An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: communication from the SSC of the ISTH

Abstract

Abnormal fibrin clot structure, in particular increased fibrin fiber density and stiffness and resistance to fibrinolysis, are reported to be linked to cardiovascular disease (CVD) and a higher incidence of venous and arterial thromboembolic events 1, 2. Clot structure is, to a large extent, kinetically controlled and determined by the early stages of fibrin assembly, polymerization and lateral aggregation 3. Knowledge of the transformation of soluble polymers to an insoluble elastic gel is fundamentally important in understanding blood clotting, fibrinolysis, wound healing and thrombosis 4. In addition, several clinical diagnostic tools currently rely on fibrin polymerization as a molecular marker of thrombin generation and/or intravascular fibrin deposition by monitoring changes in D‐dimer, fibrinopeptide A or soluble fibrin precursors 5. In the research setting, turbidity analysis is used as a quantitative high‐throughput technique to monitor clot formation and structure in large datasets 6. In a similar but separate assay, clot lysis time (CLT) can be calculated to determine the plasma fibrinolytic potential of an individual, with application in both hypercoagulable and hyperfibrinolytic conditions 6-13. Combining the turbidity and clot lysis assays has the added benefit of directly relating lysis times to clot formation and structure, ultimately resulting in a more comprehensive characterization of plasma clot properties