What is the recommended evaluation and treatment approach for a patient with suspected Immune Thrombocytopenic Purpura (ITP)?

ITP Test Evaluation

The diagnostic workup for suspected ITP requires a focused history, physical examination, complete blood count with peripheral smear review, and selective testing to exclude secondary causes—bone marrow examination is not routinely necessary in typical presentations. 1

Essential Clinical Assessment

History Taking

Document these specific elements to exclude alternative diagnoses:

• Bleeding manifestations: Assess for petechiae, purpura, mucosal bleeding (epistaxis, gingival bleeding), gastrointestinal hemorrhage, or intracranial hemorrhage 1
• Medication exposure: Review all prescription and non-prescription drugs, recent transfusions, and recent immunizations that may cause thrombocytopenia 1, 2
• Infection history: Screen for recent viral illnesses, HIV risk factors, hepatitis C exposure, and vaccination history (particularly MMR) 1, 2
• Systemic symptoms: Evaluate for fever, weight loss, night sweats, which suggest lymphoproliferative disorders or autoimmune conditions rather than primary ITP 1, 2
• Autoimmune conditions: Assess for systemic lupus erythematosus, antiphospholipid syndrome, thyroid disease, and other immunodeficiency disorders 1
• Liver disease: Document alcohol use and signs of chronic liver disease 1

Physical Examination

The physical examination should be normal except for bleeding manifestations 1:

• Mild splenomegaly may be present in younger patients, but moderate or massive splenomegaly strongly suggests an alternative diagnosis such as lymphoproliferative disease or portal hypertension 1, 2
• Hepatomegaly or lymphadenopathy indicates underlying disorders like HIV, SLE, or lymphoma rather than primary ITP 1

Mandatory Laboratory Testing

Basic Evaluation (Required for All Patients)

Complete blood count (CBC): Must demonstrate isolated thrombocytopenia (platelet count <100 × 10⁹/L) with otherwise normal hemoglobin and white blood cell count 1, 2. Anemia may be present only if proportional to bleeding duration 1.

Peripheral blood smear: Must be reviewed by a qualified hematologist/pathologist to confirm true thrombocytopenia, exclude pseudothrombocytopenia from EDTA-dependent platelet agglutination, and assess platelet morphology 1, 2. The smear should show a small number of large platelets with normal morphology and no increased schistocytes 1, 3.

Reticulocyte count: Should be normal or elevated if anemia is present from bleeding 1

Infectious Disease Screening (Recommended for All Adults)

HIV and HCV testing: Recommended for all adult patients regardless of geographic location or documented risk factors, as these infections can present identically to primary ITP years before other symptoms develop 1. Control of these infections may result in complete hematologic remission 1.

H. pylori testing: Should be performed using urea breath test or stool antigen test (preferred over serology) in adults where eradication therapy would be used if positive 1. Eradication therapy is recommended for all H. pylori-positive patients 1.

Additional Testing Based on Clinical Context

Blood type and Rh(D) status: Essential if anti-D immunoglobulin therapy is being considered 1, 2

Direct antiglobulin test (DAT): Helps exclude Evans syndrome (combined autoimmune hemolytic anemia and thrombocytopenia) 1

Quantitative immunoglobulin levels: Should be considered in children with ITP and is recommended in those with persistent or chronic ITP 1

Pregnancy test: Required in women of childbearing potential 1

Tests of Potential Utility (Not Routine)

These tests should be ordered based on clinical suspicion:

• Antinuclear antibodies (ANA): May predict chronicity in childhood ITP and help identify SLE-associated secondary ITP 1
• Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant): Found in ~40% of ITP patients but do not affect treatment response; test only if antiphospholipid syndrome symptoms present 1
• Antithyroid antibodies and TSH: 8-14% of ITP patients develop clinical hyperthyroidism; consider testing to identify at-risk patients 1
• Viral PCR for parvovirus and CMV: Consider in patients with persistent infections 1

Bone Marrow Examination

Bone marrow examination is NOT routinely necessary in patients presenting with typical ITP 1. Consider bone marrow aspirate and biopsy (with flow cytometry and cytogenetics) only in these specific situations 1:

• Patients older than 60 years of age
• Presence of systemic symptoms or abnormal physical findings
• Abnormalities in the CBC beyond isolated thrombocytopenia
• Consideration of splenectomy in some cases
• Atypical presentations with low immature platelet fraction 4

Tests of Unproven Benefit (Not Recommended)

Do not routinely order these tests 1:

• Platelet-associated IgG (PaIgG): Elevated in both immune and non-immune thrombocytopenia; lacks specificity 1
• Glycoprotein-specific antibody testing: Not routinely recommended due to poor sensitivity and specificity 1
• Thrombopoietin (TPO) levels: No proven diagnostic role 1
• Reticulated platelets: Not established for routine use 1
• Platelet survival studies: Not clinically useful 1
• Bleeding time: No proven benefit 1
• Serum complement: Not routinely indicated 1

Critical Pitfalls to Avoid

Do not confuse ITP with TTP: If the patient has severe thrombocytopenia with microangiopathic hemolytic anemia and schistocytes on peripheral smear, suspect thrombotic thrombocytopenic purpura (TTP) instead—this requires immediate therapeutic plasma exchange without waiting for ADAMTS13 results 5, 6.

Do not miss secondary causes: The diagnosis of ITP is one of exclusion 1, 7. Failure to identify secondary causes (HIV, HCV, SLE, lymphoproliferative disorders, drug-induced) leads to inappropriate treatment 1, 8.

Do not delay hematology referral: All newly diagnosed or relapsed ITP patients require immediate hematology referral within 24-72 hours 2.

Disposition Criteria

Hospital admission is indicated for 2:

• Platelet count <20 × 10⁹/L with significant mucous membrane bleeding
• Severe life-threatening bleeding at any platelet count
• Patients refractory to treatment with social concerns or significant comorbidities