Non-uniformity of intracellular polymer formation in sickle erythrocytes: possible correlation with severity of hemolytic anemia.

Intact sickle erythrocytes were fractionated to obtain a more uniform population in mean corpuscular hemoglobin concentration (MCHC). Polymer fraction at complete deoxygenation varied with increasing MCHC and, at varying oxygen saturation, was in good agreement with theoretical predictions based on solubility and the non-ideal behavior of concentrated hemoglobin solution and of water. These data and the theoretical analysis indicate that, in uniform sickle erythrocytes at 34 g/dl, polymer is only detected below 84% oxygen saturation. Non-uniformity of unfractionated sickle erythrocytes causes this critical oxygen saturation to shift to higher values (over 90%). The implication is that polymer may exist in arterial blood, a possibility which must be considered in therapeutic strategies. Recently, we showed that polymer formation correlated with the severity of hemolysis for 12 sickle syndromes varying from sickle trait to hemoglobin SS (African) disease.