What is the initial workup for a patient presenting with thrombocytopenia (low platelet count)?

Initial Workup for Thrombocytopenia

Begin with a complete blood count (CBC) and peripheral blood smear examination to confirm true thrombocytopenia and exclude pseudothrombocytopenia, followed by targeted testing based on clinical presentation to distinguish between primary and secondary causes. 1, 2

Confirm True Thrombocytopenia

• Repeat the platelet count using a different anticoagulant (heparin or sodium citrate tube) to exclude pseudothrombocytopenia, which occurs in approximately 0.1% of adults due to EDTA-induced platelet clumping 1, 3
• Direct examination of the peripheral blood smear is mandatory to confirm thrombocytopenia and assess platelet morphology 1

Essential Initial Tests

Complete Blood Count and Peripheral Smear

• Examine platelet size and morphology: Normal to large platelets support ITP; consistently giant platelets (approaching RBC size) suggest alternative diagnoses 1
• Assess red blood cell morphology: Schistocytes suggest thrombotic microangiopathy (TTP/HUS); normal morphology supports ITP 1
• Evaluate white blood cell count and differential: Leukocytosis, leukopenia, or immature cells suggest alternative diagnoses like leukemia or myelodysplasia 1

Mandatory Screening Tests

• HIV and HCV testing is strongly recommended for all patients with suspected ITP (grade 1B) 2
• Coagulation studies (PT/aPTT) to exclude coagulopathy 1, 2
• Pregnancy test in women of childbearing age 1

History and Physical Examination Priorities

Critical History Elements

• Bleeding symptoms: Type, severity, and duration of bleeding (petechiae, purpura, mucosal bleeding) 1
• Medication review: Heparin, quinidine/quinine, sulfonamides, alcohol, and antiplatelet agents are common culprits 1, 3
• Recent vaccination history (within 5-42 days) to assess for vaccine-induced immune thrombocytopenia and thrombosis (VITT) 1
• Systemic symptoms: Fever, weight loss, arthralgias suggest secondary causes 1
• Family history of thrombocytopenia or bleeding disorders 1

Physical Examination Focus

• Splenomegaly or lymphadenopathy: Presence argues strongly against primary ITP (found in <3% of ITP patients) 1
• Signs of liver disease: Jaundice, stigmata of chronic liver disease suggest hepatic thrombocytopenia 1
• Neurologic examination: Establish baseline for potential CNS bleeding 1
• Funduscopic examination: Assess for retinal hemorrhages 1

Risk Stratification by Platelet Count

• >50,000/μL: Generally asymptomatic, rarely requires intervention 3, 4
• 20,000-50,000/μL: May have mild skin manifestations (petechiae, purpura); treatment indicated if significant mucous membrane bleeding present 2, 3
• 10,000-20,000/μL: Treatment generally indicated 2
• <10,000/μL: High risk of serious bleeding; constitutes indication for treatment 2, 3
• <5,000/μL: Risk of spontaneous bleeding; hematologic emergency 4

Additional Testing Based on Clinical Context

When Bone Marrow Examination is NOT Necessary

• Bone marrow examination is not necessary for patients presenting with typical ITP regardless of age (grade 2C) 2
• Consider bone marrow only if: abnormalities beyond thrombocytopenia on CBC, atypical features, or failure to respond to initial therapy 1, 2

Secondary Workup (If Indicated by Clinical Features)

• D-dimer: If thrombosis suspected or recent vaccination (VITT concern); level >4000 μg/mL (FEU) supports VITT diagnosis 1
• Anti-PF4 antibody ELISA: If VITT suspected based on vaccination history and thrombosis 1
• H. pylori testing: Should be considered in ITP patients in whom eradication therapy would be used if positive (grade 2C) 2
• ANA, direct antiglobulin test: Uncertain necessity for routine use; consider if autoimmune features present 1
• Liver function tests: Appropriate for patients with risk factors for liver disease 2

Common Pitfalls to Avoid

• Do not assume thrombocytopenia without confirming on peripheral smear - pseudothrombocytopenia is a common laboratory artifact 1, 3
• Do not overlook drug-induced thrombocytopenia - this is among the most common causes and is reversible 1, 3
• Do not routinely perform bone marrow examination in patients with isolated thrombocytopenia and typical ITP features 2
• Do not miss VITT - always ask about recent vaccination (5-42 days prior) and assess for thrombosis 1
• Splenomegaly essentially excludes primary ITP - pursue alternative diagnoses aggressively 1

Urgent Evaluation Triggers

Immediate hospitalization and emergency workup required for:

• Platelet count <20,000/μL with significant mucous membrane bleeding 2
• Any signs of life-threatening bleeding 2
• Suspected thrombotic microangiopathy (schistocytes on smear, hemolysis, renal dysfunction) 3, 4
• Suspected heparin-induced thrombocytopenia (thrombosis with thrombocytopenia) 3, 4
• Pregnancy with HELLP syndrome features 3, 4