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AbstractIntroductionSouth‐East Asian ovalocytosis (SAO) is a common inherited red blood cell polymorphism in South‐East Asian and Melanesian populations, coinciding with areas of malaria endemicity. Validation of light microscopy as a diagnostic alternative to molecular genotyping may allow for its cost‐effective use either prospectively or retrospectively by analysis of archived blood smears.MethodsWe assessed light microscopic diagnosis of SAO compared to standard PCR genotyping. Three trained microscopists each assessed the same 971 Giemsa‐stained thin blood films for which SAO genotypic confirmation was available by PCR. Generalized mixed modeling was used to estimate the sensitivity, specificity, positive predictive value, and negative predictive value of light microscopy vs “gold standard” PCR.ResultsAmong red cell morphologic parameters evaluated, knizocytes, rather than ovalocytic morphology, proved the strongest predictor of SAO status (odds ratio [OR] = 19.2; 95% confidence interval [95% CI] = 14.6‐25.3; P ≤ 0.0001). The diagnostic performance of a knizocyte‐centric microscopic approach was microscopist dependent: two microscopists applied this approach with a sensitivity of 0.89 and a specificity of 0.93. Inter‐rater reliability among the microscopists (κ = 0.20) as well as between gold standard and microscopist (κ = 0.36) underperformed due to misclassification of stomatocytes as knizocytes by one microscopist, but improved substantially when excluding the error‐prone reader (κ = 0.65 and 0.74, respectively).ConclusionLight microscopic diagnosis of SAO by knizocyte visual cue performed comparable to time‐consuming and costlier molecular methods, but requires specific training that includes successful differentiation of knizocytes from stomatocytes.

Original publication

DOI

10.1111/ijlh.12900

Type

Journal article

Journal

International Journal of Laboratory Hematology

Publisher

Wiley

Publication Date

12/2018

Volume

40

Pages

655 - 662