Universal screening for hemoglobinopathies in today's multi-ethnic societies: How and when

Table 1 Cross table indicating the risk for the progeny of carriers of the common β globin gene defects

β traits	β minor	HbS	HbE	HbC	HbD	HbY
β minor	β major
HbS	SCD	SCD
HbE	β major	SCD	β minor
HbC	β minor?	SCD	β minor	β minor
HbD	β minor	SCD	β minor	Normal	Normal
HbX	?	?	?	?	?	?

Hb: Hemoglobin; SCD: Sickle cell disease; HbD: HbD^Punjab.

Table 2 Genotype/phenotype correlation, indicative MCV/MCH values, HPLC/CE separations and presence of HbH or Hb Bart's and genetic risk in alpha thalassemia

Genotype	α-thalassemia	Phenotype	MCV	HPLC	HbH (adult)	Genetic risk for the
	Condition name		MCH	CE	Hb Bart’s (newborn)	progeny of carriers
αα/αα	Normal	Normal	Normal	Normal	Absent	None
					Absent
-α/αα	α+ heterozygous	Eventually anemic	borderline	Normal	Absent	HbH
					0%-5%
-α/-α	α+ homozygous	Mildly anemic	Low	Normal	Absent	HbH
				HbA2↓	5%-10%
--/αα1	α° heterozygous	Mildly anemic	Low	Normal	Absent	HbH or Hb Bart’s HF
				HbA2↓	5%-10%
--/-α2	HbH disease	Intermediate	Lower	HbH	0%-10%	HbH or Hb Bart’s HF
		hemolytic anemia		Hb Bart’s	10%-30%
				HbA2↓↓
--/--	Hb Bart’s	Severe intrauterine	Severe	No HbA or HbF in newborn	Hb Portland	Lethal to newborn.
	Hydrops Fetalis	hemolytic anemia	morphology		Hb Bart’s	Life threatening for mother

¹Rare positive cells after inclusion bodies staining;

²Many positive cells after inclusion bodies staining (Figure 2). MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; Hb: Hemoglobin; HPLC: High performance liquid chromatography; CE: Capillary electrophoresis.

Table 3 Indicative parameters usually associated with carrier states

Carrier of	Hb	MCV	MCH	RBC	HbA2	HbF	Approximately HbS (%)	Approximately HbC (%)	Approximately HbE (%)	Approximately HbD (%)	Smear
Alpha thal	L2	L2	L2	N	N1	N					TC, APC
Beta thal	L	L	L	N or E	E4	N or E					TC, APC
HbS	N1	N1	N1	N	N3	N	45-256				Normal5
HbC	N1	N1	N1	N	N	N		45-256			TC
HbE	L-N	L-N	L-N	N	N	N or E			± 25		TC, APC
HbD	N1	N1	N1	N	N	N				± 45	Normal

¹Could be lower in case of alpha thal;

²Low depending on the form of the defect (see Table 2);

³Could be higher due to HPLC artifact;

⁴Some rare beta thal carriers have normal HbA2;

⁵Positive on sickle test;

⁶%HbS or C reduced in the presence of alpha thal. L: Low; N: Normal; E: Elevated; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; RBC: Red blood cell; TC: Target cells; APC: Anisopoikilocytosis; Hb: Hemoglobin.