fibrinopeptide-a and Graft-Occlusion--Vascular

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Arteriosclerosis; Diabetic Angiopathies; Female; Fibrinopeptide A; Graft Occlusion, Vascular; Heparin; Humans; Intermittent Claudication; Ischemia; Leg; Leg Ulcer; Male; Middle Aged; Postoperative Complications; Premedication

To minimize intraoperative blood loss a watertight knitted Dacron aortoiliac prosthesis has been developed by impregnation with bovine collagen. A potential disadvantage is that collagen may be associated with an increase in thrombus formation. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortoiliac operation as such on the coagulation mechanism during the first 10 days after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who underwent cholecystectomies served as controls. Three markers of the coagulation mechanism were monitored: beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation products. We found no significant differences in median beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation product levels between patients in the collagen-impregnated prosthesis group and patients in the nonimpregnated prosthesis group. This indicates that collagen does not stimulate the coagulation cascade any more than conventional Dacron protheses do. In a comparison of patients who underwent aortoiliac reconstruction and patients who underwent cholecystectomies, the results indicated a significant increased platelet activation and fibrin metabolism in aortoiliac reconstruction group compared with the control group. Finally, we observed a significantly higher preoperative fibrin metabolism in patients with vascular disease than in control subjects. This difference is attributable to the high preoperative fibrin/fibrinogen degradation product values in patients with aortic aneurysms.

Topics: Adult; Aged; Aged, 80 and over; Aorta; Aortic Aneurysm; Arterial Occlusive Diseases; beta-Thromboglobulin; Blood Vessel Prosthesis; Collagen; Female; Femoral Artery; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Graft Occlusion, Vascular; Humans; Iliac Artery; Male; Middle Aged; Platelet Activation; Polyethylene Terephthalates

We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo.. Preclotted and nonpreclotted (collagen-coated) polyester grafts were studied before and 24 hours after implantation into pig femoral arteries. After incubation of explanted grafts was performed with plasma depleted of vitamin K-dependent coagulation factors by barium chloride adsorption (Ba-plasma), graft-associated thrombin activity was determined by radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels reflect thrombin-mediated fibrin formation. Factor Xa activity was characterized by measuring activation of prothrombin added to Ba-plasma.. Thrombin and factor Xa were associated with the luminal surfaces of preclotted grafts before and 24 hours after implantation. Nonpreclotted grafts had negligible procoagulant activity before implantation. After 24 hours in vivo graft-associated factor Xa activity was similar in both nonpreclotted and preclotted grafts; however, more thrombin was bound to nonpreclotted coated grafts (p < 0.01).. The procoagulant activity of small-diameter prosthetic grafts persists for 24 hours after implantation and is attributable not only to graft-associated thrombin but also to de novo thrombin elaboration induced by factor Xa. Moreover, graft-associated procoagulant activity is not dependent on preclotting because it develops on nonpreclotted, collagen-coated grafts as well. Treatment strategies to attenuate graft thrombosis may require the inhibition of both thrombin and factor Xa.

Topics: Adsorption; Animals; Barium Compounds; Blood Coagulation; Blood Vessel Prosthesis; Chlorides; Collagen; Factor Xa; Femoral Artery; Fibrin; Fibrinopeptide A; Graft Occlusion, Vascular; Polyesters; Polyethylene Terephthalates; Prosthesis Design; Prothrombin; Surface Properties; Swine; Thrombin; Thrombosis; Vitamin K