JBM  Vol.4 No.3 , March 2016
Modeling and Simulation of the Autocatalytic Kinetics of Haemoglobin SS Polymerization: Onset of Polymerization
Abstract: We report a fresh and simpler approach to the modelling of the kinetics of the polymerization of Hb SS in sickle cell patients that couples the kinetics and the hydrodynamics of blood flow in mechanistic understanding of the process. The well-known two-step autocatalytic reaction scheme was used for the polymerization reaction with the assumption of simpler first-order reaction scheme for each stage. In addition, the forces acting on a particle in motion were also introduced to account for compelling settling of the red cells that lead to vessel occlusion (vaso-occlusion). A first attempt on the prediction of vessel blockage was made using this novel model. The time for the onset of the polymerization reaction was derived from hydrodynamic considerations and kinetics while the kinetic rate constants were obtained from the autocatalytic nature of the reaction. Experimental data for model validation were obtained from recruited SS patients and in vitro data of Hofrichter. Over 100 volunteers were recruited for participation in this work but less than 40% met the inclusion criteria. Participants were of age range 13 - 43 (with a mean of 26 ± 8 years) for SCD patients and 18 - 43 (with a mean of 28 ± 7 years) for control participants. Blood indices and Transcranial Doppler (TCD) test parameters of all participants were the principal parameters used for model validation. Constant k2/k1 ratios was obtained for individual in vivo/in vitro system. This ratio is unique for any individual, independent on protein sequence and also suggests the degree of expression of the symptoms of Sickle Cell Disease (SCD) with higher values reflecting greater propensity to pain crisis. Delay time, tD, was found to have an inverse relationship with the kinetic constant for the residual reaction, k1. Therefore, long delay times calculated, offer insight on why SCD patients are not in perpetual crises because enough time is provided the cells to escape microcirculation while keeping the residual reaction at the minimum. Sensitivity analysis was carried out to obviate the limitations encountered in the course of the work. Results showed the onset of occlusion to be most sensitive to the diameter of the blood vessel.  
Cite this paper: Alagbe, E. , Susu, A. and Dosunmu, A. (2016) Modeling and Simulation of the Autocatalytic Kinetics of Haemoglobin SS Polymerization: Onset of Polymerization. Journal of Biosciences and Medicines, 4, 21-27. doi: 10.4236/jbm.2016.43004.

[1]   Pauling, L., Itano, H.A., Singer, S.J. and Wells, I.C. (1949) Sickle Cell Anemia: A Molecular Disease. Science, 10, 543-548.

[2]   Petsko, G.A. and Ringe, D. (2004) Protein Structure and Function. New Science Press Ltd., UK.

[3]   FAO (1990) Conducting Small-Scale Nutrition Surveys: A Field Manual. Rome.

[4]   Magnanni, R. (1997) Sampling Guide. IMPACT Food Security and Nutrition Monitoring Project. Arlington, Va.

[5]   UNICEF (1995) Monitoring Progress towards the Goals of the World Food Summit for Children: A Practical Handbook for Multiple Indicator Surveys. New York.

[6]   Boudart, M. (1968) Kinetics of Chemical Processes. Prentice-Hall, INC.

[7]   Susu, A.A. (1997) Chemical Kinetics and Heterogeneous Catalysis. CJC Publishers Nig. Ltd.

[8]   Susu, A.A. and Kunugi, T. (1980) A Novel Pyrolytic Decomposition of n-Erosane with Synthesis gas and K2CO3 Catalyzed Shift Reaction. I & EC Proc. Des. Dev., 19, 693-699.

[9]   Charm, S.E. and Kurland, G.S. (1974) Blood Flow and Microcirculation. John Wiley & Sons.

[10]   Hofrichter, J., Ross, P.D. and Eaton, W.A. (1974) Kinetics and Mechanism of Deoxyhe-moglobin S Gelation: A New Approach to Understanding Sickle Cell Disease. Proc. Natl. Acad. Sci. USA, 71, 4864-4868.

[11]   Stuart, M.J. and Nagel, R.L. (2004) Sickle-Cell Disease. 364.