PURPOSE: The rate of progression of major organ failure in sickle cell anemia is genetically controlled. It is the direct consequence of the sickle cell-evoked vasculopathy. PATIENTS AND METHODS: Presence of the beta S gene cluster haplotypes and alpha 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 alpha-thalassemia-2 decreases the risk of soft tissue organ failure in all haplotype combinations. RESULTS: Other laboratory abnormalities, when combined with haplotype and alpha 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 (approximately 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 beta S gene cluster haplotype and alpha-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.
PURPOSE: The rate of progression of major organ failure in sickle cell anemia is genetically controlled. It is the direct consequence of the sickle cell-evoked vasculopathy. PATIENTS AND METHODS: Presence of the beta S gene cluster haplotypes and alpha 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 alpha-thalassemia-2 decreases the risk of soft tissue organ failure in all haplotype combinations. RESULTS: Other laboratory abnormalities, when combined with haplotype and alpha 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 (approximately 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 beta S gene cluster haplotype and alpha-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.
Authors: Mathias Currat; Guy Trabuchet; David Rees; Pascale Perrin; Rosalind M Harding; John B Clegg; André Langaney; Laurent Excoffier Journal: Am J Hum Genet Date: 2001-12-06 Impact factor: 11.025
Authors: Steven R Goodman; Betty S Pace; Kirk C Hansen; Angelo D'alessandro; Yang Xia; Ovidiu Daescu; Stephen J Glatt Journal: Exp Biol Med (Maywood) Date: 2016-03-27
Authors: Christopher J Bean; Sheree L Boulet; Genyan Yang; Amanda B Payne; Nafisa Ghaji; Meredith E Pyle; W Craig Hooper; Pallav Bhatnagar; Jeffrey Keefer; Emily A Barron-Casella; James F Casella; Michael R Debaun Journal: Br J Haematol Date: 2013-08-16 Impact factor: 6.998
Authors: Li Liu; Alexander Pertsemlidis; Liang-Hao Ding; Michael D Story; Martin H Steinberg; Paola Sebastiani; Carolyn Hoppe; Samir K Ballas; Betty S Pace Journal: Exp Biol Med (Maywood) Date: 2016-03-27
Authors: J A Moreira; R P G Machado; M R Laurentino; Romelia Pinheiro Gonçalves Lemes; M C Barbosa; T E Santos; I C J Bandeira; A M C Martins Journal: Dis Markers Date: 2016-05-04 Impact factor: 3.434