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      Drugs & Diseases > Hematology

      Immune Thrombocytopenia (ITP) Workup

      Updated: Jul 20, 2023
      • Author: Craig M Kessler, MD, MACP; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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      Workup

      Laboratory Studies

      The workup for immune thrombocytopenia (ITP) starts with a complete blood cell (CBC) count. The hallmark of ITP is isolated thrombocytopenia; anemia and/or neutropenia may indicate other diseases

      On peripheral blood smear, the morphology of red blood cells (RBCs) and leukocytes is normal. The morphology of platelets is typically normal, with varying numbers of large platelets. Some persons with acute ITP may have megathrombocytes or stress platelets, reflecting the early release of megakaryocytic fragments into the circulation. If most of the platelets are large, approximating the diameter of RBCs, or if they lack granules or have an abnormal color, consider an inherited platelet disorder.

      Clumps of platelets on a peripheral smear prepared from ethylenediaminetetraacetic acid (EDTA)–anticoagulated blood are evidence of pseudothrombocytopenia. [3] The diagnosis of this type of pseudothrombocytopenia is established if the platelet count is normal when repeated on a sample from heparin-anticoagulated or citrate-anticoagulated blood.

      In patients who have risk factors for HIV infection, a blood sample should be tested with an enzyme immunoassay for anti-HIV antibodies. [47] During the acute HIV retroviral syndrome, the results of the anti-HIV assay may be negative. In this situation, a polymerase chain reaction for HIV DNA is more reliable than the anti-HIV assay.

      In selected women, the medical history may suggest a chronic, recurrent, multisystemic illness with vague, generalized signs or symptoms, such as recurrent, multiple, painful, tender, or swollen joints. In such cases, a negative antinuclear antibody (ANA) result is useful in diagnosing ITP if the patient's thrombocytopenia becomes chronic and resistant to treatment.

      If anemia and thrombocytopenia are present, a positive direct antiglobulin (Coombs) test result may help establish a diagnosis of Evans syndrome.

      In children with ITP who have already received their first dose of measles-mumps-rubella (MMR) vaccine, the American Society of Hematology recommends measuring vaccine titers. If the titers indicate full immunity (as is the case in up to 95% of children), then no further MMR vaccine should be given. If the titers indicate inadequate immunity, the child should receive further immunization with MMR vaccine at the recommended age. [8]

      Assays for platelet antigen–specific antibodies, platelet-associated immunoglobulin, or other antiplatelet antibodies are available in some medical centers and certain mail-in reference laboratories. The reliability of the results of a platelet antibody test is highly specific to the laboratory used. A negative antiplatelet antibody assay result does not exclude the diagnosis of ITP. [48] The authors do not recommend this test as part of the routine evaluation. Testing for antiplatelet antibodies is not required to diagnose ITP.

      Studies from Italy, [49, 50] Japan, [51, 52] and Korea [53] indicate that many persons with ITP have Helicobacter pylori gastric infections and that eradication of H pylori results in increased platelet counts. In the United States and Spain, however, the prevalence of H pylori infections does not appear to be increased in persons with ITP, and eradication of H pylori has not increased platelet counts. [54, 55] Therefore, routine testing for H pylori infections in adults and children with ITP is not recommended.

      Results of a study from Taiwan suggest that ITP may be an early hematologic manifestation of HIV infection. Lai et al reported that patients with ITP were 6.47-fold more likely to have HIV infection than those without ITP, and recommended considering the possibility of undiagnosed HIV infection in patients presenting with ITP. [56]

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      Imaging Studies

      Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are relatively benign and useful noninvasive imaging studies that can be used to rule out other causes of thrombocytopenia. However, they are not part of the routine evaluation of patients who may have immune thrombocytopenia (ITP). However, prompt CT scanning or MRI is indicated when the medical history or physical findings suggest serious internal bleeding.

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      Histologic Findings

      Bone marrow aspirate

      The cellularity of the aspirate and the morphology of erythroid and myeloid precursors should be normal. The number of megakaryocytes may be increased. Because the peripheral destruction of platelets is increased, megakaryocytes may be large and immature, although in many cases the megakaryocyte morphology is normal. Older patients require a careful examination of megakaryocyte morphology to exclude an early myelodysplastic syndrome.

      Bone marrow biopsy

      Sections of a needle biopsy specimen or marrow clot should reveal normal marrow cellularity, without evidence of hypoplasia or increased fibrosis.

      Splenic evaluation

      The spleen reveals no specific findings. In adults, the microscopic finding of extramedullary hematopoiesis is atypical and indicates myeloid metaplasia. Spleens removed from patients with immune thrombocytopenia (ITP) should be carefully examined for a primary splenic lymphoma or granuloma or other signs of an undiagnosed infectious disease.

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      Bone Marrow Examination

      Bone marrow aspiration and biopsy in patients with immune thrombocytopenia (ITP) demonstrates a normal-to-increased number of megakaryocytes in the absence of other significant abnormalities. The value of bone marrow evaluation for a diagnosis of ITP is unresolved, and more data are needed to establish clear guidelines. [4]

      Recommendations for adult patients are as follows:

      • In adults who are thrombocytopenic and older than 60 years, examine the bone marrow to exclude myelodysplastic syndrome or leukemia.

      • In adults whose treatment includes corticosteroids, baseline pretreatment bone marrow aspiration may be useful for future reference. Many adults have treatment-resistant chronic ITP evident after 3-6 months of treatment, and an alternative diagnosis may be pursued vigorously at that time. Marrow aspirate obtained before any steroid-induced changes may have occurred can be useful.

      • Perform bone marrow aspiration and biopsy to evaluate for possible hypoplasia or fibrosis before splenectomy is performed.

      American Society of Hematology guidelines advise that bone marrow examination is not necessary in children and adolescents with the typical features of ITP, or in children in whom intravenous immunoglobulin therapy fails. The guidelines suggest that bone marrow examination is also not necessary in similar patients before initiation of treatment with corticosteroids or before splenectomy. [57]

      Bone marrow examination is indicated in children with atypical hematologic findings, such as immature cells on the peripheral smear or persistent neutropenia. [5] Many children with acute ITP have an increased number of normal or atypical lymphocytes on the peripheral smear, reflecting a recent viral illness. Unresponsiveness to standard treatment after 6 months is an indication for bone marrow aspiration.

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