Heterogeneity and Variation of Clinical and Haematological Expression of Haemoglobin S in Saudi Arabs

Abstract

Sickle cell haemoglobin (Hb S) occurs at a high frequency in the Eastern (EP), South-Western (SWP) and North-Western (NWP) Provinces of Saudi Arabia and the presentation of the Hb S is believed to exhibit clinical diversity in the different regions. Three areas of Saudi Arabia were screened to determine the frequency of Hb S and α- and β-thalassaemias and glucose-6-phosphate de-hydrogenase deficiency genes. Furthermore, in an attempt to investigate and compare the clinical and haematological presentation of sickle cell disease (SCD) in the different regions of Saudi Arabia, the individuals identified as Hb S homozygotes were investigated further. The patients were further classified on the basis of whether there was associated α- or β-thalassaemia. A severity index (SI) was calculated for each patient and the clinical presentations and laboratory findings were compared. The results showed significantly variable severity of SCD in patients from different regions. The patients from the EP generally had a mild clinical presentation, while in the SWP and NWP majority of the patients suffered from a severe disease as judged by the SI. No correlation could be established between Hb F level and SI, though the WBC level correlated positively with the SI. The lowest SI values were encountered in patients with associated α-thalassaemia who also had the lowest WBC count and MCV and the highest RBC count and packed cell volume.

Fibrocongestive splenomegaly in sickle cell disease: A distinct clinicopathological entity in the Eastern province of Saudi Arabia

“…Such mildness is postulated to be due to the cumulative effect of multiple factors, chief among them being the higher HbF levels. The inhibitory effect of HbF upon the process of RBC sickling by interfering with the formation of HbS polymers has been extensively documented; it has been further observed that patients having HbF levels >20% are more likely to have milder sickling manifestations in sickle cell disease [1,[3][4][5]7,11,22,25]. In the present study, 75% of total patients, belonging to the ''SCA with high HbF'' and ''S-b thalassemia'' groups, had HbF levels > 20%.…”

“…Sickle cell disease in Saudi Arabia is a major health concern with significant human, financial, and medical resources devoted for its investigation, screening, and management [1,3,5,21]. Two distinctive patterns of sickle cell disease occur in western and eastern Saudi Arabia regions; the disease in western Saudi Arabia resembles that associated with Benin haplotype of b S globin gene.…”

“…Multiple responsible factors have been evaluated to explain this progression, the most widely accepted being the occurrence of Asian haplotype of b S globin gene, high levels of fetal hemoglobin (HbF), and frequent a-thalassemia [1][2][3][4][5][6][7][8][9].…”

Fetal hemoglobin in sickle cell anemia

“…10,11,14,74 As in Southwestern patients, splenomegaly is common and stroke and leg ulcers are rare. The rarity of stroke might be a result of the higher hemoglobin concentration and a high incidence of ␣-thalassemia; little information on the incidence of pulmonary vasculopathy is available.…”

“…[10][11][12][13][14] Some patients who have other HbS-associated haplotypes also have very high HbF. Notwithstanding the high HbF levels of all these patients, acute painful episodes and other symptoms of sickle cell disease still occur, perhaps because the heterogeneous cellular distribution of HbF does not equally protect all erythrocytes from polymerizationinduced damage.…”