Sonographic Assessment of the Size and Parenchymal Echo Texture of the Spleen among Sickle Cell Disease Patients at University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria

CHAPTER ONE

INTRODUCTION

Background of the Study: Sickle cell disease (SCD) is an autosomal recessive genetic disorder of the blood characterized by red blood cells (RBCs) that assume abnormal, rigid and sickle shapes. This condition stimulates high blood viscosity, low oxygen affinity in RBCs, vaso-occlusions, especially in the tiny blood vessels, ischaemias, acute pains, infarctions and fibrosis of dependant tissues. SCD is among the inborn errors of metabolism that has no known cure. It is associated with pathologic consequences of chronic and life-long illnesses. Patients with SCD often have different forms of sickle cell crises (Aldrich et al., 1998). The provisional agenda item 11.4 as reported by the secretariat of the fifty-ninth World Health Assembly (WHO, 2006) said that sickle cell disease (SCD) was a common genetic condition that was globally wide-spread. Oguejiofor (1999) opined that SCD was a disease of the black race, and warned that millions of Nigerians might be affected if properly investigated. But, WHO (2006) found that SCD was particularly common among people whose ancestors come from sub- Saharan Africa, India, Saudi Arabia, and Mediterranean countries emphasizing that migration raised the frequency of the gene in American and European continents. Oguejiofor (1999) suggested that the “Ogbanjes” of the South-eastern Nigeria and the “Abicus” of the South- western Nigeria were probably undiagnosed sickle cell disease individuals.

This World body (WHO, 2006) opined that 5% of the world’s population carried genes responsible for SCD. They estimated the frequency of sickle cell trait in West African countries like Ghana and Nigeria to be 15% to 30%.. World Health Organization (2006) observed that Sickle cell gene was common in Africa because the sickle cell trait conferred some resistance to falciparum malaria infection during the critical period of early childhood, and that the frequency of the carrier state determined the prevalence of SCD at birth. This world body noted that it was only inheritance of a single abnormal gene - sickle cell trait - which offered protection against malaria, and that inheritance of two abnormal genes (sickle cell disease) conferred no such protection. Hence, they warned that malaria was a major cause of ill-health and death in children with SCD.

This Assembly found that each year about 300,000 infants were born with major haemoglobin (Hb) disorders, SCD, globally, out of which about 200,000 cases occurred in Africa, and 150,000 of these children were born annually in Nigeria alone. They opined that SCD contributed the equivalent of 5% of under-five deaths on the African continent, more than 9% in West Africa, and up to 16% of under-five deaths in individual West African countries like Nigeria. This world body found that half of those with SCD usually die by the age of 5 years in sub-saharan Africa from infections such as malaria, pneumococcal sepsis, and anaemia.

Haemoglobinopathy, abnormality of the haemoglobin of the red blood cells, is a genetic disorder including sickle cell disease and thalassaemia. Sickle cell disease is a qualitative genetic disorder in which there is alteration in the normal globin chain, while thalassaemia refers to a quantitative haemoglobin disorder in which there is reduced or even absent synthesis of normal globin chains (Lanzkowsky et al., 2011; Dorland et al., 2009; Desai et al., 2004; Oguejiofor, 1999). Of the organs like liver, spleen, gallbladder, kidneys, and bone marrow, that are mainly affected by the acute and chronic complications of SCD, the spleen experiences the insult first. This is due to its peculiar anatomy and physiology - it has narrow blood vessels and filters the systemic blood (de Montalembert et al., 2008; Stuart et al., 2004; Steimberg et al., 1995). The spleen played a prominent role in the early discovery of SCD, hence, there was early belief that splenic involvement was responsible for repeated attacks of abdominal pains in the sickle cell disease patients. This erroneous early belief culminated in the wrong early definition of SCD as a familial and hereditary defect of the spleen (Desai et al., 2004).

Okoye et al (2005) opined that spleen responded to different pathologic states such as fever and sickle cell disease by dimensional changes. The fifty-ninth World Health Assembly of WHO, 2006, concluded that there was need to develop models of care appropriate to the management of sickle cell disease in Sub-Saharan Africa in which Nigeria held dominance because of her large population. This model of care will be based on constant monitoring, early detection of crises, and early presentation to the specialist treatment centers. Early monitoring and detection are enhanced by ultrasonography of the Spleen (Curry, 1995). Regional variations in splenic size and spleen parenchymal echo-texture among sickle cell disease (SCD) patients exist in different publications. No such study has been documented from this locality. The present study therefore aims at sonographic evaluation of the sizes and parenchymal echo-textures of the spleen among SCD patients at University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. Information from this study will add to the pool of knowledge on SCD and enhance the management of such patients in this region.

Statement of the Problem

Spleen is the most affected organ in sickle cell disease (Olatunji et al., 2001), because of its peculiar anatomy and physiology - it possesses tiny blood vessels and it is the largest organ of the reticulo-endothelial system that filters the entire human blood - (Steimberg et al., 1995). This is why it receives the insults of these clinical conditions earlier than the other vulnerable body organs (Stuart et al., 2004).

There are variations in the results of splenic size determined in both normal populations and in sickle cell disease (SCD) patients in related previous studies done in Nigeria, Africa and in some Caucasian environments (Ahmed Al-Salem et al., 1998; Olatunji et al., 2001; Awotua-Efebo et al., 2004; Mohanti et al., 2004; Babadoko et al., 2012). In those studies, authors differ on the probable features of SCD like the frequency and percentage of auto-splenectomy, incidence of shrunken spleen, trend of splenomegaly, persistence of splenomegaly into various adult ages, and the age range of maximum spleen size. They also disagree in the degree of spleen parenchymal anomalies such as infarctions, abscesses, fibrotic scars, calcifications, and tumors, in sickle cell disease.

The results of previous works done on splenic size assessment show that the presence and degree of spleen features in sickle cell disease condition are regional (Olatunji et al., 2001; Awotua- Efebo et al., 2004; Mohanti et al., 2004; Babadoko et al., 2012; Eze et al., 2013). And no such study has been documented in our own locality, Enugu, South east Nigeria.

​​​​​​​Purpose of the Study

To assess the sizes and parenchymal echo-textures of the spleens in the different hypothetical age groups of sickle cell disease patients in our environment.

Specific Objectives of the Study

1. To determine the sizes of the spleens of the sickle cell disease patients in apparently stable condition and those of the healthy controls in different age groups.

2. To compare the sizes of the spleens of the sickle cell disease patients in apparently stable condition with those of apparently healthy controls.

3. To ascertain the relationships of age, height, and weight with the splenic sizes of stable sickle cell disease patients and healthy controls.

4. To characterize the parenchymal echo-texture of the spleens of the sickle cell disease patients in apparently stable condition.

5. To determine the trends of splenomegaly and the frequency of auto-splenectomy among sickle cell disease patients in apparently stable condition.

Significance of the Study

1. Information from the present study will add to the pool of knowledge on SCD, and increase the quality of management of such patients in our locality, Enugu.

2. Variations in sizes and parenchymal echo-texture of spleens may be used to predict crisis among SCD patients.

3. Implementation of the recommendations of this study will enhance the early detection of acute and chronic complications of SCD such as acute splenic sequestration crisis, hyper-splenism, massive splenic infarction and marked splenic abscess, and their early presentation to specialist centers.

4. This study will assist the clinicians that manage SCD patients to know when to carry out surgical splenectomy, which is a sure treatment for acute splenic sequestrationcrisis, hyper- splenism, massive splenic infarction and marked splenic abscess.

5. Knowledge of the common sonographic appearances of spleen of sickle cell disease patients in our environment would be used to predict a case of sickle cell disease in unscreened individuals.

Scope of the Study

This study covers SCD patients, of all age groups and sexes, who are in stable condition, that are being managed in the sickle cell clinics of University of Nigeria Teaching Hospital (UNTH), Ituku – Ozalla, Enugu. Some apparently healthy subjects on referral for routine abdomino-pelvic ultrasound examination in radiation medicine department of UNTH will be included too. These healthy subjects will serve as control.

​​​​​​​Operational Definition of Terms

1. Sickler. This refers to a person living with sickle cell disease (Desai et al.,2004).

2. Sickle cell patient. Is a person living with sickle cell disease (Oguejiofor,1999).

3. Sickle cell disease (SCD). This is a general and non-specific term for a group of autosomal, recessive, genetic abnormality of the blood (Steimberg et al.,1995).

4. Autosomal. This refers to non-sex cells (Dorland, 2009).

5. Recessive. This is a gene that does not dominate/manifest in a group of another allele (Stedman,2006).

6. Genetics. Means inheritance.

7. Allele. Is one of two or more alternative forms of a gene occurring at a particular chromosomal locus (Stedman.,2006).

8. Sickle cell. This refers to a cell that is shaped like a sickle.

9. Sickle cell anaemia (SCA). Is a specific name for a type of sickle cell disease in which the patients red blood cells assume various abnormal shapes under low oxygen supply (Wellems et al.,2009).

10. Red blood cell. This is one of the cells in the human blood that is responsible for the red colour of the human blood (Hillman et al.,2005).

11. Haemoglobin (Hb). Is a protein constituent of red blood cells that makes the red blood cells red, and distributes oxygen in the body (Hillman et al.,2005).

12. Spleen. Is a secondary lymphoid, intra-abdominal organ .

13. Polymerization. This refers to an aggregation or crowding together of tissues like sickled red blood cells.

14. Homozygous. Means same or similar, two identical genes.

15. Heterozygous. Is two non-identical genes (one normal and one abnormal).

16. Compound heterozygous. Two non-identical, abnormal genes (two different types of abnormal genes )-(Claster et al., 2003).

17. Sickle cell carrier. This refers to a heterozygous person.

18. Sickle cell trait. Existence of one normal and one abnormal genes in blood.

19. Vaso-occlusive. Is obstruction of any blood vessel.

1. Ischaemia. Refers to a deficiency of blood supply.

1. Infarction. Means death of tissues due to blocking of their arterial blood supply .

1. Infarct. Refers to a localized dead tissue.

1. Sickling. Is formation of sickle cells or abnormally shaped cells in the human blood.

2. Acute chest syndrome. Is a type of sickle cell crises characterized by fever, chest pain, hard breathing, and pulmonary infiltrate on chest x-ray (Stuart et al., 2004).

3. Aplastic crises. Is a type of sickle cell crises characterized by acute anaemia as a result of temporary cessation of erythropoiesis (Platt, 2008).

4. Splenic sequestration. Is a sudden increase in size of spleen (Desai et al., 2004).

1. Stroke. Refers to a cessation of blood supply to, or hypoxia of, brain tissues.

1. Hypoxia. Is deficiency of oxygen supply.

1. Cholelithiasis. Means stone in the gall bladder .

1. Cholecystitis. Is inflammation of the gall bladder.

1. Hyposplenism. Is deficient functioning of the spleen.

1. Priapism. Abnormally sudden and painful erection of the penis.

1. Massive splenic infarction. This refers to splenic infarction involving more than half the size of the spleen (Charache et al.,1995).

1. Abicus . Is a term in the south western part of Nigeria that refers to those infants that die regularly and cyclically after birth in the same families.

Ogbanje. Is also a term in the south eastern region of Nigeria that represents the newborns that die shortly and repeatedly after birth in the same families too.