INTRODUCTION:

Sickle cell anemia is an inherited genetic disorder caused by a mutation on chromosome 11 and thus replacing glutamic acid with valin in the sixth position of the β globin chain^1,2.The homozygous SS is the commonest phenotype³.This disease is characterized by chronic hemolytic anemia caused by destruction of the sickle-shaped red blood cells⁴, as a result of this chronic hemolysis, the bilirubin production is continuous²,that leads to cholelithiasis and growth of bilirubincrystals, thus form gallstones^5,6,7. About 15% of SCD children are younger than 10 years⁸. The prevalence of gallstones has varied according to geographic regions around the world ⁶. For instance, high rate on USA (22–34%), on the contrary 8 % in Saudi Arabia⁶. There is no information available on the prevalence of gallstones in patients with sickle cell disease in Lattakia, Syria. Therefore, the main objective of this study is to determine the prevalence of gallstones in SCD patients admitted to Obstetrics and Pediatrics Hospital in Lattakia, Syria.

MATERIAL AND METHODS:

The study design:

A retrospective descriptive study was conducted in Thalassemia and Sickle Center at Obstetrics and Pediatrics Hospital in Lattakia, Syria over the period of two years from January 2017 to December 2018. Ethical committee of the hospital approved the general protocol of this study. All data were collected from patients’ files, so no need for written informed consent. Patients’ data remained confidential.

Patients and methodology:

This investigate included 175 homozygous sickle cell disease admitted to the center at Obstetrics and Pediatrics Hospital. The blood samples were taken into EDTA tubes. The diagnosis of SCD and hemoglobin profile were performed utilizing HPLC–68 (Japan). Other information including, age (we divided the patients into five age groups: <10 years, 10-20 years, 20-30 years, 30-40 years and > 40 years) and gender (male, female) were collected. Total bilirubin was analysis by spectrophotometer (Total and direct bilirubin kit, BioSystems©, Spain) (Up to 2.0mg/dL was considered as a reference value). Diagnosis of gallstones was performed by abdominal ultrasound. Data are represented as percentage for categorical variables and as mean ±SD for continuous ones, the differences were calculated by T student test.

RESULTS:

A total number of 175 SCD patients included in this study. Ninety-nine patients were males, while seventy-six were females. The age range of the SCD patients was (2–59) years and the mean age 17±12.5 years. Gallstones were seen in 24 SCD patients (13.7%) and the prevalence of gallstones was equal among males and females, with male: female ratio of (1:1).

Table (1): shows the distribution of total 175 SCD patients according to age, gender.

%	n	Age group (years)
30.28	53	<10
40.57	71	10 – 20
13.71	24	20 – 30
8	14	30 – 40
7.42	13	>40
		Gender
56.57	99	Male
43.42	76	Female

Table (2): Shows the distribution of SCD patients according to the presence of gallstones.

The mean age ±SD (Years)	%	n
27 ± 15.4	13.7	24	Patients with gallstones
15 ± 11.3	86.3	151	Patients without gallstones
17 ± 12.5	100	175	Total

Table (3): Shows the prevalence of gallstones according to age, gender.

%	n	Age group (years)
12.5	3	<10
20.8	5	10 – 20
29.1	7	20 – 30
16.5	4	30 – 40
20.8	5	>40
		Gender
50	12	Male
50	12	Female

Table (4): Shows the HbF levels, Total bilirubin in patients with and without gallstones.

Patients without gallstones	Patients with Gallstones		Variable
P value Mean ± SD%	P value Mean ± SD%
24.65 ± 18.9	0.658	26.08 ± 18.7	0.663	HbF levels (%)
2.7 ± 2.5	4.1 ± 2.5		Total bilirubin (mg/dl)

DISCUSSION:

Gallstones is an important complication of sickle cell disease^4,8. The prevalence of gallstones in SCD patients varies according to different geographic regions, races over the world^6,9. The variation also depends on the age of the patients and HbF levels^10.The result of this investigation shows that the prevalence of gallstones in SCD was 24/175 (13.7%). This result is similar to that reported in previous studies, such as study conducted by AL–Salem AH et al in Saudi Arabia (1992) (19.3 %)¹⁰and Karayalein et al (1984) (17%)¹¹. Contrarily, high frequency of SCD patients with gallstones was reported in the study conducted by Gumiero APS et al in (2008) found that the prevalence of gallstones was 45% in Brazilian SCD patients⁵and 52.7% in another study conducted by Walker TM et al in Jamaica (2000)¹². On the other hand, the results of the study accomplished by Nzeh DA et al (1989) shows low percentage of SCD patients with gallstones (4.2%)¹³. This contradictory results may be due to the differences in age range included in various studies. The mean age of SCD patients with gallstones in this study is 27 years (range: 3–59 years). The highest prevalence of gallstones was in age group 20–30 years (29.1%). This is consistent with the study conducted by Billa RF et al (1991) in Cameroon (38.1%)¹⁴and Martins RA et al (2017) in Brazil (35.48%)². Contrary to the findings of AL–Salem AH et al in Saudian SCD patients (1992)¹⁰ and Bond LR et al in the UK (1987)¹⁵which showed that the highest prevalence of gallstones was in the age group 30–40 years (44.4%) and more than 30 years (83%) respectively. Overall, the prevalence of gallstones increases with age^5,9. Regarding the distribution of prevalence according to the gender of patients, an equal radio was recorded between males and females (1:1), this is similar to the result recorded by Qhalib HA et al in Yemen (2014)¹⁶. Most studies have reported male preponderance over females in cases of gallstones in SCD patients; M:F radio was 4:1 in Nigeria³, 7:1 in India⁶ 1.5:1 in Sudan⁹, 12:1 in Ghana¹⁷ and 1.7:1 in Jamaica¹⁸. Few studies have reported more prevalence of gallstones in females than males (64% in females, 61.5% in females) in Bahrain¹, Cameron¹⁴ respectively.

High serum bilirubin levels were seen in SCD patients with gallstones compared with those without gallstones. Similarly to AL–Salem AH et al(1992)¹⁰, Abdulla etal (2017)^1,TripathyD et al (1997)⁶ and Saied DA et al (2017)⁴.The levels of hemoglobin F (HbF) was higher in SCD patients with gallstones than ones without gallstones, there is no statistically significant relation between HbF levels and gallstones (p=0.663), in contrast to the results recorded by Tripathy D et al ⁶and Webb DKH et al¹⁸; They noted that low levels of fetal hemoglobin are associated with a higher rate of hemolysis.Therefore, a higher rate of gallstones.

CONCLUSION:

Gallstones are important and common complication among sickle cell patients. The prevalence increases with age. Routine abdominal ultrasound examination should be applied to all sickle cell patients for early detection, in addition to hematological analysis like Hb, HbS, HbF, total bilirubin. Additional studies are recommended to investigate the role of other hemolytic disorders in formation of gallstones.

ACKNOWLEDGEMENTS:

We would like to thank all staff at Thalassemia and Sickle Center and the Central Laboratory at Obstetrics and Pediatrics Hospital for their assistance in conducting this study.

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Received on 30.08.2019 Modified on 08.10.2019

Research J. Pharm. and Tech. 2020; 13(8):3615-3617.

DOI: 10.5958/0974-360X.2020.00639.3