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Review

Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

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Pages 653-664 | Published online: 26 Jul 2021

References

  • Harrington WJ, Minnich V, Hollingsworth JW, et al. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38(1):1–10.
  • Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci. 2006;124(2):499–542. doi:10.1111/j.1749-6632.1965.tb18984.x
  • Ballem PJ, Segal GM, Stratton JR, et al. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80(1):33–40. doi:10.1172/JCI113060
  • Al-Samkari H, Rosovsky RP, Karp Leaf RS, et al. A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv. 2020;4(1):9–18. doi:10.1182/bloodadvances.2019000868
  • Cheloff AZ, Kuter DJ, Al-Samkari H. Serum complement levels in immune thrombocytopenia: characterization and relation to clinical features. Res Pract Thromb Haemost. 2020;4(5):807–812. doi:10.1002/rth2.12388
  • 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. doi:10.1182/blood-2008-07-162503
  • 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. doi:10.1182/blood-2010-08-302984
  • Weycker D, Hanau A, Hatfield M, et al. Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis. J Med Econ. 2020;23(2):184–192. doi:10.1080/13696998.2019.1669329
  • Cohen YC, 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(11):1630–1638. doi:10.1001/archinte.160.11.1630
  • Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–186. doi:10.1182/blood-2009-06-225565
  • Al-Samkari H, Kuter DJ. Immune thrombocytopenia in adults: modern approaches to diagnosis and treatment. Semin Thromb Hemost. 2020;46(3):275–288. doi:10.1055/s-0039-1700512
  • Slichter SJ, Harker LA. Thrombocytopenia: mechanisms and management of defects in platelet production. Clin Haematol. 1978;7(3):523–539. doi:10.1016/S0308-2261(21)00047-3
  • Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010;362(7):600–613. doi:10.1056/NEJMoa0904084
  • Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost. 2008;3(3):160–174. doi:10.1055/s-0028-1086135
  • Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med. 1972;287(4):155–159. doi:10.1056/NEJM197207272870401
  • Piel-Julian ML, Mahevas M, Germain J, et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost. 2018;16(9):1830–1842. doi:10.1111/jth.14227
  • Hato T, Shimada N, Kurata Y, et al. Risk factors for skin, mucosal, and organ bleeding in adults with primary ITP: a nationwide study in Japan. Blood Adv. 2020;4(8):1648–1655. doi:10.1182/bloodadvances.2020001446
  • McVerry BA. Management of idiopathic thrombocytopenic purpura in adults. Br J Haematol. 1985;59(2):203–208. doi:10.1111/j.1365-2141.1985.tb02985.x
  • Shulman NR, Weinrach RS, Libre EP, et al. The role of the reticuloendothelial system in the pathogenesis of idiopathic thrombocytopenic purpura. Trans Assoc Am Physicians. 1965;78:374–390.
  • Gernsheimer T, Stratton J, Ballem PJ, et al. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med. 1989;320(15):974–980. doi:10.1056/NEJM198904133201505
  • Pang SJ, Lazarus AH. Mechanisms of platelet recovery in ITP associated with therapy. Ann Hematol. 2010;89(Suppl 1):31–35. doi:10.1007/s00277-010-0916-2
  • Li J, Wang Z, Hu S, et al. Correction of abnormal T cell subsets by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. Immunol Lett. 2013;154(1–2):42–48. doi:10.1016/j.imlet.2013.08.006
  • Hou Y, Feng Q, Xu M, et al. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood. 2016;127(12):1587–1597. doi:10.1182/blood-2015-10-674531
  • Kitchens CS. Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit. J Clin Invest. 1977;60(5):1129–1134. doi:10.1172/JCI108864
  • 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–e96. doi:10.1016/S2352-3026(16)30109-0
  • Hansen RJ, Balthasar JP. Mechanisms of IVIG action in immune thrombocytopenic purpura. Clin Lab. 2004;50(3–4):133–140.
  • Crow AR, Lazarus AH. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know? Transfus Med Rev. 2008;22(2):103–116. doi:10.1016/j.tmrv.2007.12.001
  • Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol. 2008;26:513–533. doi:10.1146/annurev.immunol.26.021607.090232
  • Brückner C, Lehmann C, Dudziak D, et al. Sweet SIGNs: IgG glycosylation leads the way in IVIG-mediated resolution of inflammation. Int Immunol. 2017;29(11):499–509. doi:10.1093/intimm/dxx053
  • Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol. 2013;13(3):176–189. doi:10.1038/nri3401
  • Qin YH, Zhou TB, Su LN, et al. The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura: a meta-analysis of 13 randomized controlled trials. Blood Coagul Fibrinolysis. 2010;21(8):713–721. doi:10.1097/MBC.0b013e3283401490
  • Zhou Z, Qiao Z, Li H, et al. Different dosages of intravenous immunoglobulin (IVIg) in treating immune thrombocytopenia with long-term follow-up of three years: results of a prospective study including 167 cases. Autoimmunity. 2016;49(1):50–57. doi:10.3109/08916934.2015.1104671
  • Newman GC, Novoa MV, Fodero EM, et al. 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(4):1076–1078. doi:10.1046/j.1365-2141.2001.02627.x
  • Tarantino MD, Young G, Bertolone SJ, et al. 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(4):489–494. doi:10.1016/j.jpeds.2005.11.019
  • Ware RE, Zimmerman SA. Anti-D: mechanisms of action. Semin Hematol. 1998;35(1Suppl 1):14–22.
  • Rodeghiero F, Schiavotto C, Castaman G, et al. A follow-up study of 49 adult patients with idiopathic thrombocytopenic purpura treated with high-dose immunoglobulins and anti-D immunoglobulins. Haematologica. 1992;77(3):248–252.
  • Scaradavou A, Woo B, Woloski BM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89(8):2689–2700. doi:10.1182/blood.V89.8.2689
  • Moulis G, Germain J, Comont T, et al. Newly diagnosed immune thrombocytopenia adults: clinical epidemiology, exposure to treatments, and evolution. Results of the CARMEN multicenter prospective cohort. Am J Hematol. 2017;92(6):493–500. doi:10.1002/ajh.24702
  • Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–3866. doi:10.1182/bloodadvances.2019000966
  • Stasi R, Stipa E, Masi M, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995;98(5):436–442. doi:10.1016/s0002-9343(99)80342-8
  • Rodeghiero F. A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP. Br J Haematol. 2018;181(2):183–195. doi:10.1111/bjh.15090
  • Kojouri K, Vesely SK, Terrell DR, 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;104(9):2623–2634. doi:10.1182/blood-2004-03-1168
  • Bisharat N, Omari H, Lavi I, et al. Risk of infection and death among post-splenectomy patients. J Infect. 2001;43(3):182–186. doi:10.1053/jinf.2001.0904
  • Boyle S, White RH, Brunson A, et al. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood. 2013;121(23):4782–4790. doi:10.1182/blood-2012-12-467068
  • Ruggeri M, Tosetto A, Palandri F, et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014;12(8):1266–1273. doi:10.1111/jth.12636
  • Deshayes S, Khellaf M, Zarour A, et al. Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: results at 5 years from the French prospective registry ITP-ritux. Am J Hematol. 2019;94(12):1314–1324. doi:10.1002/ajh.25632
  • Ghanima W, Khelif A, Waage A, et al. 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. doi:10.1016/S0140-6736(14)61495-1
  • 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(2):e75–e81. doi:10.1016/S2352-3026(15)00003-4
  • Arnold DM, Dentali F, Crowther MA, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25–33. doi:10.7326/0003-4819-146-1-200701020-00006
  • Tjønnfjord E, Holme PA, Darne B, et al. Long-term outcomes of patients treated with rituximab as second-line treatment for adult immune thrombocytopenia - follow-up of the RITP study. Br J Haematol. 2020;191(3):460–465. doi:10.1111/bjh.16672
  • Zaja F, Vianelli N, Volpetti S, et al. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010;85(4):329–334. doi:10.1111/j.1600-0609.2010.01486.x
  • Mahevas M, Ebbo M, Audia S, et al. Efficacy and safety of rituximab given at 1000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia. Am J Hematol. 2013;88(10):858–861. doi:10.1002/ajh.23518
  • 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(2):243–251. doi:10.1111/bjh.13029
  • Zhou H, Liu L, Shu X, et al. Clinical efficacy and safety of high-dose dexamethasone plus low-dose rituximab as first-line therapy in newly diagnosed primary immune thrombocytopenia. Indian J Hematol Blood Transfus. 2019;35(3):507–512. doi:10.1007/s12288-018-1061-7
  • Raso S, Napolitano M, Arrigo G, et al. Antimicrobial prophylaxis in patients with immune thrombocytopenia treated with rituximab: a retrospective multicenter analysis. Ann Hematol. 2021;100:653–659. doi:10.1007/s00277-021-04438-7
  • Nazi I, Kelton JG, Larché M, et al. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood. 2013;122(11):1946–1953. doi:10.1182/blood-2013-04-494096
  • Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98(1):10–23. doi:10.1007/s12185-013-1382-0
  • Birocchi S, Podda GM, Manzoni M, et al. Thrombopoietin receptor agonists for the treatment of primary immune thrombocytopenia: a meta-analysis and systematic review. Platelets. 2020;32:1–11. doi:10.1080/09537104.2020.1745168.
  • Al-Samkari H, Kuter DJ. Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. Ther Adv Hematol. 2019;10:2040620719841735. doi:10.1177/2040620719841735
  • Al-Samkari H, Van Cott EM, Kuter DJ. Platelet aggregation response in immune thrombocytopenia patients treated with romiplostim. Ann Hematol. 2019;98(3):581–588. doi:10.1007/s00277-018-3556-6
  • Amgen Inc. Nplate (Romiplostim) [Prescribing Information]. Thousand Oaks, CA: Amgen; 2017.
  • 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. doi:10.1016/S0140-6736(08)60203-2
  • 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. doi:10.1056/NEJMoa1002625
  • Kuter DJ, Arnold DM, Rodeghiero F, et al. Safety and efficacy of self-administered romiplostim in patients with immune thrombocytopenia: results of an integrated database of five clinical trials. Am J Hematol. 2020;95(6):643–651. doi:10.1002/ajh.25776
  • Al-Samkari H, Grace RF, Kuter DJ. The role of romiplostim for pediatric patients with immune thrombocytopenia. Ther Adv Hematol. 2020;11:2040620720912992. doi:10.1177/2040620720912992
  • GlaxoSmithKline. Promacta (Eltrombopag) [Prescribing Information]. Research Triangle Park, NC.: GlaxoSmithKline; 2017.
  • Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113(10):2161–2171. doi:10.1182/blood-2008-04-150078
  • 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. doi:10.1016/S0140-6736(10)60959-2
  • 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(5):799–806. doi:10.1111/j.1538-7836.2012.04695.x
  • 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. Blood. 2014;124(21):1464. doi:10.1182/blood.V124.21.1464.1464
  • Elgebaly AS, Ashal GE, Elfil M, et al. Tolerability and efficacy of eltrombopag in chronic immune thrombocytopenia: meta-analysis of randomized controlled trials. Clin Appl Thromb Hemost. 2017;23(8):928–937. doi:10.1177/1076029616663849
  • 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(4):764–776. doi:10.1016/j.clinthera.2009.04.010
  • 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(3):699–709. doi:10.1016/j.clinthera.2012.01.011
  • González-Porras JR, Godeau B, Carpenedo M. Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol. 2019;10:2040620719837906. doi:10.1177/2040620719837906
  • 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. doi:10.1111/bcp.13717
  • AkaRx. DOPTELET (Avatrombopag) [Prescribing Information]. Durham, NC: AkaRx; 2020.
  • Bussel JB, Kuter DJ, Aledort LM, et al. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014;123(25):3887–3894. doi:10.1182/blood-2013-07-514398
  • Al-Samkari H, Nagalla S. Efficacy and safety evaluation of avatrombopag in immune thrombocytopenia: analyses of a phase III study and long-term extension. Platelets. 2021;1–8. doi:10.1080/09537104.2021.1881952
  • 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(3):479–490. doi:10.1111/bjh.15573
  • Cheloff AZ, Al-Samkari H. Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease. J Blood Med. 2019;10:313–321. doi:10.2147/jbm.S191790
  • Terrault N, Chen YC, Izumi N, et al. Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia. Gastroenterology. 2018;155(3):705–718. doi:10.1053/j.gastro.2018.05.025
  • Virk ZM, Kuter DJ, Al-Samkari H. An evaluation of avatrombopag for the treatment of thrombocytopenia. Expert Opin Pharmacother. 2021;22(3):273–280. doi:10.1080/14656566.2020.1841748
  • Al-Samkari H. Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease. Drugs Today. 2018;54(11):647–655. doi:10.1358/dot.2018.54.11.2899441
  • Thrombopoietin Receptor Agonists. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
  • 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(2):168. doi:10.1111/bjh.15432
  • Arnall JR, DiSogra KY, Downing L, et al. Comparative utilization and efficacy of thrombopoietin receptor agonists in relapsed/refractory immune thrombocytopenia. Am J Ther. 2021;Publish Ahead of Print. doi:10.1097/mjt.0000000000001335
  • Zhang J, Liang Y, Ai Y, et al. Eltrombopag versus romiplostim in treatment of adult patients with immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis. PLoS One. 2018;13(6):e0198504. doi:10.1371/journal.pone.0198504
  • Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780–3817. doi:10.1182/bloodadvances.2019000812
  • Iino M, Sakamoto Y, Sato T. Treatment-free remission after thrombopoietin receptor agonist discontinuation in patients with newly diagnosed immune thrombocytopenia: an observational retrospective analysis in real-world clinical practice. Int J Hematol. 2020;112(2):159–168. doi:10.1007/s12185-020-02893-y
  • Cuker A, Despotovic JM, Grace RF, et al. Tapering thrombopoietin receptor agonists in primary immune thrombocytopenia: expert consensus based on the RAND/UCLA modified delphi panel method. Res Pract Thromb Haemost. 2021;5(1):69–80. doi:10.1002/rth2.12457
  • Lucchini E, Palandri F, Volpetti S, et al. Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: results of a phase II, multicentre, prospective study. Br J Haematol. 2021;193:386–396. doi:10.1111/bjh.17334
  • 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. doi:10.1002/ajh.25275
  • Markham A. Fostamatinib: first global approval. Drugs. 2018;78(9):959–963. doi:10.1007/s40265-018-0927-1
  • 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(7):921–930. doi:10.1002/ajh.25125
  • 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(5):546–553. doi:10.1002/ajh.25444
  • Langrish CL, Bradshaw JM, Francesco MR, et al. Preclinical efficacy and anti-inflammatory mechanisms of action of the bruton tyrosine kinase inhibitor rilzabrutinib for immune-mediated disease. J Immunol. 2021;206(7):1454–1468. doi:10.4049/jimmunol.2001130
  • Smith PF, Krishnarajah J, Nunn PA, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton’s tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017;83(11):2367–2376. doi:10.1111/bcp.13351
  • Li G, Wang S, Li N, et al. Proteasome inhibition with bortezomib induces apoptosis of long-lived plasma cells in steroid-resistant or relapsed immune thrombocytopaenia. Thromb Haemost. 2018;118(10):1752–1764. doi:10.1055/s-0038-1669921
  • Beckman JD, Rollins-Raval MA, Raval JS, et al. Bortezomib for refractory immune-mediated thrombocytopenia purpura. Am J Ther. 2018;25(2):e270–e272. doi:10.1097/mjt.0000000000000517
  • Cuker A, Neunert CE. How I treat refractory immune thrombocytopenia. Blood. 2016;128(12):1547–1554. doi:10.1182/blood-2016-03-603365
  • Miltiadous O, Hou M, Bussel JB. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood. 2020;135(7):472–490. doi:10.1182/blood.2019003599
  • Mahévas M, Gerfaud-Valentin M, Moulis G, et al. Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia. Blood. 2016;128(12):1625–1630. doi:10.1182/blood-2016-03-704734
  • Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood. 2003;102(13):4306–4311. doi:10.1182/blood-2002-10-3317
  • Al-Jama FE, Rahman J, Al-Suleiman SA, et al. Outcome of pregnancy in women with idiopathic thrombocytopenic purpura. Aust N Z J Obstet Gynaecol. 1998;38(4):410–413. doi:10.1111/j.1479-828X.1998.tb03099.x
  • Nicolescu A, Vladareanu AM, Voican I, et al. Therapeutic options for Immune Thrombocytopenia (ITP) during pregnancy. Maedica. 2013;8(2):182–188.
  • Michel M, Ruggeri M, Gonzalez-Lopez TJ, et al. Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study. Blood. 2020;136(26):3056–3061. doi:10.1182/blood.2020007594
  • Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013;121(1):38–47. doi:10.1182/blood-2012-08-448944
  • 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. doi:10.1016/S0140-6736(09)60402-5
  • 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(1):71–80. doi:10.1007/s12185-011-0886-8
  • Quiquandon I, Fenaux P, Caulier MT, et al. 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(2):223–228. doi:10.1111/j.1365-2141.1990.tb02569.x
  • Verlin M, Laros RK, Penner JA. Treatment of refractory thrombocytopenic purpura with cyclophosphamine. Am J Hematol. 1976;1(1):97–104. doi:10.1002/ajh.2830010111
  • 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(6):1179–1183. doi:10.1182/blood.V64.6.1179.1179
  • Choudhary DR, Naithani R, Mahapatra M, et al. Efficacy of cyclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura. Haematologica. 2008;93(10):e61–e62;discussion e63. doi:10.3324/haematol.13481
  • 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(1):121–125. doi:10.1046/j.1365-2141.2001.02893.x
  • Fenaux P, Quiquandon I, Huart JJ, et al. The role of danazol in the treatment of refractory idiopathic thrombocytopenic purpura. A report of 22 cases. Nouv Rev Fr Hematol. 1990;32(2):143–146.
  • Li HQ, Zhang L, Zhao H, et al. Chronic idiopathic thrombocytopenic purpura in adult Chinese patients: a retrospective single-centered analysis of 1791 cases. Chin Med J (Engl). 2005;118(1):34–37.
  • 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(8):727–733. doi:10.1177/1076029615622002
  • Maloisel F, Andres E, Zimmer J, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med. 2004;116(9):590–594. doi:10.1016/j.amjmed.2003.12.024
  • Damodar S, Viswabandya A, George B, et al. Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients. Eur J Haematol. 2005;75(4):328–331. doi:10.1111/j.1600-0609.2005.00545.x
  • 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(2):336–339. doi:10.1046/j.1365-2141.1997.412687.x
  • Zaja F, Marin L, Chiozzotto M, et al. Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab. Am J Hematol. 2012;87(3):321–323. doi:10.1002/ajh.22266
  • 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(6):353–357. doi:10.1034/j.1600-0609.2003.00076.x
  • Taylor A, Neave L, Solanki S, et al. Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol. 2015;171(4):625–630. doi:10.1111/bjh.13622
  • Zhang WG, Ji L, Cao XM, et al. Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura. Acta Pharmacol Sin. 2005;26(5):598–602. doi:10.1111/j.1745-7254.2005.00088.x
  • Ahn YS, Harrington WJ, Mylvaganam R, et al. Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura. Ann Intern Med. 1984;100(2):192–196. doi:10.7326/0003-4819-100-2-192
  • Facon T, Caulier MT, Wattel E, et al. 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(3):678–680. doi:10.1111/j.1365-2141.1994.tb04810.x
  • Fenaux P, Quiquandon I, Caulier MT, et al. Slow infusions of vinblastine in the treatment of adult idiopathic thrombocytopenic purpura: a report on 43 cases. Blut. 1990;60(4):238–241. doi:10.1007/BF01728791
  • Park YH, Yi HG, Lee MH, et al. 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(2):180–188. doi:10.1007/s12185-015-1903-0