Elastic modulus-based thrombelastographic quantification of plasma clot fibrinolysis with progressive plasminogen activation

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Abstract
Thrombelastographic detection of fibrinolysis has been critical in the identification and treatment of coagulopathy in many perioperative settings. However, the fibrinolytic assessments have been at best non-parametric, amplitude-based determinations (e.g. estimated % lysis, clot lysis time or clot lysis rate). Recognizing this limitation, a methodology was developed to measure the onset, speed and extent of clot disintegration by changes in elastic modulus derived from the amplitude. Using this approach, our goal was to characterize the clot disintegration kinetics of progressive plasminogen activation with tissue plasminogen activator (tPA) and to determine the extent of inhibition of fibrinolysis mediated by tPA with aprotinin and activated factor XIII. While the estimated % lysis and clot lysis time were significantly affected by tPA (0-300 U/ml), elastic modulus-based analyses in a more activity-specific fashion demonstrated significantly decreased onset, increased rate and increased extent of fibrinolysis. Furthermore, aprotinin was found to inhibit the onset, rate and extent of fibrinolysis in an activity-dependent fashion, whereas activated factor XIII was noted to enhance the speed of onset of clot growth and delay the onset of fibrinolysis. In summary, our results serve as the rational basis to utilize this elastic modulus-based approach to quantify the extent of fibrinolysis in clinical and laboratory settings, as well as potentially guiding antifibrinolytic therapy.