Distinguishing True Thrombocytopenia from Pseudothrombocytopenia: Insights from Platelet Aggregation and Morphological Features

Abstract

Background: Automated hematology analyzers may report low platelet counts that represent either true thrombocytopenia or pseudothrombocytopenia caused by in-vitro platelet aggregation and related counting artifacts. Accurate differentiation is essential to avoid misdiagnosis, unnecessary transfusion, invasive investigation, or inappropriate clinical management. Objective: To compare demographic, hematological, and peripheral-smear morphological features between pseudothrombocytopenia and true thrombocytopenia among analyzer-flagged thrombocytopenic complete blood count reports. Methods: This retrospective observational laboratory-based study was conducted at the Department of Hematology, Fatima Memorial Hospital, Lahore, Pakistan, using complete blood count reports from January to December 2024. Reports with automated platelet counts below 150×10⁹/L on the Sysmex XN-1000 analyzer were included when paired manual platelet counts and peripheral-smear findings were available. Reports correcting to ≥150×10⁹/L on manual verification were classified as pseudothrombocytopenia, while those remaining below 150×10⁹/L were classified as true thrombocytopenia. Results: Of 2,021 reports, 244 (12.1%) were classified as pseudothrombocytopenia and 1,777 (87.9%) as true thrombocytopenia. Platelet clumping was present in 99.6% of pseudothrombocytopenia reports and 25.1% of true thrombocytopenia reports. Higher hemoglobin and female sex were independently associated with pseudothrombocytopenia, while platelet anisocytosis, nucleated red blood cells, and schistocytes were associated with lower adjusted odds of pseudothrombocytopenia. Conclusion: Peripheral-smear review and manual platelet verification are essential for distinguishing pseudothrombocytopenia from true thrombocytopenia. Platelet clumping should prompt confirmatory interpretation but should not be used alone as a diagnostic label