INTRODUCTION:

Sickle cell anemia (SCA)is an inherited disease that is characterized by several clinical symptoms and signs especially hemolytic anemia [1,2]. It also causes several complications like pain crises, Leg ulcer, bone and joint complications, etc. This genetic disorder leads to production of abnormal hemoglobin called hemoglobin S (HbS). It results from mutation on chromosome 11 in position 6 of normal beta glob in [1,3,4], thus replacing glutamic acid with valine. In normal adult people, the hemoglobin types include 96-98% HbA, up to 3-5% HbA2 and less than 1% HbF (fetal hemoglobin), while patients with sickle cell anemia who have two copies of the altered gene (homozygous)produce 80-90% hemoglobin S with no normal hemoglobin A [1,4]. The production of HbS represents the pathogenesis of sickle cell anemia. Fetal hemoglobin (HbF) reduces HbS concentration by inhibition deoxygenation induced polymerization of HbS [5,6].

As a result, high levels of HbF are clinically useful in reducing the severity of the disease and protecting against various complications [4,7,8]. So far, there is no study conducted in Syria to evaluate fetal hemoglobin levels in sickle cell patients. The aim of this study was to evaluate fetal hemoglobin levels in patients with sickle cell anemia, and their effect on complications of the disease at Obstetrics and Pediatric Hospital in Lattakia, Syria.

MATERIALS AND METHODS:

The retrospective descriptive study was conducted at Obstetrics and Pediatrics Hospital in Lattakia, Syria in the period between 2017-2018. The hematological, clinical and personal data were collected from patients’ files, so no need for written informed consent. The ethics and research committee of this hospital approved the principle of the study. The obtained data remained confidential. This investigation included 175 sickle cell patients (SS) admitted to Thalassemia and Sickle Center at the hospital, about 3 ml intravenous blood samples were taken in EDTA containing tubes. The high-pressure liquid chromatography HPLC_G8 (Japan) was utilized to determine the hemoglobin profile. Other information like age, gender and the presence of complications were also recorded. We recorded the results as percentage, mean ± SD and calculated the differences using T student test.

RESULTS:

The present study included 175 patients with sickle cell anemia, dating from January 2017 to December 2018. The main objective is to evaluate the fetal hemoglobin (HbF) levels in SCA patients who were admitted to the hospital. Of the 175 patients enrolled in the study, 99 (56.57%) were males and 76(43.4%) were females. Their age ranged from two to 59 years with mean (17±12.50) years. The mean level of HbF in patients with SCA was 24.79 ± 18.8%. The patients were divided into five age groups and HbF levels were recorded in three groups (normal levels<2%, low levels (2-10%) and high levels >10%). As regards to the relationship of HbF levels with SCD complications, there was no statistically significant association with all complication except pain crisis (p= 0.000).

Table (1): shows the distribution of the SCA patients according to age, gender, and their HbF levels.

	SCD Patients		HbF levels
Age	*(N)*	*(%)*	*Mean*	*±SD %*
<10	53	30.28	27.22	±18.60
10_20	71	40.57	24.87	±17.80
20_30	24	13.71	20.84	±15.75
30_40	14	8	25.06	±27.65
>40	13	7.42	20.93	±21.04
Gender	*(N)*	*(%)*	*mean*	*±SD %*
Male	99	56.57	26.71	±19.32
Female	76	43.42	22.2	±18.09
Total	175	100

Table (2): shows the SCD patients’ distribution according the HbF levels groups.

SCD Patients
HbF levels	(N)	%
<2%	16	9.14
2-10%	33	18.8
>10%	126	72
Total	175	100

Table (3): Shows HbF levels among SCD patients with various complications.

SCD Complications	N (%)	HbF levels mean ±SD	P value
Pain crises	29(16.5)	11.26±12.24	0.000
Acute chest syndrome	18(10.2)	20.37±14.32	0.3
Leg ulcer	4(2.28)	17.62±16.36	0.446
Infection	6(3.42)	28.76±24.14	0.693
Splenic sequestration	1(0.57)	23.9	0.964
Bone and joint complication	27(15.4)	30.42±24.8	0.09

DISCUSSION:

Sickle cell disease (SCD) is one of the most common hereditary diseases worldwide [9]. Several studies have been concerned with HbF level among sickle cell patients and its effect on complications [10]. Despite the high prevalence of sickle cell anemia in Syria, there is no information about HbF levels among SCD patients.

The percentage of SCD patients belonging to the group of high levels of HbF was 72%, this was higher than the levels in studies conducted in Uganda [9], Nigeria [11] and Senegal [12] (37%, 17%, 25%, respectively). The mean level of HbF in patients with SCA in the present study is 24.79±18.8%. Itis considered a high result compared with the results of another studies conducted by TshildoL et al in Congo [13], IsahIZ et al in Sokoto [14], and El-Hazmi MAF in Saudi Arabia [15]. (7.2 ±5%, 2.99±5.16%, 9.1% respectively), and similar to the results by Mahajan A R et al in Indian SCD patients (22.5±1.16%) [4]. Several suggested causes may lead to these contradictory results, including age differences of patients, differences in haplotypes of the beta globin [16] and differences in hemoglobin separation methods. Therefore, we utilizedHPLC method to separate and identifyHbF levels in the present study, which considered more sensitive than other methods.

The HbF levels in SCD males were recorded higher compared to females (26.78%±19.52% in males to 18.09%±22.20 in females). This result corresponds with the results of Nigerian studies [17,18], and contradict with the results of Zade V S et al [8] and Olaniyi J.A et al [19]. These differences may be due to the effect of hormonal variations between females and males.About the HbF levels among different age groups, the highest value was recorded in the age group of <10 years (27.22 ±18.6%) followed by the age group (30-40) years (25.06 ±27.65%)and the lowest one was in the age group (20-30) years (20.89± 15.75%). Different findings were recorded according to different geographic regions like the study conducted byMahajan A R et al [4] that reported the highest value was in the age group 11-20 years whereas the study conducted by Olaniyi J. Aet al [19] showed the highest value was in the age group 20-30 years. Overall, mean fetal hemoglobin levels decrease with increasing age.

As shown in most previous study, the level of HBF affects on the severity of SCA i.e. patients with SCA have fewer complications when the levels of HBF are high (20,21).In current study the relationship between HbF levels and the incidence complications including pain crises , acute chest syndrome, infections, leg ulcers, splenic sequestration and bone and joint complication was investigated, but no statistically significant relationship was recorded between them and HbF levels expect for pain crises (P value≈0.000, 0.3,0.693, 0.446, 0.964, 0.09) respectively. Theprevalence of the complications was (16.5%, 10.2%, 3.42%, 2.28%, 0.57%, 15.4%) respectively. Unlike the study performed on Nigerian SCD patients by SaganwanASet al, they recorded the prevalence of pain crisis, acute chest syndrome and Musculo-skeletal disorders was (45.1%, 0.5%, 2.5%) respectively [22], and (43.93%, 36.99%) forpain crisis and Joint Pain respectively in the study of Shah V et al [23], the mean level of HbF is 16.78 ±8.60% (23). Moreover, in the study performed to evaluate the HbF levels effect on avascular necrosis of the femoral head by Hhawker H et al [24], a statistically significant correlation wasreported.

CONCLUSION:

The conclusion of this study shows that HbF levels was high, HPLC was used to separate and identify hemoglobin in all patients, sickle cell disease is a common disease and the factors causing its complications in some patients and not in others are still unclear. Therefore, we recommendcarrying out more specialized studies.

ACKNOWLEDGEMENT:

We are grateful to DR. Wafaa Ahmad, Head of Thalassemia and Sickle Center at Obstetrics and Pediatrics Hospital for her support and encouragement. We also would like to thank all staff in Central Laboratory for helping us to conduct this study.

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Received on 30.08.2019 Modified on 08.10.2019

Research J. Pharm. and Tech. 2020; 13(7): 3246-3248.

DOI: 10.5958/0974-360X.2020.00575.2