Management of immune thrombocytopenia in elderly patients

Published:September 29, 2018DOI:


      • Special attention must be reserved for elderly patients with thrombocytopenia.
      • The diagnosis of primary ITP is challenging, mainly due to multiple comorbidities.
      • The increased risk of bleeding, thrombosis and infections impact treatment choice.
      • Steroids remain the first-line treatment, there is no consensus for subsequent line.
      • The balance between individual risks and benefits should drive treatment pathway.


      Despite the improvement in understanding its pathogenesis and the introduction of novel treatment options, the management of primary immune thrombocytopenia (ITP) still remains challenging. Considering its increased incidence with aging and prolonged life-expectancy, ITP is often diagnosed in elderly patients, a subset that deserves some special precautions. Ensure the diagnosis is a crucial step, and carefully attention must be given in excluding other causes of thrombocytopenia, especially among older people that frequently suffer from many comorbidities. When it comes to treatment decision, it is worth keeping into account that the elderly have an increased risk of bleeding, thrombosis and infections, that they often require many concomitant therapies, including antiplatelet or anticoagulant agents, and that treatment-related toxicities are often increased and sometimes more dangerous that the disease itself. There are not dedicated guidelines, and only few specific studies. Steroids with or without IVIG remain the first-line treatment. Splenectomy is less effective than in youngers and burdened by an increased thrombotic and infectious risk. Rituximab is a good option in non-immunocompromised patients, but long-term remissions are few. Eltrombopag and romiplostim have a good safety and efficacy profile, and have become a prominent drug in this subset, even if they are associated with a possible increased risk of thrombosis, and long-term toxicity is unknown. Other drugs, such as dapsone and danazol, have a well-known efficacy and safety profile, and still represent a valid option among elderly patients.


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        • Rodeghiero F.
        • et al.
        Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group standardization of terminology, definitions and outcome criteria in immune thrombocyt.
        vol. 113. 2009: 2386-2393
        • Cines D.B.
        • Blanchette V.S.
        Immune Thrombocytopenic Purpura.
        N Engl J Med. 2002; 346: 995-1008
        • Stasi R.
        How to approach thrombocytopenia.
        Hematology Am Soc Hematol Educ Program. 2012; 2012: 191-197
        • Harrington W.J.
        • Minnich V.
        • Hollingsworth J.W.
        • Moore C.V.
        Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura.
        J Lab Clin Med. 1990; 115: 636-645
        • Nugent D.
        • McMillan R.
        • Nichol J.L.
        • Slichter S.J.
        Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production.
        Br J Haematol. 2009; 146: 585-596
        • Semple J.W.
        • et al.
        Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity.
        Blood. 1996; 87: 4245-4254
        • Panitsas F.P.
        • et al.
        Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response.
        Blood. 2004; 103: 2645-2647
        • Zhao C.
        • et al.
        Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies.
        Haematologica. 2008; 93: 1428-1430
        • Olsson B.
        • et al.
        T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura.
        Nat Med. 2003; 9: 1123-1124
        • Liu B.
        • et al.
        Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura.
        Eur J Haematol. 2007; 78: 139-143
        • Yu J.
        • et al.
        Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura.
        Blood. 2008; 112: 1325-1328
        • Li X.
        • et al.
        Defective regulatory B-cell compartment in patients with immune thrombocytopenia.
        Blood. 2012; 120: 3318-3325
        • Olsson B.
        • Ridell B.
        • Carlsson L.
        • Jacobsson S.
        • Wadenvik H.
        Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1.
        Blood. 2008; 112: 1078-1084
        • McMillan R.
        • Nugent D.
        The effect of antiplatelet autoantibodies on megakaryocytopoiesis.
        Int J Hematol. 2005; 81: 94-99
        • Kosugi S.
        • et al.
        Circulating thrombopoietin level in chronic immune thrombocytopenic purpura.
        Br J Haematol. 1996; 93: 704-706
        • Cooper N.
        • Bussel J.
        The pathogenesis of immune thrombocytopaenic purpura.
        Br J Haematol. 2006; 133: 364-374
        • Audia S.
        • Mahévas M.
        • Samson M.
        • Godeau B.
        • Bonnotte B.
        Pathogenesis of immune thrombocytopenia.
        Autoimmun Rev. 2017; 16: 620-632
        • Cines D.B.
        • Liebman H.
        • Stasi R.
        Pathobiology of secondary immune thrombocytopenia.
        Semin Hematol. 2009; 46
        • Frederiksen H.
        • Schmidt K.
        The incidence of idiopathic thrombocytopenic purpura in adults increases with age.
        Blood. 1999; 94: 909-913
        • Neylon A.J.
        • Saunders P.W.G.
        • Howard M.R.
        • Proctor S.J.
        • Taylor P.R.A.
        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
        • Marieke Schoonen W.
        • et al.
        Epidemiology of immune thrombocytopenic purpura in the general practice research database.
        Br J Haematol. 2009; 145: 235-244
        • Moulis G.
        • et al.
        Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France.
        Blood. 2014; 124: 3308-3315
        • Stasi R.
        • et al.
        Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura.
        Am J Med. 1995; 98: 436-442
        • Provan D.
        • et al.
        International consensus report on the investigation and management of primary immune thrombocytopenia.
        Blood. 2010; 115: 168-186
        • Cooper N.
        State of the art – how I manage immune thrombocytopenia.
        Br J Haematol. 2017; 177: 39-54
        • Stasi R.
        Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias.
        Semin Hematol. 2009; 46
        • Hayashi H.
        • Beppu T.
        • Shirabe K.
        • Maehara Y.
        • Baba H.
        Management of thrombocytopenia due to liver cirrhosis: a review.
        World J Gastroenterol. 2014; 20: 2595-2605
        • Neunert C.
        • et al.
        The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia.
        Blood. 2011; 117: 4190-4207
        • McMillan R.
        Antiplatelet antibodies in chronic immune thrombocytopenia and their role in platelet destruction and defective platelet production.
        Hematol Oncol Clin North Am. 2009; 23: 1163-1175
        • Tefferi A.
        • Vardiman J.
        Myelodysplastic syndromes.
        N Engl J Med. 2009; 361: 1872-1885
        • Rollison D.E.
        • et al.
        Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs.
        Blood. 2008; 112: 45-52
        • Kantarjian H.
        • et al.
        The incidence and impact of thrombocytopenia in myelodysplastic syndromes.
        Cancer. 2007; 109: 1705-1714
        • Waisbren J.
        • et al.
        Disease characteristics and prognosis of myelodysplastic syndrome presenting with isolated thrombocytopenia.
        Int J Hematol. 2016; 1
        • Sashida G.
        • et al.
        Clinico-hematologic features of myelodysplastic syndrome presenting as isolated thrombocytopenia: an entity with a relatively favorable prognosis.
        Leuk Lymphoma. 2003; 44: 653-658
        • Bennett C.M.
        Drug-induced thrombocytopenia.
        in: Transfusion medicine and hemostasis. 2009: 487-490
        • Reese J.A.
        • et al.
        Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods.
        Blood. 2010; 116: 2127-2133
        • Arnold D.M.
        Platelet count or bleeding as the outcome in ITP trials.
        Am J Hematol. 2012; 87: 945-946
        • Cortelazzo S.
        • et al.
        High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura.
        Blood. 1991; 77: 31-33
        • Cohen Y.C.
        • 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: 1630-1638
        • Zhou H.
        • et al.
        Immune thrombocytopenia in the elderly: Clinical course in 525 patients from a single center in China.
        Ann Hematol. 2013; 92: 79-87
        • Sarpatwari A.
        • et al.
        Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom general practice research database.
        Haematologica. 2010; 95: 1167-1175
        • Severinsen M.T.
        • et al.
        Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study.
        Br J Haematol. 2011; 152: 360-362
        • Enger C.
        • Bennett D.
        • Forssen U.
        • Fogarty P.F.
        • McAfee A.T.
        Comorbidities in patients with persistent or chronic immune thrombocytopenia.
        Int J Hematol. 2010; 92: 289-295
        • Ruggeri M.
        • 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: 1266-1273
        • Nørgaard M.
        Thrombosis in patients with primary chronic immune thrombocytopenia.
        Thromb Res. 2012; 130
        • Naess I. a
        • et al.
        Incidence and mortality of venous thrombosis: a population-based study.
        J Thromb Haemost. 2007; 5: 692-699
        • Catalá-López F.
        • Corrales I.
        • Martín-Serrano G.
        • Tobías A.
        • Calvo G.
        Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: systematic review and meta-analysis of randomized controlled trials.
        Med Clin (Barc). 2012; 139: 421-429
        • Rodeghiero F.
        Is ITP a thrombophilic disorder?.
        Am J Hematol. 2016; 91: 39-45
        • Álvarez-Román M.T.
        • et al.
        Procoagulant profile in patients with immune thrombocytopenia.
        Br J Haematol. 2016; 175: 925-934
        • Jy W.
        • Johansen M.E.
        • Bidot C.
        • Horstman L.L.
        • Ahn Y.S.
        Red cell-derived microparticles (RMP) as haemostatic agent.
        Thromb Haemost. 2013; 110: 751-760
        • Alvarez Román M.T.
        • et al.
        Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia.
        Thromb Haemost. 2014; 112: 65-72
        • Vasilopoulos T.
        • et al.
        Comorbidity and chronic conditions in the National Social Life, Health and Aging Project (NSHAP), Wave 2.
        J Gerontol B Psychol Sci Soc Sci. 2014; 69: S154-S165
        • Hylek E.M.
        • Evans-Molina C.
        • Shea C.
        • Henault L.E.
        • Regan S.
        Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation.
        Circulation. 2007; 115: 2689-2696
        • Sørensen R.
        • et al.
        Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data.
        Lancet. 2009; 374: 1967-1974
        • Nørgaard M.
        • et al.
        Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study.
        Blood. 2011; 117: 3514-3520
        • McMillan R.
        • Bussel J.B.
        • George J.N.
        • Lalla D.
        • Nichol J.L.
        Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura.
        Am J Hematol. 2008; 83: 150-154
        • Deuson R.
        • Danese M.
        • Mathias S.D.
        • Schoonen M.
        • Fryzek J.
        The burden of immune thrombocytopenia in adults: Evaluation of the thrombopoietin receptor agonist romiplostim.
        J Med Econ. 2012; 15: 956-976
        • Snyder C.F.
        • et al.
        Health-related quality of life of immune thrombocytopenic purpura patients: results from a web-based survey.
        Curr Med Res Opin. 2008; 24: 2767-2776
        • George J.N.
        • et al.
        Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials.
        Br J Haematol. 2009; 144: 409-415
        • Kuter D.J.
        • et al.
        Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care.
        Am J Hematol. 2012; 87: 558-561
        • Bussel J.B.
        • 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
        • Michel M.
        • et al.
        Characteristics and outcome of immune thrombocytopenia in elderly: results from a single center case-controlled study.
        Am J Hematol. 2011; 86: 980-984
        • Daou S.
        • et al.
        Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center.
        Eur J Intern Med. 2008; 19: 447-451
        • G., M., A., P. & L., S
        Corticosteroid risk function of severe infection in primary immune thrombocytopenia adults. A nationwide nested case-control study.
        PLoS One. 2015; 10e0142217
        • M., R
        • et al.
        Guidelines for the diagnosis, prevention and management of osteoporosis.
        Reumatismo. 2016; 68: 1-39
        • Bizzoni L.
        • et al.
        Idiopathic thrombocytopenic purpura (ITP) in the elderly: Clinical course in 178 patients.
        Eur J Haematol. 2006; 76: 210-216
        • Cheng Y.
        • et al.
        Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone.
        N Engl J Med. 2003; 349: 831-836
        • Mazzucconi M.G.
        • et al.
        Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience.
        Blood. 2007; 109: 1401-1407
        • Mithoowani S.
        • et al.
        High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis.
        Lancet Haematol. 2016; 3: e489-e496
        • Wei Y.
        • et al.
        High-dose dexamethasone versus prednisone for treatment of adult immune thrombocytopenia: A prospective multicenter randomized trial.
        Blood. 2015; 127 (blood-2015-07-659656)
        • Hsia C.C.
        • et al.
        Intravenous Immunoglobulin (IVIg) utilization in Immune Thrombocytopenia (ITP): a multi-center, retrospective review.
        Drugs. 2015; 2: 35-42
        • Caress J.B.
        • Kennedy B.L.
        • Eickman K.D.
        Safety of intravenous immunoglobulin treatment.
        Expert Opin Drug Saf. 2010; 9: 971-979
        • Marie I.
        • Maurey G.
        • Hervé F.
        • Hellot M.-F.
        • Levesque H.
        Intravenous immunoglobulin-associated arterial and venous thrombosis; report of a series and review of the literature.
        Br J Dermatol. 2006; 155: 714-721
        • Mahévas M.
        • Michel M.
        • Godeau B.
        How we manage immune thrombocytopenia in the elderly.
        Br J Haematol. 2016; 173: 844-856
        • Provan D.
        • Newland A.C.
        Current Management of Primary Immune Thrombocytopenia.
        Adv Ther. 2015; 32: 875-887
        • Gaines A.R.
        Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.
        Blood. 2000; 95: 2523-2529
        • Zaja F.
        • et al.
        Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia.
        Blood. 2010; 115: 2755-2762
        • Gudbrandsdottir S.
        • et al.
        Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia.
        Blood. 2013; 121: 1976-1981
        • Gómez-Almaguer D.
        • et al.
        Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults.
        Blood. 2014; 123: 3906-3908
        • Spahr J.E.
        • Rodgers G.M.
        Treatment of immune-mediated thrombocytopenia purpura with concurrent intravenous immunoglobulin and platelet transfusion: a retrospective review of 40 patients.
        Am J Hematol. 2008; 83: 122-125
        • Sigdel M.R.
        • Shah D.S.
        • Kafle M.P.
        • Raut K.B.
        Severe immune thrombocytopenic purpura treated with plasma exchange.
        Kathmandu Univ Med J. 2012; 10: 85-87
        • Rodeghiero F.
        A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP.
        Br J Haematol. 2018; 181: 183-195
        • Guan Y.
        • et al.
        Long-term results of splenectomy in adult chronic immune thrombocytopenia.
        Eur J Haematol. 2017; 98: 235-241
        • Vianelli N.
        • et al.
        Splenectomy as a curative treatment for immune thrombocytopenia: A retrospective analysis of 233 patients with a minimum follow up of 10 years.
        Haematologica. 2013; 98: 875-880
        • Gonzalez-Porras J.R.
        • et al.
        Safety and efficacy of splenectomy in over 65-yrs-old patients with immune thrombocytopenia.
        Eur J Haematol. 2013; 91: 236-241
        • Park Y.H.
        • et al.
        Clinical outcome and predictive factors in the response to splenectomy in elderly patients with primary immune thrombocytopenia: A multicenter retrospective study.
        Acta Haematol. 2016; 135: 162-171
        • Delaitre B.
        • et al.
        Laparoscopic splenectomy for idiopathic thrombocytopenic purpura.
        Surg Laparosc Endosc Percutan Tech. 2002; 12: 412-419
        • Palandri F.
        • et al.
        Have splenectomy rate and main outcomes of ITP changed after the introduction of new treatments? A monocentric study in the outpatient setting during 35 years.
        Am J Hematol. 2016; 91: E267-E272
        • Keidar A.
        • Feldman M.
        • Szold A.
        Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count.
        Am J Hematol. 2005; 80: 95-100
        • Chen X.
        • et al.
        Laparoscopic splenectomy for patients with immune thrombocytopenia and very low platelet count: is platelet transfusion necessary?.
        J Surg Res. 2011; 170: e225-e232
        • Boyle S.
        • White R.H.
        • Brunson A.
        • Wun T.
        Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia.
        Blood. 2013; 121: 4782-4790
        • Thai L.H.
        • et al.
        Long-term complications of splenectomy in adult immune thrombocytopenia.
        Medicine (United States). 2016; 95e5098
        • Lutwick L.I.
        Overwhelming postsplenectomy infection.
        in: Clinical infectious disease. 2nd ed. 2015: 629-636
        • Sarpatwari A.
        • et al.
        Autologous 111In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry.
        Br J Haematol. 2010; 151: 477-487
        • Khellaf M.
        • et al.
        Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients.
        Blood. 2014; 124: 3228-3236
        • Patel V.L.
        • et al.
        Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia.
        Blood. 2012; 119: 5989-5995
        • Hasan A.
        • et al.
        Repeated courses of Rituximab in chronic ITP: three different regimens.
        Am J Hematol. 2009; 84: 661-665
        • Chapin J.
        • Lee C.S.
        • Zhang H.
        • Zehnder J.L.
        • Bussel J.B.
        Gender and duration of disease differentiate responses to rituximab–dexamethasone therapy in adults with immune thrombocytopenia.
        Am J Hematol. 2016; 91: 907-911
        • Zaja F.
        • et al.
        Low-dose rituximab in adult patients with primary immune thrombocytopenia.
        Eur J Haematol. 2010; 85: 329-334
        • Chugh S.
        • et al.
        Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis.
        Lancet Haematol. 2015; 2: e75-e81
        • Nazi I.
        • et al.
        The effect of rituximab on vaccine responses in patients with immune thrombocytopenia.
        Blood. 2013; 122: 1946-1953
        • Cho C.H.
        • Hwang W.L.
        • Cheng S. Bin
        • Lee T.Y.
        • Teng C.L.
        Hepatitis B reactivation induced by Rituximab maintenance therapy for lymphoma.
        Ann Hematol. 2011; 90: 111-112
        • Gea-Banacloche J.C.
        Rituximab-associated infections.
        Semin Hematol. 2010; 47: 187-198
        • Dunleavy K.
        • Tay K.
        • Wilson W.H.
        Rituximab-associated neutropenia.
        Semin Hematol. 2010; 47: 180-186
        • Carson K.R.
        • 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; 113: 4834-4840
        • Wong R.S.M.
        • et al.
        Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: Final results of the EXTEND study.
        Blood. 2017; 130: 2527-2536
        • Kuter D.J.
        • et al.
        Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: Safety and efficacy.
        Br J Haematol. 2013; 161: 411-423
        • Zhang J.
        • et al.
        Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysish.
        Sci Rep. 2018; 8
        • Bussel J.B.
        • et al.
        Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP.
        Blood. 2009; 113: 2161-2171
        • Cines D.B.
        • 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: 259-270
        • Brynes R.K.
        • et al.
        A 2-year, longitudinal, prospective study of the effects of eltrombopag on bone marrow in patients with chronic immune thrombocytopenia.
        Acta Haematol. 2017; 137: 66-72
        • Janssens A.
        • 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
        • Boiocchi L.
        • et al.
        Bone marrow fibrosis in immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (TRA)-a single center long-term follow-up.
        Lab. Investig. 2014; 336A: 94
        • Ghanima W.
        • et al.
        Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents.
        Br J Haematol. 2011; 155: 248-255
        • Michel M.
        • et al.
        Efficacy and safety of the thrombopoietin receptor agonist romiplostim in patients aged ≥65 years with immune thrombocytopenia.
        Ann Hematol. 2015; 94: 1973-1980
        • Steurer M.
        • et al.
        A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice.
        Eur J Haematol. 2017; 98: 112-120
        • Gonzalez-Lopez T.J.
        • et al.
        Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice.
        Eur J Haematol. 2016; 97: 297-302
        • Bussel J.B.
        • Wang X.
        • Lopez A.
        • Eisen M.
        Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim .
        Hematology. 2016; 21: 257-262
        • González-López T.J.
        • et al.
        Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.
        Am J Hematol. 2015; 90: E40-E43
        • Cantoni S.
        • et al.
        Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: a retrospective collaborative survey from Italian hematology centers.
        Am J Hematol. 2018; 93: 58-64
        • Kuter D.J.
        • et al.
        Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim.
        Int J Hematol. 2015; 101: 255-263
        • Durand J.M.
        • Lefèvre P.
        • Hovette P.
        • Mongin M.
        • Soubeyrand J.
        DAPSONE for idiopathic autoimmune thrombocytopenic purpura in elderly patients.
        Br J Haematol. 1991; 78: 459-460
        • Godeau B.
        • Oksenhendler E.
        • Bierling P.
        Dapsone for autoimmune thrombocytopenic purpura.
        Am J Hematol. 1993; 44: 70-72
        • Zaja F.
        • et al.
        Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab.
        Am J Hematol. 2012; 87: 321-323
        • Godeau B.
        • et al.
        Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases.
        Br J Haematol. 1997; 97: 336-339
        • Sauvetre G.
        • et al.
        Cutaneous rash and dapsone-induced hypersensitivity syndrome a common manifestation in adult immune thrombocytopenia. Presentation and outcome in 16 cases.
        Am J Hematol. 2015; 90: E201-E202
        • Liu W.
        • 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. 2016; 22: 727-733
        • Ahn Y.S.
        • et al.
        Danazol for the treatment of idiopathic thrombocytopenic purpura.
        N Engl J Med. 1983; 308: 1396-1399
        • Maloisel F.
        • et al.
        Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: Long-term results.
        Am J Med. 2004; 116: 590-594
        • Ahn Y.S.
        • et al.
        Low-dose danazol therapy in idiopathic thrombocytopenic purpura.
        Ann Intern Med. 1987; 107: 177-181
        • Audia S.
        • Godeau B.
        • Bonnotte B.
        Is there still a place for ‘old therapies’ in the management of immune thrombocytopenia?.
        Rev Med Interne. 2016; 37: 43-49
        • Sussman L.N.
        Azathioprine in refractory idiopathic thrombocytopenic purpura.
        JAMA. 1967; 202: 259-263
        • Taylor A.
        • et al.
        Mycophenolate mofetil therapy for severe immune thrombocytopenia.
        Br J Haematol. 2015; 171: 625-630
        • Kappers-Klunne M.C.
        • Van'T Veer M.B.
        Cyclosporin a for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.
        Br J Haematol. 2001; 114: 121-125
        • Khellaf M.
        • et al.
        Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies.
        Am J Hematol. 2014; 89: 194-198
        • Stirnemann J.
        • et al.
        Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients.
        Eur J Haematol. 2016; 96: 269-275
        • Sikorska A.
        • Słomkowski M.
        • Marlanka K.
        • Konopka L.
        • Górski T.
        The use of vinca alkaloids in adult patients with refractory chronic idiopathic thrombocytopenia.
        Clin Lab Haematol. 2004; 26: 407-411