Nonlinear Relationships of Fibrin Network Structure as a Function of Fibrinogen and Thrombin Concentrations for Purified Fibrinogen and Plasma Clots

BackgroundFibrinogen levels are associated with bleeding disorders and thrombotic disease. Thrombin converts fibrinogen to fibrin, producing the load-bearing fibrin scaffold that governs clot mechanics and transport. ObjectiveQuantitatively map how fibrinogen and thrombin concentrations program fibrin architecture in human plasma and purified Peak 1 fibrinogen. MethodsScanning electron microscopy quantified single-fiber morphology--fiber diameter and branch-to-branch segment length from a standardized sample-preparation protocol. Confocal microscopy quantified network architecture (projected fiber density and pore/bubble size). Results and ConclusionsAcross plasma and purified systems, diverse readouts collapsed onto compact multiplicative scaling laws [Formula]. The exponent patterns reveal a division of labor: thrombin primarily controls single-fiber growth kinetics, strongly shortening branch-to-branch segment length and modestly thinning fibers, whereas fibrinogen primarily controls space filling, strongly increasing fiber density and reducing pore/bubble size while thickening fibers. Network metrics further followed an approximately geometric packing relation (pore/bubble size {propto} fiber density-1/2) across systems. For matched [Fgn]0 and [Thr]0, purified fibrinogen formed denser networks with smaller pores than plasma, consistent with environment-dependent effective assembly conditions. These parameterized scaling relations allow prediction linking composition to fibrin microstructure across plasma and purified fibrinogen clots, and they motivate a mechanistic picture in which thrombin sets the kinetic/length scale of single-fiber growth while fibrinogen tunes space-filling architecture. Fiber length analysis suggests that each thrombin molecule nucleates one fiber. These relationships provide the baseline for extensive, quantitative modeling work of blood clotting.