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Semin Thromb Hemost 2011; 37(6): 621-630
DOI: 10.1055/s-0031-1291372
© Thieme Medical Publishers

Current Therapies in Primary Immune Thrombocytopenia

Salley G. Pels1
  • 1Section of Hematology Oncology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
Further Information

Publication History

Publication Date:
18 November 2011 (online)

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ABSTRACT

Immune thrombocytopenia (ITP) has long been characterized as an autoimmune disease that exhibits antibody-mediated destruction of platelets. Many of the therapies have targeted reducing the antibody production and/or the platelet destruction process within the reticuloendothelial system, including steroids, immunoglobulin, anti-RhD immunoglobulin, splenectomy, and rituximab. Relatively new insights into the pathophysiology of this disorder have led to the introduction of new therapies, such as the use of thrombopoietic agents to enhance platelet production. This review outlines many of the most commonly used therapeutic agents for the treatment of severe thrombocytopenia associated with both newly diagnosed and chronic ITP.

KEYWORDS

Immune thrombocytopenia - corticosteroids - immunoglobulin - rituximab - thrombopoietin

REFERENCES

  • 1 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
    Search in Google Scholar
  • 2 Beardsley D S. Pathophysiology of immune thrombocytopenic purpura.  Blood Rev. 2002;  16 (1) 13-14
    Search in Google Scholar
  • 3 Cines D B, Liebman H A. The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation.  Hematol Oncol Clin North Am. 2009;  23 (6) 1155-1161
    Search in Google Scholar
  • 4 Evans R S, Takahashi K, Duane R T, Payne R, Liu C. Primary thrombocytopenic purpura and acquired hemolytic anemia; evidence for a common etiology.  AMA Arch Intern Med. 1951;  87 (1) 48-65
    Search in Google Scholar
  • 5 Panitsas F P, Theodoropoulou M, Kouraklis A et al.. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response.  Blood. 2004;  103 (7) 2645-2647
    Search in Google Scholar
  • 6 Stasi R, Cooper N, Del Poeta G et al.. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab.  Blood. 2008;  112 (4) 1147-1150
    Search in Google Scholar
  • 7 Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+ Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome.  Eur J Haematol. 2007;  79 (4) 310-316
    Search in Google Scholar
  • 8 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 (4) 1364-1369
    Search in Google Scholar
  • 9 Provan D, Stasi R, Newland A C et al.. International consensus report on the investigation and management of primary immune thrombocytopenia.  Blood. 2010;  115 (2) 168-186
    Search in Google Scholar
  • 10 Dickerhoff R, von Ruecker A. The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment.  J Pediatr. 2000;  137 (5) 629-632
    Search in Google Scholar
  • 11 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;  88 (1) 3-40
    Search in Google Scholar
  • 12 Kühne T, Buchanan G R, Zimmerman S Intercontinental Childhood ITP Study Group et al. A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group.  J Pediatr. 2003;  143 (5) 605-608
    Search in Google Scholar
  • 13 George J N. Initial management of immune thrombocytopenic purpura in children: is supportive counseling without therapeutic intervention sufficient?.  J Pediatr. 2000;  137 (5) 598-600
    Search in Google Scholar
  • 14 Tarantino M D, Buchanan G R. The pros and cons of drug therapy for immune thrombocytopenic purpura in children.  Hematol Oncol Clin North Am. 2004;  18 (6) 1301-1314 viii
    Search in Google Scholar
  • 15 De Mattia D, Del Principe D, Del Vecchio G C et al.. Acute childhood idiopathic thrombocytopenic purpura: AIEOP consensus guidelines for diagnosis and treatment. Associazione Italiana di Ematologia e Oncologia Pediatrica.  Haematologica. 2000;  85 (4) 420-424
    Search in Google Scholar
  • 16 Buchanan G R, de Alarcon P A, Feig S A et al.. Acute idiopathic thrombocytopenic purpura—management in childhood.  Blood. 1997;  89 (4) 1464-1465 author reply 1466
    Search in Google Scholar
  • 17 Bolton-Maggs P H. Acute idiopathic thrombocytopenic purpura—management in childhood.  Blood. 1997;  89 (4) 1465 author reply 1466
    Search in Google Scholar
  • 18 Sutor A H, Dickeroff R, Gaedicke G et al.. Hamostasiologie: acute postinffektiose immunothrombozytopenie im kindersalter. [Acute postinfectious immune thrombocytopenia in children.] In: Leitlinien kenderheilkunde und jugendmedizin. [Guidelines for pediatric and youth medicine.]. Munich, Germany: Urban & Fischer; 1999: 23-27
    Search in Google Scholar
  • 19 Provan D, Newland A, Norfolk D British Committee for Standards in Haematology General Haematology Task Force et al. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy.  Br J Haematol. 2003;  120 (4) 574-596
    Search in Google Scholar
  • 20 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 (11) 1630-1638
    Search in Google Scholar
  • 21 Imbach P, Barandun S, d'Apuzzo V et al.. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood.  Lancet. 1981;  1 (8232) 1228-1231
    Search in Google Scholar
  • 22 Crow A R, Lazarus A H. 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
    Search in Google Scholar
  • 23 Blanchette V S, Luke B, Andrew M et al.. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura.  J Pediatr. 1993;  123 (6) 989-995
    Search in Google Scholar
  • 24 Blanchette V, Imbach P, Andrew M et al.. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.  Lancet. 1994;  344 (8924) 703-707
    Search in Google Scholar
  • 25 Beck C E, Nathan P C, Parkin P C, Blanchette V S, Macarthur C. Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in children: a systematic review and meta-analysis of randomized controlled trials.  J Pediatr. 2005;  147 (4) 521-527
    Search in Google Scholar
  • 26 Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management.  Hematol Oncol Clin North Am. 2010;  24 (1) 249-273
    Search in Google Scholar
  • 27 Godeau B, Chevret S, Varet B French ATIP Study Group et al. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial.  Lancet. 2002;  359 (9300) 23-29
    Search in Google Scholar
  • 28 Balaraman R. Treatment of severe autoimmune thrombocytopenic purpura.  Lancet. 2002;  359 (9325) 2279-2280 author reply 2279-2280
    Search in Google Scholar
  • 29 Carradice D. Treatment of severe autoimmune thrombocytopenic purpura.  Lancet. 2002;  359 (9325) 2279 author reply 2279-2280
    Search in Google Scholar
  • 30 Schiavotto C, Ruggeri M, Rodeghiero F. Adverse reactions after high-dose intravenous immunoglobulin: incidence in 83 patients treated for idiopathic thrombocytopenic purpura (ITP) and review of the literature.  Haematologica. 1993;  78 (6, Suppl 2) 35-40
    Search in Google Scholar
  • 31 Cayco A V, Perazella M A, Hayslett J P. Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature.  J Am Soc Nephrol. 1997;  8 (11) 1788-1794
    Search in Google Scholar
  • 32 Sartorius J A. Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study.  Am J Pediatr Hematol Oncol. 1984;  6 (2) 165-169
    Search in Google Scholar
  • 33 Carcao M D, Zipursky A, Butchart S, Leaker M, Blanchette V S. Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP).  Acta Paediatr Suppl. 1998;  424 71-74
    Search in Google Scholar
  • 34 Ozsoylu S, Irken G, Karabent A. High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura.  Eur J Haematol. 1989;  42 (5) 431-435
    Search in Google Scholar
  • 35 Ancona K G, Parker R I, Atlas M P, Prakash D. Randomized trial of high-dose methylprednisolone versus intravenous immunoglobulin for the treatment of acute idiopathic thrombocytopenic purpura in children.  J Pediatr Hematol Oncol. 2002;  24 (7) 540-544
    Search in Google Scholar
  • 36 Naithani R, Mahapatra M, Kumar R, Mishra P, Saxena R. High dose dexamethasone therapy shows better responses in acute immune thrombocytopenia than in chronic immune thrombocytopenia.  Platelets. 2010;  21 (4) 270-273
    Search in Google Scholar
  • 37 Cheng Y, Wong R S, Soo Y O et al.. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone.  N Engl J Med. 2003;  349 (9) 831-836
    Search in Google Scholar
  • 38 Borst F, Keuning J J, van Hulsteijn H, Sinnige H, Vreugdenhil G. High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults.  Ann Hematol. 2004;  83 (12) 764-768
    Search in Google Scholar
  • 39 Mazzucconi M G, Fazi P, Bernasconi S Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience.  Blood. 2007;  109 (4) 1401-1407
    Search in Google Scholar
  • 40 Alpdogan O, Budak-Alpdogan T, Ratip S et al.. Efficacy of high-dose methylprednisolone as a first-line therapy in adult patients with idiopathic thrombocytopenic purpura.  Br J Haematol. 1998;  103 (4) 1061-1063
    Search in Google Scholar
  • 41 Kuku I, Aydogdu I, Kaya E et al.. The early and long-term results of oral high-dose methylprednisolone treatment in adult patients with idiopathic thrombocytopenic purpura.  Eur J Haematol. 2005;  74 (3) 271-272
    Search in Google Scholar
  • 42 Cheung E, Liebman H A. Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia.  Biologics. 2009;  3 57-62
    Search in Google Scholar
  • 43 Scaradavou A, Woo B, Woloski B M et al.. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.  Blood. 1997;  89 (8) 2689-2700
    Search in Google Scholar
  • 44 Tarantino M D, Madden R M, Fennewald D L, Patel C C, Bertolone S J. Treatment of childhood acute immune thrombocytopenic purpura with anti-D immune globulin or pooled immune globulin.  J Pediatr. 1999;  134 (1) 21-26
    Search in Google Scholar
  • 45 Tarantino M D, Young G, Bertolone S J Acute ITP Study Group 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
    Search in Google Scholar
  • 46 Kane I, Ragucci D, Shatat I F, Bussel J, Kalpatthi R. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.  Br J Haematol. 2010;  149 (1) 79-83
    Search in Google Scholar
  • 47 Shahgholi E, Vosough P, Sotoudeh K et al.. Intravenous immune globulin versus intravenous anti-D immune globulin for the treatment of acute immune thrombocytopenic purpura.  Indian J Pediatr. 2008;  75 (12) 1231-1235
    Search in Google Scholar
  • 48 Newman G C, Novoa M V, Fodero E M, Lesser M L, Woloski B M, Bussel J B. 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
    Search in Google Scholar
  • 49 Gaines A R, Lee-Stroka H, Byrne K et al.. Investigation of whether the acute hemolysis associated with Rh(o)(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model.  Transfusion. 2009;  49 (6) 1050-1058
    Search in Google Scholar
  • 50 Gaines A R. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.  Blood. 2005;  106 (5) 1532-1537
    Search in Google Scholar
  • 51 Saleh M N, Gutheil J, Moore M et al.. A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with refractory immune thrombocytopenia.  Semin Oncol. 2000;  27 (6, Suppl 12) 99-103
    Search in Google Scholar
  • 52 Stasi R, Stipa E, Forte V, Meo P, Amadori S. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura.  Blood. 2002;  99 (10) 3872-3873
    Search in Google Scholar
  • 53 Wang J, Wiley J M, Luddy R, Greenberg J, Feuerstein M A, Bussel J B. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment.  J Pediatr. 2005;  146 (2) 217-221
    Search in Google Scholar
  • 54 Bennett C M, Rogers Z R, Kinnamon D D et al.. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura.  Blood. 2006;  107 (7) 2639-2642
    Search in Google Scholar
  • 55 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
    Search in Google Scholar
  • 56 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
    Search in Google Scholar
  • 57 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
    Search in Google Scholar
  • 58 Fianchi L, Rossi E, Murri R, De Stefano V, Pagano L, Leone G. Severe infectious complications in a patient treated with rituximab for idiopathic thrombocytopenic purpura.  Ann Hematol. 2007;  86 (3) 225-226
    Search in Google Scholar
  • 59 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;  113 (20) 4834-4840
    Search in Google Scholar
  • 60 Hitzrot J M. Splenectomy in Hemorrhagic Purpura: Idiopathic Purpura, Essential Thrombopenie (Frank). Purpura Hemorrhagic Protopathique (Hayem).  Ann Surg. 1923;  78 (2) 185-190
    Search in Google Scholar
  • 61 Kühne T, Blanchette V, Buchanan G R Intercontinental Childhood ITP Study Group et al. Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group.  Pediatr Blood Cancer. 2007;  49 (6) 829-834
    Search in Google Scholar
  • 62 Mantadakis E, Buchanan G R. Elective splenectomy in children with idiopathic thrombocytopenic purpura.  J Pediatr Hematol Oncol. 2000;  22 (2) 148-153
    Search in Google Scholar
  • 63 El-Alfy M S, El-Tawil M M, Shahein N. 5- to 16-year follow-up following splenectomy in chronic immune thrombocytopenic purpura in children.  Acta Haematol. 2003;  110 (1) 20-24
    Search in Google Scholar
  • 64 Aronis S, Platokouki H, Avgeri M, Pergantou H, Keramidas D. Retrospective evaluation of long-term efficacy and safety of splenectomy in chronic idiopathic thrombocytopenic purpura in children.  Acta Paediatr. 2004;  93 (5) 638-642
    Search in Google Scholar
  • 65 Bolton-Maggs P H, Dickerhoff R, Vora A J. The nontreatment of childhood ITP (or “the art of medicine consists of amusing the patient until nature cures the disease”).  Semin Thromb Hemost. 2001;  27 (3) 269-275
    Search in Google Scholar
  • 66 Schwartz J, Leber M D, Gillis S, Giunta A, Eldor A, Bussel J B. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP).  Am J Hematol. 2003;  72 (2) 94-98
    Search in Google Scholar
  • 67 Han J J, Baek S K, Lee J J, Kim S Y, Cho K S, Yoon H J. Long-term outcomes of a 5-year follow up of patients with immune thrombocytopenic purpura after splenectomy.  Korean J Hepatol. 2010;  45 (3) 197-204
    Search in Google Scholar
  • 68 Kojouri K, Vesely S K, Terrell D R, George J N. 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
    Search in Google Scholar
  • 69 Stasi R, Newland A, Thornton P, Pabinger I. Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate.  Ann Hematol. 2010;  89 (12) 1185-1195
    Search in Google Scholar
  • 70 Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients.  J Infect. 2001;  43 (3) 182-186
    Search in Google Scholar
  • 71 Kaushansky K, Lok S, Holly R D et al.. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin.  Nature. 1994;  369 (6481) 568-571
    Search in Google Scholar
  • 72 Kuter D J. New thrombopoietic growth factors.  Blood. 2007;  109 (11) 4607-4616
    Search in Google Scholar
  • 73 Buchanan G R, Bomgaars L, Bussel J B et al.. A Randomized, Double-Blind, Placebo-Controlled Phase 1/2 Study to Determine the Safety and Efficacy of Romiplostim in Children with Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP).  Blood (ASH Annual Meeting Abstracts). 2009;  114 680
    Search in Google Scholar
  • 74 Elalfy M S, Abdelmaksoud A A, Eltonbary K Y. Romiplostim (N-Plate) In Children with Chronic Refractory ITP.  Blood (ASH Annual Meeting Abstracts). 2010;  116 1443
    Search in Google Scholar
  • 75 Kuter D J, Bussel J B, Lyons R M et al.. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.  Lancet. 2008;  371 (9610) 395-403
    Search in Google Scholar
  • 76 Bussel J B, Kuter D J, Pullarkat V, Lyons R M, Guo M, Nichol J L. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP.  Blood. 2009;  113 (10) 2161-2171
    Search in Google Scholar
  • 77 Kuter D J, Bussel J B, Newland A et al.. Long-Term Efficacy and Safety of Romiplostim Treatment of Adult Patients with Chronic Immune Thrombocytopenia (ITP): Final Report from an Open-Label Extension Study.  Blood (ASH Annual Meeting Abstracts). 2010;  116 68
    Search in Google Scholar
  • 78 Bussel J B, 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
    Search in Google Scholar
  • 79 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;  377 (9763) 393-402
    Search in Google Scholar
  • 80 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
    Search in Google Scholar

Salley G PelsM.D. 

Instructor, Section of Hematology Oncology, Department of Pediatrics, Yale University School of Medicine

333 Cedar Street, New Haven, Connecticut 06520

Email: salley.pels@yale.edu