What are the diagnostic criteria and steps for Immune Thrombocytopenic Purpura (ITP)?

How to Diagnose ITP

ITP is a diagnosis of exclusion requiring isolated thrombocytopenia (platelet count <100 × 10⁹/L) with normal red and white blood cells, confirmed by peripheral blood smear examination showing normal-sized or slightly enlarged platelets without schistocytes, leukocyte abnormalities, or other morphologic features suggesting alternative diagnoses. 1

Essential Diagnostic Steps

1. Patient History - Identify Red Flags

Obtain detailed history focusing on conditions that mimic or cause secondary ITP:

• Infections: HIV, hepatitis C, recent viral illness, H. pylori status 1
• Autoimmune disorders: Systemic lupus erythematosus, antiphospholipid syndrome, common variable immunodeficiency 1
• Medications: All prescription and non-prescription drugs, quinine exposure (tonic water), recent vaccinations 1
• Malignancy risk: Lymphoproliferative disorders, chronic lymphocytic leukemia 1
• Family history: Inherited thrombocytopenias (Wiskott-Aldrich, MYH9-related disease, Bernard-Soulier syndrome) 1
• Recent transfusions: Possibility of post-transfusion purpura 1
• Alcohol use: Liver disease, cirrhosis 1

2. Physical Examination - What Should and Should NOT Be Present

Findings consistent with ITP:

• Petechiae, purpura, or mucosal bleeding only 1, 2
• Otherwise completely normal examination 1
• Mild splenomegaly may occur in younger patients 1

Findings that exclude primary ITP:

• Moderate or massive splenomegaly - suggests lymphoproliferative disease, portal hypertension 1
• Hepatomegaly or lymphadenopathy - indicates HIV, SLE, or malignancy 1, 2
• Fever or weight loss - suggests underlying systemic disorder 1

3. Complete Blood Count - The Pattern Matters

Required findings for ITP:

• Isolated thrombocytopenia (platelet count <100 × 10⁹/L) 1
• Normal hemoglobin (unless proportional blood loss from bleeding) 1
• Normal white blood cell count and differential 1
• If anemia present, check reticulocyte count to distinguish blood loss from hemolysis 1

Findings that exclude ITP:

• Pancytopenia - suggests bone marrow disorder 3
• Leukocytosis, leukopenia, or immature cells - indicates leukemia or myelodysplasia 1, 3

4. Peripheral Blood Smear - Critical for Diagnosis

A qualified hematologist or pathologist must review the smear 1

Findings consistent with ITP:

• Normal or slightly enlarged platelets 1, 2
• Normal red blood cell morphology 1
• Normal white blood cell morphology 1

Findings that exclude ITP:

• Schistocytes - indicates thrombotic thrombocytopenic purpura or hemolytic uremic syndrome 1
• Consistently giant platelets (approaching RBC size) - suggests inherited thrombocytopenia 1
• Leukocyte inclusion bodies - indicates MYH9-related disease 1
• Platelet clumping - confirms pseudothrombocytopenia from EDTA-dependent agglutination 1, 3

5. Mandatory Laboratory Testing in Adults

Test all adults regardless of risk factors:

• HIV serology 1, 2
• Hepatitis C serology 1, 2
• H. pylori testing (urea breath test or stool antigen preferred over serology) 1

Additional testing based on clinical suspicion:

• Direct antiglobulin test (Coombs) - if anemia present 1
• Quantitative immunoglobulins - to exclude common variable immunodeficiency 1, 3
• Antinuclear antibodies - if SLE suspected 1
• Antiphospholipid antibodies - if thrombosis or pregnancy loss history 1
• Pregnancy test in women of childbearing age 1

6. Bone Marrow Examination - When Required

Bone marrow is NOT routinely necessary for typical ITP 1, 3

Mandatory indications for bone marrow examination:

• Age >60 years - to exclude myelodysplastic syndrome, leukemia 1, 3
• Systemic symptoms (fever, weight loss, bone pain) 1, 3
• Abnormal findings beyond isolated thrombocytopenia (anemia, leukopenia, abnormal differential) 1, 3
• Atypical peripheral smear findings 1, 3
• Before splenectomy (recommended by some experts) 1
• Failure to respond to first-line ITP therapies 3

When performed, obtain both aspirate and biopsy with flow cytometry and cytogenetic testing 1, 3

Common Diagnostic Pitfalls to Avoid

• Pseudothrombocytopenia: Always exclude EDTA-dependent platelet clumping by examining the smear periphery and repeating count in citrate or heparin tube 1, 3
• Missing secondary ITP: Failure to test for HIV, HCV, and H. pylori leads to missed treatable causes 1, 3
• Inherited thrombocytopenias: Family history and consistently large or small platelets on smear provide critical clues 1, 3
• Drug-induced thrombocytopenia: Obtain comprehensive medication history including over-the-counter drugs and supplements 1, 3
• Myelodysplastic syndrome with isolated thrombocytopenia: Particularly in patients >60 years, can mimic refractory ITP - bone marrow examination is essential 3, 4
• Overlooking constitutional symptoms: Fever, weight loss, or night sweats indicate alternative diagnoses requiring immediate investigation 1, 3

Diagnostic Algorithm Summary

1. Confirm true thrombocytopenia - exclude pseudothrombocytopenia via smear review 1, 3
2. Verify isolated thrombocytopenia - normal hemoglobin and WBC 1
3. Expert smear review - rule out schistocytes, giant platelets, abnormal cells 1
4. Screen for secondary causes - HIV, HCV, H. pylori in all adults 1
5. Assess for red flags - splenomegaly, lymphadenopathy, systemic symptoms 1, 3
6. Bone marrow if indicated - age >60, atypical features, treatment failure 1, 3

No single test confirms ITP - response to ITP-specific therapy (IVIg, anti-D, corticosteroids) supports but does not confirm the diagnosis, as secondary ITP may also respond 1