What can falsely cause thrombocytopenia (low platelet count)?

Causes of False Thrombocytopenia

Pseudothrombocytopenia is the most common cause of falsely low platelet counts and should be excluded before initiating any investigation or treatment for true thrombocytopenia. 1

Laboratory-Related Causes of Pseudothrombocytopenia

• EDTA-dependent platelet agglutination: The most common cause of pseudothrombocytopenia is in vitro platelet clumping due to EDTA anticoagulant in collection tubes 1
• Improper sample collection: Clotted specimens can lead to falsely low platelet counts 2
• Platelet satellitism: Platelets adhering to white blood cells can cause falsely low counts 2

Technical Factors

• Inappropriate anticoagulant-to-blood ratio: In patients with polycythemia, using standard amounts of anticoagulant with reduced plasma volume can cause falsely low platelet counts 3
• Automated analyzer errors: Large platelets may be counted as red or white blood cells by automated analyzers 2

Diagnostic Approach to Confirm Pseudothrombocytopenia

• Peripheral blood smear examination: Essential to identify platelet clumping or satellitism 1, 2
• Alternative anticoagulants: Collect blood in tubes containing sodium citrate or heparin instead of EDTA to confirm pseudothrombocytopenia 2
• Rapid processing: Immediate processing of samples can reduce the likelihood of platelet clumping 2

Clinical Conditions That Can Mimic Thrombocytopenia

• Polycythemia: In cyanotic congenital heart disease, increased hematocrit reduces plasma volume, requiring adjustment of anticoagulant volume to avoid falsely low platelet counts 3
• Giant platelets: Certain inherited disorders can cause large platelets that may be missed by automated counters 2

Special Considerations in Laboratory Testing

• Alloantibody testing: False-negative results in testing for platelet alloantibodies can occur due to delayed appearance of antibodies or low-affinity antibodies 3
• Drug-dependent antibodies: Testing for drug-induced thrombocytopenia may yield false-negative results if testing is performed after thrombocytopenia resolves or if a metabolite rather than the parent drug is responsible 3

Distinguishing from True Thrombocytopenia

• Heparin-induced thrombocytopenia (HIT): Has a characteristic temporal pattern (typically 5-10 days after starting heparin) and may be associated with thrombotic events 3, 4
• Immune thrombocytopenia: True reduction in platelet count due to immune-mediated destruction 2, 5
• Drug-induced thrombocytopenia: Various medications can cause true thrombocytopenia through immune or non-immune mechanisms 2

Practical Approach to Suspected Pseudothrombocytopenia

1. Examine peripheral blood smear to identify platelet clumping 1, 2
2. Repeat platelet count using alternative anticoagulants (sodium citrate or heparin) 2
3. Review previous platelet counts to distinguish acute from chronic thrombocytopenia 2
4. Consider clinical context: Absence of bleeding symptoms despite very low platelet counts suggests pseudothrombocytopenia 2

Remember that confirming pseudothrombocytopenia is crucial to avoid unnecessary and potentially harmful interventions such as platelet transfusions, immunosuppressive therapy, or postponement of essential procedures 2.