Sickle Cell Anemia; 3 Years Clinical Experience in Bisha, Saudi Arabia (2010-2013)

Objective Three-year clinical experience of patients diagnosed with Sickle cell disease in Bisha, South Western region of Saudi Arabia is analyzed. Methodology A retrospective analysis was done on data recruited from 2011 to 2013 of all the patients presented with sickle cell anemia. The demographic data, clinical presentation, course of disease, complications and chronic conditions were collected. The descriptive percentage of data with years of presentation and its incidence rate per 100 person-years were also taken with the cause mortality. Results Total 386 patients were analyzed, among them 45.2% were females and 54.8% were males. According to our study, the sickle cell crises included as acute chest syndrome (26%), pulmonary hypertension (21%), Splenomegaly (7%), septicemia (11%), acute Vaso-occlusive crisis (10%), and other sickle cell crisis (2-10%) of patients. It was also found that about 48% of patients suffered from 1 or more irreversible organ damage. The survival rate of male and female are not significant, however total 82 patients died of sickle cell anemia. Conclusions Sickle cell disease represents high mortality in Saudi Arabia, comprising distinctive diseases characteristic in different regions. The qualitative and quantitative study of genetic and environmental factors in relation to disease complications need to be done.


Introduction
Sickle Cell Anemia is a single gene hemoglobinopathy, which represent the abnormal production of hemoglobin S. This autosomal recessive disorder has a high occurrence among all other hemoglobinopathies 1 . The genetic carriers of Sickle Cell Anemia comprise about 3% of the total world's population, as mentioned by the World Health Organization 2 . The Sickle Cell Anemia affected about 100, 000 people of the United States, among them 2 million are carrier 3 however, embarked decline in the mortality 4 and the mean age of death in male is 53 years and in female about 58 years 5 . In Pakistan, 0.5-1% of populationis carriers of Hemoglobin S 6 , whereas about 5.1% of prevalence found in Karachi 7 . The prevalence of Sickle cell disease is 1.4% in some regions of Saudi Arabia 8 . The high regional prevalence of Sickle Anemia led to the commencement of national and regional sickle cell screening programs in newborn and married couples 9 .
In this study, the findings from three years' clinical experience of patients with sickle cell disease in Bisha, Saudi Arabia are evaluated. Moreover, the overview of the mortality and morbidity is also analysed along with the reversible and irreversible life threatening complications.

Ethical Consideration
The study was approved by the ethical committee of respective institutions. Written consent was taken from all the recipients. The personnel of the recipients were made hidden to secure confidentiality.

Results
The total population size of our study was 386 sickle cell disease patients, among them 45.2% were females and 54.8% were males, whereas, 6.20% were of less than 11 years of age, 16.16% were less than 15 years of age, 50.30% were about15-20 years, and 27.24% were between 20-24 years. However, 39% of the patients inducted into the study during 2011, and 26%, and 17% entered during the 2012 to 2013, respectively (Table 1). It is also noted that the rate of hospitalization is increased with the presentation of acute sickle crisis during the year 2012 and 2013, in relation with the age group, having 77% hospitalization rate.
According to our analysis, the hospitalization rate is associated with the associated primary complications such as 26% of acute chest syndrome, 21% of pulmonary hypertension, 11% Bacterial infection and 7% of splenomegaly with acute splenic sequestrations. However, hypersplenism was noted more in young children of age group less than 11 years of age. Acute Vaso-occlusive crisis was noted in 10% of cases. Other sickle cell crisis like Aplastic crisis, Bone infarction, Neurologic disorder, Dactylitis and Priapism were reported in 2-10% of patients ( Table 2).
The irreversible organ damage in sickle cell anemia was presented in patient having 24.21% of gall bladder disease, 22.19% of avascular necrosis, 16.22% of chronic lung diseases, 0.9% of leg ulcers, 6.30% of priapism, 7.6% of renal failure, 10.59%cerebrovascular diseases, and 5.7% of retinopathy. Moreover, it was also found that about 48% of patients suffered from 1 or more of these diseases due to sickle cell anemia. Chronic conditions which are not related to sickle cell disease are found to occur in 3% of patients (

Discussion
Sickle cell anemia is coupled with high mortality due to acute sickle crisis and irreversible organ damage. However, since the implementation of the Saudi Premarital Screening and Genetic Counseling (PMS&GC) in 2004, the mortality is significantly reduced 9 . In South Western Region of Saudi Arabia, the prevalence of SCD is reported as about 28.5%. The present retrospective three-year observational study was done to analyze the mortality and morbidity of Sickle Cell Disease in Bisha, Saudi Arabia. Among the 386 recruitment of SCD as outpatient or admission to hospital, 82 patients died. There was no significant difference in mortality of male and female, having the mean age of 23 for female and 24 for males. The mortality ratio is significantly high as compared to other regions of Saudi Arabia and other part of world 10 . Whereas, the mean age is of survival is low as compare to United States and Africa, where the mean age reaches to 30 years or older 11,12 . The main culprit of death in the Bisha region was acute sickle crisis with or without irreversible organ damage.
Acute chest syndrome is responsible for high mortality and reported as the major complication of death. It is noted that the frequency of hospitalization with acute chest syndrome is higher as compared to Eastern region of Saudi Arab 13 . Moreover, the increase mortality due to acute chest syndrome is higher in younger age groups 14 , as found in our study. The prior complain of asthma was also noted in young children that depicts the finding of previous studies 15 . Moreover, the increase leukocyte counts found in our patients represented the proinflammatory cause of acute chest syndrome as seen in most of the patients 16 .
Pulmonary hypertension is another common consequence of sickle cell anemia as per study. The main cause of death in SCD is pulmonary hypertension, comprising 11.2% prevalence in United States and United There was comparatively low incidence of leg ulcers and priapism in Bisha region similar to prior findings 21 . Priapism is under reporting complication, rather knowing that it might worsen the disease 22 . However, the low incidence of leg ulcers represented the distinction of genotype and environmental factors 23 .

Conclusion
The complications and severity of Sickle cell disease vary with the genotype and environmental factors. Our study is limited by not evaluating genotype of Sickle cell disease and limited age group majority was greater than 15 years old. This qualitative and quantitative measure would embark the significance of large study comparing both genotype and environmental factors with disease presentation.