Simulation of coupled enzyme assays for clotting factors and its application to a new method for the determination of human plasminogen

✍ Scribed by O. Richter; E. Jacobi

• Publisher: Elsevier Science
• Year: 1978
• Tongue: English
• Weight: 696 KB
• Volume: 11
• Category: Article
• ISSN: 0010-4809
• DOI: 10.1016/0010-4809(78)90024-1

✦ Synopsis

The enzymatic assay for the determination of human plasminogen via the clotting time is based on the following sequence of reactions: Human plasminogen is converted to an activator by streptokinase. This activator converts bovine plasminogen to bovine plasmin which splits the fibrinogen present in the assay during a defined incubation time. The thrombin clotting time of the resulting mixture containing fibrinogen and fibrinogendegradation products depends on the amount of fibrinogen degraded and is thus related to the concentration of human plasminogen. This assay is described by a kinetic model in terms of nonlinear differential equations. On the basis of this model, the clotting time can be computed as a function of the parameters of the assay: concentration of fibrinogen, human plasminogen, bovine plasminogen, and the incubation time. By computer simulation an optimal parameter set is obtained for which the resulting calibration curve is linear and only slightly sensitive against changes in the variance of the reagent. Furthermore, the model gives a detailed insight into the mechanisms involved in the interaction of human plasminogen, fibrinogen, bovine plasminogen, and thrombin.