Biomechanics, Energetics, and Structural Basis of Rupture of Fibrin Networks

Abstract

Fibrin provides the main structural integrity and mechanical strength to blood clots. Failure of fibrin clots can result in life‐threating complications, such as stroke or pulmonary embolism. The dependence of rupture resistance of fibrin networks (uncracked and cracked) on fibrin(ogen) concentrations in the (patho)physiological 1–5 g/l range was explored by performing the ultrastructural studies and theoretical analysis of the experimental stress‐strain profiles available from mechanical tensile loading assays. Fibrin fibers in the uncracked network stretched evenly, whereas in the cracked network, fibers around the crack tip showed greater deformation. Unlike fibrin fibers in cracked networks formed at the lower 1–2.7 g/l fibrinogen concentrations, fibers formed at the higher 2.7‐5 g/l concentrations align and stretch simultaneously. Cracked fibrin networks formed in higher fibrinogen solutions are tougher, yet, less extensible. Statistical modeling revealed that the characteristic strain for fiber alignment, crack size, and fracture toughness of fibrin networks control their rupture resistance. The results obtained provide a structural and biomechanical basis to quantitatively understand the material properties of blood plasma clots and to illuminate the mechanisms of their rupture.This article is protected by copyright. All rights reserved

Comprehensive Analysis of the Role of Fibrinogen and Thrombin in Clot Formation and Structure for Plasma and Purified Fibrinogen

“…We assessed the effect of fibrinogen concentration (1, 2.7, 5, and 10 mg/mL) on the resulting fiber and network structure in clots made from purified fibrinogen (Figure 1) and pooled human plasma (Figure 2) with a fixed thrombin concentration of 0.1 NIH-U/mL for the purified fibrinogen samples and 75 pM tissue factor for plasma samples, which is the concentration of TFused for diagnostic testing [48,49]. For both sample types, fiber diameter increased with increasing fibrinogen concentration (Figures 1A-D,I and 2A-D,I).…”

Injury Severity is a Key Contributor to Coagulation Dysregulation and Fibrinogen Consumption

“…TIC leads to changes in the factors present in the blood, altering fibrin network formation, resulting in increases in maladaptive thrombosis or hemorrhage [9,[14][15][16]. Alterations in the fibrin component of the blood clot and occurrence of fibrinolysis have been shown to impact clot structural mechanics and network properties [16][17][18][19][20]. Furthermore, changes to thrombin generation have been observed following injury in both animal models and trauma patients, leading to additional changes in fibrin structure and resulting clot stability [16,19,21,22].…”