Image-based analysis and simulation of the effect of platelet storage temperature on clot mechanics under uniaxial strain

Optimal strength and stability of blood clots are keys to hemostasis and in prevention of hemorrhagic or thrombotic complications. Clots are biocomposite materials composed of fibrin network enmeshing platelets and other blood cells. We have previously shown that the storage temperature of platelets significantly impacts clot structure and stiffness. The objective of this work is to delineate the relationship between morphological characteristics and mechanical response of clot networks. We examined scanning electron microscope images of clots prepared from fresh apheresis platelets, and from apheresis platelets stored for 5 days at room temperature or at 4 degrees C, suspended in pooled plasma. Principal component analysis of nine different morphometric parameters revealed that a single principal component (PC1) can distinguish the effect of platelet storage on clot ultrastructure. Finite element analysis of clot response to uniaxial strain was used to map the spatially heterogeneous distribution of strain energy density for each clot. At modest deformations (25% strain), a single principal component (PC2) was able to predict these heterogeneities as quantified by variability in strain energy density distribution and in linear elastic stiffness, respectively. We have identified structural parameters that are primary regulators of stress distribution, and the observations provide insights into the importance of spatial heterogeneity on hemostasis and thrombosis.