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Idiopathic thrombocytopenic purpura-a literature based review
Corresponding Author(s) : Narender Boggula
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 11 No. 3 (2023): 2023 Volume -11 - Issue 3
Abstract
Immune thrombocytopenia (ITP) is a syndrome in which platelets become coated with autoantibodies to platelet membrane antigens, resulting in splenic sequestration and phagocytosis by mononuclear macrophages. Immune thrombocytopenic purpura (ITP) is an autoimmune pathology characterized by a low platelet count, purpura, and hemorrhagic episodes caused by antiplatelet autoantibodies. The exclusion typically makes the diagnosis of the known causes of thrombocytopenia. IgG autoantibodies sensitize the circulating platelets. It leads to the accelerated removal of these cells by antigen-presenting cells (macrophages) of the spleen and sometimes the liver or other components of the monocyte-macrophage system. Bone marrow compensates the platelet destruction by increasing platelet production. ITP most often occurs in healthy children and young adults within a few weeks following a viral infection. Certain drugs can also cause immune thrombocytopenia indistinguishable from ITP. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein (GP) IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. It should be limited in duration unless demonstrated that symptomatic thrombocytopenia persists. Patients with mild, asymptomatic thrombocytopenia, discovered incidentally on a routine blood count, should not be treated. We present a case report on ITP and summarize the key points in the diagnosis and management of ITP. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.
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- Ponzetto A, Figura N, Fiorini G. Immune thrombocytopenic purpura and infections. Intern Emerg Med. 2018;13(7):1137. doi: 10.1007/s11739-018-1908-9, PMID 30030700.
- Moulis G, Palmaro A, Montastruc JL, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014;124(22):3308-15. doi: 10.1182/blood-2014-05-578336, PMID 25305203.
- Moulis G, Comont T, Adoue D. New insights into the epidemiology of immune thrombocytopenia in adult patients: impact for clinical practice. Rev Med Interne. 2021;42(1):11-5. doi: 10.1016/j.revmed.2020.05.018, PMID 32798089.
- Weycker D, Hanau A, Hatfield M, Wu H, Sharma A, Bensink ME, 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):184-92. doi: 10.1080/13696998.2019.1669329, PMID 31547724.
- Matzdorff A, Wörmann B. Diagnosis and Therapy of Immune thrombocytopenia. Dtsch Med Wochenschr. 2018;143(15):1076-81. doi: 10.1055/a-0384-4703, PMID 30060276.
- George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood. 2010;116(20):4060-9. doi: 10.1182/blood-2010-07-271445.
- Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346(13):995-1008. doi: 10.1056/NEJMra010501, PMID 11919310.
- Abboud MR, Laver J, Xu F, Weksler B, Bussel JB. Serum levels of GM-CSF are elevated in patients with thrombocytopenia. Br J Haematol. 1996;92(2):486-8. doi: 10.1046/j.1365-2141.1996.d01-1464.x, PMID 8603021.
- Zhou B, Zhao H, Yang RC, Han ZC. Multi- dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol. 2005;54(2):107-16. doi: 10.1016/j.critrevonc.2004.12.004, PMID 15843093.
- Liu Y, Chen S, Sun Y, Lin Q, Liao X, Zhang J, et al. Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: a retrospective study. Med (Baltim). 2016;95(50):e5565. doi: 10.1097/MD.0000000000005565, PMID 27977588.
- Frederiksen H, Maegbaek ML, Nørgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2014;166(2):260-7. doi: 10.1111/bjh.12869, PMID 24690142.
- Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90(7):914-23. PMID 15996929.
- Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 2003;102(3):887-95. doi: 10.1182/blood-2002-05-1475, PMID 12676790.
- Prasad VK, Kim IK, Farrington K, Bussel JB. TTP following ITP in an HIV-positive boy. J Pediatr Hematol Oncol. 1996;18(4):384-6. doi: 10.1097/00043426-199611000-00010, PMID 8888747.
- Doobaree IU, Nandigam R, Bennett D, Newland A, Provan D. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016;97(4):321-30. doi: 10.1111/ejh.12777, PMID 27199203.
- Baron BW, Martin MS, Sucharetza BS, Jeon H-R, Baron JM. Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange. J Clin Apher. 2001;16(4):179-85. doi: 10.1002/jca.1031, PMID 11835414.
- Stein RS, Flexner JM. Idiopathic thrombocytopenic purpura during remission of thrombotic thrombocytopenic purpura. South Med J. 1984;77(12):1599-601. doi: 10.1097/00007611-198412000-00034, PMID 6542250.
- Wang Y, Yu T, Dong Q, Liu S, Yu Y, Zhao HY, et al. Clonal hematopoiesis in primary immune thrombocytopenia. Blood Cancer J. 2022;12(3):40. doi: 10.1038/s41408-022-00641-5, PMID 35293382.
- Rodeghiero F. ITP and thrombosis: an intriguing association. Blood Adv. 2017;1(24):2280. doi: 10.1182/bloodadvances.2017007989, PMID 29296876.
- Lin HC, Huang J, Huang J, Zhang LJ, Yin XW, Yang JC et al. Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature. J Med Case Rep. 2023;17(1):38. doi: 10.1186/s13256-023-03762-y, PMID 36750960.
- Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237-47. doi: 10.1056/NEJMoa073275, PMID 18046028.
- Visweshwar N, Ayala I, Jaglal M, Killeen R, Sokol L, Laber DA et al. Primary immune thrombocytopenia: a ’diagnosis of exclusion’? Blood Coagul Fibrinolysis. 2022;33(6):289-94. doi: 10.1097/MBC.0000000000001144, PMID 35867940.
- Swan D, Newland A, Rodeghiero F, Thachil J. Thrombosis in immune thrombocytopenia: current status and future perspectives. Br J Haematol. 2021;194(5):822-34. doi: 10.1111/bjh.17390, PMID 33822358.
- Torrez M, Chabot-Richards D, Babu D, Lockhart E, Foucar K. How I investigate acquired megaloblastic anemia. Int J Lab Hematol. 2022;44(2):236-47. doi: 10.1111/ijlh.13789, PMID 34981651.
- Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-66. doi: 10.1182/bloodadvances.2019000966, PMID 31794604.
- Young NS. Aplastic anemia. N Engl J Med. 2018;379(17):1643-56. doi: 10.1056/NEJMra1413485, PMID 30354958.
- Santoshi RK, Patel R, Patel NS, Bansro V, Chhabra G. A comprehensive review of thrombocytopenia with a spotlight on intensive care patients. Cureus. 2022;14(8):e27718. doi: 10.7759/cureus.27718, PMID 35949449.
- Cooper N, Ghanima W. Immune thrombocytopenia. N Engl J Med. 2019;381(10):945-55. doi: 10.1056/NEJMcp1810479, PMID 31483965.
- Vrbensky JR, Nazy I, Toltl LJ, Ross C, Ivetic N, Smith JW et al. Megakaryocyte apoptosis in immune thrombocytopenia. Platelets. 2018;29(7):729-32. doi: 10.1080/09537104.2018.1475637, PMID 29787328.
- Kaushansky KK. Thrombopoietin: a tool for understanding thrombopoiesis. J Thromb Haemost. 2003;1(7):1587-92. doi: 10.1046/j.1538-7836.2003.00273.x, PMID 12871295.
- Ingram M, Coopersmith A. Reticulated platelets following acute blood loss. Br J Haematol. 1969;17(3):225-9. doi: 10.1111/j.1365-2141.1969.tb01366.x, PMID 5806433.
- Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, 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, PMID 17200219.
- British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96. doi: 10.1046/j.1365-2141.2003.04131.x, PMID 12588344.
- Salama A, Mueller-Eckhardt C, Kiefel V. Effect of intravenous immunoglobulin in immune thrombocytopenia. Lancet. 1983;2(8343):193-5. doi: 10.1016/s0140-6736(83)90175-7, PMID 6135031.
- Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79(4):504-22. doi: 10.4065/79.4.504, PMID 15065616.
References
Ponzetto A, Figura N, Fiorini G. Immune thrombocytopenic purpura and infections. Intern Emerg Med. 2018;13(7):1137. doi: 10.1007/s11739-018-1908-9, PMID 30030700.
Moulis G, Palmaro A, Montastruc JL, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014;124(22):3308-15. doi: 10.1182/blood-2014-05-578336, PMID 25305203.
Moulis G, Comont T, Adoue D. New insights into the epidemiology of immune thrombocytopenia in adult patients: impact for clinical practice. Rev Med Interne. 2021;42(1):11-5. doi: 10.1016/j.revmed.2020.05.018, PMID 32798089.
Weycker D, Hanau A, Hatfield M, Wu H, Sharma A, Bensink ME, 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):184-92. doi: 10.1080/13696998.2019.1669329, PMID 31547724.
Matzdorff A, Wörmann B. Diagnosis and Therapy of Immune thrombocytopenia. Dtsch Med Wochenschr. 2018;143(15):1076-81. doi: 10.1055/a-0384-4703, PMID 30060276.
George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood. 2010;116(20):4060-9. doi: 10.1182/blood-2010-07-271445.
Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346(13):995-1008. doi: 10.1056/NEJMra010501, PMID 11919310.
Abboud MR, Laver J, Xu F, Weksler B, Bussel JB. Serum levels of GM-CSF are elevated in patients with thrombocytopenia. Br J Haematol. 1996;92(2):486-8. doi: 10.1046/j.1365-2141.1996.d01-1464.x, PMID 8603021.
Zhou B, Zhao H, Yang RC, Han ZC. Multi- dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol. 2005;54(2):107-16. doi: 10.1016/j.critrevonc.2004.12.004, PMID 15843093.
Liu Y, Chen S, Sun Y, Lin Q, Liao X, Zhang J, et al. Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: a retrospective study. Med (Baltim). 2016;95(50):e5565. doi: 10.1097/MD.0000000000005565, PMID 27977588.
Frederiksen H, Maegbaek ML, Nørgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2014;166(2):260-7. doi: 10.1111/bjh.12869, PMID 24690142.
Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90(7):914-23. PMID 15996929.
Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 2003;102(3):887-95. doi: 10.1182/blood-2002-05-1475, PMID 12676790.
Prasad VK, Kim IK, Farrington K, Bussel JB. TTP following ITP in an HIV-positive boy. J Pediatr Hematol Oncol. 1996;18(4):384-6. doi: 10.1097/00043426-199611000-00010, PMID 8888747.
Doobaree IU, Nandigam R, Bennett D, Newland A, Provan D. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016;97(4):321-30. doi: 10.1111/ejh.12777, PMID 27199203.
Baron BW, Martin MS, Sucharetza BS, Jeon H-R, Baron JM. Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange. J Clin Apher. 2001;16(4):179-85. doi: 10.1002/jca.1031, PMID 11835414.
Stein RS, Flexner JM. Idiopathic thrombocytopenic purpura during remission of thrombotic thrombocytopenic purpura. South Med J. 1984;77(12):1599-601. doi: 10.1097/00007611-198412000-00034, PMID 6542250.
Wang Y, Yu T, Dong Q, Liu S, Yu Y, Zhao HY, et al. Clonal hematopoiesis in primary immune thrombocytopenia. Blood Cancer J. 2022;12(3):40. doi: 10.1038/s41408-022-00641-5, PMID 35293382.
Rodeghiero F. ITP and thrombosis: an intriguing association. Blood Adv. 2017;1(24):2280. doi: 10.1182/bloodadvances.2017007989, PMID 29296876.
Lin HC, Huang J, Huang J, Zhang LJ, Yin XW, Yang JC et al. Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature. J Med Case Rep. 2023;17(1):38. doi: 10.1186/s13256-023-03762-y, PMID 36750960.
Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237-47. doi: 10.1056/NEJMoa073275, PMID 18046028.
Visweshwar N, Ayala I, Jaglal M, Killeen R, Sokol L, Laber DA et al. Primary immune thrombocytopenia: a ’diagnosis of exclusion’? Blood Coagul Fibrinolysis. 2022;33(6):289-94. doi: 10.1097/MBC.0000000000001144, PMID 35867940.
Swan D, Newland A, Rodeghiero F, Thachil J. Thrombosis in immune thrombocytopenia: current status and future perspectives. Br J Haematol. 2021;194(5):822-34. doi: 10.1111/bjh.17390, PMID 33822358.
Torrez M, Chabot-Richards D, Babu D, Lockhart E, Foucar K. How I investigate acquired megaloblastic anemia. Int J Lab Hematol. 2022;44(2):236-47. doi: 10.1111/ijlh.13789, PMID 34981651.
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-66. doi: 10.1182/bloodadvances.2019000966, PMID 31794604.
Young NS. Aplastic anemia. N Engl J Med. 2018;379(17):1643-56. doi: 10.1056/NEJMra1413485, PMID 30354958.
Santoshi RK, Patel R, Patel NS, Bansro V, Chhabra G. A comprehensive review of thrombocytopenia with a spotlight on intensive care patients. Cureus. 2022;14(8):e27718. doi: 10.7759/cureus.27718, PMID 35949449.
Cooper N, Ghanima W. Immune thrombocytopenia. N Engl J Med. 2019;381(10):945-55. doi: 10.1056/NEJMcp1810479, PMID 31483965.
Vrbensky JR, Nazy I, Toltl LJ, Ross C, Ivetic N, Smith JW et al. Megakaryocyte apoptosis in immune thrombocytopenia. Platelets. 2018;29(7):729-32. doi: 10.1080/09537104.2018.1475637, PMID 29787328.
Kaushansky KK. Thrombopoietin: a tool for understanding thrombopoiesis. J Thromb Haemost. 2003;1(7):1587-92. doi: 10.1046/j.1538-7836.2003.00273.x, PMID 12871295.
Ingram M, Coopersmith A. Reticulated platelets following acute blood loss. Br J Haematol. 1969;17(3):225-9. doi: 10.1111/j.1365-2141.1969.tb01366.x, PMID 5806433.
Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, 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, PMID 17200219.
British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96. doi: 10.1046/j.1365-2141.2003.04131.x, PMID 12588344.
Salama A, Mueller-Eckhardt C, Kiefel V. Effect of intravenous immunoglobulin in immune thrombocytopenia. Lancet. 1983;2(8343):193-5. doi: 10.1016/s0140-6736(83)90175-7, PMID 6135031.
Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79(4):504-22. doi: 10.4065/79.4.504, PMID 15065616.