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Interpretive Handbook

Test 8270 :
Hemoglobin F, Red Cell Distribution, Blood

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

More than 75% of the hemoglobin of the newborn is hemoglobin F (Hb F); it diminishes over a period of several months to adult levels, becoming <2% by 1 year-of-age and <1% by 2 years.


Hb F may constitute 90% of the total hemoglobin in patients with beta-thalassemia major or other combinations of beta thalassemia and fetal hemoglobin (HPFH) mutations.


Hb F is often mildly to moderately elevated in sickle cell disease, aplastic anemia, acute leukemia, myeloproliferative disorders such as juvenile myelomonocytic leukemia (JMML), hereditary spherocytosis, and alpha-thalassemia minor. It is commonly increased in hemoglobinopathies associated with hemolysis. Hb F increases to as high as 10% during normal pregnancy. Hb F is also increased due to medications such as hydroxyurea, decitabine, and lenalidomide. Elevation in Hb F has a been cited as a discriminator between Diamond-Blackfan congenital pure red cell aplasia (elevated) and transient erythroblastopenia of childhood (normal) but whether this simply reflects the chronicity of anemia inherent to the former condition rather than a specific finding is unclear.


In the common (large deletional) form of the genetic trait hereditary persistence of HPFH, all of the erythrocytes contain Hb F. When tested by flow cytometry using specificity for Hb F, these HPFH cases display a homocellular distribution pattern of Hb F within the red cell population. Other causes of increased Hb F including delta beta thalassemia, hydroxyurea, and some nondeletional HPFH mutations typically display a heterocellular distribution of Hb F within the red cells, reflecting disparate populations of F cells and cells lacking Hb F. Quantification of Hb F percentage should be determined prior to flow cytometry of Hb F red cell distribution to establish the appropriateness of this test. The flow cytometry analysis of elevated Hb F levels is useful when Hb F percentage is between 15% to 35% and the clinical differential diagnosis includes large deletional HPFH. Hb F percentages below 15% are likely not due to large deletional HPFH and causes of Hb F percentages above 35% are better confirmed by molecular and family studies. This test is not to be ordered for fetal-maternal bleed. If fetal maternal bleed assessment is desired, please see FMB / Fetomaternal Bleed, Flow Cytometry, Blood.

Useful For Suggests clinical disorders or settings where the test may be helpful

Distinguishing large deletional hereditary persistence of fetal hemoglobin from other conditions with increased percentage of fetal hemoglobin

Interpretation Provides information to assist in interpretation of the test results

Homocellular distribution of fetal hemoglobin is found in large deletional hereditary persistence of fetal hemoglobin.

Heterocellular distribution is found in delta beta thalassemia, medication induced, and other causes of increased hemoglobin F.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

For hereditary persistence of fetal hemoglobin only. Not to be ordered for fetal-maternal bleed (see FMB / Fetomaternal Bleed, Flow Cytometry, Blood).


With hemoglobin F values >35%, most specimens show a homocellular pattern; this does not necessarily indicate hereditary persistence of fetal hemoglobin. Clinical correlation is needed.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Reported as heterocellular or homocellular

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Kleihauer E, Braun H, Betke K: Demonstration von fetalem Hamoglobin in den Erythrocyten eines Blutaustrichs. Klin Wschr 1957;35:637-638

2. Shepard MK, Weatherall DJ, Conley CC: Semi-quantitative estimation of the distribution of fetal hemoglobin in red cell populations. Bull Johns Hopkins Hospital 1962;110:293-310

3. Davis BH, Olsen S, Bigelow NC, Chen JC: Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry. Transfusion 1998;38:749-756

4. Hoyer JD, Penz CS, Fairbanks VF, et al: Flow cytometric measurement of hemoglobin F in RBCs: diagnostic usefulness in the distinction of hereditary persistence of fetal hemoglobin (HPFH) and hemoglobin S-hPFH from other conditions with elevated levels of hemoglobin F. Am J Clin Pathol 2002 Jun;117(6):857-863

5. Stephens AD, Angastiniotis M, Baysal E, et al: International Council for The Standardisation of Haematology (ICSH). ICSH recommendations for the measurement of haemoglobin F. Int J Lab Hematol 2012 Feb;34(1):14-20