What labs should be ordered to investigate mild thrombocytopenia (low platelet count)?

Laboratory Investigations for Mild Thrombocytopenia

The initial workup for mild thrombocytopenia should include a complete blood count with differential, peripheral blood smear examination, and targeted laboratory tests based on clinical suspicion to identify the underlying cause and guide management. 1

Essential Initial Laboratory Tests

• Complete blood count and reticulocyte count to determine if thrombocytopenia is isolated or associated with other cytopenias 2, 1
• Peripheral blood film examination by a qualified hematologist or pathologist to exclude pseudothrombocytopenia and identify morphologic abnormalities (including checking for giant or small platelets that may indicate inherited thrombocytopenia) 2, 1
• Quantitative immunoglobulin level measurement, particularly important in children with persistent thrombocytopenia 2, 1
• HIV and HCV testing for all adult patients with suspected ITP regardless of local prevalence or risk factors 2
• Blood sample collection in a tube containing acid citrate dextrose solution-A (ACD-A) if specialized platelet antibody testing is planned 2

Second-Line Laboratory Tests

• Helicobacter pylori testing (preferably urea breath test or stool antigen test) in adults where it may have clinical impact 2
• Blood group Rh(D) typing if anti-D immunoglobulin therapy is being considered 2
• Bone marrow examination in selected patients, including those older than 60 years, those with systemic symptoms or abnormal signs, or when splenectomy is considered 2
• Flow cytometry and cytogenetic testing of bone marrow samples when performed 2

Additional Tests Based on Clinical Context

• Antiphospholipid antibodies (including anticardiolipin antibodies and lupus anticoagulant) when clinically indicated, found in approximately 40% of typical adult ITP patients 2
• Antinuclear antibodies (ANA), which may predict chronicity in childhood ITP 2, 1
• Antithyroid antibodies and thyroid function tests, as 8-14% of ITP patients develop hyperthyroidism and mild thrombocytopenia can be associated with thyroid dysfunction 2
• Testing for other acute and persistent infections (e.g., parvovirus and CMV) when clinically indicated 2, 1
• Pregnancy test in women of childbearing potential 2, 1

Tests of Limited Utility

• Glycoprotein-specific antibody testing is not routinely recommended as platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia 2
• If platelet antibody testing is performed, it should use direct tests that detect glycoprotein-specific antibodies using assays such as MAIPA or MACE 2
• For specialized platelet antibody testing, a minimum of 30 mL whole blood for adults and 10 mL for children is recommended 2

Important Clinical Considerations

• Always exclude pseudothrombocytopenia due to EDTA-dependent platelet agglutination before proceeding with extensive workup 2, 1
• Consider inherited thrombocytopenias when peripheral blood smear shows abnormal platelet morphology 2, 3
• Thrombocytopenia does not protect against thrombosis, and antithrombotic therapy should not be withheld based on thrombocytopenia alone 4
• The severity, timing, and association with bleeding are important clues to diagnosis 4, 5

Common Pitfalls to Avoid

• Failing to check a peripheral blood smear, which is essential for distinguishing true thrombocytopenia from pseudothrombocytopenia 1, 3
• Performing unnecessary bone marrow examination in young patients with typical features of ITP and no abnormal signs 2, 1
• Missing delayed alloantibodies that may appear several weeks after birth in cases of neonatal thrombocytopenia 2
• Overlooking medication-induced thrombocytopenia, which is a common and potentially reversible cause 6, 5