Abstract

Fibrinogen concentrates are used widely as a sealant during and after surgery to reduce blood loss. Commercially available fibrin sealants are made from pooled human blood, which carries the risk of blood-borne diseases, and are expensive. These concerns have brought to focus the need for autologous fibrinogen concentrates. This need has been addressed by utilizing a unique approach in which fibrinogen is precipitated from plasma with protamine. The physical properties of fibrin sealant prepared from fibrinogen precipitated with protamine were evaluated. The optimal precipitation conditions included a plasma protamine concentration of 10 mg/mL at room temperature. Under these conditions 96% ± 4% of the fibrinogen present in the plasma was precipitated and 98% ± 0.9% of the precipitated fibrinogen was clottable. In addition, it was shown that almost 50% of the factor XIII in the plasma was also precipitated along with the fibrinogen. The tensile and adhesion strengths and kinetics of fibrin sealant prepared from protamine-fibrinogen concentrate were evaluated. Tensile strength and adhesion strength both increased with increasing fibrinogen concentration. Addition of calcium chloride significantly increased the tensile and adhesion strengths. The addition of aprotinin and ε-aminocaproic acid (used to inhibit natural fibrinolysis) to the fibrinogen concentrate was shown to have no effect on the mechanical properties of the sealant. Kinetic experiments showed that the clotting time decreased as the thrombin and fibrinogen concentrations were increased. A rat model with controlled renal incisions was employed to evaluate the hemostatic efficacy of the fibrin sealant made from the protamine-fibrinogen concentrate. The fibrin sealant significantly reduced the blood loss and bleeding time when compared with controls (no sealant, plasma, and a commercial product). The sealant also significantly reduced blood loss and bleeding time in rats that were anticoagulated with heparin. A mathematical model based on tensile strength and adhesion strength was developed to predict the bleeding time in the animal wound. Model predictions showed that the ability of the fibrin sealant to reduce bleeding time, and therefore blood loss, was limited by the adhesion strength.

Degree

PhD

College and Department

Ira A. Fulton College of Engineering and Technology; Chemical Engineering

Rights

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