Immune thrombocytopenia (ITP) is a common acquired autoimmune disease characterized by low platelet counts and an increased risk of bleeding. The incidence of ITP is approximately 3.3 per 100,000 adults.1 There is considerable controversy about all aspects of the disease, with little “hard” data on which to base decisions given the lack of randomized clinical trials to address most clinical questions. This article reviews the presentation and diagnosis of ITP and its treatment options and discusses management of ITP in specific clinical situations.
Pathogenesis and Epidemiology
ITP is caused by autoantibodies binding to platelet surface proteins, most often to the platelet receptor GP IIb/IIIa.2-4 These antibody-coated platelets then bind to Fc receptors in macrophages and are removed from circulation. The initiating event in ITP is unknown. It is speculated that the patient responds to a viral or bacterial infection by creating antibodies which cross-react with the platelet receptors. Continued exposure to platelets perpetuates the immune response. ITP that occurs in childhood appears to be an acute response to viral infection and usually resolves. ITP in adults may occur in any age group but is seen especially in young women.
Despite the increased platelet destruction that occurs in ITP, the production of new platelets often is not significantly increased. This is most likely due to lack of an increase in thrombopoietin, the predominant platelet growth factor.5
It had been thought that most adult patients who present with ITP go on to have a chronic course, but more recent studies have shown this is not the case. In modern series the percentage of patients who are “cured” with steroids ranges from 30% to 70%.6–9 In addition, it has been appreciated that even in patients with modest thrombocytopenia, no therapy is required if the platelet count remains higher than 30 × 103/µL. However, this leaves a considerable number of patients who will require chronic therapy.
Presentation can range from a symptomatic patient with low platelets found on a routine blood count to a patient with massive bleeding. Typically, patients first present with petechiae (small bruises 1 mm in size) on the shins. True petechiae are seen only in severe thrombocytopenia. Patients will also report frequent bruising and bleeding from the gums. Patients with very low platelet counts will notice “wet purpura,” which is characterized by blood-filled bullae in the oral cavity. Life-threatening bleeding is a very unusual presenting sign unless other problems (trauma, ulcers) are present. The physical examination is only remarkable for stigmata of bleeding such as the petechiae. The presence of splenomegaly or lymphadenopathy weighs strongly against a diagnosis of ITP. Many patients with ITP will note fatigue when their platelets counts are lower.10
Extremely low platelet counts with a normal blood smear and an otherwise healthy patient are diagnostic of ITP. The platelet count cutoff for considering ITP is 100 × 103/µL as the majority of patients with counts in the 100 to 150 × 103/µL range will not develop greater thrombocytopenia.11 Also, the platelet count decreases with age (9 × 103/µL per decade in one study), and this also needs to be factored into the evaluation.12 The finding of relatives with ITP should raise suspicion for congenital thrombocytopenia.13 One should question the patient carefully about drug exposure (see Drug-Induced Thrombocytopenia), especially about over-the-counter medicines, “natural” remedies, or recreational drugs.
There is no laboratory test that rules in ITP; rather, it is a diagnosis of exclusion. The blood smear should be carefully examined for evidence of microangiopathic hemolytic anemias (schistocytes), bone marrow disease (blasts, teardrop cells), or any other evidence of a primary bone marrow disease. In ITP, the platelets can be larger than normal, but finding some platelets the size of red cells should raise the issue of congenital thrombocytopenia.14 Pseudo-thrombocytopenia, which is the clumping of platelets due to a reaction to the EDTA anticoagulant in the tube, should be excluded. The diagnosis is established by drawing the blood in a citrated (blue-top) tube to perform the platelet count. There is no role for antiplatelet antibody assay because this test lacks sensitivity and specificity. In a patient without a history of autoimmune disease or symptoms, empiric testing for autoimmune disease is not recommended.
Patients who present with ITP should be tested for both HIV and hepatitis C infection.15,16 These are the most common viral causes of secondary ITP, and both have prognostic and treatment implications. Some authorities also recommend checking thyroid function as hypothyroidism can present or aggravate the thrombocytopenia.