What are the diagnostic steps for a patient with suspected Immune Thrombocytopenic Purpura (ITP)?

How to Diagnose ITP

ITP is a diagnosis of exclusion requiring isolated thrombocytopenia on complete blood count, confirmation via peripheral blood smear, and systematic exclusion of secondary causes through targeted testing—bone marrow examination is not routinely necessary in patients with typical features. 1, 2

Essential Initial Diagnostic Steps

Complete Blood Count and Peripheral Blood Smear

• Obtain a complete blood count with differential to confirm isolated thrombocytopenia versus pancytopenia 2
• Examine the peripheral blood smear immediately to exclude pseudothrombocytopenia (EDTA-dependent platelet clumping can falsely lower counts) 2, 3
• The smear should show a small number of large platelets with normal morphology, no schistocytes, and no abnormal white blood cells 2, 3
• Any abnormalities beyond isolated thrombocytopenia (anemia not attributed to blood loss, leukopenia, abnormal white cell morphology) require further investigation before diagnosing ITP 1, 2

Physical Examination Red Flags

• Physical examination should be normal aside from bleeding manifestations (petechiae, purpura, mucosal bleeding) 2
• The presence of splenomegaly, hepatomegaly, or lymphadenopathy excludes primary ITP and mandates investigation for secondary causes 1, 2
• Constitutional symptoms (fever, weight loss, bone pain) suggest underlying disorders rather than primary ITP and require bone marrow examination 2

Mandatory Testing to Exclude Secondary Causes

Infectious Etiologies

• Test all adults with suspected ITP for HIV and hepatitis C virus, as treatment of the underlying infection may alter the course of secondary ITP 1, 2
• Consider H. pylori testing, as eradication therapy can resolve thrombocytopenia in H. pylori-associated ITP 2

Additional Laboratory Evaluation

• Obtain basic coagulation studies (PT, aPTT, fibrinogen, D-dimers) if severe thrombocytopenia is present to evaluate for disseminated intravascular coagulation 2
• Consider immunoglobulin measurement to exclude common variable immune deficiency, as ITP can be a presenting feature 2

When Bone Marrow Examination IS Required

Bone marrow examination is not necessary in patients presenting with typical ITP features irrespective of age 1, 2, but is mandatory in the following situations:

• Age ≥60 years to exclude myelodysplastic syndromes, leukemias, or other malignancies 2
• Abnormalities in the blood count or peripheral smear beyond isolated thrombocytopenia (anemia, leukopenia, abnormal white cell morphology) 1, 2
• Systemic symptoms present (fever, weight loss, bone pain) 2
• Atypical peripheral smear findings (schistocytes, leukocyte inclusion bodies) 2
• Minimal or no response to first-line ITP therapies (IVIg, anti-D, corticosteroids) 2
• When splenectomy is being considered 2

Diagnostic Algorithm

1. Confirm true thrombocytopenia: Review peripheral blood smear to exclude pseudothrombocytopenia 2, 3

2. Verify isolated thrombocytopenia: Ensure CBC shows no other cytopenias (except microcytic anemia from chronic blood loss) 1, 2

3. Perform targeted physical examination: Look specifically for splenomegaly, hepatomegaly, lymphadenopathy, non-petechial rash, or systemic symptoms—any of these findings require additional workup 2

4. Obtain mandatory infectious disease testing: HIV, HCV, and consider H. pylori 1, 2

5. Assess need for bone marrow examination: Proceed directly if age ≥60 years, systemic symptoms present, organomegaly/lymphadenopathy detected, or abnormal blood count parameters beyond thrombocytopenia 2

6. If typical ITP features present (age <60, isolated thrombocytopenia, normal physical exam except bleeding, normal peripheral smear): Diagnosis of ITP can be made without bone marrow examination 1, 2

Critical Pitfalls to Avoid

• Missing pseudothrombocytopenia: Always review the peripheral blood smear personally—automated counts can be falsely low due to platelet clumping 2, 3
• Overlooking secondary causes: Failing to test for HIV, HCV, and H. pylori can lead to missed diagnoses with different natural histories and treatment responses 2
• Ignoring age thresholds: Patients ≥60 years require bone marrow examination regardless of how typical the presentation appears, due to increased risk of myelodysplastic syndromes and malignancies 2
• Not considering inherited thrombocytopenias: Family history and platelet size on smear provide critical clues—large platelets may suggest inherited disorders rather than ITP 2
• Relying on anti-platelet antibody testing: These tests have insufficient evidence for routine diagnostic use and do not change management 2
• Assuming elevated immature platelet fraction (IPF) confirms ITP: Severe ITP can present with low IPF, and this finding should prompt bone marrow examination 2, 4

When to Reassess the Diagnosis

If atypical features develop during treatment or monitoring—such as new abnormalities in white blood cell count, lymphadenopathy, or multiple cytopenias—the diagnosis of ITP must be reassessed with bone marrow examination 1, 2