What is the initial workup for a patient with suspected Immune Thrombocytopenic Purpura (ITP) or Thrombotic Thrombocytopenic Purpura (TTP)?

Workup for ITP and TTP

ITP Workup

The diagnosis of ITP is made by exclusion and requires only a complete blood count, peripheral blood smear examination by a qualified hematologist/pathologist, HIV testing, and HCV testing—bone marrow examination is not necessary regardless of patient age. 1

Essential Initial Tests

• Complete blood count: Must show isolated thrombocytopenia with otherwise normal CBC (anemia may be present only if proportional to bleeding and duration, potentially causing iron deficiency) 1
• Peripheral blood smear review by qualified hematologist/pathologist: Critical to exclude schistocytes (which indicate TTP-HUS), leukocyte inclusion bodies (MYH9-related disease), excessive giant/small platelets (inherited thrombocytopenias), and EDTA-dependent platelet agglutination (pseudothrombocytopenia) 1
• HIV testing: Mandatory for all patients with suspected ITP (grade 1B), as HIV-associated thrombocytopenia is clinically indistinguishable from primary ITP and can occur years before other HIV symptoms 1
• HCV testing: Mandatory for all patients with suspected ITP (grade 1B), regardless of risk factors or local prevalence 1

Additional Tests Based on Clinical Context

• H. pylori testing: Should be considered in adults where eradication therapy would be used if positive (preferably urea breath test or stool antigen test, not serology which is less sensitive/specific and may be false positive after IVIG) 1, 2
• Blood group Rh(D) typing: Important if anti-D immunoglobulin treatment is being considered 1
• Reticulocyte count: If anemia is present, helps determine if due to blood loss versus hemolysis 1

When to Perform Additional Investigations

• Bone marrow examination: Only indicated if patient >60 years, has systemic symptoms/abnormal signs, or if considering splenectomy—should include aspirate, biopsy, flow cytometry, and cytogenetics 1
• Further workup: Required if abnormalities exist beyond isolated thrombocytopenia (other than microcytic anemia from chronic blood loss) 1

Tests NOT Recommended

• Antiplatelet antibody assays: Not routinely recommended as platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia 1
• Antiphospholipid antibodies: Not recommended routinely unless symptoms of antiphospholipid syndrome are present 1

Physical Examination Red Flags

• Mild splenomegaly: May be found in younger patients 1
• Moderate/massive splenomegaly, hepatomegaly, lymphadenopathy: Suggests alternative diagnosis (HIV, SLE, lymphoproliferative disease) 1
• Constitutional symptoms: Fever or weight loss indicates underlying disorder requiring further investigation 1

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TTP Workup

For suspected TTP presenting with microangiopathic hemolytic anemia and thrombocytopenia, immediately obtain ADAMTS13 activity level (<10% confirms diagnosis), peripheral smear showing schistocytes, and initiate empirical treatment with therapeutic plasma exchange, corticosteroids, and rituximab before ADAMTS13 results return. 3

Essential Immediate Tests

• Peripheral blood smear: Must show schistocytes (fragmented red blood cells) indicating microangiopathic hemolysis—this distinguishes TTP from ITP 1, 3
• ADAMTS13 activity level: Severely low activity (<10%) confirms immune TTP diagnosis 3
• ADAMTS13 autoantibody: Detects autoantibody causing immune TTP 3
• Complete blood count: Shows thrombocytopenia (often platelet count <30 × 10⁹/L) 3
• Lactate dehydrogenase (LDH): Elevated due to hemolysis 3
• Creatinine: Often <2.0 mg/dL (176.8 μmol/L) in TTP, helping distinguish from other thrombotic microangiopathies 3

Additional Laboratory Tests

• Reticulocyte count: Elevated due to hemolytic anemia 3
• Haptoglobin: Decreased due to intravascular hemolysis 3
• Indirect bilirubin: Elevated from hemolysis 3
• Direct antiglobulin test (Coombs): Negative (distinguishes from autoimmune hemolytic anemia) 3

Clinical Prediction Score Application

Use clinical prediction scores with platelet count <30 × 10⁹/L and creatinine <2.0 mg/dL to guide empirical treatment initiation before ADAMTS13 results are available—do not delay treatment waiting for confirmatory testing. 3

Common Presenting Features

• Neurologic symptoms: Headache, confusion, or seizures (39-80% of patients) 3
• Abdominal pain: Present in 35-39% of patients 3
• Microangiopathic hemolytic anemia: Universal finding 3
• Thrombocytopenia: Universal finding 3

Critical Pitfall to Avoid

The key distinction between ITP and TTP on peripheral smear is the presence of schistocytes in TTP—missing this finding delays life-saving treatment, as untreated TTP has near-zero survival versus 93% survival with prompt therapy. 1, 3