STUDIES ON THE DESTRUCTION OF RED BLOOD CELLS. XII. FACTORS INFLUENCING THE ROLE OF S HEMOGLOBIN IN THE PATHOLOGIC PHYSIOLOGY OF SICKLE CELL ANEMIA AND RELATED DISORDERS 1

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Abstract
Patients (21) with various hereditary hemoglobinopathies involving S hemoglobin were studied with respect to the concentration of the different hemoglobins in their red cells, the clinical manifestations of the sickling phenomenon, and the changes in viscosity of their bloods upon deoxygenation in vitro under standard conditions of hematocrit, CO2 tension and temperature. A general relationship was demonstrated between the mean corpuscular S hemoglobin concentration (MCSHC) and the clinical manifestations of the S hemoglobinopathies. Patients in whom the MCSHC was less than 15% were not anemic and had no painful crises. Those in whom the MCSHC was 15-18% had evidence only of a mild hemolytic anemia. Significant anemia, bony lesions, and painful crises were limited to patients with MCSHC values of more than 20%. The effect of progressive deoxygenation upon the viscosity of whole blood at standard hematocrit and pH was also a function of MCSHC. In the pH range 7.1-7.4, the changes in viscosity upon deoxygenation were similar to those of solutions of S hemoglobin and viscosities rose sharply as the concentrations of S hemoglobin increased above 10 g%. Similarly, less complete deoxygenation was necessary to elicit the first changes in viscosity at higher than at lower S hemoglobin concentrations. Viscosity changes in bloods from patients with S hemoglobinopathies were also related to pH. Decreasing the pH of such bloods when partially deoxygenated led to increases in viscosity maximal at about pH 6.8-7.0. Conversely, raising the Ph decreased the viscosity of partially deoxygenated blood. However, decreasing the pH of fully reduced S-S blood did not significantly increase its viscosity, whereas with fully reduced S-A blood the effect was striking. The evidence suggests that at pH values of 7.2 to 7.4, the hemoglobin concentrations are the major determinations of the changes in viscosity upon deoxygenation, but that at lower pH values S hemoglobin interacts with other hemoglobins. The observations are consistent with the previously expressed concepts that the increased viscosity of blood that occurs upon deoxygenation is a major factor in the pathophysiology of the S hemoglobinopathies. From the in vitro data it may be inferred that the changes in viscosity are greatest at sites of erythroconcentration, and are augmented by lowering the pH and diminished by raising the pH of the blood.