 Al-Samkari H, Marshall AL, Goodarzi K, Kuter DJ. The use of romiplostim in treating chemotherapy-induced thrombocytopenia in patients with solid tumors. Haematologica 2018; 103 (04) e169-e172
    Suche in Google Scholar
  • 65 Al-Samkari H, Marshall AL, Goodarzi K, Kuter DJ. Romiplostim for the management of perioperative thrombocytopenia. Br J Haematol 2018; 182 (01) 106-113
    Suche in Google Scholar
  • 66 Kantarjian H, Fenaux P, Sekeres MA. et al. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol 2010; 28 (03) 437-444
    Suche in Google Scholar
  • 67 Cheng G, Saleh MN, Marcher C. et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011; 377 (9763): 393-402
    Suche in Google Scholar
  • 68 Kuter DJ, Bussel JB, Lyons RM. et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371 (9610): 395-403
    Suche in Google Scholar
  • 69 Bussel JB, Provan D, Shamsi T. et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373 (9664): 641-648
    Suche in Google Scholar
  • 70 González-López TJ, Pascual C, Álvarez-Román MT. et al. Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol 2015; 90 (03) E40-E43
    Suche in Google Scholar
  • 71 Makar RS, Zhukov OS, Sahud MA, Kuter DJ. Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. Am J Hematol 2013; 88 (12) 1041-1044
    Suche in Google Scholar
  • 72 Kuter DJ, Meibohm A, Lopez A. TPO concentrations and response to romiplostim. Am J Hematol 2014; 89 (12) 1155-1156
    Suche in Google Scholar
  • 73 Nomoto M, Ferry J, Hussein Z. Population pharmacokinetic/pharmacodynamic analyses of avatrombopag in patients with chronic liver disease and optimal dose adjustment guide with concomitantly administered CYP3A and CYP2C9 inhibitors. J Clin Pharmacol 2018; 58 (12) 1629-1638
    Suche in Google Scholar
  • 74 Williams DD, Peng B, Bailey CK. et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther 2009; 31 (04) 764-776
    Suche in Google Scholar
  • 75 Wire MB, Bruce J, Gauvin J. et al. A randomized, open-label, 5-period, balanced crossover study to evaluate the relative bioavailability of eltrombopag powder for oral suspension (PfOS) and tablet formulations and the effect of a high-calcium meal on eltrombopag pharmacokinetics when administered with or 2 hours before or after PfOS. Clin Ther 2012; 34 (03) 699-709
    Suche in Google Scholar
  • 76 Al-Samkari H. Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease. Drugs Today (Barc) 2018; 54 (11) 647-655
    Suche in Google Scholar
  • 77 Al-Samkari H, Kuter DJ. Relative potency of the thrombopoietin receptor agonists eltrombopag, avatrombopag and romiplostim in a patient with chronic immune thrombocytopenia. Br J Haematol 2018; 183 (02) 168
    Suche in Google Scholar
  • 78 Kuter DJ, Macahilig C, Grotzinger KM. et al. Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim. Int J Hematol 2015; 101 (03) 255-263
    Suche in Google Scholar
  • 79 GlaxoSmithKline. Promacta (Eltrombopag) [Prescribing Information]. Research Triangle Park, NC: 2017
    Suche in Google Scholar
  • 80 Al-Samkari H, Kuter DJ. An alternative intermittent eltrombopag dosing protocol for the treatment of chronic immune thrombocytopenia. Br J Clin Pharmacol 2018; 84 (11) 2673-2677
    Suche in Google Scholar
  • 81 Amgen I. Nplate (Romiplostim) [Prescribing Information]. Thousand Oaks, CA: Amgen; October 2017
    Suche in Google Scholar
  • 82 Kuter DJ, Rummel M, Boccia R. et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med 2010; 363 (20) 1889-1899
    Suche in Google Scholar
  • 83 Steurer M, Quittet P, Papadaki HA. et al. A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice. Eur J Haematol 2017; 98 (02) 112-120
    Suche in Google Scholar
  • 84 Jurczak W, Chojnowski K, Mayer J. et al. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol 2018; 183 (03) 479-490
    Suche in Google Scholar
  • 85 Psaila B, Bussel JB, Linden MD. et al. In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. Blood 2012; 119 (17) 4066-4072
    Suche in Google Scholar
  • 86 Al-Samkari H, Van Cott EM, Kuter DJ. Platelet aggregation response in immune thrombocytopenia patients treated with romiplostim. Ann Hematol 2019; 98 (03) 581-588
    Suche in Google Scholar
  • 87 Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009; 113 (10) 2161-2171
    Suche in Google Scholar
  • 88 Cines DB, Gernsheimer T, Wasser J. et al. Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim. Int J Hematol 2015; 102 (03) 259-270
    Suche in Google Scholar
  • 89 Kuter DJ, Mufti GJ, Bain BJ, Hasserjian RP, Davis W, Rutstein M. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 2009; 114 (18) 3748-3756
    Suche in Google Scholar
  • 90 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; 95 (07) 1077-1087
    Suche in Google Scholar
  • 91 Kantarjian HM, Fenaux P, Sekeres MA. et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol 2018; 5 (03) e117-e126
    Suche in Google Scholar
  • 92 Ghanima W, Khelif A, Waage A. et al; RITP Study Group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015; 385 (9978): 1653-1661
    Suche in Google Scholar
  • 93 Pasa S, Altintas A, Cil T, Danis R, Ayyildiz O. The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura. J Thromb Thrombolysis 2009; 27 (03) 329-333
    Suche in Google Scholar
  • 94 Červinek L, Černá O, Čaniga M. et al. Efficacy of rituximab in primary immune thrombocytopenia: an analysis of adult pretreated patients from everyday hematological practice. Int J Hematol 2012; 96 (05) 594-599
    Suche in Google Scholar
  • 95 Mahévas M, Ebbo M, Audia S. et al. Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia. Am J Hematol 2013; 88 (10) 858-861
    Suche in Google Scholar
  • 96 Tran H, Brighton T, Grigg A. et al. A multi-centre, single-arm, open-label study evaluating the safety and efficacy of fixed dose rituximab in patients with refractory, relapsed or chronic idiopathic thrombocytopenic purpura (R-ITP1000 study). Br J Haematol 2014; 167 (02) 243-251
    Suche in Google Scholar
  • 97 Khellaf M, Charles-Nelson A, Fain O. et al. Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients. Blood 2014; 124 (22) 3228-3236
    Suche in Google Scholar
  • 98 Zaja F, Vianelli N, Volpetti S. et al. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol 2010; 85 (04) 329-334
    Suche in Google Scholar
  • 99 Zaja F, Volpetti S, Chiozzotto M. et al. Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia. Am J Hematol 2012; 87 (09) 886-889
    Suche in Google Scholar
  • 100 Vikse J, Jonsdottir K, Kvaløy JT, Wildhagen K, Omdal R. Tolerability and safety of long-term rituximab treatment in systemic inflammatory and autoimmune diseases. Rheumatol Int 2019; 39 (06) 1083-1090
    Suche in Google Scholar
  • 101 Markham A. Fostamatinib: first global approval. Drugs 2018; 78 (09) 959-963
    Suche in Google Scholar
  • 102 Bussel J, Arnold DM, Grossbard E. et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol 2018; 93 (07) 921-930
    Suche in Google Scholar
  • 103 Bussel JB, Arnold DM, Boxer MA. et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol 2019; 94 (05) 546-553
    Suche in Google Scholar
  • 104 Tomiyama Y, Miyakawa Y, Okamoto S. et al. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost 2012; 10 (05) 799-806
    Suche in Google Scholar
  • 105 Yang R, Hou M, Li J. et al. Effect of eltrombopag on platelet response and safety results in Chinese adults with chronic ITP-primary result of a phase III study [abstract]. Blood 2014; 124 (21) 1464
    Suche in Google Scholar
  • 106 Shirasugi Y, Ando K, Miyazaki K. et al. Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial. Int J Hematol 2011; 94 (01) 71-80
    Suche in Google Scholar
  • 107 Al-Samkari H, Kuter DJ. Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. Ther Adv Hematol 2019. Doi: 10.1177/2040620719841735 [epub ahead of print]
  • 108 Quiquandon I, Fenaux P, Caulier MT, Pagniez D, Huart JJ, Bauters F. Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases. Br J Haematol 1990; 74 (02) 223-228
    Suche in Google Scholar
  • 109 Verlin M, Laros Jr RK, Penner JA. Treatment of refractory thrombocytopenic purpura with cyclophosphamine. Am J Hematol 1976; 1 (01) 97-104
    Suche in Google Scholar
  • 110 Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: multicentric trial of the Cooperative Latin American group on hemostasis and thrombosis. Blood 1984; 64 (06) 1179-1183
    Suche in Google Scholar
  • 111 Choudhary DR, Naithani R, Mahapatra M, Kumar R, Mishra P, Saxena R. Efficacy of cyclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura. Haematologica 2008; 93 (10) e61-e62 , discussion e63
    Suche in Google Scholar
  • 112 Kappers-Klunne MC, van't Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol 2001; 114 (01) 121-125
    Suche in Google Scholar
  • 113 Fenaux P, Quiquandon I, Huart JJ, Caulier MT, Bauters F. The role of danazol in the treatment of refractory idiopathic thrombocytopenic purpura. A report of 22 cases. Nouv Rev Fr Hematol 1990; 32 (02) 143-146
    Suche in Google Scholar
  • 114 Li HQ, Zhang L, Zhao H, Ji LX, Yang RC. Chronic idiopathic thrombocytopenic purpura in adult Chinese patients: a retrospective single-centered analysis of 1791 cases. Chin Med J (Engl) 2005; 118 (01) 34-37
    Suche in Google Scholar
  • 115 Liu W, Gu X, Fu R. et al. The effect of danazol in primary immune thrombocytopenia: an analysis of a large cohort from a single center in China. Clin Appl Thromb Hemost 2016; 22 (08) 727-733
    Suche in Google Scholar
  • 116 Maloisel F, Andrès E, Zimmer J. et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med 2004; 116 (09) 590-594
    Suche in Google Scholar
  • 117 Damodar S, Viswabandya A, George B, Mathews V, Chandy M, Srivastava A. Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients. Eur J Haematol 2005; 75 (04) 328-331
    Suche in Google Scholar
  • 118 Godeau B, Durand JM, Roudot-Thoraval F. et al. Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases. Br J Haematol 1997; 97 (02) 336-339
    Suche in Google Scholar
  • 119 Zaja F, Marin L, Chiozzotto M, Puglisi S, Volpetti S, Fanin R. Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab. Am J Hematol 2012; 87 (03) 321-323
    Suche in Google Scholar
  • 120 Hou M, Peng J, Shi Y. et al. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura. Eur J Haematol 2003; 70 (06) 353-357
    Suche in Google Scholar
  • 121 Taylor A, Neave L, Solanki S. et al. Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol 2015; 171 (04) 625-630
    Suche in Google Scholar
  • 122 Zhang WG, Ji L, Cao XM. et al. Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura. Acta Pharmacol Sin 2005; 26 (05) 598-602
    Suche in Google Scholar
  • 123 Ahn YS, Harrington WJ, Mylvaganam R, Allen LM, Pall LM. Slow infusion of Vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura. Ann Intern Med 1984; 100 (02) 192-196
    Suche in Google Scholar
  • 124 Facon T, Caulier MT, Wattel E, Jouet JP, Bauters F, Fenaux P. A randomized trial comparing vinblastine in slow infusion and by bolus i.v. injection in idiopathic thrombocytopenic purpura: a report on 42 patients. Br J Haematol 1994; 86 (03) 678-680
    Suche in Google Scholar
  • 125 Fenaux P, Quiquandon I, Caulier MT, Simon M, Walter MP, Bauters F. Slow infusions of vinblastine in the treatment of adult idiopathic thrombocytopenic purpura: a report on 43 cases. Blut 1990; 60 (04) 238-241
    Suche in Google Scholar
  • 126 Park YH, Yi HG, Lee MH, Kim CS, Lim JH. Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study. Int J Hematol 2016; 103 (02) 180-188
    Suche in Google Scholar