Quantitative Assay of Fibrinogen and Fibrinolytic Activity.

ECENT YEARS have brought increased appreciation of the importance of the role of fibrinolysis in the regulation of normal hemostasis and in the production of abnormal bleeding. The mechanisms by which active fibrinolysis is induced are far from clear, but it does seem likely that it can be brought about by shock,1 severe emotional stress,2 injection of adrenalin,2 anoxia3 and liberation of activators from damaged tissue.4 The vastly complex procedure of open heart surgery provides many opportunities on a theoretical basis for activation of fibrinolysis. Reports in the literature leave no room to question the fact that severe degrees of fibrinolysis have been responsible for massive bleeding in a few eases.57 The extent to which moderate degrees of fibrinolysis may aggravate the degree of post-operative bleeding in most cases is not clear. A number of groups have addressed themselves to the problem of evaluating the degree of fibrinolysis during and following open heart Surgery.59 The present study was undertaken in the belief that there was a need for more accurate quantitation of the over-all fibrinolytic state during open heart surgery. In the course of these investigations, a technic was evolved which appears to measure over-all fibrinolytic activity in a sensitive quantitative way’ providing information which is more readily related to other changes going on in the patient at the same time. The method is based on duplicate fibrinogen determinations. One tube of each pair contains an inhibitor of fibrinolvsin; during the period of incubation after fibrin has been formed, the inhibitor prevents destruction of the fibrin. In the other tube, fibrin is lysed to an extent proportional to the fibrinolytic activity. Comparison of the results obtained quantitatively in the two tubes provides an index of fibrinolysis. In an effort to evaluate this approach, studies were carried out to answer the following questions: (1) Are the level of fibrinogen and the degree of fibrinolytic activity stable in the sample during the period prior to assay? (2) Does the fibrinolysin inhibitor interfere in any way with the results of the assay? (3) How much inhibitor is needed to prevent lysis in the control tube? (4) What period of incubation provides the most convenient and satisfactory discrimination between normals and those with increased fibrinolytic activity? In the course of this study, information was obtained on the effects of various modifications of technic on the accuracy of the fibrinogen assay. Normal values were established for this and for the fibrinolysin assay. The fibrinolysis technic