What are the initial laboratory evaluations for a patient presenting with thrombocytopenia (low platelet count)?

Initial Laboratory Evaluation for Thrombocytopenia

The essential initial laboratory workup for thrombocytopenia includes a complete blood count with differential, peripheral blood smear examination, and HIV/hepatitis C testing in adults, with bone marrow examination reserved only for patients with atypical features. 1, 2

Mandatory First-Line Tests

Complete Blood Count with Differential

• Obtain CBC with differential to distinguish isolated thrombocytopenia from pancytopenia, as this fundamentally changes the differential diagnosis and urgency of evaluation 1, 2, 3
• Document the absolute platelet count, hemoglobin level, white blood cell count, and absolute neutrophil count 1, 3
• Normal hemoglobin and WBC counts support immune thrombocytopenia (ITP), while cytopenias suggest bone marrow failure, malignancy, or systemic disease 4, 5

Peripheral Blood Smear Review

• Request manual examination by a qualified hematologist or pathologist to exclude pseudothrombocytopenia from EDTA-dependent platelet clumping, which can falsely lower automated counts 1, 2, 6
• Evaluate platelet size and morphology: large platelets suggest increased turnover (destructive process), while small platelets may indicate inherited disorders 1, 7
• Identify schistocytes (suggesting thrombotic microangiopathy), abnormal white cells (suggesting leukemia), or platelet clumping (confirming pseudothrombocytopenia) 1, 2, 3

Infectious Disease Screening (Adults)

• Test all adults with suspected ITP for HIV and hepatitis C virus regardless of risk factors or geographic location, as these infections are clinically indistinguishable from primary ITP and may precede other symptoms by years 1, 2
• Consider Helicobacter pylori testing, as eradication therapy can resolve thrombocytopenia in infected patients 1, 2

Tests of Potential Utility in Selected Patients

When Coagulopathy or DIC is Suspected

• Obtain prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer if platelet count <50 × 10³/μL with active bleeding or systemic illness to evaluate for disseminated intravascular coagulation 2, 3, 6
• These tests distinguish isolated thrombocytopenia (normal coagulation) from consumptive coagulopathy (abnormal coagulation) 3, 8

When Secondary Causes are Suspected

• Antinuclear antibodies and antiphospholipid antibodies (anticardiolipin, lupus anticoagulant) if autoimmune disease is suspected 1
• Antithyroid antibodies and thyroid function tests, as 8-14% of ITP patients develop thyroid dysfunction 1, 2
• Quantitative immunoglobulin levels in children with persistent/chronic ITP to exclude common variable immunodeficiency 1
• Pregnancy test in women of childbearing potential 1

When Drug-Induced Thrombocytopenia is Suspected

• Review all medications including over-the-counter drugs and herbal supplements, particularly quinidine, heparin, sulfonamides, sulfonylureas, and antibiotics 1, 2
• Drug-dependent platelet antibody testing requires specialized immunoassays and must be collected during the acute thrombocytopenic episode or within 3 weeks, as antibodies disappear rapidly 2

When Heparin-Induced Thrombocytopenia (HIT) is Suspected

• Calculate the 4T score (degree of thrombocytopenia, timing, presence of thrombosis, absence of other causes) 2
• Test anti-PF4 antibodies immediately when clinical probability is intermediate or high based on 4T score 2
• Remember that HIT presents with moderate thrombocytopenia (30-70 × 10³/μL) occurring 5-10 days after heparin initiation and is paradoxically associated with thrombosis, not bleeding 2

When Bone Marrow Examination IS Indicated

Bone marrow aspiration and biopsy are NOT routinely necessary in patients with typical ITP features 1, 2, but are mandatory in the following situations:

• Age ≥60 years to exclude myelodysplastic syndromes, leukemias, or other malignancies 1, 2
• Any cytopenia beyond isolated thrombocytopenia (anemia not explained by blood loss, leukopenia, or abnormal white cell morphology) 1, 4, 2
• Systemic symptoms present: fever, weight loss, bone pain, night sweats 1, 2
• Abnormal physical examination: splenomegaly, hepatomegaly, or lymphadenopathy 1, 2
• Atypical peripheral smear findings: schistocytes, dysplastic cells, or leukocyte inclusion bodies 1, 2
• Failure to respond to first-line ITP therapies (IVIg, anti-D, or corticosteroids) 2
• Before splenectomy to confirm diagnosis and exclude alternative pathology 1

When performed, obtain both aspirate and biopsy with consideration for flow cytometry and cytogenetic testing 1, 3

Tests That Are NOT Useful

The following tests lack evidence for routine use and should NOT be ordered:

• Platelet-associated IgG assay: considered both unnecessary and inappropriate, with poor specificity 1
• Platelet-antigen specific antibody assay: unnecessary for diagnosis 1
• Serum complement levels: do not change management 1
• Platelet survival studies: invasive and do not alter treatment decisions 1
• Direct antiglobulin test (Coombs): unnecessary unless Evans syndrome (ITP plus autoimmune hemolytic anemia) is suspected 1
• Bleeding time: does not correlate with clinical bleeding risk 1
• Thrombopoietin levels: not validated for routine clinical use 1

Critical Pitfalls to Avoid

• Never assume automated platelet counts are accurate without peripheral smear confirmation, as pseudothrombocytopenia from EDTA-dependent clumping occurs in 0.1% of samples 2, 6
• Do not skip HIV/HCV testing in adults even without risk factors, as these infections may be occult and fundamentally change management 1, 2
• Avoid delaying bone marrow examination in patients >60 years or with any atypical features, as missing myelodysplastic syndrome or leukemia has catastrophic mortality implications 1, 2
• Do not diagnose ITP in the presence of splenomegaly, hepatomegaly, or lymphadenopathy, as these findings occur in <3% of true ITP cases and suggest alternative diagnoses 1, 2
• Never overlook a detailed medication history, as drug-induced thrombocytopenia is common and reversible with drug discontinuation 1, 2
• Do not assume thrombocytopenia and other cytopenias share the same etiology, as multiple pathologies may coexist 3

Algorithmic Approach

1. Confirm true thrombocytopenia: Repeat CBC in heparin or sodium citrate tube + manual peripheral smear review 1, 2, 6
2. Assess bleeding severity and platelet count: Spontaneous serious bleeding is rare with counts >10 × 10³/μL but occurs in 40% with counts <10 × 10³/μL 1
3. Determine if isolated or part of multisystem disorder: Check for other cytopenias, systemic symptoms, organomegaly 1, 2, 8
4. If isolated thrombocytopenia in stable patient: Obtain HIV, HCV, consider H. pylori, review medications 1, 2
5. If age ≥60 years OR atypical features present: Proceed directly to bone marrow examination 1, 2
6. If typical ITP features (age <60, isolated thrombocytopenia, normal exam, no systemic symptoms): Diagnosis can be made without bone marrow examination 1, 2