ArticleAnnals of hematology2026
Determination of mean corpuscular haemoglobin cut-off point for differentiating alpha plus and alpha zero thalassaemia in thalassaemia screening.
Article in Annals of hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
This study assesses haematological parameters as screening tools for identifying α zero (α⁰) thalassaemia candidates for DNA analysis. The Malaysia Thalassaemia Diagnosis Code (MTDC) uses mean corpuscular haemoglobin (MCH) < 25 pg to screen for suspected α⁰ thalassaemia carriers. Six haematological parameters from 304 cases genotyped by Gap-Polymerase Chain Reaction or Multiplex Ligation-dependent Probe Amplification were analyzed. Among the cases, 160 individuals (52.6%) were α+ thalassaemia silent carrier (-α/αα), comprising heterozygotes for -α3.7, -α4.2, –(α)20.5 and -α2.4. Twelve individuals (3.9%) were α+ thalassaemia carrier (-α/-α), including homozygous -α3.7 and compound heterozygous -α3.7 and -α4.2. Meanwhile, 111 individuals (36.4%) were α0 thalassaemia carrier (--/αα) consisting of heterozygotes for --SEA, --GB, --FIL, --AW, and –THAI deletions. Deletional Hb H disease (--/-α) was observed in individuals with compound genotypes such as -α3.7/--SEA, -α3.7/--GB, -α3.7/--AW, -α4.2/--SEA and -α2.4/--SEA. All parameters correlated with the number of α-globin gene deletions, with mean corpuscular volume (MCV) (r2 = 0.73) and MCH (r2 = 0.77) showing the strongest associations. Gender-specific MCH cut-offs of < 22.65 pg for males and < 22.25 pg for females demonstrated excellent diagnostic performance, with higher sensitivity and specificity in females (90.3% and 93.9%) than in males (89.5% and 88.9%). The findings indicate that the currently used MCH cut-off of 25 pg may be higher than optimal for identifying α⁰ thalassaemia carriers. A lower MCH threshold improves detection performance and may support refinement of the MTDC screening criteria to better prioritize high-risk individuals while reducing unnecessary DNA testing among α⁺ thalassaemia cases.
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