Hemoglobin (Hb), Fetal, Quantitative

CPT: 83021
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Test Details

Synonyms

  • Fetal Hemoglobin
  • Hb F
  • Hemoglobin F Quantitation

Use

Evaluate hemoglobinopathies, hemolytic anemia; diagnose hereditary persistence of fetal hemoglobin; diagnose thalassemia; evaluate sickling hemoglobins

Methodology

High-pressure liquid chromatography (HPLC)

Reference Interval

See table.

Age

Percentage

<7 mo

Not established

7 mo to 1 y

0.1% to 6.8%

≥2 y

0.0% to 2.0%

Additional Information

Fetal hemoglobin is formed of two α-chains and two γ-chains. It is the major hemoglobin during fetal life. Hb F levels decrease after birth by about 3% to 4% per week. In two to three weeks, fetal hemoglobin is about 65%. By six months of age, fetal hemoglobin is <2% of the total hemoglobin. See graph. The oxygen dissociation curve of Hb F is shifted to the left as compared with normal Hb A. This may be due to decreased binding of 2,3-DPG by Hb F (γ-chains). This facilitates placental oxygen transfer. With erythroblastosis fetalis and anoxic states of the newborn; however, Hb F is proportionally lower than in a normal newborn. Some 15 inherited abnormalities of γ-chain structure have been described1 but most are without clinical significance (fetal Hb normally forms <2% of total hemoglobin). An exception is Hb F Poole, which has been reported as a cause of hemolytic disease of the newborn.2

Nonmalignant Conditions Associated With Increased Proportions of Hb F

Condition

Hb F Value (%)

Anemias

Aplastic anemia (both congenital and acquired)

5−25

Pernicious anemia

2−6

Hereditary spherocytosis

2−5

Hereditary elliptocytosis

2−5

Congenital nonspherocytic hemolytic anemia

3−4

Anemia of chronic infection

2−3

Anemia of blood loss

2−8

Erythropoietic porphyria

2−10

Paroxysmal nocturnal hemoglobinuria

2−25

Hemoglobinopathies

Unstable hemoglobins

<10

Homozygous Hb S disease

<20

Hb Lepore trait

<5

Hb Kenya trait

6−13

Thalassemias

β-thalassemia minor

<5

β-thalassemia minor

5−20

β-thalassemia major

30−95

α-thalassemia minor

∼1

Hb H disease

5−15

Hemoglobinopathy-thalassemia interactions

S/β-thalassemia

10−30

E/β-thalassemia

10−50

C/β-thalassemia

10−30

Hereditary persistence of fetal hemoglobin (HPFH)

African-type

heterozygous

15−40

homozygous

100

Greek-type

heterozygous

10−20

Swiss-type

heterozygous

1−3

In the adult, hereditary persistence of fetal hemoglobin (HPFH) of multiple varieties is associated with varying elevations of Hb F. The homozygous form of HPFH is found only in black individuals. In the heterozygous state, the Hb F level is 15% to 35% in the black type, and 5% to 20% in the Greek type. Homozygous β-thalassemia is associated with Hb F levels <10% to >90%. About 50% of heterozygotes for β-thalassemia have elevated levels around 2%, rarely >5%. The remainder have normal Hb F. Heterozygous S/β-thalassemia may have Hb F in the 5% to 20% range. With homozygous Hb S disease, the level of Hb F varies from 0% to 20%.3 Other conditions associated with elevated Hb F include various anemias: spherocytosis, Fanconi, acquired aplastic, hemolytic hypoplastics, megaloblastic, myelophthisic, and untreated pernicious anemia; all types of leukemia (especially erythroleukemia and juvenile chronic myelogenous leukemia), multiple myeloma and lymphomas, metastatic disease of the bone marrow; pregnancy; miscellaneous disorders reported include infants small for gestational age, infants with chronic intrauterine anoxia with developmental anomalies; during anticonvulsant drug therapy; diabetes; hyper- and hypothyroidism; and macroglobulin. Elevation of Hb F should, then, raise the question of possible underlying disease.

Specimen Requirements

Specimen

Whole blood

Volume

1 mL

Minimum Volume

0.5 mL

Container

Lavender-top (EDTA) tube

Storage Instructions

Refrigerate at 2°C to 8°C.

Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Clinical Information

Footnotes

1. Weatherall DJ, Clegg JB, Higgs DR, et al. The hemoglobinopathies. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic Basis of Inherited Disease. 6th ed. New York, NY: McGraw-Hill Information Services Co;1989: 2323-2324.
2. Lee-Potter JP, Deacon-Smith RA, Simpkiss MJ, et al. A new cause of haemolytic anaemia in the newborn. A description of an unstable fetal haemoglobin: F Poole, α2 γ2 130 tryptophan yields glycine. J Clin Pathol. 1975 Apr; 28(4):317-320. 1127124
3. Warth JA, Rucknagel DL. The increasing complexity of sickle cell anemia. Prog Hematol. 1983; 13:25-47 (review).6199811

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
120900 Hgb, Fetal, Quant 4576-5 121706 Hgb F % 4576-5

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