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ORIGINAL ARTICLE
Year : 2007  |  Volume : 2  |  Issue : 4  |  Page : 158-162
Sickle cell disease patients in eastern province of Saudi Arabia suffer less severe acute chest syndrome than patients with African haplotypes


Hereditary Blood Diseases Center, King Fahad Hospital, Hofuf, Saudi Arabia

Date of Submission06-Apr-2007
Date of Acceptance19-Sep-2007

Correspondence Address:
M K Alabdulaali
Kingdom of Saudia Arabia- Al-Hassa Hereditary Blood Diseases Center, King Fahad Hofuf Hospital, P.O. Box: (1) - Postal Code: (31982) Al-Hassa
Saudi Arabia
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DOI: 10.4103/1817-1737.36550

PMID: 19727367

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   Abstract 

Background and Objectives : Genetic studies suggest that the sickle cell mutation has arisen on at least four separate occasions in Africa and as a fifth independent mutation in the Eastern Province of Saudi Arabia or India. The pathophysiology of sickle cell disease (SCD) is essentially similar in these different areas although the frequency and severity of complications may vary between areas. The aim of this study was to evaluate the prevalence and outcome of acute chest syndrome (ACS) in SCD patients from Eastern province of Saudi Arabia in comparison with patients with African haplotypes.
Materials and Methods : This was a retrospective study involving 317 SCD patients who were two years or older, admitted to King Fahad Hospital Hofuf between January-May 2003 for different etiologies. Twenty six patients presented with different causes of ACS; 11 patients presented with different pathologies other than ACS, but had past history of ACS; 280 patients presented with different pathologies and never presented with ACS. Clinical features, CBC, Hb-electrophoresis, G6PD activity, cultures, chest X-ray, arterial oxygen saturation, blood transfusion rates and outcome were studied. Univariate and multiple regression analysis were carried out to evaluate influence on ACS. Comparison between SCD patients with ACS from this study and from Eastern province of Saudi Arabia to patients with African haplotypes were carried out, using data reported in the literature.
Results : During the period of this study, 37 patients with new or previous episodes of ACS were studied (accounting for 11.67% of admitted SCD patients). Most of the patients with ACS had only one episode, but five patients (13.51%) had had episodes or more. One patient died giving an in-hospital mortality rate of 1/26 (3.85%). Comparison of recurrence of ACS and mortality between SCD patients in Eastern province of Saudi Arabia to that of patients with African haplotype showed that recurrence is significantly lower ( P <0.025) in patients from Eastern province compared to patients with African haplotype, mortality also is lower but not statistically significant.
Conclusion : Acute chest syndrome in SCD patients in Eastern province of Saudi Arabia is relatively uncommon, but causes significant morbidity and mortality. Its prevalence and recurrence is low if compared to that of patients with African haplotypes.


Keywords: Acute chest syndrome, sickle cell disease


How to cite this article:
Alabdulaali M K. Sickle cell disease patients in eastern province of Saudi Arabia suffer less severe acute chest syndrome than patients with African haplotypes. Ann Thorac Med 2007;2:158-62

How to cite this URL:
Alabdulaali M K. Sickle cell disease patients in eastern province of Saudi Arabia suffer less severe acute chest syndrome than patients with African haplotypes. Ann Thorac Med [serial online] 2007 [cited 2019 Dec 9];2:158-62. Available from: http://www.thoracicmedicine.org/text.asp?2007/2/4/158/36550



   Introduction Top


Sickle cell disease (SCD) is an autosomal inherited structural disorder of hemoglobin, associated with an amino acid substitution of valine for glutamic acid at the sixth residue of the β-chain. This genetic alteration yields an unstable RBC with a shortened survival that under stress (e.g. deoxygenation) becomes sickle-shaped. The major consequence of this sickle shape is that RBCs become much less deformable; therefore, they obstruct the microcirculation. Tissue hypoxia, which promotes further sickling, results. The clinical manifestations of SCD are diverse and any organ system may be affected. These manifestations commonly are divided into vaso occlusive, hematologic and infectious crises. Evidence from structural studies of DNA suggest that the sickle cell mutation has arisen on at least four separate occasions in Africa and as a fifth independent mutation in the Eastern Province of Saudi Arabia or India. [1],[2],[3] Currently five haplotypes are known: Senegal haplotype, Benin haplotype, Bantu haplotype, Cameroon haplotype and Asian (Arab-India) haplotype from Eastern Province of Saudi Arabia and Central India.

The pathophysiology of SCD is essentially similar in these different areas although the frequency and severity of complications may vary between areas. [4],[5]

Acute chest syndrome (ACS) is an acute pulmonary pathology that occurs in SCD patients. It is defined as a new infiltrate on chest radiograph in conjunction with other new symptom or sign: chest pain, cough, wheezing, tachypnea and/or fever (>38.5C). [6] This condition is usually described in homozygous SCD, but it rarely develops in individuals with sickle-cell trait. [7] The term "acute chest syndrome" was first suggested for this complication by Charache et al . [8] in 1979, this term reflected the unique nature of acute pulmonary illness in patients with SCD and the difficulties in determining its pathogenesis. The frequency of this complication is variable, reaching up to 45% of individuals with SCD and recurring in up to 80% of those affected. [9],[10],[11] The incidence of ACS in patients with homozygous SCD is 12.8 episodes/100 patient years. [12] Incidence is inversely related to age, with children aged two through four years having the highest incidence (25.3 episodes/100 patient-years). Risk factors for the development of ACS include a high leukocyte count, low Hb-F concentration and a high hemoglobin level. [12]

Adult patients tend to have more severe course, death rate among them is higher than children, but ACS remains an important contributor to deaths at all ages, it accounts for 25% of deaths in SCD patients. [11],[13],[14],[15]

In Hofuf area (Located in Al-Hassa region: Eastern province of Saudi Arabia) we have high prevalence of sickle cell gene; alpha, beta thalassaemia and Glucose 6 phosphate dehydrogenise (G6PD) deficiency, coexistence of these diseases in not uncommon. The frequency of sickle cell gene in Hofuf area ranges from 0.15-0.25. Homozygous SCD prevalence ranges from 1.0-1.5%. [16],[17],[18] It is believed that SCD patients in Hofuf and other areas in Eastern province of Saudi Arabia are having milder disease with less frequent complications and good outcome, due to the interaction between thalassaemia and SCD and for having Asian haplotype. The aim of the study was to evaluate the prevalence and outcome of ACS in SCD patients in Eastern province of Saudi Arabia and to compare it to patients with African haplotypes.


   Materials and Methods Top


A retrospective study of five months duration beginning January and ending May 2003 was carried out. The records of Saudi patients with SCD who were admitted to King Fahad Hospital, Hofuf for different aetiologies, during the period specified by the study were carefully studied. Three hundred and seventeen SCD patients were enrolled in the study. Their ages ranged between 2-50 years. Twenty six patients presented with different causes of ACS; 11 patients presented with different pathologies other than ACS, but had past history of ACS; 280 patients presented with different pathologies and never presented with ACS. Those admitted to this study fulfilled two criteria at presentation or on previous episodes: (a) new infiltrate on chest radiograph (X-ray) and (b) new respiratory symptom or sign mainly chest pain, cough, wheezing, tachypnea and/or fever (>38.5C). Although it is reported that rare cases of ACS presented with normal chest X-ray, [19] but still the selected criteria is keeping with the most widely accepted definition of ACS. [6] Historical data, clinical features, CBC (using automated counter), Hb-electrophoresis (using sickling test and alkaline acid gel-electrophoresis methods), G6PD activity (using fluorescent screening test), Cultures (whenever needed), radiological studies such as; plain chest X-ray; abdominal ultrasound (measurement of splenic long axis length and evaluation of hepatobiliary tree), room air arterial blood gases (were done on admission whenever possible), blood transfusion rate/year, hospitalization rate, severity status (average number of acute admission / year for crisis, ACS, priapism, stroke, etc.) [20] and the outcome was studied .

Comparison between SCD patients with ACS from this study and from Eastern province of Saudi Arabia to patients with African haplotypes was carried out. Data obtained from references 21, 22, 23, 24 and 25.

The difference between ACS prevalence and outcome in the studied groups was determined by using Chi 2analysis.


   Results Top


During the period of this study 317 SCD Saudi patients were studied. 37 patients with new or previous episodes of ACS were identified (account for 11.67% of admitted SCD patients). Most of the patients with ACS had only one episode, but five patients (13.51%) had two episodes or more, the number of admissions for each of these patients ranged from two to four (2 had 2 episodes, 2 had 3 episodes and 1 had 4 episodes). Thirty five (94.59%) are having homozygous SCD (Hb-SS), 2 (5.41%) are having sickle/B 0 (sickle/beta-thalassemia). Coexistence of G6PD deficiency was documented in 11 patients (29.73%).

Demographics, clinical features and hematological variables are shown in [Table - 1].

In this study the frequency of ACS among SCD patients in Hofuf was more frequent in younger patients <12 years than older patients 13.45% and 5.05% respectively. Castro et al. and Poncz et al ., reported much higher frequency reaching up to 30-45% respectively. [9],[12] Al-Dabbous reported 7.7% frequency In Qatif among patients younger than 12 years, [21] but in Madina (located in Western area of Saudi Arabia) the frequency of the same age group was reaching up to 22.64% as reported by Hawasawi et al. [22] [Figure - 1]. If we look at the older patients in Hofuf it was reported by Al-Suliman et al. , that the frequency among patients older than 12 years was 1.38% [23] in comparison, it was reported that frequency in adult patients with African haplotypes reaches 9.63%. [24]

In this study, males were significantly affected more than the females in the previously mentioned from Hofuf and Qatif male predominance was reported with M:F ratio were 1.5 and 3 respectively. [21],[23] On the other hand in patients with African haplotypes slight male predominance or even female predominance was reported. [24],[25] Udezue et al. , reported some differences in the severity and features of SCD between males and females in Eastern area of Saudi Arabia. [26]

In our study the mean Hb-F level in SCD patients with ACS was 25.9% which higher than that reported in patients with African haplotypes 6%. [24]

In Qatif the average length of stay in hospital was 6.7 days with 11.68% of patients requiring ICU admission, patients with African haplotypes requiring an average stay of 10-11.4 days with 28% of patients requiring ICU admission.

Comparison of recurrence and mortality between SCD patients in Eastern province of Saudi Arabia to that of patients with African haplotype were carried out. I studied the summation of results in this study together with those done in Qatif and Hofuf previously [21],[23] versus the results reported by Taylor, et al. and Bernard Maitre, et al. [24],[25] [Table - 2],[Table - 3]. I found that recurrence is significantly lower ( P <0.025) in patients from Eastern province compared to patients with African haplotype, mortality also is lower but not statistically significant [Figure - 2].

Genotype analysis was not included in this study. However; the clinical and laboratory features like splenomegaly and high Hb-F are highly suggestive of Asian haplotype predominance and/or coexistence of alpha-thalassaemia trait or hereditary persistent Hb-F.


   Discussion Top


SCD is one of the major health problems in Saudi Arabia, specially in Southern, Western and Eastern areas where the gene frequency of this disease is quite prevalent. Many studies were carried out in these areas to identify and compare the genetic variants and severity of SCD in between these areas. It is known that the Eastern areas are having different haplotypes than Southern and Western areas, [5],[18],[27],[28] so we will try to discuss the prevalence, hospital course, recurrence and outcome of ACS in SCD patients in Eastern area -that include Hofuf and Qatif- where the Asian haplotype is more frequent and compare it with patients having African haplotypes including patients from Western area of Saudi Arabia where the African haplotypes are more frequent. ACS is less frequent in Eastern province than other areas where African haplotypes is frequent.

Length of stay in hospital and ICU admission is less in patients from Eastern province compared to patients with African haplotype.

Recurrence is significantly lower in patients from Eastern province compared to patients with African haplotype, mortality also is lower but not statistically significant.

These results support the theory that SCD patients in Eastern province has in general a milder disease -Avascular necrosis of femoral head and splenic complications are exceptions with less frequent ACS crisis, most likely due to high prevalence of Asian haplotype among SCD patients in this area, [5],[18],[21],[27],[28],[29],[30] coexisting alpha-thalassaemia, [31],[32] persistence of high Hb-F levels, [33],[34] haematology, social circumstances and geographical and climatic variation. [4],[35]


   Conclusion Top


Acute chest syndrome in SCD patients in Hofuf area of Saudi Arabia is relatively uncommon, but causes significant morbidity and mortality. Its prevalence, recurrence and mortality are low if compared to that of patients with African haplotypes.

Future studies are needed to focus on diagnostic tools, course, management and outcome of this complication in SCD patients in Hofuf and other areas in Eastern province of Saudi Arabia with genotyping, using various biomarkers and including ECHO assessment.


   Acknowledgement Top


I would like to thank Dr. Ali Hajeer (Head of Immunopathology Laboratory, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia.) who made valuable contribution to this study by revision and helpful discussion.

 
   References Top

1.Pagnier J, Mears JG, Belkhodja OD, Schaefer-Rego KE, Beldjord C, Nagel RL, et al . Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. Proc Natl Acad Sci USA 1984;81:1771-3.  Back to cited text no. 1    
2.Kulozik AE, Wainscoat JS, Serjeant GR, Kar BC, Al-Awamy B, Essan GJ, et al . Geographical survey of b-globin gene haplotypes: Evidence for an independent Asian origin of the sickle cell mutation. Am J Hum Genet 1986;39:239-44.  Back to cited text no. 2    
3.Lapoumιroulie C, Dunda O, Ducrocq R, Trabuchet G, Mony-Lobe M, Bodo JM, et al . A novel sickle gene of yet another origin in Africa: The Cameroon type. Hum Genet 1992;89:333-7.  Back to cited text no. 3    
4.Serjeant GR. The clinical features of sickle cell disease. Baillieres Clin Haematol 1993;6:93-115.  Back to cited text no. 4    
5.Nagel RL, Fleming AF. Genetic epidemiology of the beta s gene. Baillieres Clin Haematol 1992;5:331-65.  Back to cited text no. 5    
6.Platt OS. The Acute Chest Syndrome of Sickle Cell Disease. N Engl J Med 2000;343:591.  Back to cited text no. 6    
7.Dourakis SP, Alexopoulou A, Papageorgiou C, Kaloterakis A, Hadziyannis SJ. Acute chest syndrome in sickle-cell trait: Two case reports in persons of Mediterranean origin and review of the literature. Eur J Intern Med 2004;15:248-50.  Back to cited text no. 7    
8.Charache S, Scott JC, Charache P. Acute chest syndrome in adults with sickle cell anemia: Microbiology, treatment and prevention. Arch Intern Med 1979;139:67-9.  Back to cited text no. 8    
9.Poncz M, Greenberg J, Gill FM, Cohen A. Hematological changes during acute chest syndrome in sickle cell disease. Am J Pediatr Hematol Oncol 1985;7:96-9.  Back to cited text no. 9    
10.Johnson CS, Verdigem TD. Pulmonary complications of sickle cell disease. Semin Respir Med 1988;9:287-96.  Back to cited text no. 10    
11.Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, et al . Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000;342:1855-65.   Back to cited text no. 11    
12.Castro O, Brambilla DJ, Thorington B, Reindorf CA, Scott RB, Gillette P, et al . The acute chest syndrome in sickle cell disease: Incidence and risk factors. Blood 1994;84:643-9.  Back to cited text no. 12    
13.Vichinsky EP, Styles LA, Colangelo LH, Wright EC, Castro O, Nickerson B. Acute chest syndrome in sickle cell disease: Clinical presentation and course. Blood 1997;89:1787-92.  Back to cited text no. 13    
14.Thomas AN, Pattison C, Serjeant GR. Causes of death in sickle cell disease in Jamaica. BMJ 1982;285:633-5.  Back to cited text no. 14    
15.Gray A, Anionwu EN, Davies SC, Brozovic M. Patterns of mortality in sickle cell disease in the United Kingdom. J Clin Pathol 1991;44:459-63.  Back to cited text no. 15    
16.Nasserullah Z, Al Jame A, Abu Srair H, Al Qatari G, Al Naim S, Al Aqib A, et al . Neonatal screening for sickle cell disease, glucose-6-phosphate dehydrogenase deficiency and a-thalassemia in Qatif and Al Hassa. Ann Saudi Med 1998;18:289-92.  Back to cited text no. 16    
17.el-Hazmi MA, Warsy AS, al-Swailem AR, al-Swailem AM, Bahakim HM. Sickle cell gene in the population of Saudi Arabia. Hemoglobin 1996;20:187-98.  Back to cited text no. 17    
18.Pearson HA. Reply: Sickle cell disease in the Kingdom of Saudi Arabia: East and West. Ann Saudi Med 1999;19:281-2.  Back to cited text no. 18    
19.Feldman L, Gross R, Garon J, Nallari A, Kaur N, Motwani B, et al . Sickle cell patient with an acute chest syndrome and a negative chest X-ray: Potential role of the ventilation and perfusion (V/Q) lung scan. Am J Hematol 2003;74:214-5.  Back to cited text no. 19    
20.Miller ST, Wright E, Abboud M, Berman B, Files B, Scher CD, et al . Impact of chronic transfusion on incidence of pain and acute chest syndrome during the stroke prevention Trial (STOP) in sickle cell anemia. J Pediatr 2001;139:785-9.  Back to cited text no. 20    
21.Al-Dabbous IA. Acute chest syndrome in sickle cell disease in Saudi Arab Children in the Eastern Province. Ann Saudi Med 2002;22:167-71.  Back to cited text no. 21    
22.Hawasawi ZM, Nabi G, Al Magamci MS, Awad KS. Sickle cell disease in childhood in Madina. Ann Saudi Med 1998;18:293-5.  Back to cited text no. 22    
23.Al-Suleiman A, Aziz G, Bagshia M, El Liathi S, Homrany H. Acute chest syndrome in adult sickle cell disease in eastern Saudi Arabia. Ann Saudi Med 2005;25:53-5.  Back to cited text no. 23    
24.Maitre B, Habibi A, Roudot-Thoraval F, Bachir D, Belghiti DD, Galacteros F, et al . Acute chest syndrome in adults with sickle cell disease. Chest 2000;117:1386-92.  Back to cited text no. 24    
25.Taylor C, Carter F, Poulose J, Rolle S, Babu S, Crichlow S. Clinical presentation of acute chest syndrome in sickle cell disease. Postgrad Med J 2004;80:346-9.   Back to cited text no. 25    
26.Udezue E, Girshab AM. Differences between males and females in adult sickle cell pain crisis in eastern Saudi Arabia. Ann Saudi Med 2004;24:179-82.  Back to cited text no. 26    
27.el-Hazmi MA. Heterogeneity and variation of clinical and haematological expression of haemoglobin S in Saudi Arabs. Acta Haematol 1992;88:67-71.  Back to cited text no. 27    
28.el-Hazmi MA, Warsy AS, Bashir N, Beshlawi A, Hussain IR, Temtamy S, et al . Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease. East Mediterr Health J 1999;5:1154-8.  Back to cited text no. 28    
29.Powars D, Hiti A. BS gene cluster haplotypes as genetic markers for severe disease expression. Am J Dis Child 1993;147:1197-202.  Back to cited text no. 29    
30.Powars DR, Meiselman HJ, Fisher TC, Hiti A, Johnson C. Beta-S gene cluster haplotypes modulate hematologic and hemorheologic expression in sickle cell anemia: Use in predicting clinical severity. Am J Pediatr Hematol Oncol 1994;16:55-61.  Back to cited text no. 30    
31.Figueiredo MS, Kerbauy J, Gonηalves MS, Arruda VR, Saad ST, Sonati MF, et al . Effect of alpha-thalassemia and beta-globin gene cluster haplotypes on the hematological and clinical features of sickle-cell anemia in Brazil. Am J Hematol 1996;53:72-6.  Back to cited text no. 31    
32.Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR, Colah RB, Kadam MD, et al . Effect of alpha-thalassemia on sickle-cell anemia linked to the Arab-Indian haplotype in India. Am J Hematol 1997;55:104-9.  Back to cited text no. 32    
33.Falusi AG, Olatungi PO. Effects of alpha thalassaemia and haemoglobin F (HbF) level on the clinical severity of sickle-cell anaemia. Eur J Haematol 1994;52:13-5.  Back to cited text no. 33    
34.Steinberg MH. Modulation of the phenotypic diversity of sickle cell anemia. Hemoglobin 1996;20:1-19.  Back to cited text no. 34    
35.Serjeant GR, Serjeant BE. Sickle cell disease in Saudi Arabia: The Asian haplotype: Reflections on a meeting at Hofuf, September 2003. Ann Saudi Med 2004;24:166-8.  Back to cited text no. 35    


    Figures

  [Figure - 1], [Figure - 2]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]

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