Measuring fibrinolysis: from research to routine diagnostic assays

Development and standardization of fibrinolysis methods have progressed more slowly than coagulation testing and routine high-throughput screening tests for fibrinolysis are still lacking. In laboratory research, a variety of approaches are available and are applied to understand the regulation of fibrinolysis and its contribution to the hemostatic balance. Fibrinolysis in normal blood is slow to develop. For practical purposes plasminogen activators can be added to clotting plasma, or euglobulin prepared to reduce endogenous inhibitors, but results are complicated by these manipulations. Observational studies to identify a 'fibrinolysis deficit' have concluded that excess fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI-1) or thrombin-activatable fibrinolysis inhibitor (TAFI), zymogen or active enzyme, may be associated with an increased risk of thrombosis. However, results are not always consistent and problems of adequate standardization are evident with these inhibitors and also for measurement of fibrin degradation products (D-dimer). Few methods are available to investigate fibrinolysis under flow, or in whole blood, but viscoelastic methods (VMs) such as ROTEM and TEG do permit the contribution of cells, and importantly platelets, to be explored. VMs are used to diagnose clinical hyperfibrinolysis, which is associated with high mortality. There is a debate on the usefulness of VMs as a point-of-care test method, particularly in trauma. Despite the difficulties of many fibrinolysis methods, research on the fibrinolysis system, taking in wider interactions with hemostasis proteins, is progressing so that in future we may have more complete models and better diagnostic methods and therapeutics.