|Values are valid only on day of printing.|
Distinguishing large deletional hereditary persistence of fetal hemoglobin from other conditions with increased percentage of fetal hemoglobin
The percent of the patient’s hemoglobin F is very important to the clinical utility of this test. HBF / Hemoglobin F, Blood will be performed at an additional charge to determine if Hemoglobin F, Red Cell Distribution testing is warranted. If the hemoglobin F value from HBF / Hemoglobin F, Blood are normal for age or if value is <5% the HPFH / Hemoglobin F, Red Cell Distribution, Blood will not be performed. Samples with hemoglobin F (Hb F) levels >35% will be accepted but are discouraged due to decreased test specificity. For these markedly elevated Hb F levels, a hemoglobin electrophoresis profile with request for beta globin gene molecular testing for elevated Hb F levels is recommended.
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.
Reported as heterocellular or homocellular
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.
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.
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