The Pattern of Sickle Cell Disease in Sickle Cell Patients
from Northwestern Nigeria
Saganuwan Alhaji Saganuwan
Department of Veterinary Physiology, Pharmacology and Biochemistry, College of Veterinary Medicine, University of Agriculture, Makurdi,
Benue, Nigeria.
Abstract: Sickle cell disease is caused due to a genetic disorder, which accounts for people dying at an early age in Nigeria. A retrospective study of
sickle cell disease patients was carried out with a view to determining the disease pattern in sickle cell patients from the Northwestern Nigeria. Case notes
of 319 sickle cell patients were collected and reviewed retrospectively. The prevalence of sickle cell trait, comorbidity of sickle cell disease and malaria, and
the effects of sickle cell disease and age on the weight and hematological parameters of sickle cell patients were determined and analyzed. Results showed
the prevalence rate of sickle cell trait to be 61.8% (197) and that of non-sickle cell trait to be 38.2% (122). The sickle cell trait comprised 96 males (48.7%)
and 101 females (51.3%). Among these patients, 51 (41.8%) males and 71 (58.2%) females had malaria. However, 35.4% (113) of sickle cell patients and 7.5%
(24) of malaria patients showed anemia. Genotyping revealed 32 AS (16.2%), 102 SS (51.8%), SS+F (3.6%), and 56 SC (28.4%). The associated prevalence
rates of clinical signs were pain/crisis 45.1% (89), pneumonia 28.4% (56), gastric disorders 9.1% (18), central nervous system (CNS) disorders 4.1% (8), renal
diseases 2.5% (5), musculo-skeletal disorders 2.5% (5), conjunctivitis 0.5% (1), acute chest syndrome 0.5% (1), cholecystitis 0.5% (1), hemophilia 0.5% (1),
fever 0.5% (1), priapism 2.0% (4), splenomegaly 2.0% (4), and epistaxis 1.5% (3). Few patients lived up to 49 years. There was significant difference (P , 0.05)
in hematological parameters of the patients from various age groups. The use of anti-sickling, hematonic, analgesic, anti-inflammatory, and antimalarial
drugs in the treatment of the affected disease in patients might have improved their quality of life.
Keywords: sickle cell, longevity, hydroxyurea, Nigeria
Citation: Saganuwan. The Pattern of Sickle Cell Disease in Sickle Cell Patients from
Northwestern Nigeria. Clinical Medicine Insights: Therapeutics 2016:8 53–57
doi: 10.4137/CMT.S38164.
TYPE: Original Research
RECEivED: december 30, 2015. RESubmiT tted: April 11, 2016. Accepted for
PubliCaTioN: april 15, 2016.
Academic editor: Garry M. Walsh, Editor in Chief
Peer Review: Three peer reviewers contributed to the peer review report.
Reviewers’ reports totaled 554 words, excluding any confidential comments to the
academic editor.
Funding: Author discloses no external funding sources.
Competing Interests: Author discloses no potential conflicts of interest.
Introduction
Protection against some infectious diseases from inheritance
of polymorphism has been established. Malaria is the most
significant disease affecting the expression of blood groups.
Abnormal red blood cells such as Fy (a-b-) phenotype and the
S-S- phenotypes have been frequently observed in Africa and
South East Asia.1 Sickle cell anemia patients between the age
of two and four years are prone to greatest risk of developing anemic crisis.2 In the United States, the life expectancy
of sickle cell patients is reduced by about 30 years.3 Sickle cell
disease (SCD), an inherited disorder of hemoglobin, occurs
in 70,000 to 80,000 Americans of African, Mediterranean,
or Middle Eastern origin.4 Nigeria has the largest population
of people living with sickle cell disorder, with about 150,000
births annually.5 More than 300,000 babies are born worldwide
with SCD mostly in low- and middle-income countries,
with the majority of these births in Africa.6 In Nigeria,
a quarter of the affected children are diagnosed before infancy
and three-quarters before they complete three years of age.7
The prevalence of sickle cell anemia ranges from 2 to 3% of
the population.8 Sickle cell anemia causes low mean weight
and height.9 The risk of asymptomatic bacterium is three times
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more common in Nigerian children with sickle cell anemia
than in children with normal hemoglobin count.10 Children
with sickle cell anemia are more prone to developing urinary
tract infections (UTIs) and other bacterial infections than
those with normal levels of hemoglobin11 and may have compromised kidney function from repeated vaso-occlusive episodes and recurrent UTI.12 The disease is also associated with
retinopathy, with higher prevalence among S-S men than
among SS women.13 The organisms causing bacteremia in
African children with sickle cell anemia are the same as those
in developed countries. Therefore, the use of conjugate vaccine
against Streptococcus pneumoniae and Haemophilus influenzae
can improve the quality of life of the patients.14 Complications
of SCD occurred in 25% of pregnancies, with birth weight of
infants being below 2.5 kg in 20% of pregnancies.15 In Nigeria,
the majority of patients with sickle cell anemia are 10 years and
below16 as opposed to 18 to 43 years in the United Kingdom.15
Sickle cell anemia is responsible for death of 25% of children
under the age of five years in Africa.17 The three most common musculoskeletal complications seen in older patients
with higher platelets count are leg ulcer, avascular necrosis,
and osteomyelitis.18 High hemoglobin levels appear to be an
Clinical Medicine Insights: Therapeutics 2016:8
53
Saganuwan
important factor for painful crisis.19 In Sudan, 54% of target
samples were heterezygous carrier (HbAS), 42% were normal (HbAA), and 4% were diagnosed with SCD.20 The only
SCD-modifying drug is hydroxyurea. But the new Aesloz
works via binding to hemoglobin and produces antisickling
effect in red blood cells.21 In view of the serious health implications of sickle cell anemia, the comorbidity of malaria in
SCD was retrospectively studied among patients presented
to the Department of Haematology, Usmanu Danfodiyo
University, Sokoto, Northwestern Nigeria.
Materials and Methods
Case notes (319) of patients presented at the Haematology
Department, Usmanu Danfodiyo University Teaching
Hospital, Northwestern Nigeria, were collected and reviewed
retrospectively. The review period was between January 1999
and December 2013. Data were sorted out according to age,
sex, weight, and incriminating hematological diseases. Cases
of sickle cell anemia and malaria were sorted out from other
hematological cases. Sickle cell disorders were also classified
based on genotype. The method of Saganuwan and Onyeyili, 22
Ganong, 23 and Guyton and Hall 24 was used to determine the
total blood volume of patients using 8% of their body weights.
The total blood volume was determined by multiplying the
plasma volume by 100/100 minus hematocrit, and red cell
volume was determined by subtracting the plasma volume
from the total blood volume. Microscopy and electrophoresis of red blood cells were used for the diagnosis of malaria
and SCD respectively. In addition, therapeutic regimens of
SCD and malaria presented to the hospital were reviewed.
All procedures were in accordance with the ethical standards
of the responsible committee on human experimentation
(institutional and national) and with the 1975 Declaration of
Helsinki, as revised in 2008. Informed consent was obtained
from all the patients for being included in the study.
Data analysis. Data on sickle cell and malaria were analyzed using chi-square at 0.1% level of significance. However,
data on incidence of sickle cell traits were presented in percentage and their mean hemoglobin values were determined.
Data on weight, packed cell volume, total blood volume, red
cell volume, plasma volume, and hemoglobin were analyzed
using analysis of variance (ANOVA) and the least significant
difference was detected at 5% level.25,26
Table 1. Incidence of sickle cell disease and malaria.
Sex
Sickle Cell Disease
Malaria
Total
Male
96
51
147
Female
101
71
172
Total
197
122
319
Out of 319 recorded cases, there were 113 (57.4%) cases
of anemia due to SCD and 24 (19.7%) caused by malaria. But
84 (42.6%) and 98 (80.3%) neither showed anemia due to
malaria nor sickle cell trait (Table 2).
Table 3 shows the incidence of genotypes of sickle cell
hemoglobin. Out of 197 recorded genotypes, 32 (16.2%)
belonged to the genotype HbA, HbS, whereas 102 (51.8%)
belonged to the HbS HbS, 56 (28.4%) belonged to HbS HbC,
and 7 (3.6%) belonged to Hbs Hbs + F respectively (Table 3).
The observed clinical signs and their frequencies associated with SCD are 89 (45.1%) pain/crisis, 56 (28.4%) pneumonia, 18 (9.1%) gastric disorders, 1 (0.5%) conjunctivitis,
1 (0.5%) acute chest syndrome, 1 (0.5%) cholecystitis, 3 (1.5%)
epistaxis, 5 (2.5%) renal diseases, 4 (2.0%) splenomegaly,
4 (2.0%) priapism, 5 (2.5%) musculoskeletal diseases, 1 (0.5%)
hemophilia, and 1 (0.5%) fever. Pneumonia was caused by Streptococcus pneumonia (Table 4). The observed disorders related to
CNS are ischemic heart disease, hypertension, and sleeplessness.
However, the observed renal diseases are anuria, urinary tract
infection, and polycystitis. But the musculo-skeletal-related
abnormalities observed are avascular necrosis of femur head,
chronic osteomyelitis of right tibia, arthritis, and acute osteomyelitis. But the gastrointestinal disorders observed are gastritis, gastroparesis, and atrophic gastritis.
The bodyweight of sickle cell patients within the age
ranges of 10–14 years, 15–19 years, 20–24 years, 25–29 years,
35–39 years, and 45–49 years were significantly higher
(P , 0.05) than the weight of the patients within the age
Table 2. Incidences of anemia caused by sickle cell and malaria.
Parameters
Sickle Cell Disease
Malaria
Total
Anemia
113
24
108
No anemia
84
98
211
Total
197
122
319
Results
Table 1 presents the epidemiology of SCD presented to the
Haematology Department of Usmanu Danfodiyo University
Teaching Hospital within the study period (2009–2013).
Out of 319 patients presented to the hospital, 197 (61.8%)
were diagnosed with sickle cell trait, comprising 96 (48.7%)
males and 101 (51.3%) females respectively. But a total of 122
(38.2%) patients were diagnosed with malaria. A total of 147
(46.1%) male and 172 (53.9%) females were presented to the
hospital (Table 1).
54
Clinical Medicine Insights: Therapeutics 2016:8
Table 3. Incidence of sickle cell genotypes.
Genotype
Incidence
Percentage
Hemoglobin lg/dL
AS
32
16.2%
8.20 ± 1.81
SS
102
51.8%
5.78 ± 1.32
SC
56
28.4%
7.14 ± 1.48
SS + F
7
3.6%
7.60 ± 1.32
Total
197
100%
–
Sickle cell disease in northwestern Nigeria
35–39 years (0.04 ± 0.00 L) respectively. Plasma volume of the
patients increased from 1.16 ± 0.15 L (10–14 years) to 1.30 ±
0.21 L (5–9 years), 1.93 ± 0.15 L (10–14 years), 2.55 ± 0.12 L
(15–19 years), 2.49 ± 0.65 L (20–24 years), 3.50 ± 0.95 L
(25–29 years), and 4.06 ± 0.00 L (35–39 years), respectively. But
in the age range of 45–49, the plasma volume (1.57 ± 0.00 L)
decreased significantly (P , 0.05). The patients within the age
ranges 0–4 years (6.20 ± 1.61 L), 5–9 years (6.95 ± 0.95 L),
10–14 years (9.97 ± 0.41 years), 25–29 years (6.33 ± 0.33 L),
35–39 years (6.33 ± 0.00 L), and 45–49 years (6.00 ± 0.00 L)
recorded significantly decreased (P , 0.05) hemoglobin as
compared with the patients within the age ranges 10–14 years
(9.97 ± 0.61 L), 15–19 years (13.11 ± 2.67 L), and 20–24 years
(13.15 ± 1.70 L), respectively (Table 5). However, in our study,
there were no recorded cases of patients within the age ranges
30–34 years and 40–44 years.
Table 4. The associated clinical signs of sickle cell disease.
Clinical Signs
No. of Patients
Percentage
Pain/crisis
89
45.1
Pneumonia
56
28.4
Gastric disorders
18
9.1
CNS disorders
8
4.1
Conjunctivitis
1
0.5
Acute chest syndrome
1
0.5
Cholecystitis
1
0.5
Epistaxis
3
1.5
Renal diseases
5
2.5
Splenomegaly
4
2.0
Priapism
4
2.0
Musculo-skeletal
disorders
5
2.5
Hemophilia
1
0.5
Fever
1
0.5
Total
197
100
Discussion
SCD is prevalent in many parts of the world, especially among
Nigerians and Americans of African, Mediterranean, and
Middle East origin. The fact that 61.8% (197) of the patients
were diagnosed with sickle cell trait and 38.2% (122) were
diagnosed with malaria is an indication that 6 in every 10
cases recorded in the hospital are of sickle cell origin. Our
findings disagree with the reports of WHO27 and Hoff brand
et al.28 indicating that West African countries including
Nigeria has the frequency of the trait ranging from 15 to 50%.
In the present study, females (51.3%) are more affected than
males (48.7%). Baum et al.19 reported that there was striking
increase in painful crisis in male patients. But the remaining
38.2% of patients diagnosed of malaria indicates that malaria
constitutes significant problem in the northwestern region
of Nigeria.
The reported cases of anemia caused by SCD and
malaria agree with the report of George and Opara29 indicating that anemia is a sign of malaria and SCD. Polypharmacy
adopted by the hospital that involves the use of anti-sickle
cell (hydroxyurea, allopurinol), antimalarial (paludrine, fansidar, coartem, lonart, artesunate), blood tonic (vitamins, B
complex, C, astymin, folic acid, fesolate), analgesic (ibuprofen,
paracetamol, tramol, DF118, diclofenac), and glucocorticoids
ranges of 0–4 years and 5–9 years. But there was no significant
difference (P . 0.05) in the packed cell volume of all the sickle
patients except for those within the age range 45–49 years,
which was significantly decreased (P , 0.05). But their range
of packed cell volume was between 18.00 ± 0.00% and 21.71 ±
2.62%. However, patients within the age ranges of 15–19
years, 20–24 years, 25–29 years, and 35–39 years recorded
significantly (P , 0.05) increased the total blood volume of
3.15 ± 0.13 L, 3.16 ± 0.64 L, 4.36 ± 0.96 L, and 4.10 ± 0.00 L
when compared to patients within the age ranges of 0–4 years
(1.48 ± 0.38 L), 5–9 years (1.6 ± 0.22 L), and 45–49 years
(1.92 ± 0.00 L) respectively. However, red blood cells volume of patients within the age ranges of 15–19 years (0.60 ±
0.01 L) and 20–24 years (0.67 ± 0.02 L) were significantly
higher than the red cells volumes of the patients within the
age range 0–4 years (0.32 ± 0.02 L), 5–9 years (0.37 ± 0.01),
10–14 years (0.46 ± 0.01), and 45–49 years (0.42 ± 0.00 L),
which were in turn higher than the red cells volumes of the
patients within the age ranges 25–29 years (0.05 ± 0.01 L) and
Table 5. Age, weight, and hematological parameters of sickle cell disease patients.
Parameters
Age and the frequencies of the affected patients
0–4(40)
Weight (kg)
5–9(60)
18.53 ± 4.84 20.8 ± 2.82
10–14(25)
15–19(20)
20–24(17)
25–29(20)
35–39(10)
45–49(5)
29.90 ± 1.24a 39.34 ± 8.02a 39.46 ± 5.09a 54.45 ± 11.95a 51.31 ± 0.00a 24.00 ± 0.00a
Packed cell volume (%) 21.71 ± 2.62 22.01 ± 3.46 19.31 ± 0.96
19.20 ± 1.67
21.25 ± 1.51
19.00 ± 1.00
19.00 ± 0.00
18.00 ± 0.00b
Hemoglobin (g/dL)
6.20 ± 1.61
6.95 ± 0.94
9.97 ± 0.41a
13.11 ± 2.67a
13.15 ± 1.70a
6.33 ± 0.33
6.33 ± 0.00
6.00 ± 0.00
Total blood volume (L)
1.48 ± 0.38
1.67 ± 0.22
2.39 ± 0.10
3.15 ± 0.13
3.16 ± 0.64
4.36 ± 0.96
4.10 ± 0.00
a
1.92 ± 0.00b
Red cells volume (L)
0.32 ± 0.04
0.37 ± 0.01
0.46 ± 0.01a
0.60 ± 0.01a
0.69 ± 0.02a
0.05 ± 0.01b
0.04 ± 0.00b
0.42 ± 0.00a
Plasma volume (L)
1.16 ± 0.14
1.30 ± 0.21
1.93 ± 0.15a
2.55 ± 0.12a
2.49 ± 0.65a
3.50 ± 0.95a
4.06 ± 0.00a
1.57 ± 0.00a
a
a
a
a
Notes: aSignificantly increased (P , 0.05). bSignificantly decreased (P , 0.05).
Clinical Medicine Insights: Therapeutics 2016:8
55
Saganuwan
(hydrocortisone, prednisolone). Surviving malaria is the most
significant selective force affecting the expression of blood
groups. Red cells lacking or having altered forms of blood
group active molecule are commonly found in regions of the
world where malaria is endemic, notably the FY (a-b) phenotype and the s-s-phenotype in Africa.1 So the presence of SS,
SS+F, and SC among the study group is corroborated by the
report of Sergeant30 indicating that SCD is caused by HbSS,
HbSC, and Hb Sathal. The S gene results from the replacement of the normal codon GAG at position a^6 by GTG. As a
result of this change, valine is inserted at this position instead
of glutamic acid usually in that position in an HbA individual.
In the deoxygenated state, the HbS molecule forms polymers,
which progress to the sickle red blood cell.30 But the 16.2%
(32) prevalence rate of heterozygous (HbAS) carrier disagrees
with the report of Munsoor and Alabid20 indicating that the
prevalence rate of heterozygous in Western Sudan is 54%.
But in our study, 51.8% (102) were diagnosed with SCD as
against 4% reported in Western Sudan.20 Although HbAS
can cause sickling symptoms during severe hypoxic states, the
complications are rare.31
The observation of pain/crisis, pneumonia, gastric, CNS,
biliary, renal and musculo-skeletal disorders, acute chest syndrome, priapism, and conjunctivitis agree with the report of
Isosa32 who had earlier attributed all the above-mentioned
signs to SCD. The isolation of Streptococcus pneumonia from
the patients presented to the teaching hospital is corroborated
by the report of Gaston et al.33 indicating that the S. pneumonia could cause an episode of life-threatening sepsis in children suffering from SCD. The ischemic heart disease observed
in our study agreed with the report of Pegelow et al.34 and
Vichinsky et al.35 indicating that SCD can cause acute ischemic
stroke in the affected adults. The acute chest syndrome (ACS)
with fever observed in our study is corroborated in the report
of Castro et al.36 indicating that ACS characterized by fever
and respiratory symptoms can be observed in SCD patients.
A major risk factor for the development of ACS is the hemoglobin genotype.36 ACS is the second most common cause of
hospitalization in sickle cell patients.37 But in our study, pain/
crisis is the most common cause of hospitalization, followed
by pneumonia, gastric disorders, renal diseases, and musculoskeletal disorders.
Sickle hemoglobinopathy can cause visual loss in 0.5%
of the affected patients. NIH38 had earlier reported that SCD
can cause conjunctivitis, which usually results in permanent,
devastating loss of vision.32 However, Cholecystitis observed
in 0.5% of the sickle cell patients agrees with the report of
Jawad et al.39 indicating that cholecystitis is one of the key
signs of SCD. Anuria, urinary tract infections, and polycystitis all observed in 2.5% of the sickle cell patients agree with
the report of Isosa, 32 and John et al.40 indicating that urinary
tract disorders are characteristic signs of SCD.
The median survival period for patients with sickle cell
anemia in the present study is 49 years and the average weight
56
Clinical Medicine Insights: Therapeutics 2016:8
(24.00 ± 0.00 kg), PVC (18.00 ± 0.00%), Hb (6.00 ± 0.00 g/dL),
TBV (1.92 ± 0.00 L), RCV (0.42 ± 0.00 L), and PV (1.57 ±
0.00 L) disagree with the report of WHO27 indicating that
there are no firm data on the median survival period of sickle
cell patients from the African continent. In the United States,
median survival was estimated in 1994 to be 42 years for men
and 48 years for women. In Jamaica, median survival was 52
years for men and 58.5 years for women.27 In the present study,
anemia of the affected SCD patients significantly increased
from the age range 0–4 years passing through 5–9 years, 25–29
years to 35–39 years with low amount of hemoglobin, total
blood volume, red cell volume, and plasma volume. This may
be an indication that much of the erythrocytes have been lysed.
Baum et al.19 had earlier reported that patients between the ages
of 15 and 25 years experience a striking increase in painful crisis
with hemoglobin levels above 8.5 g/dL. High hemoglobin levels
appear to be an important risk factor for painful crisis. The incidence of painful crisis was observed among the patients within
the age group of 10–24 years with hemoglobin range 9.97 ± 0.41
to 13.15 ± 1.70 g/dL. For those patients in this age group, there
was progressive anemia. Juwah et al.2 had reported a gradual but
progressive decline in the incidence of severe anemia in the age
range 8–16 years. Management of pain associated with SCD
consists of the use of non-steroidal anti-inflammatory drugs
(NSAIDs), opioids, and adjuvant medications.41 A sustained
release opioid preparation provides more consistent analgesia38
and by so doing facilitate rest.32 The significantly increased total
blood volume, red cells volume, and plasma volume of 15–39
years may be due to increased administration of blood tonic,
allopurinol, and hydroxyurea. Frenette and Atweh42 had earlier
reported that hydroxyurea can induce HbF production in SCD.
Hydroxyurea is an S phase-specific chemotherapeutic agent that
caused a marked increase in Hb F levels in baboons,43 decrease
in the frequency of painful crisis, acute chest syndrome, reduction in transfusion requirements, and hospitalization in adults
with moderate to severe SCD44 invariably causing improved
survival rate.45 Hydroxyurea reduces circulating white blood
cell count and perhaps also the number of adherent leukocytes
recruited to the wall of small venules, which was correlated with
the clinical hydroxyurea.46–48
Conclusion
The prevalence rate of SCD in the northwestern Nigeria is
61.8%. The affected individuals showed significant loss of
body weight, blood, and sickle cell pain/crisis and can survive
up to the age of 49 years. The use of anti-sickling, hematonic,
analgesic, anti-inflammatory, and antimalarial drugs in the
treatment of the affected patients might have improved the
quality of life of the affected individuals.
Acknowledgments
I sincerely thank Dr. Alhaji Muhammad Ndakotsu, Head of
the Department of Pathology, College of Health Sciences,
Usmanu Danfodiyo University, Sokoto for attending to the
Sickle cell disease in northwestern Nigeria
patients and allowing me to collect the data from the Department. He also provided an enabling environment during the
period of data collection.
I also thank the entire management and technologists in
the Departments of Haematology, Microbiology, Radiology,
Medicine and Ophthalmology, Usmanu Danfodiyo University, Sokoto Teaching Hospital, for their contributions in various capacities. The contribution of Kehinde Ola Emmanuel
(who typed the work), National Open University, Nigeria, is
highly appreciable.
Author Contributions
SAS generated and interpreted the data and wrote the
manuscript. The author reviewed and approved of the
final manuscript.
References
1. Anstee DJ. The relationship between blood groups and disease. Blood. 2010;
115(23):4635–463.
2. Juwah AI, Nlemadim A, Kaine W. Clinical presentation of severe anaemia
in paediatric patients with sickle cell anaemia seen in Enugu, Nigeria. Am J
Haematol. 2003;72:185–91.
3. Platt O, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. N Engl J
Med. 1994;330:1639–44.
4. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:
1021–30.
5. Anie KA, Egunjobi FE, Akinyanju OO. Psychosocial impact of sickle cell disorder: perspective from Nigeria setting. Global Health. 2010;6:2. doi: 10.1186/1744-8603-6-2.
6. Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global
health problem. Bull World Health Org. 2001;79(8):704–12.
7. Akodu SO, Draku-Akinwumi IN, Nokanma OF. Age at diagnosis of sickle cell
anaemia in Lagos, Nigeria. Mediterr J Hematol Infect Dis. 2013;5(1):e2013001.
8. Odunvbun ME, Okolo AA, Rahimy CM. Newborn screening for sickle cell disease in a Nigerian hospital. Public Health. 2008;122:1111–6.
9. Barden EM, Kawchak DA, Ohene-Frempong K, Stallings VA, Zemel BS. Body
composition in children with sickle cell disease. Am J Clin Nutr. 2002;76:218–25.
10. Chukwu B, Okafor HU, Ikefuna AN. Asymptomatic bacteriaria in children
with sickle cell anaemia at the University of Nigeria teaching hospital, Enugu,
South East, Nigeria. Ital J Paediatr. 2011;37:45.
11. Konote-Ahulu FID. Sickle Cell Disease Patients. Tetteh A’Documeno Company;
Watford. 1996:3776–7.
12. Scheinman I, Saborio P. Sickle cell nephropathy. J Am Soc Nephrol. 1999;10:187–92.
13. Leveziel N, Lalloum F, Bastuji-Garin S, et al. Sickle cell retinopathy: restrospective study of 730 patients followed in a referral centre. J Fr Ophthalmol.
2012;35(5):343–7.
14. Williams TN, Uyoga S, Macharia A, et al. Bacteraemia in Kenyan children
with sickle cell anaemia: a retrospective cohort and case-control study. Lancet.
2009;174(9698):1364–70.
15. Chase AR, Sohat M, Howard J, et al. Pregnancy outcomes in sickle cell disease:
a retrospective cohort study from two tertiary centers in the UK. Obstet Med.
2010;3(3):110–2.
16. George OI, Opara PI. Sickle cell anemia:a survey of associated morbidities in
Nigerian children. Afr J Haematol. 2011;2(2):187–190.013.
17. Brabin BJ, Premji Z, Verhoeff F. Analysis of anaemia and childhood mortality.
J Nutr. 2001;131:636–45.
18. Madu KA, Ubesie AC, Madu AJ, Duru AN. Pattern and risk factors for musculoskeletal complications of sickle cell anemia in South-eastern Nigeria.:a retrospective study. Int J Trop Dis Healt. 2013;3(3):175–183.
19. Baum KF, Dunn DT, Maude GH, Serjeant GR. The painful crisis of homogygous
sickle cell disease, a study of risk factors. J Am Med Assoc. 1987;147(7):1231–4.
20. Munsoor MM, Alabid A. SCT among relatives of sickle cell patients in Western
Sudan. Can J Med. 2011;2(2):20–5.
21. Grewal G. Catalysing drug discovery innovation at NCATs: Developing a disease modifying treatment for SCD. Abstracts. Drug Discovery and Therapy
World Congress. 3rd–6th June, Boston. 2013, 68.
22. Saganuwan SA, Onyeyili PA. Haematonic and plasma expander effects of
aqueous leaf extract of Abrus precatorius in Mus musculus. Comp Clin Pathol.
2012;21:1249–55.
23. Ganong FW. Review of Medical Physiology. 21st ed. New York: McGraw-Hill;
2003:912.
24. Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia:
Saunders; 2007:1116.
25. Kirkwood BR, Sterne JAC. Essential Medical Statistics. 2nd ed. Massachusetts,
USA: Blackwell Science Inc; 2005:501.
26. Zar JH. Bio-Statistical Analysis. New Delhi: Pearson Education; 2008:536.
27. WHO. Sickle cell anaemia. Report by the Secretariat. Fifty-ninth World Health
Assembly. 2006. Provisional Agenda Item U.4, A59/9, Geneva. 1–5.
28. Hoff brand AW, Moss PAH, Pettit JE. Essential Haematology. 5th ed. Victoria,
Australia: Blackwell Publishing Ltd; 2006:24–6.
29. George IC, Opara PI. Sickle cell anaemia: a survey of associated morbidities in
Nigerian children. Haematol Oncol. 2011;2(2):187–90.
30. Sergeant GR. Historical review. The emerging of sickle cell disease. Br J Haematol.
2001;112:3–18.
31. Akinyanju O. Control of sickle cell disorder in Africa. Niger J Clin Biomed Res.
2006;1(1):24–30.
32. Isosa EM. Current trends in the management of sickle cell disease: an overview.
J Basic Clin Reprod Sci. 2012;1(1):50–60.
33. Gaston MH, Verter JI, Wood G, et al. Prophylaxis with oral penicillin in children
with sickle cell anaemia. A randomized trial. N Engl J Med. 1986;314:1593–9.
34. Pegelow CH, Adams RJ, Mckie V, et al. Risk of recurrent stroke in patients
with sickle cell disease treated with erythrocytes transfusions. J Paediatr.
1995;126:896–9.
35. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes of outcomes of the acute
chest syndrome in sickle cell disease. N Engl J Med. 2000;342:1855–65.
36. Castro O, Brambilla DJ, Thorington B, et al. The acute chest syndrome in sickle
cell disease; incidence and risk factors. Blood. 1994;84:643–9.
37. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison of conservative
and aggressive transfusion regimens in the perioperative management of sickle
cell disease. N Engl J Med. 1995;333:206–13.
38. NIH. Publication No. 02 – 2117. 4th ed. National Institutes of Health, National
Heart, Lung and Blood Institute; New York. 2002.
39. Jawad AJ, Kurban K, El-Bakry A, Al-Rabeeah A, Seraj M, Ammar A. Laparoscopic cholecystectomy for cholelithiasis during infancy: cost analysis and review
of current indications. World J Surg. 1998;22:69–73.
40. John EG, Schade SG, Spigos DG, et al. Effectiveness of triglycyl vasopressin in
persistent haematuria associated with sickle cell haemoglobin. Arch Intern Med.
1980;140:1589–93.
41. Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice
Guideline. Rockville, MD: Agency for Health Care Policy and Research, Public
Health Science, US Department of Health and Human Services; 1994. AHCPR
Pub. No. 94–0592.
42. Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts and
future promising. J Clin Invest. 2007;117(4):850–8.
43. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions
in children with sickle cell anemia and abnormal results on transcranial Doppler
ultrasonography. N Engl J Med. 1998;339:5–11.
44. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the multicellular
study of hydroxyurea in sickle cell anemia. N Engl J Med. 1995;332:1317–22.
45. Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and
morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment.
JAMA. 2003;289:1645–51.
46. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia.
Clinical utility of myclosuppressive “switching agent”. The multicellular study of
hydroxyurea in sickle cell anemia. Medicine (Baltimore). 1996;75:300–26.
47. Krukemerer MG, Wagner W. Cancer and nanotechnology. Abstracts Drug Discovery and Therapy World Congress. 3rd–6th June, Boston. 2013.
48. WMA. WMA Declaration of Helsinki-Ethical Principles for Medical Research
Involving Human Subjects, Adopted by the 18th WMA General Assembly,
Helsinki, Finland, 1984.
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