J.A. Olaniyi1; O.G Arinola2; A.B. Odetunde3
- Department of Haematology, University College Hospital, Ibadan, Nigeria.
- Department of Chemical Pathology; University College Hospital, Ibadan, Nigeria.
- IMRAT, College of Medicine, University of Ibadan.
Aim: Elevated HbF, among other biological and environmental factors, is responsible for decrease in mortality in sickle cell anaemia (SCA). This study determined the levels of HbF in adult SCA patients in steady state compared with HbAA controls. HbF was discussed in line with the clinical course of the disease so as to emphasize the relevance of hydroxyurea in the management of adult SCA patients.
Materials and methods: The HbF levels of 66 confirmed SCA patients and 31 HbAA controls were estimated using Betke method and HbF percentage was calculated using formula: %HbF percentage = A413 filtrate x 100A413 standard x 20.
Result: A statistical significant difference in the mean of the levels of HbF in patients (5.16±4.04) compared to controls (1.04±0.44) (p = 0.000) was observed. The mean levels of HbF for males (4.71±3.49) compared to that of females (4.99) were statistically similar (p =0.773). It was also observed that the mean HbF level appears to be declining as age advances. SCA patients were classified to three categories viz: HbF <2% (21.2% SCA patients); HbF of 2.1% -10%, (68.2% SCA patients); and HbF of 10.1% -16%, (10.6% SCA patients).
Conclusion: Substantial proportion of our patients actually will require treatment with hydroxylurea to stimulate HbF production especially those with HbF percentage of <2 and some with HbF percentage of 2.1 – 10%. HPFH may be considered rare since only 10. 6% had HbF at the range of 10.1-16%. This study showed that in treating our SCA patients in Nigeria we need to adopt and encourage the use of HbF activating agents like hydroxyurea or any other safe agent that will be found to stimulate HbF production in SCD patients.
Keywords: Sickle cell anaemia, HbF levels, Hydroxyurea use
Department of Haematology
University College Hospital, Ibadan,
HbF (α2γ2), the main haemoglobin component in the foetus, is present at levels of 65 to 90% at birth and usually drops to less than 2% by 6 to 12 months of age(1). HbF levels may also be elevated as a result of genetic abnormalities of haemoglobin production or because of haemopoietic stress.
After birth, the HbF- gama-gene is switched down and the HbA beta-gene is switched on so that adults mainly produce HbA (α2β2). After this developmental switch, low levels of HbF are still produced, and this is distributed heterogeneously with some red cells (F cells) expressing more HbF than others (2). The level of HbF, and the associated proportion of F cells, is a highly heritable trait (3), and within a normal population the distribution of HbF is much skewed. Most healthy individuals produce <0.6% HbF distributed among 1–7% F cells, but a small proportion (about 2%) produce up to 5% HbF and 25% F cells and such individuals are said to have heterocellular hereditary persistence of fetal Hb (hHPFH) (4). SCA patients with high HbF levels not only have less severe clinical course, but also have mild clinical complications because an increase in haemoglobin F inhibits polymerization of sickle haemoglobin.
The varying levels of foetal haemoglobin in erythrocytes account for a larger part of clinical heterogeneity observed in patients with sickle cell anaemia(5). It is also a major prognostic factor for several clinical complications. (6, 7, 8)
The strong relationship existing between percentage HbF level and disease severity in SCA suggests that baseline measurement of percentage HbF is paramount in predicting important aspects of clinical course and in advocating usage of hydroxyurea, which is in low ebb in Nigeria, in order to achieve as much as 40% reduction in mortality long observed in SCA by Steinberge et al in 2003 (9)
MATERIALS AND METHODS
Ninety seven subjects were enrolled. This included 66 SCA patients in steady state attending Medical Out Patient clinic who were consecutively recruited into the study after an informed consent. Also, 31 consenting healthy, HbAA adults were enrolled into the study. These were medical health workers or voluntary blood donors.
Five milliliters of venous blood was collected by clean venepuncture from each patient via the ante-cubital vein using a plastic syringe with minimum stasis, into commercially prepared concentrations of sequestrene ethylene di-amine tetra-acetic acid (EDTA) bottles. Each sample was mixed gently and thoroughly to ensure anticoagulation and to prevent cell lysis. One milliliter of this blood was used to prepare haemolysate for HbF estimation and haemoglobin electrophoresis using Cellulose acetate at pH 8.6 to confirm HbA and HbS status.
Measurement of HbF was done using the Betke method (10). HbF percentage was calculated using the formula: % HbF = A413 filtrate x100 A413 standard x 20
Statistical analysis was performed using SPSS 15.0. Results were expressed as mean ± SD. The difference between mean was compared using the Student’s t test