MCV Fails to Reliably Separate Sickle Cell and Thalassemia in Western Kenya Study

Mean corpuscular volume, the routine blood-count measure widely used as a first-line screen for haemoglobin disorders in resource-limited settings, performs poorly as a diagnostic tool in Western Kenya, according to a retrospective analysis of 773 participants published in Annals of Hematology. The study, led by Benard Mutua with Rose Chelangat and Patrick Okoth, found that MCV could not reliably distinguish people with sickle cell disease or β-thalassemia phenotypes from healthy controls when haemoglobin status was confirmed by high-performance liquid chromatography.

The cohort included 388 individuals with the normal HbAA haemoglobin phenotype and 385 people with confirmed haemoglobinopathies, all classified by HPLC, the reference method for haemoglobin characterization. Receiver operating characteristic analysis yielded an area under the curve of just 0.528 for detecting combined haemoglobinopathies.

The best-performing MCV threshold, identified at 75.3 femtolitres, achieved only 50.4 percent sensitivity and 42.8 percent specificity. In clinical terms, the cut-off missed roughly half of true haemoglobinopathy cases while incorrectly flagging more than half of unaffected individuals as positive. The authors conclude that MCV has limited diagnostic utility for haemoglobinopathy detection in this population, despite its entrenched role as a preliminary screening tool based on the assumption that haemoglobin disorders typically present with microcytosis, abnormally small red blood cells.

A striking finding concerned sickle cell disease phenotypes specifically. When interpreted against population-based Kenyan reference ranges, SCD phenotypes in this cohort were predominantly normocytic, meaning red cells fell within the normal size distribution, in contrast to iron deficiency and other microcytic anemias that typically reduce MCV. The ROC-derived optimal threshold for SCD detection was 76.9 fL, which fell squarely within the population reference distribution, where the median MCV was 76.8 fL with an interquartile range of 11.6 fL. Maximum detection of sickle cell disease therefore occurred within normocytic ranges, not below conventional microcytosis cut-offs.

This result challenges the standard laboratory convention of 80 to 100 fL as the normal MCV interval. The authors emphasize that locally derived MCV reference ranges, rather than conventional thresholds imported from other populations, are essential for meaningful interpretation in Kenyan settings. A population with a median MCV near 77 fL would see many healthy individuals classified as microcytic under the conventional 80 fL lower limit, distorting both clinical triage and research phenotyping.

Sickle cell trait and thalassemia trait carriers showed a different pattern. The overlap means a low MCV cannot separate a thalassemia carrier from someone with iron deficiency or another cause of small red cells, and the authors state plainly that MCV cannot reliably identify carrier states at all.

The study was retrospective and confined to a single Western Kenyan cohort whose phenotypes were already confirmed by HPLC, so the reported sensitivity and specificity describe MCV performance against a known-diagnosis reference standard rather than real-world screening performance in unselected patients. Even so, the near-chance AUC and the normocytic presentation of SCD in this population suggest that the microcytosis assumption underlying MCV-based screening does not hold locally.

The practical implication is that while MCV may still assist in triaging suspected cases where advanced diagnostics are scarce, it cannot substitute for definitive haemoglobin characterization. The authors conclude that accurate diagnosis and effective haemoglobinopathy screening in the region depend on confirmatory methods such as HPLC, with locally validated reference ranges used to interpret any red-cell indices that are measured along the way.

Subject of Research: Diagnostic performance of mean corpuscular volume for detecting sickle cell disease and β-thalassemia in Western Kenya

Article Title: Empirical evaluation of MCV in differentiating sickle cell and β-thalassemia phenotypes in Western Kenya: a receiver operating characteristic (ROC) analysis

Article References: Mutua, B., Chelangat, R., & Okoth, P. (2026). Empirical evaluation of MCV in differentiating sickle cell and β-thalassemia phenotypes in Western Kenya: a receiver operating characteristic (ROC) analysis. Annals of Hematology. https://doi.org/10.1007/s00277-026-07330-4

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07330-4

Keywords: MCV, sickle cell disease, beta-thalassemia, hemoglobinopathies, ROC analysis, Kenya, HPLC, microcytosis, diagnostic screening, hematology, normocytic anemia, reference ranges