HEMOGLOBIN-S POLYMERIZATION - PRIMARY DETERMINANT OF THE HEMOLYTIC AND CLINICAL SEVERITY OF THE SICKLING SYNDROMES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (1) , 183-189
Abstract
The extent to which the intracellular polymerization of sickle Hb (HbS) can account for the severity of anemia and of vaso-occlusive manifestations in the various sickling syndromes was examined. Polymer formation in sickle cell disease depends principally on the intraerythrocytic Hb composition and concentration. The polymer fraction in sickle red cells was determined from reported mean values for Hb composition and mean corpuscular Hb concentration (MCHC) in 12 groups of patients with sickle hemoglobinopathies (homozygotes for HbS, with and without coexistent .alpha.-thalassemia or various forms of the hereditary persistence of fetal Hb [HPFH], .beta.+-, .beta.0- and .delta..beta.-thalassemia, and heterozygotes for HbS with HbA). The calculated HbS polymer fractions at full deoxygenation and at physiologic oxygen saturation values were closely correlated with mean blood Hb concentrations. In addition, polymer fraction correlated with the ranking of the sickling syndromes by vaso-occlusive severity. Polymer fraction accounts for about 80% of the variability in hemolytic and clinical severity. The method of analysis presented here provides a quantitative and systematic means of assessing the role of polymer formation in the pathophysiologic manifestations of the sickling syndromes. The intracellular polymerization of HbS is the primary determinant of the severity of both anemia and clinical symptomatology in the sickle hemoglobinopathies.