TY - JOUR
T1 - Thrombogenicity of small-diameter prosthetic grafts
T2 - Relative contributions of graft-associated thrombin and factor Xa
AU - Toursarkissian, B.
AU - Eisenberg, P. R.
AU - Abendschein, D. R.
AU - Rubin, B. G.
N1 - Funding Information:
Purpose: We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo. Methods: 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 adsorbtion (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. Results: 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). Conclusions: 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 nonpreclot-ted, collagen-coated grafts as well. Treatment strategies to attenuate graft thrombosis may require the inhibition of both thrombin and factor Xa. (J Vasc Surg 1997; 25:730-5.) The widespread use of small-diameter prosthetic grafts for distal lower extremity revascularization has been limited by their high early failure rates. ~ Although the graft material itself is inert, 2 the rapid accumulation of coagulation proteins on the luminal surface after implantation results in significant graft-associated procoagulant activity. 3,4 This has prompted the search for new strategies to reduce graft thrombogenicity. The development of novel therapeutic approaches is dependent on a detailed knowledge of coagulation protein deposition on From the Departments of Surgery and Medicine, Washington University School of Medicine. This work was funded in part by a LifelineA ward Research Grant from the Societyf or Vascular Surgery/International Societyf or Cardiovascular Surgery and by a Monsanto-Washington Uni-versity BiomedicalR esearch Grant. Reprint requests: Brian G. Rubin, MD, 216 South Kingshighway, Department of Surgery, Room 3510, St. Louis, MO 63110. Copyright © 1997 by The Societyf or Vascular Surgery and Inter-national Society for Cardiovascular Surgery, North American Chapter. 0741-5214/97/$5.00 + 0 24/1/78149
PY - 1997
Y1 - 1997
N2 - Purpose: We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo. Methods: 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 adsorbtion (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. Results: 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). Conclusions: 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.
AB - Purpose: We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo. Methods: 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 adsorbtion (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. Results: 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). Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=0030892974&partnerID=8YFLogxK
U2 - 10.1016/S0741-5214(97)70302-1
DO - 10.1016/S0741-5214(97)70302-1
M3 - Article
C2 - 9129631
AN - SCOPUS:0030892974
SN - 0741-5214
VL - 25
SP - 730
EP - 735
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
IS - 4
ER -