When the Count Lies: EDTA-dependent Leukoagglutination Unmasked by a Peripheral Smear in Chronic Hepatitis C Infection

Abstract

Automated complete blood count analysers can generate spuriously low cell counts when anticoagulant-dependent aggregation occurs, creating a risk of misclassification as true cytopenia. This case report describes EDTA-dependent leukoagglutination in a 70-year-old man with chronic hepatitis C infection who presented with worsening lethargy, pallor, mild jaundice, and mild hepatosplenomegaly. Initial testing of an EDTA-anticoagulated sample showed severe anaemia, borderline leukopenia, and mild thrombocytopenia. Peripheral blood smear examination demonstrated compact aggregates of morphologically unremarkable segmented neutrophils, associated cytoplasmic debris, and occasional adhering platelets, while free nonaggregated leukocytes were sparse. The red cell population showed anisopoikilocytosis with occasional schistocytes. Recollection into sodium citrate abolished the leukocyte aggregation. Repeat analysis produced a total leukocyte count of 4.4 × 10⁹/L, an absolute neutrophil count of 3.1 × 10⁹/L, and a platelet count of 115 × 10⁹/L before correction for citrate dilution; the corresponding corrected values were 4.84 × 10⁹/L, 3.41 × 10⁹/L, and 126.5 × 10⁹/L. The disappearance of aggregates with normalisation of leukocyte and neutrophil counts confirmed EDTA-dependent leukoagglutination as the cause of pseudoleukopenia. This case highlights the diagnostic value of correlating automated counts with peripheral smear morphology and confirmatory testing using an alternative anticoagulant when an apparent cytopenia is discordant with microscopic findings.