Blood Tests for Immune Thrombocytopenic Purpura (ITP)
The essential blood tests for evaluating suspected ITP are a complete blood count with differential and a peripheral blood smear reviewed by a hematopathologist, combined with mandatory HIV and hepatitis C testing in all adults. 1, 2
Core Diagnostic Laboratory Tests
Mandatory Initial Tests
Complete blood count (CBC) with differential – confirms isolated thrombocytopenia (platelet count <100 × 10⁹/L) and excludes pancytopenia, which would mandate bone marrow examination. 1, 2
Peripheral blood smear review by a hematopathologist – this is the single most critical test because automated counters miss pseudothrombocytopenia in approximately 0.1% of samples and fail to detect schistocytes, giant platelets, or abnormal white cells that indicate life-threatening alternative diagnoses. 1, 2
HIV antibody testing – required in all adults regardless of risk factors, because HIV-associated thrombocytopenia is clinically indistinguishable from primary ITP and may precede other HIV manifestations by years. 1, 2
Hepatitis C virus (HCV) serology – mandatory in all adults, as chronic HCV can cause secondary ITP that resolves after successful antiviral therapy. 1, 2
Expected Peripheral Smear Findings in ITP
Platelets are normal-sized or only mildly enlarged; giant platelets approaching red blood cell size suggest inherited thrombocytopenias (MYH9-related disease, Bernard-Soulier syndrome) rather than ITP. 1, 2
Red blood cell morphology is normal without schistocytes; the presence of schistocytes indicates thrombotic microangiopathy (TTP, HUS, DIC), which carries >90% mortality if untreated. 2, 3
White blood cell morphology is normal without immature cells, blasts, or inclusion bodies; abnormal leukocytes raise suspicion for leukemia or myelodysplastic syndrome. 1, 2
Additional Context-Specific Tests
When to Add These Tests
Helicobacter pylori testing (urea-breath test or stool antigen, not serology) – eradication normalizes platelet counts in a subset of adult ITP patients, especially in high-prevalence regions. 1, 2
Pregnancy test – required in all women of childbearing potential to differentiate gestational thrombocytopenia, pre-eclampsia, or HELLP syndrome from primary ITP. 2
Quantitative immunoglobulin levels – to exclude common variable immune deficiency (CVID), which can present initially as ITP. 1, 2
Direct antiglobulin test (DAT) – to exclude Evans syndrome (combined autoimmune hemolytic anemia and ITP). 2
Rh(D) blood typing – necessary only if anti-D immunoglobulin therapy is being considered. 2
Tests That Should NOT Be Ordered Routinely
The following tests lack diagnostic specificity or proven clinical utility in ITP and should not be performed routinely: 1, 2
- Platelet-associated IgG (PaIgG)
- Glycoprotein-specific antiplatelet antibodies
- Thrombopoietin (TPO) levels
- Immature platelet fraction (IPF) or reticulated platelet counts
- Bleeding time
- Antiphospholipid antibodies (unless clinical features of antiphospholipid syndrome are present)
- Antinuclear antibodies (ANA) (unless systemic lupus erythematosus is suspected)
When Bone Marrow Examination Is Required
Bone marrow aspiration and biopsy with flow cytometry and cytogenetics are mandatory when ANY of the following are present: 1, 2
- Age ≥60 years – to exclude myelodysplastic syndrome, leukemia, or other malignancies
- Systemic constitutional symptoms (fever, unexplained weight loss, night sweats, bone pain)
- Abnormal CBC parameters beyond isolated thrombocytopenia (unexplained anemia, leukopenia, or leukocytosis)
- Atypical peripheral smear findings (schistocytes, immature white cells, giant platelets, leukocyte inclusion bodies)
- Splenomegaly, hepatomegaly, or lymphadenopathy on physical examination
- Minimal or no response to first-line ITP therapies (IVIg, corticosteroids, anti-D)
- Prior to splenectomy in chronic ITP
Bone marrow examination is NOT necessary in patients with typical ITP features: isolated thrombocytopenia, age <60 years, normal physical exam except for bleeding manifestations, normal smear morphology, and no systemic symptoms. 1, 2
Critical Diagnostic Pitfalls to Avoid
Never diagnose ITP without hematopathologist review of the peripheral smear – automated counters miss pseudothrombocytopenia (EDTA-dependent platelet clumping), giant platelets, and schistocytes. 1, 2
Never omit HIV and HCV testing in adults, even in low-risk populations, because these infections can masquerade as primary ITP for years before other symptoms develop. 1, 2
The presence of splenomegaly, hepatomegaly, or lymphadenopathy excludes primary ITP and mandates investigation for HIV, systemic lupus erythematosus, lymphoproliferative disorders, or chronic liver disease. 1, 2
Missing thrombotic microangiopathy (TTP, HUS, DIC) carries catastrophic mortality risk – untreated TTP has >90% mortality; prompt smear review and coagulation studies are essential. 2, 3
If heparin exposure occurred within the past 3 months, immediately calculate the 4T score and obtain anti-PF4 antibody testing if intermediate or high probability, as heparin-induced thrombocytopenia carries a 30-50% thrombosis risk. 2
Diagnostic Algorithm Summary
Confirm true thrombocytopenia – repeat platelet count in citrate or heparin tube if pseudothrombocytopenia is suspected. 2
Obtain CBC with differential – verify isolated thrombocytopenia; any additional cytopenias trigger bone marrow work-up. 1, 2
Mandatory hematopathologist smear review – assess platelet size, exclude schistocytes, verify normal leukocyte morphology. 1, 2
Perform focused physical examination – organomegaly or lymphadenopathy excludes primary ITP. 1, 2
Conduct mandatory infectious disease testing – HIV, HCV, and H. pylori in all adults. 1, 2
Add context-specific tests – pregnancy test, DAT, quantitative immunoglobulins as indicated. 2
Reserve bone marrow examination for patients meeting any of the criteria listed above. 1, 2
If all typical features are present and secondary causes are excluded, diagnose primary ITP without bone marrow examination. 1, 2