Approach

Immune thrombocytopenia (ITP) is a diagnosis of exclusion; history, examination, and tests are directed at ruling out other potential causes of a low platelet count.

History

Patients may present with bleeding (e.g., bruising, petechiae, haemorrhagic bullae, bleeding gum). Fatigue is also commonly reported, and there may be a preceding viral illness (particularly in children), but otherwise the patient usually feels well. Some patients present with no signs or symptoms. In about half of adult cases, thrombocytopenia is an incidental finding on routine full blood count (FBC) or during investigation for another illness.

History should include differential diagnoses of thrombocytopenia and secondary causes of ITP. A full medication history (including herbal remedies) should be carried out to identify potential causative agents for thrombocytopenia.

There are no known risk factors for ITP apart from a higher prevalence in women of childbearing age, and in males and females younger than 5 years and older than 65 years.[6][8][9]​​​ The co-existence of other factors or diseases prompts the diagnosis of secondary ITP.[15]

Examination

Physical examination is often normal except for possible bruising, petechiae, or bleeding related to thrombocytopenia. Specifically, there should be no lymphadenopathy or hepatosplenomegaly. A standardised bleeding assessment tool can be used to evaluate bleeding symptoms of ITP and to score its severity.​[15][16]

Investigations

FBC and peripheral blood smear:

  • FBC reveals isolated thrombocytopenia (platelet count <100 × 10⁹/L [<100 × 10³/microlitre]) without other abnormalities. There should be no evidence of myelodysplasia or other disorders (i.e., Pelger-Huet anomaly, nucleated red blood cell, schistocytes, immature granulocytes, large granular lymphocytes). Other cell lines (i.e., red cells and white cells) should be normal.

  • Peripheral blood smear distinguishes between true thrombocytopenia and pseudothrombocytopenia (a spuriously low platelet count in blood samples collected into ethylenediaminetetraacetate [EDTA]-containing collection tubes; occurs in about 0.1% of adults); this can be uncovered by a normal platelet count on peripheral blood smear or by using a citrate tube instead of an EDTA tube.

Bone marrow biopsy and/or aspirate (with flow cytometry and cytogenetic testing):

  • Only considered if atypical blood film features are present. Not routinely recommended at initial diagnosis, but it may be considered in patients who are unresponsive to medical therapy, or prior to splenectomy.[15]

Exclusion of secondary causes

Exclusion of the many secondary ITPs is of critical importance, because most of these forms have a different natural history and require different management (e.g., treatment of underlying disease, such as systemic lupus erythematosus, or antiretroviral therapy for newly diagnosed HIV disease; acute management of ITP may also be required if acute thrombocytopenia or bleeding symptoms/signs are present).

Routine testing for HIV and hepatitis C infection is recommended for adult patients to exclude important differentials.[15]

Testing for Helicobacter pylori infection (urea breath test or stool antigen test) is indicated in patients with appropriate risk factors or in high-prevalence areas (e.g., southern and eastern Europe, South America, and Asia).[15][17][18]​​​ However, very low platelet counts (i.e., <10 × 10⁹/L [<10 × 10³/microlitre]) are not usually observed in patients with H pylori infection, and eradication of infection is not considered curative for ITP.

Quantitative immunoglobulin level testing is recommended to exclude an immune deficiency syndrome (i.e., common variable immunodeficiency or selective immunoglobulin A [IgA] deficiency), or before treatment with intravenous immune globulin (IVIG). In children, it may be considered at baseline, and should be measured to re-evaluate persistent or chronic ITP.[15]

Pregnancy testing should be considered in women of childbearing age. Thrombocytopenia in pregnancy may be due to a pregnancy-related cause, rather than ITP.[19]​ Among other possible causes, gestational thrombocytopenia, hypertensive disorders of pregnancy (e.g., pre-eclampsia or haemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome), and acute fatty liver disease should be considered and excluded. These usually develop in late pregnancy, whereas ITP is the most common cause of thrombocytopenia in early pregnancy. Gestational thrombocytopenia accounts for 70% to 80% of thrombocytopenia in pregnancy.[20]

Other tests to consider

Additional tests may include thyroid function tests (TFTs) and antithyroid antibody tests, because approximately 8% to 14% of patients with ITP develop clinical hyperthyroidism on prolonged follow-up, and patients may develop antibodies to thyroglobulin.[21] Mild thrombocytopenia has been associated with hyperthyroidism (reduced platelet survival) and hypothyroidism (possible decreased platelet production), which may resolve with restoration of the euthyroid status.[15]

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