Immune Thrombocytopenia (ITP)


Immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenic purpura, is an autoimmune, hematologic disorder characterized by the premature destruction of platelets due to autoantibodies directed against normal platelet surface membrane antigens. This results in a decreased number of functional, circulating platelets, which subsequently increases bleeding risk.1

Demographic Risk Factors

The risk of developing ITP increases depending on demographic factors such as age and sex. Children, and especially boys, between the ages of 1 and 6 years have a higher risk of developing ITP. In adults, it affects middle-aged women more frequently, while its onset is rarer in people over 60 years of age.1,2 

Patients with ITP over the age of 70 years demonstrate an increased risk of spontaneous bleeding and more serious bleeding complications, including death from intracranial hemorrhage.1

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Genetic Risk Factors

People with single nucleotide polymorphisms in genes associated with immune system functioning or regulation are more likely to develop ITP. Scientists have identified polymorphisms in genes that encode B-cell activating factor, mannose binding lectin (MBL), glycoprotein Ia (GPIa), and various cytokines and chemokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-alpha (TNFα), tumor growth factor-beta (TGF-β), and interferon-gamma (IFN-γ), as genetic risk factors for the development of ITP.3-8 

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Environmental Risk Factors

Exposure to specific infections increases the risk of ITP, especially in children. Bacterial infections, such as Helicobacter pylori, and viral infections, such as hepatitis C, human immunodeficiency virus (HIV), Epstein Barr virus (EBV), cytomegalovirus, and coronavirus disease 2019 (COVID-19), have all been associated with the activation of autoimmune responses that contribute to ITP development.3,9 

Another environmental factor that predisposes patients to developing ITP includes exposure to certain drugs that may cause drug-induced ITP. Such medications that induce ITP include heparin, chemotherapeutic agents, antirheumatic agents, antimicrobial agents, platelet inhibitors, cinchona alkaloids, histamine-receptor antagonists, diuretic agents, analgesic agents, anticonvulsants, sedative agents, and immunosuppressive agents.13-15

Patients diagnosed with primary ITP demonstrate increased cancer risk, especially for lymphoid, hematological, skin, and gastrointestinal cancers, compared with the general population.10 However, patients with solid tumor malignancies, such as breast cancer, also show an increased risk for developing ITP-related complications.11,12

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Other Autoimmune Conditions

Patients diagnosed with other autoimmune conditions, especially rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome, have an increased risk of developing ITP. Comorbid autoimmune conditions are more common in patients with ITP.2,16,17

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References

  1. Kessler CM. Immune thrombocytopenia (ITP). Medscape. Updated January 7, 2021. Accessed October 10, 2022.
  2. Immune thrombocytopenia (ITP). Mayo Clinic. February 25, 2021. Accessed October 10, 2022.
  3. Swinkels M, Rijkers M, Voorberg J, Vidarsson G, Leebeek FWG, Jansen AJG. Emerging concepts in immune thrombocytopenia. Front Immunol. 2018;9:880. doi:10.3389/fimmu.2018.00880
  4. Wu KH, Peng CT, Li TC, et al. Interleukin 4, interleukin 6 and interleukin 10 polymorphisms in children with acute and chronic immune thrombocytopenic purpura. Br J Haematol. 2005;128(6):849-852. doi:10.1111/j.1365-2141.2005.05385.x
  5. Emmerich F, Bal G, Barakat A, et al. High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2007;136(2):309-314. doi:10.1111/j.1365-2141.2006.06431.x
  6. Rocha AMC, De Souza C, Rocha GA, et al. IL1RN VNTR and IL2−330 polymorphic genes are independently associated with chronic immune thrombocytopenia. Br J Haematol. 2010;150(6):679-684. doi:10.1111/j.1365-2141.2010.08318.x
  7. Pehlivan M, Okan V, Sever T, et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets. 2011;22(8):588-595. doi:10.3109/09537104.2011.577255
  8. Saitoh T, Tsukamoto N, Koiso H, et al. Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia. Eur J Haematol. 2011;87(3):253-258. doi:10.1111/j.1600-0609.2011.01651.x
  9. Bomhof G, Mutsaers PGNJ, Leebeek FWG, et al. COVID‐19‐associated immune thrombocytopenia. Br J Haematol. 2020;190(2):e61-e64. doi:10.1111/bjh.16850
  10. Ekstrand C, Bahmanyar S, Cherif H, Kieler H, Linder M. Cancer risk in patients with primary immune thrombocytopenia – a Swedish nationwide register study. Cancer Epidemiol. 2020;69:101806. doi:10.1016/j.canep.2020.101806
  11. Hügli S, Hügli A, Simonetta F, Chalandon Y. A rare case of immune thrombocytopenia secondary to breast cancer. Clin Case Rep. 2018;7(1):170-174. doi:10.1002/ccr3.1939
  12. Ghanavat M, Ebrahimi M, Rafieemehr H, Maniati M, Behzad MM, Shahrabi S. Thrombocytopenia in solid tumors: prognostic significance. Oncol Rev. 2019;13(1):413. doi:10.4081/oncol.2019.413
  13. Kam T, Alexander M. Drug-induced immune thrombocytopenia. J Pharm Pract. 2014;27(5):430-439. doi:10.1177/0897190014546099
  14. Chong BH, Choi PYI, Khachigian L, Perdomo J. Drug-induced immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3):521-540. doi:10.1016/j.hoc.2013.02.003
  15. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357(6):580-587. doi:10.1056/NEJMra066469
  16. Ichikawa N, Harigai M, Nakajima A, Hara M, Kamatani N. Immune thrombocytopenic purpura associated with rheumatoid arthritis – a report of five cases and review of the literature. Mod Rheumatol. 2001;11(3):246-250. doi:10.3109/s101650170013
  17. Roussotte M, Gerfaud-Valentin M, Hot A, et al. Immune thrombocytopenia with clinical significance in systemic lupus erythematosus: a retrospective cohort study of 90 patients. Rheumatology (Oxford). 2022;61(9):3627-3639. doi:10.1093/rheumatology/keab925

Reviewed by Hasan Avcu, MD, on 10/17/2022.

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