Immune Thrombocytopenia (ITP)


Immune thrombocytopenia (ITP) is a bleeding disorder involving an unusually low platelet count, often to values below 100,000/µL. In ITP, the white blood cell and hemoglobin levels are normal, and patients present with a generalized purpuric rash.1,2

Types and Epidemiology of ITP

ITP can be acute or chronic. Acute ITP is the most common form of the disease and usually affects children between 2 and 6 years old. In these patients, symptoms can develop after a viral infection and disappear after a few weeks to 6 months. Chronic ITP affects persons of any age, most often women, and lasts for at least 6 months. This form of ITP can recur, so that continuous medical monitoring is required.2 

The annual incidence of ITP in children is estimated to be 1 to 6.4 cases per 100,000, and in adults, it is estimated to be 1 to 6 cases per 100,000.3 

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Symptoms and Diagnosis of ITP

Patients with ITP present with petechiae, purpura, ecchymoses that appear at the elbows and knees following movement, nosebleed, mucosal bleeding (in the mouth and/or around the gums), hematuria, and increased menstrual bleeding. Hematuria and gastrointestinal bleeding are less common. However, they are susceptible to thrombosis. Also, patients may have an enlarged spleen due to a coexisting viral infection or Evans syndrome.2,4

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Rarely, patients may present with platelet counts below 5000/µL, a critical situation that increases the risk for life-threatening hemorrhage in the brain, lungs, and gastrointestinal tract.5,6 A severe complication of ITP is intracranial hemorrhage (ICH), which may occur when platelet levels decrease to below 10,000/µL. ICH manifests as headache, persistent vomiting, altered mental status, seizures, and focal neurological findings.1 This is a rare complication that occurs mainly in older patients with comorbidities and in children, who commonly present with self-limited disease.7 Although most patients present with a platelet count below 20,000/µL, severe, life-threatening bleeding is infrequent.8

ITP is frequently diagnosed by exclusion together with the patient’s history, physical examination findings, complete blood cell count, and blood smear.3,9 Rarely, bone marrow aspiration may be needed if an abnormal cell count or blood smear indicates other findings in addition to thrombocytopenia.3

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Differential Diagnosis of ITP

The differential diagnosis of ITP includes acute lymphocytic leukemia, autoimmune hemolytic anemia, active infections such as hepatitis C and HIV-1 infection, systemic lupus erythematosus, autoimmune lymphoproliferative syndrome, bone marrow failure, and exposure to drugs such as heparin and vancomycin.1

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Etiology of ITP

ITP most often derives from the development of immunoglobulin G (IgG) autoantibodies against proteins of the platelet membrane, typically glycoprotein (GP) IIb/IIIa complex, GP Ib/IIa, and GP VI. The autoantibodies cause an increase in the removal of platelets in the spleen by splenic macrophages.1,6 Platelet production is also inhibited.3 Viral and bacterial antigens may induce the production of autoantibodies; in addition, autoimmune conditions such as antiphospholipid syndrome, systemic lupus erythematosus, and Evans syndrome can trigger autoimmunity.1

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Prognosis of ITP

ITP can worsen during pregnancy and increase the risk of maternal morbidity. The trigger of ITP in adults is unknown, but in some countries like Japan and Italy, it can be associated with H. Pylori infection. Treatment of the infection can lead to remission of the ITP. Although less than 10% of adult patients gain spontaneous remission, following the completion of initial treatment, nearly one-third of patients experience remission. Approximately 75% of patients feel significant improvements within 5 years.4

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Treatment of ITP

The initial management of ITP in children is based on avoiding triggers of bleeding, including activities such as contact sports, when platelet counts are below 30,000/µL. Both children and adults should also avoid the use of nonsteroidal anti-inflammatory drugs and aspirin. When platelet counts decrease to values below 20,000/µL, patients should not use anticoagulants.1

First-line therapy in ITP includes corticosteroid therapy. Even though approximately 80% of patients respond to this treatment, the risk for relapse is high.5 When corticosteroids are not recommended, intravenous immunoglobulin or anti-D immunoglobulin can be administered.1 Second-line therapy is available and includes thrombopoietin receptor agonists (TPO-RAs), such as eltrombopag, romiplostim, and rituximab.1,5 Other immunosuppressants are available (cyclophosphamide, cyclosporine, mycophenolate, and azathioprine) for patients who do not respond to these drugs and have severe, symptomatic thrombocytopenia.3

A surgical alternative, splenectomy, is available for children who present with severe thrombocytopenia and hemorrhagic symptoms that require treatment with multiple drugs, although this approach should be delayed as long as possible because of the potential for spontaneous remission.10 Response rates of 70% to 80% are achieved with splenectomy, with a low incidence of complications.3

Patients who have severe thrombocytopenia require hospitalization to increase their platelet counts. Emergency treatment relies on corticosteroid therapy or intravenous immunoglobulins. Transfusions with platelet concentrates may be also used, and this approach can be supplemented with the administration of intravenous immunoglobulins.5

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References

1. Pietras NM, Pearson-Shaver AL. Immune thrombocytopenic purpura. In: StatPearls [Internet]. StatPearls Publishing: 2022. Accessed October 3, 2022.

2. Idiopathic thrombocytopenic purpura. John Hopkins Medicine. Accessed October 3, 2022.

3. Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol. 2010;85(3):174-180. doi:10.1002/ajh.21616 

4. Kuter DJ. Immune thrombocytopenia (ITP). MSD Manual Professional Version. Revised June 2022. Modified September 2022. Accessed October 3, 2022. 

5. Onisâi M, Vlădăreanu AM, Spînu A, Găman M, Bumbea H. Idiopathic thrombocytopenic purpura (ITP) – new era for an old disease. Rom J Intern Med. 2019;57(4):273-283. doi:10.2478/rjim-2019-0014

6. Kayal L, Jayachandran S, Singh K. Idiopathic thrombocytopenic purpura. Contemp Clin Dent. 2014;5(3):410-414. doi:10.4103/0976-237X.137976

7. Immune thrombocytopenia. Orphanet. Accessed October 3, 2022.

8. Kochhar M, Neunert C. Immune thrombocytopenia: a review of upfront treatment strategies. Blood Rev. 2021;49:100822. doi:10.1016/j.blre.2021.100822

9. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346(13):995-1008. doi:10.1056/NEJMra010501

10. 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. Erratum in: Blood Adv. 2020 Jan 28;4(2):252

Reviewed by Debjyoti Talukdar, MD, on 10/10/2022.