What is the confirmatory test for a patient suspected of having Immune Thrombocytopenic Purpura (ITP)?

Confirmatory Test for ITP

ITP remains a diagnosis of exclusion with no single confirmatory test—diagnosis requires demonstrating isolated thrombocytopenia on peripheral blood smear while systematically excluding all other causes through targeted testing. 1, 2

Essential Diagnostic Steps

Primary Diagnostic Requirements

• Peripheral blood smear examination by a qualified hematologist or pathologist is the most critical initial test, confirming true thrombocytopenia (excluding pseudothrombocytopenia from EDTA-dependent platelet clumping), evaluating platelet morphology, and identifying features inconsistent with ITP 1, 2

• Complete blood count with differential must demonstrate isolated thrombocytopenia (platelet count <100 × 10⁹/L) with otherwise normal hemoglobin, white blood cell count, and differential 1, 2

• Physical examination should be entirely normal except for bleeding manifestations—the presence of splenomegaly, hepatomegaly, or lymphadenopathy definitively excludes primary ITP and mandates investigation for secondary causes 1, 2

Characteristic Laboratory Findings in ITP

• Platelets appear normal-sized or slightly enlarged on smear; consistently giant platelets approaching red blood cell size suggest inherited thrombocytopenias instead 1

• Red blood cell morphology must be normal without schistocytes or poikilocytosis (except polychromatophilia from bleeding response), as their presence suggests thrombotic microangiopathy 1

• White blood cell morphology must be normal without immature or abnormal cells, which would suggest bone marrow disorders 1

Mandatory Testing to Exclude Secondary Causes

All adults with suspected ITP must undergo HIV and hepatitis C virus testing regardless of risk factors, as these infections can be clinically indistinguishable from primary ITP and may precede other symptoms by years 1, 2

• H. pylori testing should be performed in adults, preferably with urea breath test or stool antigen test, as eradication therapy can resolve thrombocytopenia 1, 2

• Review all medications including over-the-counter drugs and herbal supplements to identify potential drug-induced thrombocytopenia 1

When Bone Marrow Examination Becomes Mandatory

Bone marrow examination is not necessary in patients with typical ITP features, but becomes mandatory in specific situations 1, 2:

• Age ≥60 years (to exclude myelodysplastic syndromes, leukemias, or other malignancies)
• Presence of systemic symptoms (fever, weight loss, bone pain)
• Abnormal blood count parameters beyond isolated thrombocytopenia
• Atypical peripheral smear findings (schistocytes, leukocyte abnormalities)
• Failure to respond to first-line ITP therapies
• Before splenectomy in patients with persistent disease

When performed, both aspirate and biopsy should be obtained with consideration for flow cytometry and cytogenetic testing 1, 2

Tests That Are NOT Confirmatory

• Anti-platelet antibody testing has insufficient evidence for routine diagnostic use—these tests have high specificity but low sensitivity and do not change management 1, 3, 4

• Coagulation studies (PT, aPTT, fibrinogen) are not indicated for ITP diagnosis, as it is a disorder of platelet destruction, not coagulation factor deficiency 1

• ADAMTS13 activity testing is only relevant when thrombotic thrombocytopenic purpura (TTP) is suspected based on presence of microangiopathic hemolytic anemia and schistocytes on smear 5, 6

Critical Diagnostic Algorithm

1. Verify true thrombocytopenia: Obtain peripheral blood smear to exclude pseudothrombocytopenia 1, 2

2. Confirm isolated thrombocytopenia: CBC shows no other cytopenias except possible microcytic anemia from chronic blood loss 1

3. Perform mandatory infectious disease testing: HIV, HCV, and consider H. pylori 1, 2

4. Ensure normal physical examination: Absence of organomegaly or lymphadenopathy 1, 2

5. If typical ITP features present: Diagnosis can be made without bone marrow examination in patients <60 years 1

6. If atypical features exist: Proceed immediately to bone marrow examination 1, 2

Common Diagnostic Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear, as automated counts can miss pseudothrombocytopenia, giant platelets, or schistocytes 1

• Never skip HIV and HCV testing in adults, even without apparent risk factors 1, 2

• Failing to recognize that any abnormalities beyond isolated thrombocytopenia require further investigation before diagnosing ITP 1

• Overlooking drug-induced thrombocytopenia by not obtaining comprehensive medication history including recent exposures 1

• Missing constitutional symptoms (fever, weight loss) that suggest underlying disorders rather than primary ITP 1