The reaction of fibrinogen with thrombin to produce fibrin goes through a multistep sequence in which up to four peptides are cleaved off. When this reaction takes place at pH 6.3 in a shear flow field, the formation of fibrous product is retarded as compared with stagnant conditions. The retardation is greater at 50 s−1 than at 135 s−1. The morphology of the coagulated product appears to be different when produced at 50 s−1 than at either stagnant or 135 s−1, with the material at 50 s−1 having a sheetlike appearance in contrast to a fibrous appearance for the material at 135 s−1 and stagnant conditions: The explanation of the retardation may lie in the separation of thrombin from fibrinogen during the sheared reactions. Shear rate varies more in the vascular bed than does pH or ionic strength and probably is a more important factor in controlling physiological coagulation than these more frequently studied variables.
The reaction of fibrinogen and thrombin has been carried out in a Couette-flow apparatus over a range of rates of shear from 0-150 s-1 and at pH’s from 6.4 - 6.8. A minimum is found in the rate of formation of insoluble fibrin at shear rates of 30-60 s-1 (well within the physiological range). The position of the minimum is determined by the concentration of reactants. Rate decreases of up to 50% have been observed. Hirudin quenching of thrombin activity shows that formation of fibrin monomer is unaffected by shear rate, hence the effect is due to changes in fibrin aggregation. The same sort of minimum has been observed when a solution of fibrin monomer is made to precipitate by altering pH and ionic strength in shear fields. The release of B-peptide as analyzed by HPLC appears to be less at the minimum.These results are interpreted as resulting from a lowering of the growth of fibrin particles at low shear rate and an increase in nucleation of particles at higher shear rates.
Fibrinogen reacted with thrombin at pH 6.3 in shear flow fields varying from 0 to 150 sec-1 gives insoluble fibrin at differing ratio, with a minimum rate near 50 sec-1. The relative rate of release of A and B peptides is also altered by the shear flow field. The release or B peptide is faster in stagnant solutions than in the higher shear flow.
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