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Immune Thrombocytopenia (ITP)

(Idiopathic Thrombocytopenic Purpura; Immune Thrombocytopenic Purpura)

By

David J. Kuter

, MD, DPhil, Harvard Medical School

Last full review/revision Jun 2022| Content last modified Jun 2022
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Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size is normal in the absence of another underlying condition. Diagnosis is usually clinical, based on exclusion of other causes of thrombocytopenia (eg, HIV infection, hepatitis C infection). Treatment includes corticosteroids, splenectomy, immunosuppressants, thrombopoietin receptor agonist drugs, or the spleen tyrosine kinase inhibitor fostamatinib. For life-threatening bleeding, platelet transfusions, IV corticosteroids, IV anti-D immune globulin, or IV immune globulin may be used individually or in combination.

Immune thrombocytopenia usually results from development of an autoantibody directed against a structural platelet antigen. These antiplatelet antibodies lead to increased platelet destruction, usually in the spleen, and inhibition of platelet production and release from megakaryocytes. In childhood ITP, the autoantibody may be triggered by viral antigens. The trigger in adults is unknown, although in some countries (eg, Japan, Italy), ITP has been associated with Helicobacter pylori infection, and treatment of the infection has been followed by remission of the ITP ( 1 General reference Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more General reference ). COVID-19 infection rarely causes ITP, but COVID-19 vaccination may worsen thrombocytopenia in 2 to 12% of patients with ITP. ITP tends to worsen during pregnancy Immune Thrombocytopenia in Pregnancy Autoimmune disorders are 5 times more common among women, and incidence tends to peak during reproductive years. Thus, these disorders commonly occur in pregnant women. Antiphospholipid antibody... read more and increases the risk of maternal morbidity.

General reference

  • 1. Kuter DJ: The treatment of immune thrombocytopenia (ITP)—focus on thrombopoietin receptor agonists. Annals of Blood Volume 6 March 2021

Symptoms and Signs of ITP

Although often asymptomatic and identified only by a low platelet count on a routine assay, when present the symptoms and signs of immune thrombocytopenia are

  • Petechiae

  • Purpura and/or ecchymoses

  • Mucosal bleeding

  • Increased menstrual bleeding

Gross gastrointestinal (GI) bleeding and hematuria are less common. The spleen is of normal size unless it is enlarged by a coexisting viral infection or autoimmune hemolytic anemia Autoimmune Hemolytic Anemia Autoimmune hemolytic anemia is caused by autoantibodies that react with red blood cells at temperatures ≥ 37° C (warm antibody hemolytic anemia) or 37° C (cold agglutinin disease). Hemolysis... read more Autoimmune Hemolytic Anemia (Evans syndrome). Like the other disorders of increased platelet destruction, ITP is also associated with an increased risk of thrombosis.

Manifestations of Immune Thrombocytopenia

Diagnosis of ITP

  • Complete blood count (CBC) with platelets and peripheral blood smear

  • Rarely bone marrow aspiration

  • Exclusion of other thrombocytopenic disorders

Immune thrombocytopenia is suspected in patients with isolated thrombocytopenia (ie, otherwise normal CBC and peripheral blood smear). Because manifestations of immune thrombocytopenia (ITP) are nonspecific, other reversible causes of isolated thrombocytopenia Thrombocytopenia Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more Thrombocytopenia (eg, drugs, alcohol, lymphoproliferative disorders, other autoimmune diseases, viral infections) need to be excluded by clinical evaluation and appropriate testing. Typically, patients have coagulation studies, liver tests, and tests for infection with hepatitis C and HIV. Peripheral blood smear must be reviewed to assess platelet size and granularity and to help exclude other major causes of thrombocytopenia such as thrombotic thrombocytopenic purpura Thrombotic Thrombocytopenic Purpura (TTP) Thrombotic thrombocytopenic purpura (TTP) is an acute, fulminant disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations may include alterations... read more Thrombotic Thrombocytopenic Purpura (TTP) (TTP), inherited thrombocytopenia, and leukemia Overview of Leukemia Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms... read more . Testing for antiplatelet antibodies may aid the diagnosis in some cases (1) Diagnosis reference Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Diagnosis reference . The immature platelet fraction may be elevated in ITP when the platelet count is < 50,000/mcL (< 50 × 109/L).

Bone marrow examination is not required to make the diagnosis but is done if blood counts or blood smear reveals abnormalities in addition to thrombocytopenia, when clinical features are not typical, or if patients fail to respond to standard therapies (eg, corticosteroids). In patients with ITP, bone marrow examination reveals normal or possibly increased numbers of megakaryocytes in an otherwise normal bone marrow sample.

Diagnosis reference

  • 1. Al-Samkari H, Rosovsky RP, Karp Leaf RS: A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 4(1):9–18, 2020. doi: 10.1182/bloodadvances.2019000868

Prognosis for ITP

Children typically recover spontaneously, even from severe thrombocytopenia, in several weeks to months.

In adults, spontaneous remission occurs in under 10%. With completion of initial treatment, about one-third of patients undergo remission. Up to 75% of patients improve within 5 years ( 1 Prognosis reference Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Prognosis reference ). However, many patients have mild and stable disease (ie, platelet counts > 30,000/mcL [> 30 × 109/L]) with minimal or no bleeding; they are often discovered by the automated platelet counting now routinely done with complete blood count.

Prognosis reference

Treatment of ITP

  • Oral corticosteroids

  • IV immune globulin (IVIG)

  • IV anti-D immune globulin

  • Sometimes, splenectomy

  • Thrombopoietin receptor agonists (TPO-RA)

  • Rituximab

  • Fostamatinib

  • Other immunosuppressants

  • For severe bleeding, IVIG, IV anti-D immune globulin, IV corticosteroids, and/or platelet transfusions

2019 guidelines are now available (1,2) Treatment references Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Treatment references . Asymptomatic patients with a platelet count > 30,000/mcL (> 30 × 109/L) and no bleeding do not require treatment and can monitored.

Adults with newly diagnosed ITP with bleeding and a platelet count < 30,000/mcL (< 30 × 109/L) are usually given an oral corticosteroid (eg, prednisone 1 mg/kg orally once a day) initially. An alternative, probably equally effective, corticosteroid regimen is dexamethasone 40 mg orally once a day for 4 days. In most patients, the platelet count increases within 2 to 5 days. However, in some patients, a response may take 2 to 4 weeks. When the corticosteroid is tapered after response, most adult patients relapse. Repeated corticosteroid treatments may be effective but increase the risk of adverse effects. Corticosteroids should not usually be continued beyond the first several months; other drugs may be tried in an attempt to avoid splenectomy. If medical therapy is effective, most guidelines recommend continuing it for at least one year before considering splenectomy.

Oral corticosteroids, IVIG, or IV anti-D immune globulin may also be given when a transient increase of the platelet count is required for tooth extractions, childbirth, surgery, or other invasive procedures. Thrombopoietin receptor agonists (TPO-RA, eg, romiplostim, eltrombopag, avatrombopag) can also be used before invasive procedures but should not be used for childbirth. IVIG and IV anti-D immune globulin are also useful for life-threatening bleeding in immune thrombocytopenia Life-threatening bleeding in ITP Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Life-threatening bleeding in ITP (ITP) but are rarely used for chronic treatment because their response may last for only a few days to weeks.

Splenectomy can achieve a complete remission in about two thirds of patients who relapse after initial corticosteroid therapy. Splenectomy is usually reserved for patients with severe thrombocytopenia (eg, < 15,000/mcL [< 15 × 109/L]) in whom bleeding risk cannot be controlled with medical therapy or those whose disease persists after 12 months. If thrombocytopenia can be controlled with second-line medical therapies, splenectomy is often not necessary ( 1, 2 Treatment references Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Treatment references ). Splenectomy results in an increased risk of thrombosis and infection (particularly with encapsulated bacteria such as pneumococcus); patients require vaccination against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis (ideally > 2 weeks before the procedure).

Second-line medical therapies

Second-line medical therapies are available for patients with immune thrombocytopenia

  • Who are seeking to defer splenectomy in hope of a spontaneous remission

  • Who are not candidates for or refuse splenectomy

  • In whom splenectomy has not been effective

Such patients usually have platelet counts < 10,000 to 20,000/mcL (< 10 to 20 × 109/L), and thus are at risk for bleeding. Second-line medical therapies include thrombopoietin receptor agonists (TPO-RAs), rituximab, fostamatinib, or other immunosuppressive drugs.

Thrombopoietin receptor agonists, such as romiplostim 1 to 10 mcg/kg subcutaneously once a week, eltrombopag 25 to 75 mg orally once a day, and avatrombopag 20 mg orally once a dayy have response rates > 85%. TPO-RAs often need to be administered continuously to maintain the platelet count > 50,000/mcL (> 50 × 109/L), but data suggest that one third of adults will undergo a treatment-free remission after 1 year and > 50% after 2 years.

Rituximab (375 mg/m2 IV once a week for 4 weeks) has a response rate of 57%, but only 21% of adult patients remain in remission after 5 years ( 3 Treatment references Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Treatment references ). Alternate dosing schemes are also effective (eg, doses of 1000 mg IV given 2 weeks apart). Rituximab may affect the ability to respond to vaccination for 6 to 12 months.

Fostamatinib, a spleen tyrosine kinase inhibitor, has a reported response rate of 18%. The dose is 100 mg orally twice a day, increasing to 150 mg twice a day after 1 month if the platelet count has not increased to > 50,000/mcL (> 50 × 109/L— 4 Treatment references Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Treatment references ).

More intensive immunosuppression may be required with drugs such as cyclophosphamide, cyclosporine, mycophenolate, and azathioprine in patients unresponsive to other drugs who have severe, symptomatic thrombocytopenia.

Life-threatening bleeding in ITP

In children or adults with immune thrombocytopenia and life-threatening bleeding, rapid phagocytic blockade is attempted by giving IVIG 1 g/kg once a day for 1 to 2 days or, in Rh-positive patients, a single dose of IV anti-D immune globulin 75 mcg/kg. IV anti-D immunoglobulin is only effective in patients who have not had a splenectomy and may be associated with severe complications such as severe hemolysis and disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more . This treatment usually causes the platelet count to rise within 2 to 4 days, but the count remains high for only 2 to 4 weeks.

High-dose methylprednisolone (1 g IV once a day for 3 days) is easier to administer than IVIG or IV anti-D immune globulin but may not be as effective. Patients with ITP and life-threatening bleeding are also given platelet transfusions. Platelet transfusions are not used prophylactically.

Vincristine (1.4 mg/m2; maximum dose of 2 mg) has also been used in emergency situations but may produce neuropathy with repeated administration.

Treatment of children with ITP

Treatment of children with immune thrombocytopenia is usually supportive because most children spontaneously recover. Even after months or years of thrombocytopenia, most children have spontaneous remissions. If mucosal bleeding occurs, corticosteroids or IVIG may be given. Corticosteroid and IVIG use is controversial because the increased platelet count may not improve clinical outcome. Splenectomy is rarely done in children. However, if thrombocytopenia is severe and symptomatic for > 6 months, then thrombopoietin receptor agonists (eg, romiplostim, eltrombopag) should be considered.

Treatment references

  • 1. Neunert C, Terrell DR, Arnold DM, et al: American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 3(23):3829–3866, 2019. doi: 10.1182/bloodadvances.2019000966

  • 2. Provan D, Arnold DM, Bussel JB, et al: Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 3(22):3780–3817, 2019. doi: 10.1182/bloodadvances.2019000812

  • 3. Patel VL, Mahevas M, Lee SY, et al: Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 119:5989–5995, 2012. doi: 10.1182/blood-2011-11-393975

  • 4. Bussel J, Arnold DM, Grossbard E, et al: Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo‐controlled trials. Am J Hematol 93: 921–930, 2018. doi: 10.1002/ajh.25125

  • 5. Kuter DJ, Tarantino MD, Lawrence T: Clinical overview and practical considerations for optimizing romiplostim therapy in patients with immune thrombocytopenia. Blood Rev 49:100811, 2021. doi: 10.1016/j.blre.2021.100811

  • 6. Lozano ML, Godeau B, Grainger J, et al: Romiplostim in adults with newly diagnosed or persistent immune thrombocytopenia. Expert Rev Hematol 13(12):1319–1332, 2020. doi: 10.1080/17474086.2020.1850253

Key Points

  • In immune thrombocytopenia (ITP), the immune system destroys platelets in the circulation and at the same time may attack bone marrow megakaryocytes, thereby reducing platelet production.

  • Other causes of isolated thrombocytopenia (eg, drugs, alcohol, lymphoproliferative disorders, other autoimmune diseases, viral infections) need to be excluded.

  • Children usually have spontaneous remission; in adults, spontaneous remission may occur during the first year but is less common (about 33%) than in children.

  • Corticosteroids (and sometimes intravenous immune globulin (IVIG) or IV anti-D immune globulin) are first-line treatments for bleeding or severe thrombocytopenia.

  • Bone marrow biopsy is typically not needed unless there are other concerning red or white blood cell abnormalities or in patients being considered for splenectomy who have not responded to standard treatment with corticosteroids or IVIG.

  • Thrombopoietin receptor agonists are highly effective in maintaining a safe platelet count in > 85% of adults.

  • COVID-19 infection rarely causes ITP, but COVID-19 vaccination may worsen thrombocytopenia in 2 to 12% of patients with ITP.

  • Splenectomy is often effective but is reserved for patients in whom medical therapy is ineffective or those whose disease persists after 12 months.

  • Platelet transfusion is given only for life-threatening bleeding.

Drugs Mentioned In This Article

Drug Name Select Trade
TAVALISSE
Gammagard S/D
RITUXAN
RAYOS
OZURDEX
NPLATE
PROMACTA
DOPTELET
No US brand name
NEORAL, SANDIMMUNE
CELLCEPT
IMURAN
MEDROL
MARQIBO KIT
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