ITP Workup
The diagnosis of ITP is primarily clinical, based on history, physical examination, complete blood count (CBC), and peripheral blood smear examination to exclude other causes of thrombocytopenia—bone marrow examination is NOT routinely required for initial diagnosis. 1
Essential Initial Workup
History and Physical Examination
- Bleeding history: Document presence and severity of petechiae, purpura, mucosal bleeding (epistaxis, gingival bleeding, menorrhagia), or life-threatening hemorrhage 1, 2
- Medication review: Identify drugs that may cause thrombocytopenia, recent transfusions (posttransfusion purpura), and recent immunizations 1
- Infection exposure: Recent viral illnesses, HIV risk factors, hepatitis C exposure, and vaccination history (particularly for vaccine-induced thrombotic thrombocytopenia [VITT]) 1
- Systemic symptoms: Fever, weight loss, night sweats suggesting lymphoproliferative disorders or autoimmune conditions 1
- Physical findings: Examination should be normal except for bleeding manifestations; mild splenomegaly may occur in younger patients, but moderate/massive splenomegaly suggests alternative diagnosis 1
Required Laboratory Tests
Mandatory initial tests:
- Complete blood count: ITP is characterized by isolated thrombocytopenia (platelet count <100 × 10⁹/L) with otherwise normal CBC 1, 2
- Peripheral blood smear: Must be reviewed by a qualified hematologist/pathologist to confirm true thrombocytopenia, exclude pseudothrombocytopenia (EDTA-dependent agglutination), identify schistocytes (suggesting TTP-HUS), and assess platelet morphology 1, 2
- Blood type and Rh(D) status: Essential if anti-D immunoglobulin therapy is being considered 1
Additional testing based on clinical context:
- HIV and HCV serology: Recommended for all adults regardless of risk factors, as these infections can present identically to primary ITP 1
- Helicobacter pylori testing: Consider urea breath test or stool antigen test in adults (more sensitive/specific than serology); routine testing in children not supported except in high-prevalence areas 1
- Pregnancy test: For women of childbearing age, as management differs in pregnancy 1
- Direct antiglobulin test (Coombs): If anemia is present to exclude Evans syndrome 1
Tests NOT Routinely Indicated
Bone marrow examination is NOT required for initial diagnosis in most patients, but should be performed in: 1
- Patients >60 years of age
- Those with systemic symptoms or abnormal physical findings
- Patients with abnormal CBC findings beyond isolated thrombocytopenia
- Those unresponsive to IVIG therapy
- Patients with persistent thrombocytopenia lasting >6-12 months
- When splenectomy is being considered
Other tests generally NOT indicated routinely: 1
- Antiplatelet antibody assays (not specific; elevated in both immune and non-immune thrombocytopenia)
- Antiphospholipid antibodies (unless symptoms of antiphospholipid syndrome present)
- Antinuclear antibodies (may predict chronicity in children but doesn't change initial management)
- Antithyroid antibodies
- Abdominal imaging (only if splenomegaly suspected on physical examination) 1
Special Considerations for VITT
If recent vaccination (particularly COVID-19 or adenovirus vector vaccines) within 4-42 days: 1
- D-dimer measurement: Markedly elevated (>2000 FEU) suggests VITT
- Coagulation screen: Including Clauss fibrinogen assay
- Anti-PF4 antibody testing: ELISA for platelet factor 4 antibodies
- Imaging based on symptoms: Head CT venogram/MRA for suspected cerebral venous sinus thrombosis, abdominal ultrasound/venogram for portal/splanchnic thrombosis, CT pulmonary angiography for PE
Common Pitfalls to Avoid
- Pseudothrombocytopenia: Always review peripheral smear to exclude EDTA-dependent platelet clumping before initiating treatment 1, 2
- Missing alternative diagnoses: Schistocytes suggest TTP-HUS (not ITP); leukocyte inclusion bodies suggest MYH9-related disease; excessive giant/small platelets suggest inherited thrombocytopenia 1
- Overtesting: Routine antiplatelet antibody testing, bone marrow examination in typical presentations, and extensive autoimmune panels are not indicated and delay appropriate management 1
- Treating platelet numbers rather than bleeding risk: The decision to treat should be based on bleeding symptoms and bleeding risk, not platelet count alone 3, 4
Disposition and Follow-up
- Immediate hematology referral (within 24-72 hours) is required for all newly diagnosed or relapsed ITP patients 1
- Hospital admission indicated for: 1
- Platelet count <20 × 10⁹/L with significant mucous membrane bleeding
- Any severe, life-threatening bleeding regardless of platelet count
- Patients refractory to treatment with social concerns or significant comorbidities
- Outpatient management acceptable for: 1
- Platelet count ≥20 × 10⁹/L who are asymptomatic or have only minor mucocutaneous bleeding
- Must ensure expedited hematology follow-up and patient education