VPB0962 - Fracture mechanics of human blood clots: fibrinogen concentration is a critical determinant of clot toughness

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Ranjini Ramanujam, MS

Doctoral student
Rutgers University
New Brunswick, New Jersey, United States

Co-Author(s)

KG

Konstantinos Garyfallogiannis

Doctoral student
university of Pennsylvania
Philadelphia, Pennsylvania, United States
TY

Tony Yu

Post-doctoral researcher
Rutgers-State University of New Jersey
Philadelphia, Pennsylvania, United States
CN

Chandrasekaran Nagaswami

Senior researcher
university of Pennsylvania
Philadelphia, Massachusetts, United States
Rustem I. Litvinov, MD, PhD

Senior researcher
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, United States
John W. Weisel, PhD

Professor
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, United States
JL

John L. Bassani

Professor
university of Pennsylvania
Philadelphia, Pennsylvania, United States
PK

Prashant K. Purohit

Associate Professor
university of Pennsylvania
Philadelphia, Pennsylvania, United States
VT

Valerie Tutwiler

Assistant Professor
Rutgers-State University of New Jersey
Piscataway, New Jersey, United States

Background: Embolization, or rupture of a thrombus, is a complication of thrombosis that increases mortality risk by up to 30%. Fibrin provides mechanical and structural stability to blood clots. Increased fibrin(ogen) concentration, which is a thrombophilia, is associated with (pro)-thrombotic conditions and embolization risk.

Aims: To characterize the dependence of mechanical toughness (resistance to rupture), on fibrin(ogen) concentration.

Methods: We performed single edge notch fracture tests to examine fibrin rupture under a constant strain rate (Figure 1A). We utilized confocal and scanning electron microscopy to quantify fibrin network structure. A finite element model using fibrin constitutive laws was used to independently probe the relationship between fibrin(ogen) concentration and resistance to rupture.

Results: Our results revealed that increasing fibrin(ogen) concentration (1-10mg/ml) results in an increase in toughness (Gc) (3-15 N/m p< 0.0001) (Figure 1B) and the maximum force prior to rupture (Fmax) (0.08-0.43N p< 0.0001). Correlation analysis revealed no dependence of Gc on initial crack lengths across all fibrinogen concentrations studied, demonstrating that toughness is a well-defined material parameter. Increased fibrinogen concentration resulted in fewer (16-10 number of fibers p< 0.0001), thicker (0.15-0.35 µm p< 0.0001) fibrin fibers with a reduction in pore size (2.3-2 µm p< 0.0001).
Finite element modeling was required to capture the dissipative effects of fluid flow on the resistance to rupture; these effects cannot be easily measured experimentally. Our modeling suggests a power law relationship of the toughness to fibrinogen concentration (Figure 1C), suggesting a critical strain drives scission of the fibrin fibers.

Conclusion(s): These findings reveal a significant contribution of fibrin(ogen) concentration to the resistance of fibrin clots to rupture, suggesting a role in propensity for embolization.