The long term immunological response of swine after two exposures to a salmon thrombin and fibrinogen hemostatic bandage.

Experimental salmon thrombin/fibrinogen dressings have been shown to provide effective hemostasis in severe hemorrhage situations. The hypothesis for this study was that swine would still remain healthy without coagulopathy six months after exposure to salmon thrombin/fibrinogen dressings. Initial exposure was by insertion of the salmon dressing into the peritoneal cavity. Three months after the initial exposure, the same animals were subjected to two full thickness dermal wounds on the dorsal surface. One wound was bandaged with the salmon thrombin/fibrinogen bandage and the other wound was dressed with a standard bandage. The animals were monitored for an additional three months. Blood was drawn every 14 days over the six months for immunological and coagulation function analysis. All of the animals (8 pigs) remained healthy during the six month period and the dermal wounds healed without incidence. Lymph nodes and spleen showed signs of normal immune response and Western blots showed development of antibodies against salmon fibrinogen, but none of the animals made antibodies that recognized any species of thrombin. Coagulation parameters (fibrinogen concentration, thrombin time, PT and aPTT) and hematological parameters remained normal over the course of the study when compared to initial values of the subject swine.

Wound healing and the immune response in swine treated with a hemostatic bandage composed of salmon thrombin and fibrinogen.

We investigated the inflammatory response in pigs exposed to salmon fibrinogen/thrombin dressings. Animals were exposed to the material in 3 ways: (a) thrombin and fibrinogen were injected intravenously, (b) dual full-thickness skin lesions were surgically created on the dorsal aspect of the swine and treated with the fibrinogen/thrombin bandage and a commercial bandage or (c) a fibrinogen/thrombin bandage was inserted through an abdominal incision into the peritoneal cavity. Blood was collected twice weekly and animals were sacrificed at 7, 10 or 28 days. Animals in the 28-day dermal lesion group were given an injection of salmon fibrinogen/thrombin at the 10 day point to simulate a second bandage application. The immune response manifested itself as induction of germinal centers in mesenteric lymph nodes and in the white pulp of the spleen. Examination of the histology of the skin and organs showed a cellular inflammatory response with granulation tissue and signs of edema that resolved by the 28-day stage. Antibodies reactive to salmon and human thrombin and fibrinogen were detected, but fibrinogen levels and coagulation processes were not affected. In conclusion, animals treated with salmon fibrinogen/thrombin bandages demonstrated a smooth recovery course in terms of both tissue healing and the immune response without adverse effects from the exposure to the fish proteins.

A salmon thrombin-fibrin bandage controls arterial bleeding in a swine aortotomy model.

BACKGROUND: Recently, a wide variety of bandages have been formulated to attempt to improve the effectiveness of emergency intervention in situations of uncontrolled bleeding. The best of these dressings contain a mixture of human thrombin and fibrinogen. The presence of human components in these bandages, although effective, increases the cost of the dressing and raises questions of availability of raw materials and transmission of pathogens. The purpose of this study was to investigate the efficacy of dressings composed of salmon thrombin and fibrinogen in a swine aortotomy model. METHODS: A 4.4-mm aortotomy was produced in the abdominal aorta of 19 anesthetized, splenectomized swine. The United States Army standard field gauze was applied to 8 animals, and the salmon thrombin-fibrin dressing (SFD) was applied to 11 animals. Survival, blood loss, and other parameters were measured over a 60-minute period. RESULTS: All 11 animals that received the SFD survived the aortotomy injury, and bleeding stopped within 7.5 +/- 1.5 min. Seven of 8 animals in the control group were killed when bleeding continued and blood pressures decreased to the cutoff values as outlined in the animal protocol. Bleeding was significantly less in the SFD group compared with the gauze group (241 +/- 65.3 vs. 932.7 +/- 142.4 mL). CONCLUSION: Fibrin dressing using salmon-derived thrombin and fibrinogen is effective in controlling severe, uncontrolled bleeding. This dressing may offer an alternative to dressings composed of human coagulation proteins.