Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is an autoimmune primary disorder of hemostasis characterized by a low platelet count in the absence of other causes. ITP often results in an increased risk of bleeding from mucosal surfaces (such as the nose or gums) or the skin (causing purpura and bruises). Depending on which age group is affected, ITP causes two distinct clinical syndromes: an acute form observed in children and a chronic form in adults. Acute ITP often follows a viral infection and is typically self-limited (resolving within two months), while the more chronic form (persisting for longer than six months) does not yet have a specific identified cause. Nevertheless, the pathogenesis of ITP is similar in both syndromes involving antibodies against various platelet surface antigens such as glycoproteins. Diagnosis of ITP involves identifying a low platelet count through a complete blood count, a common blood test. However, since the diagnosis relies on excluding other potential causes of a low platelet count, additional investigations, such as a bone marrow biopsy, may be necessary in certain cases. For mild cases, careful observation may be sufficient. However, in instances of very low platelet counts or significant bleeding, treatment options may include corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive medications. Refractory ITP, which does not respond to conventional treatment or shows constant relapse after splenectomy, requires treatment to reduce the risk of significant bleeding. Platelet transfusions may be used in severe cases with extremely low platelet counts in individuals experiencing bleeding. In some cases, the body may compensate by producing abnormally large platelets.
Signs and symptoms Signs of ITP include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), especially on the extremities. Additionally, bleeding from the nostrils and/or gums, as well as menorrhagia (excessive menstrual bleeding), may occur if the platelet count falls below 20,000 per μL. A platelet count below 10,000 per μL can lead to the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Furthermore, bleeding time from minor lacerations or abrasions is usually prolonged.
In cases where platelet counts drop to extremely low levels (<5,000 per μL), serious and potentially fatal complications may arise. These complications include subarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lower gastrointestinal bleeding, or other internal bleeding. A person with ITP with an extremely low platelet count is susceptible to internal bleeding resulting from blunt abdominal trauma, such as in a motor vehicle crash. These complications are more likely to occur when the platelet count is less than 20,000 per μL.
Pathogenesis In approximately 60 percent of cases, antibodies against platelets can be detected. Most often these antibodies are against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and are of the immunoglobulin G (IgG) type. The Harrington–Hollingsworth experiment established the immune pathogenesis of ITP. The coating of platelets with IgG renders them susceptible to opsonization and phagocytosis by splenic macrophages, as well by Kupffer cells in the liver. The IgG autoantibodies are also thought to damage megakaryocytes, the precursor cells to platelets, although this is believed to contribute only slightly to the decrease in platelet numbers. Recent research now indicates that impaired production of the glycoprotein hormone, thrombopoietin, which is the stimulant for platelet production, may be a contributing factor to the reduction in circulating platelets. This observation has led to the development of a class of ITP-targeted medications referred to as thrombopoietin receptor agonists. The stimulus for auto-antibody production in ITP is probably abnormal T cell activity. Preliminary findings suggest that these T cells can be influenced by medications that target B cells, such as rituximab.
Diagnosis
The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (around 5–10 percent of suspected ITP cases) should be excluded including medications (quinine or heparin), viral infection (HIV or HCV), malignancy (leukemia), autoimmune conditions (systemic lupus erythematosus or antiphospholipid syndrome), onyalai, and others. All patients with presumed ITP should be tested for HIV and hepatitis C virus, as platelet counts may be corrected by treating the underlying disease. In approximately 2.7 to 5 percent of cases, autoimmune hemolytic anemia and ITP coexist, a condition referred to as Evans syndrome. Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.
Treatment With rare exceptions, there is usually no need to treat based on platelet counts. Many older recommendations suggested a certain platelet count threshold (usually somewhere below 20.0/nL) as an indication for hospitalization or treatment. Current guidelines recommend treatment for adults with significant bleeding or counts below 30/nL, with very low certainty of evidence. Treatment recommendations sometimes differ for adult and pediatric ITP.
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