Studies on the destruction of red blood cells. XIII. Observations on the role of pH in the pathogenesis and treatment of painful crisis in sickle-cell disease.

The chief clinical features of sickle-cell anemia are chronic hemolytic anemia and episodic painful crises; the underlying defect is the presence of S hemoglobin* in the red blood cells from patients with this disease. The deoxygenation of S hemoglobin leads to the formation of irregular elongated molecular masses—tactoids—which give to the red cells the distorted shape from which the disease derives its name. 1,5 The manner in which the sickling phenomenon accounts for the physiological and pathological disturbances that characterize sickle-cell anemia has been a major interest of Castle and his associates. 6,7 The chronic hemolytic anemia has been explained on the basis of the increased mechanical fragility that accompanies the sickled state, 6,8-10 with diminished life span of the erythrocytes in vivo. 11 The painful crises have been related to the increased viscosity of the blood that is proportional to the degree of sickling. 6,7 Factors which impede the