PB1374 Identifying Failure Mechanisms in Plasma Based Models of Coagulopathy

Background To prevent bleeding and hemorrhage after injury, clots must withstand diverse mechanical stresses. Clot failure may occur at the vessel-clot interface (adhesive) or within the fibrin network (cohesive: tensile and burst failure). Fibrinogen and fibrin network alterations affect tensile fracture of plasma clots, but their role in other failure modes is undefined. Aims To define resistance to adhesive, burst and tensile failure of platelet poor plasma (PPP) clots. Methods PPP clots (2.5-0.83mg/mL fibrinogen) were formed in-vitro with 20mM CaCl2 and 1-150pM Tissue Factor (TF). Mechanical properties of PPP clots were measured using a Biomomentum mechanical tester with three assays, Burst testing to measure puncture failure mimicking blood pressure, Tensile testing measured resistance to uniaxial tension, and Adhesive peel tests measured force required for clot-collagen interface failure. Force-displacement curves were normalized to account for geometry changes across testing methods (Figure 1). Results To compare across methods, PPP clots were formed with varying geometries but fixed clotting conditions. Burst testing was identified as having the highest Fmax and sample thickness normalized force at failure, higher than other tested methods (Figure 1). When normalizing for geometry differences, thickness-normalized force at failure was normalized to the cross-sectional area of samples. Burst remained the most resistant to failure, with tensile and adhesive failure occurring at similar force/mm2 (Figure 1E,F). Individual assessment of failure modes identified that independently reducing fibrinogen concentration and independently increasing TF activation, reduced burst force and displacement at failure (Figure 2). Conclusions Clot resistance to failure is dependent upon the type of force applied and makeup of the clot being tested. Burst failure demonstrated the highest resistance. With low fibrinogen and high TF creating weaker clots. Underscoring the importance of bulk mechanical and interfacial properties contributing to post injury bleeding.