ASSESSMENT OF THE RELATIONSHIP BETWEEN FOETAL HAEMOGLOBIN LEVELS, MARKERS OF TISSUE DESTRUCTION AND DISEASE SEVERITY IN INDIVIDUALS WITH SICKLE CELL ANAEMIA

ASSESSMENT OF THE RELATIONSHIP BETWEEN FOETAL HAEMOGLOBIN LEVELS, MARKERS OF TISSUE DESTRUCTION AND DISEASE SEVERITY IN INDIVIDUALS WITH SICKLE CELL ANAEMIA

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ABSTRACT

Sickle-cell Anaemia is a genetic disorder that leads to the production of Sickle haemoglobin, whichresults in abnormal functions of the red blood cell under hypoxic conditions.The aim of this study was to assess the relationship between Foetal haemoglobin, markers of tissue destruction and disease severity among individuals with sickle cell anaemia. Thirty seven adults with sickle cell anaemia with average age of 26.24±7.32 years were enrolled in this study. Twenty four of them were females while thirteen were males. Participants enrolled were individuals attending clinic at Haematology Department, Ahmadu Bello University Teaching Hospital Zaria who have been diagnosed with Sickle cell anaemia and were confirmed by cellulose acetate electrophoresis. Foetal haemoglobin was assayed using betke‟s alkali denaturation method and complete blood count was done using automated haematology analyzer. Lactate dehydrogenase (LDH) activity and bilirubin concentration were determined by spectrophotometric method while disease severity was computed based on the scores obtained from the clinical and haematological data. From our findings, there was a significant difference (P<0.05) in foetal haemoglobin (HbF) levels and LDH activity between individuals in steady state and those in crises condition. Also there was a significant inverse correlation between HbF levels and LDH activity (P= 0.01, r=-0.59) and between LDH activity and disease severity (P=0.01, r=0.42) but there was no significant (P>0.05) relationship between HbF levels & disease severity (P = 0.69, r = -0.07) and HbF levels & bilirubin concentration (P=0.78, r=-0.05).Therefore the present study suggested that HbF level has an inverse relationship with disease severity and tissue destruction. However, disease severity has a direct relationship with tissue destruction.

 CHAPTER ONE

1.0.      Introduction

Sickle cell anaemia (SCA) is a disorder of the Haemoglobin caused by inheritance of a single

abnormal haemoglobin (termed sickle haemoglobin- HbS) which results in physical and chemical

modifications of the haemoglobin molecule (Damanhouriet al., 2015). Under conditions of low

oxygen concentration, the sickle haemoglobin causes the red blood cell to become fragile and prone

to rupture. This condition causes the aggregation of haemoglobin (polymerization) and reduces the

overall capacity of the haemoglobin to convey oxygen to tissues by impeding free passage of blood

in the vessels (vaso-occlusion) to tissues. Increased rupturing of red blood cells leads to anaemia

(reduction in number of red blood cells) (Elias et al., 2012; Damanhouriet al., 2015).

Lactate dehydrogenase (LDH), an enzyme of the glycolytic pathway that catalyzes the inter

conversion of pyruvate to lactate is found in abundance in all tissues. It consist of five (5)

isoenzymes forms classified according to their electrophoretic mobility. The concentration of these

isoenzymes varies from one organ to the other, with LDH1 and LDH2 found primarily in RBCs and

heart muscle (Ballas, 2013). There is increased level of LDH in the general blood circulation of

individuals with SCA. This is due to the increased breakdown of diseased RBCs and other tissues

and has been used as a marker of hemolysis and tissue damage. The haemolysis/tissue damage

increases further in individuals with Sickle cell anaemia in crises state (Kato et al., 2006; Ballas

2013). Numerous studies have associated SCA individuals with high LDH level to high prevalence

of pulmonary hypertension, renal failure and early death (Kato et al., 2013). High LDH observed in

this individuals is as a result of haemolysis and tissue destruction (Mehdiet al., 2013; Alzahriet al.,

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2015). Despite the importance of LDH as a gold standard marker for tissue damage information

about LDH in population suffering from SCA in Nigeria is scarce.

SCA studies have shown that individuals with HbF>10% are regarded as having high HbF (Moreira

et al., 2015). SCA Individuals with high HbF, like those from eastern Saudi Arabia and India have

been found to experience mild clinical complications of the disease (Miller et al., 1986). Foetal

hemoglobin is a type of haemoglobin composed of two subunits of α- globin peptide chains, two

subunits of γ globin peptides and a heme moieties necessary for this molecule‟s oxygen-carrying

capacity. It is the dominant haemoglobin synthesized in the foetus (Sankaran and Orkin, 2013). It is

produced by a fraction of RBCs called F-cells that are able to produce HbF alongside other

haemoglobins. The F-cells have the advantage of longer life cycle compared to non-F-cells, and the

higher the HbF content the longer the life span of the F-cells. The long life span of F-cell is

associated with the characteristic of HbF which is able to resist polymerization caused by sickle

haemoglobin (HbS) (Colella&Traina, 2015). This has prompted studies into HbF composition from

other regions of the world, with the aim of understanding the role of HbF in ameliorating SCA

complications. Although the HbF levels are known in several populations around the world, only

fewstudies have examined HbF level in patients in Nigeria. Knowledge of the HbF levels will be

important in assessing the possible impact of introducing disease modifying drugs (DMD) on the

individuals with SCA in Nigeria.

SCA is known to exhibit great clinical diversity. Though the same disease, the effect of disease

complications vary significantly from one individual to another.     The clinical variation at one

extreme are a group that may need close care and at the other end, are a group that may not require

any care. Classification of individuals into disease severity group can help detect which severity

group they belong and respective care given accordingly based on their need (Mpalampaet al., 2012).

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Unlike in the developed countries where advancement in technology can be used to identify who will

need close attention, in developing countries these equipment‟s are not available (Okochaet al.,

2015). Because of this and many other factors the rate of morbidity and mortality is still high


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