Can Couples With MCV≥80, MCH<26, HbA2<3.2, HbF<3 be Classified as Low-risk β-Thalassemia Group?

Thalassemia screening instructions in Iran categorizes couples with mean corpuscular volume (MCV)=75 to 80, mean corpuscular hemoglobin (MCH)=26 to 27, hemoglobin A2 (HbA2)<3.5, and hemoglobin fetal (HbF)<3 indices as low-risk couples, and therefore further genetic testing is not obligatory. This study examined the possibility of classifying couples with MCH<26 and MCV≥80 indices in the low-risk group when their HbF was <3 and HbA2 was <3.2.

This was a cross-sectional study. The data included results from cell blood count and HbA2 prenatal diagnosis (PND) and HbF tests taken by 22 health care centers in Esfahan province, central Iran, throughout the years 2012-2016. The inclusion criterion was the registering of MCV, MCH, and PND results of the participants. From the 5804 participants, 5624 individuals were included in the study.

The sensitivity and specificity of the screening program were 99.7 and 53.12, respectively. Ten cases (0.18%) with thalassemia trait had indices MCV≥80 and MCH≥26 including 3 cases (0.05%) with concurrent α and β-thalassemia mutations and 7 cases (0.12%) with HbS mutations. Altogether, 553 subjects (9.83%) had MCV≥80 and MCH<26 indices, and only 1 case (0.018%) was found with β-thalassemia mutations (codon8 (-AA)/WT genotype).

Subjects with MCV≥80, MCH<26, HbA2<3.2, and HbF<3 cell blood count indices could be grouped as low-risk couples if normal HbA2 and HbF values are considered. The results of this study also indicate that there is a chance of missing concurrent α and β-thalassemia or HbS hemoglobinopathies in the current screening program given the fact that genetic testing is not considered for couples with MCV and MCH in the low-risk range. HbF testing could be conducted to prevent these missing cases.