Beyond cell based models of coagulation: Analyses of coagulation with clot "lifespan" resistance-time relationships

Cell based models of coagulation (CBM) have provided mechanistic insight into numerous hematological issues for nearly two decades. This review discusses another coagulation model system - the clot lifespan model (CLSM) - that has been designed to compliment the CBM-based approach to elucidating the mechanisms responsible for a variety of hemostatic disorders/phenomena. The CLSM is a thrombelastograph-based approach that utilizes a standardized clotting stimulus (e.g., celite, tissue factor) and a fibrinolytic stimulus (e.g., tissue type plasminogen activator) to assess clot growth and disintegration via changes in clot resistance. The CLSM utilizes parametric, elastic modulus-based parameters to document these phenomena. The CLSM has recently been employed to discern the effects of protamine and hydroxyethyl starch on key fibrinolytic-antifibrinolytic protein interactions, as well as demonstrating differences in fibrinolytic kinetics dependent on whether contact pathway proteins or tissue factor is used to initiate coagulation. The CLSM is presently being utilized to investigate the effects of ventricular assist device placement on fibrinolysis, and it is anticipated that this model system will be employed in both basic science and clinical investigations in the future.