Kinetics of polymerization of deoxyhemoglobin S and mixtures of hemoglobin A and hemoglobin S at high hemoglobin concentrations

Transverse water proton relaxation times (T₂) have been measured as a function of time after deoxygenation of solutions containing hemoglobin S. The shortened T₂ values observed upon deoxygenation of hemoglobin S result from an increase in the correlation time (τ_c) of the water fraction irrotationally bound to deoxyhemoglobin S as it polymerizes. Therefore, the change in τ_c as a function of time after deoxygenation can be used to measure the rate of polymer formation. The change in τ_c observed is reasonably fit by the first-order equation τ = τ₀ (1 ? e^?kt) + τ_oxy. At a total hemoglobin concentration of approximately 300 mg/ml, the pseudo-first-order rate constant in a heterozygous AS sample is 25 times slower than in a homozygous S sample, k = 0.019 and 0.47 s^?1, respectively. Since the transit time for an erythrocyte in vivo is approximately 15 s, these results suggest that the heterozygous A/S erythrocyte would traverse the circulation and become reoxygenated before extensive polymerization and, therefore, cell sickling could occur. For the homozygous S/S erythrocyte, there is ample time for polymerization and for cell sickling during circulation.