Purification of Pharmaceutical Grade Salmon-Derived Thrombin and Fibrinogen for Hemostatic Bandages

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Senior Design Reports (CBE)
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Biochemical and Biomolecular Engineering
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Debes, Jesse
Elmongy, Hanna
Keenan, Shannon
Kirby, Kristin

Hemorrhage due to trauma is the leading cause of preventable death among American soldiers, according the National Institute of Trauma. Uncontrollable bleeding is also seen regularly in civilian incidences of trauma and is a common major surgical complication. The human blood clotting process involves a complex cascade of tightly regulated enzymatic reactions. Two of the most important proteins in this cascade are fibrinogen and thrombin. Thrombin is an enzyme that activates fibrinogen monomers to form a polymeric fibrin network, forming the basis of a blood clot. During trauma, a state of consumptive coagulopathy, the body depletes these two proteins causing severe bleeding. A novel way to counteract hemorrhage is to supply additional thrombin and fibrinogen to the focal injury site. However, as of yet fibrinogen has proved technically challenging to produce recombinantly, and mammalian-based proteins carry the risk of pathogen transmission and immune response. Salmon-derived proteins, on the other hand, overcome both of these obstacles. DiamondStat is a novel hemostatic bandage that delivers fibrinogen and thrombin purified from salmon blood. It is a 4 x 4 inch adhesive bandage that delivers 10 mg/cm2 of fibrinogen and 90 units/cm2 of thrombin to effectively stop hemorrhage. The production of DiamondStat bandages begins with harvesting blood from salmon. Through a series of centrifugations and precipitations, prothrombin (a zymogen precursor to thrombin) and fibrinogen are extracted from the blood. Additional precipitations and filtrations further purify the fibrinogen solution to pharmaceutical-grade. The prothrombin is converted to thrombin in an immobilized snake venom catalyst column. Thrombin is then purified through an affinity column and ultrafiltration. Both thrombin and fibrinogen solutions are run through endotoxin removal columns and then sprayed onto pieces of gauze. The proteins are lyophilized onto the gauze and 2 the final bandage, which consists of fibrinogen and thrombin gauze pieces and an adhesive backing, is assembled. Bandages are sterilized via gamma irradiation and ready for use. At a capacity of 300,000 bandages per year and $800 per bandage, DiamondStat production is very profitable. It will yield an internal rate of return of 289.76% and a net present value of over $489 million. Extensive sensitivity analysis indicates that the project will be profitable in all likely scenarios. Investment in the DiamondStat processing plant is highly recommended. It is an economically viable project with the potential to save the lives of hundreds of thousands of American servicemen and women.

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