Hemoglobinopathies are inherited disorders of red blood cells and constitute an important cause of morbidity and mortality. Thalassemia major, sickle cell disease and HbE are the three most important clinical syndromes among hemoglobinopathies in India.(1)
According to the government, India has the largest number of children with thalassemia major in the world – about 150,000.(1) There are almost 42 million carriers of β-thalassemia trait.(1) It is estimated that there is a prevalence rate of 3-17% all over India with a high frequency observed in certain communities, such as Sindhis, Punjabis, Gujaratis, Bengalis, Mahars, Kolis, Saraswats, Lohanas and Gaurs.(1,2) An estimated 10,000 -15,000 babies with thalassemia major are born every year.(1)
HbE is a variant hemoglobin that significantly contributes to the disease burden of hemoglobinopathies, especially in West Bengal, and the North Eastern States. In certain communities in this region, the carrier frequency of HbE is as high as 50%. However, HbE alone, whether heterozygous or homozygous form, does not cause clinically significant disease.(1)
The prevalence of sickle cell disease is variable (1% – 44%), with very high frequency in many tribal communities.(1,2) However, it is not restricted only to the tribal communities, as due to migration and inter-community, marriages affected persons are found in most states.(1)
Another variant, HbD-Punjab is not uncommon in India but its homozygous form is very rare.(3) Heterozygous HbD is a clinically silent condition, but coinheritance of HbD with HbS or β-thalassemia produces clinically significant conditions like sickle cell anemia and chronic hemolytic anemia of moderate severity. HbD-Punjab occurs with greatest prevalence (2%) among Sikhs in Punjab, India, whereas the reported prevalence rate in Gujarat province, in western India, is 1%.(3)
Ideally, it is best to conduct pre-marriage screening to identify carriers of β-thalassemia and structural hemoglobinopathies like sickle cell trait but is often not acceptable due to social and cultural reasons.(4)
Although very difficult in the Indian situation, preconception screening should be done wherever possible.(4) Preconception screening is essential for all couples coming to infertility clinics for assisted conception. If the woman is a carrier of a significant hemoglobinopathy, her partner or sperm donor should be screened and in case of an ovum donor, the donor should also be screened.(4)
All pregnant women should be screened in all antenatal clinics irrespective of the gestational age:(4)
It is mentioned in the Ministry of Health and Family Welfare’s (MOHFW) policy that screening of pregnant women should be done, preferably in the first trimester, for carrier status. If the husband also tests positive, this will enable at-risk couples to avail services for prenatal diagnosis to prevent the birth of an affected child.(1)
The MOHFW in its policy document states that while POC tests may be used for screening, all positive cases must be confirmed by HPLC.(1) The BSH and ACOG guidelines both recommend that HPLC should be the primary methodology or, at the very least, part of the diagnostic algorithm.(5,6)
When we analysed the data from Hb electrophoresis screening of patients as part of antenatal screening at Suburban during a 6-month period in 2019, we found that 93.77% of all women screened did not have any hemoglobinopathy. Of the remaining, 3.27% had beta-thalassemia trait, 0.62% had sickle cell trait. 0.16% had HbD Punjab heterozygous and another 0.16% had delta beta thalassemia heterozygous. 1.71% of the patients had a borderline HbA2 value with other parameters not fitting into any clear category and which require more advanced testing to resolve.
The average Hb and MCV values for the HbD, HbE and HbS heterozygous cases seen in our data were between 10-12 g/dl and 80-83 fL.
This indicates that these cases would have easily gone undiagnosed from just a CBC, as mild anemia is quite common in pregnant Indian women.