Beta-S Gene Cluster Haplotypes Modulate Hematologic and Hemorheologic Expression in Sickle Cell Anemia

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Abstract

Patients and Methods

Presence of the (βs gene cluster haplotypes and gene deletions as genetic markers indicate the expected frequency of illness and the risk of end-stage major organ failure. The risk of irreversible soft tissue organ failure is greatest in patients with a Central African Republic (CAR) chromosome, whereas morbidity is consistently lowest in patients with a Senegalese chromosome. Presence of thalassemia-2 decreases the risk of soft tissue organ failure in all haplotype combinations.

Results

Other laboratory abnormalities, when combined with haplotype and gene status, also predict the risk of clinical morbidity. The mean hemoglobin level (or red blood cell count) is lowest in patients with the most severe clinical manifestations. On the other hand, the platelet count and leukocyte count as well as the plasma fibrinogen level are elevated in the sickest patients. A threshold level of hemoglobin F at 1.2 g/dl (∼20% hemoglobin F) decreases the risk of major organ failure and is attained most frequently in those with a Senegalese chromosome. Hemorheologic findings observed during the most stable state of patients with sickle cell anemia indicate two trends: (a) the mean percentage of dense red cells is nearly twice as high in the maximal severity patients as compared with the minimal severity patients; and (b) mean red cell rigidity is greatest in the maximal severity group and least in the minimal severity group. These findings suggest that a greater percentage of dense, poorly deformable red cells are present in sickle cell patients in the genotypic category of maximal severity.

Conclusions

The combination of the (βs gene cluster haplotype and gene status correlates with both phenotypic laboratory findings (hematologic profile) and morbidity. These associations increase our ability to predict clinical severity and the future risk of major organ failure.

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