Efficacy of local inhibition of procoagulant activity associated with small-diameter prosthetic vascular grafts

L. Oltrona, P. R. Eisenberg, D. R. Abendschein, B. G. Rubin

Research output: Contribution to journalArticle

Abstract

Purpose: Graft procoagulant activity is determined by thrombin (IIa) and activated factor X (Xa) that binds to thrombus. Thrombus-associated factor Xa and thrombin are resistant to antithrombin III-dependent therapy (heparin). To avoid complications and costs associated with systemic administration, we evaluated whether locally applied antithrombotic agents inhibit prosthetic graft procoagulant activity under no-flow and low-flow conditions. Methods: Four-millimeter-diameter collagen-coated grafts were preclotted in recalcified human plasma, washed, immersed in antithrombotic agents (either 100 nm hirudin, 20 μm D-Phe-L-Pro-L-Arg chloromethylketone, 5 μm tick anticoagulant peptide or 5 or 10 μg/ml tissue factor pathway inhibitor) or saline solution, and extensively rewashed. Grafts were exposed to recalcified plasma either in multiwell plates or underwent perfusion at 1 ml/min flow rate. Fibrinopeptide A, which reflects fibrin elaboration, was measured as a marker of thrombin activity. Results: Inhibitors reduced fibrinopeptide generation at 8 minutes by 55% (tissue factor pathway inhibitor), 57% (hirudin), or 63% (tick anticoagulant peptide and D-Phe-L-Pro-L- Argchloromethylketone) compared with the control agents (p <0.05). Under low-flow conditions tissue factor pathway inhibitor and hirudin reduced fibrinopeptide generation at 13 minutes by 61% and 49%, respectively, when compared with control agents (p <0.05). Conclusions: Graft-associated inhibitors targeted at factors IIa, Xa, or tissue factor/VIIa/Xa complex effectively reduce procoagulant activity on prosthetic grafts. The success of local application of antithrombotic agents in attenuating early fibrin formation suggests that this strategy could favorably influence acute graft patency, and we speculate these agents may improve long-term graft patency as well.

Original languageEnglish
Pages (from-to)624-631
Number of pages8
JournalJournal of Vascular Surgery
Volume24
Issue number4
DOIs
Publication statusPublished - 1996

Fingerprint

Blood Vessels
Factor Xa
Transplants
Hirudins
Fibrinolytic Agents
Thrombin
Fibrin
Thrombosis
Fibrinopeptide A
Factor VIIa
Antithrombin III
Thromboplastin
Sodium Chloride
Heparin
Collagen
Perfusion
Costs and Cost Analysis
lipoprotein-associated coagulation inhibitor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Efficacy of local inhibition of procoagulant activity associated with small-diameter prosthetic vascular grafts. / Oltrona, L.; Eisenberg, P. R.; Abendschein, D. R.; Rubin, B. G.

In: Journal of Vascular Surgery, Vol. 24, No. 4, 1996, p. 624-631.

Research output: Contribution to journalArticle

Oltrona, L. ; Eisenberg, P. R. ; Abendschein, D. R. ; Rubin, B. G. / Efficacy of local inhibition of procoagulant activity associated with small-diameter prosthetic vascular grafts. In: Journal of Vascular Surgery. 1996 ; Vol. 24, No. 4. pp. 624-631.
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abstract = "Purpose: Graft procoagulant activity is determined by thrombin (IIa) and activated factor X (Xa) that binds to thrombus. Thrombus-associated factor Xa and thrombin are resistant to antithrombin III-dependent therapy (heparin). To avoid complications and costs associated with systemic administration, we evaluated whether locally applied antithrombotic agents inhibit prosthetic graft procoagulant activity under no-flow and low-flow conditions. Methods: Four-millimeter-diameter collagen-coated grafts were preclotted in recalcified human plasma, washed, immersed in antithrombotic agents (either 100 nm hirudin, 20 μm D-Phe-L-Pro-L-Arg chloromethylketone, 5 μm tick anticoagulant peptide or 5 or 10 μg/ml tissue factor pathway inhibitor) or saline solution, and extensively rewashed. Grafts were exposed to recalcified plasma either in multiwell plates or underwent perfusion at 1 ml/min flow rate. Fibrinopeptide A, which reflects fibrin elaboration, was measured as a marker of thrombin activity. Results: Inhibitors reduced fibrinopeptide generation at 8 minutes by 55{\%} (tissue factor pathway inhibitor), 57{\%} (hirudin), or 63{\%} (tick anticoagulant peptide and D-Phe-L-Pro-L- Argchloromethylketone) compared with the control agents (p <0.05). Under low-flow conditions tissue factor pathway inhibitor and hirudin reduced fibrinopeptide generation at 13 minutes by 61{\%} and 49{\%}, respectively, when compared with control agents (p <0.05). Conclusions: Graft-associated inhibitors targeted at factors IIa, Xa, or tissue factor/VIIa/Xa complex effectively reduce procoagulant activity on prosthetic grafts. The success of local application of antithrombotic agents in attenuating early fibrin formation suggests that this strategy could favorably influence acute graft patency, and we speculate these agents may improve long-term graft patency as well.",
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T1 - Efficacy of local inhibition of procoagulant activity associated with small-diameter prosthetic vascular grafts

AU - Oltrona, L.

AU - Eisenberg, P. R.

AU - Abendschein, D. R.

AU - Rubin, B. G.

PY - 1996

Y1 - 1996

N2 - Purpose: Graft procoagulant activity is determined by thrombin (IIa) and activated factor X (Xa) that binds to thrombus. Thrombus-associated factor Xa and thrombin are resistant to antithrombin III-dependent therapy (heparin). To avoid complications and costs associated with systemic administration, we evaluated whether locally applied antithrombotic agents inhibit prosthetic graft procoagulant activity under no-flow and low-flow conditions. Methods: Four-millimeter-diameter collagen-coated grafts were preclotted in recalcified human plasma, washed, immersed in antithrombotic agents (either 100 nm hirudin, 20 μm D-Phe-L-Pro-L-Arg chloromethylketone, 5 μm tick anticoagulant peptide or 5 or 10 μg/ml tissue factor pathway inhibitor) or saline solution, and extensively rewashed. Grafts were exposed to recalcified plasma either in multiwell plates or underwent perfusion at 1 ml/min flow rate. Fibrinopeptide A, which reflects fibrin elaboration, was measured as a marker of thrombin activity. Results: Inhibitors reduced fibrinopeptide generation at 8 minutes by 55% (tissue factor pathway inhibitor), 57% (hirudin), or 63% (tick anticoagulant peptide and D-Phe-L-Pro-L- Argchloromethylketone) compared with the control agents (p <0.05). Under low-flow conditions tissue factor pathway inhibitor and hirudin reduced fibrinopeptide generation at 13 minutes by 61% and 49%, respectively, when compared with control agents (p <0.05). Conclusions: Graft-associated inhibitors targeted at factors IIa, Xa, or tissue factor/VIIa/Xa complex effectively reduce procoagulant activity on prosthetic grafts. The success of local application of antithrombotic agents in attenuating early fibrin formation suggests that this strategy could favorably influence acute graft patency, and we speculate these agents may improve long-term graft patency as well.

AB - Purpose: Graft procoagulant activity is determined by thrombin (IIa) and activated factor X (Xa) that binds to thrombus. Thrombus-associated factor Xa and thrombin are resistant to antithrombin III-dependent therapy (heparin). To avoid complications and costs associated with systemic administration, we evaluated whether locally applied antithrombotic agents inhibit prosthetic graft procoagulant activity under no-flow and low-flow conditions. Methods: Four-millimeter-diameter collagen-coated grafts were preclotted in recalcified human plasma, washed, immersed in antithrombotic agents (either 100 nm hirudin, 20 μm D-Phe-L-Pro-L-Arg chloromethylketone, 5 μm tick anticoagulant peptide or 5 or 10 μg/ml tissue factor pathway inhibitor) or saline solution, and extensively rewashed. Grafts were exposed to recalcified plasma either in multiwell plates or underwent perfusion at 1 ml/min flow rate. Fibrinopeptide A, which reflects fibrin elaboration, was measured as a marker of thrombin activity. Results: Inhibitors reduced fibrinopeptide generation at 8 minutes by 55% (tissue factor pathway inhibitor), 57% (hirudin), or 63% (tick anticoagulant peptide and D-Phe-L-Pro-L- Argchloromethylketone) compared with the control agents (p <0.05). Under low-flow conditions tissue factor pathway inhibitor and hirudin reduced fibrinopeptide generation at 13 minutes by 61% and 49%, respectively, when compared with control agents (p <0.05). Conclusions: Graft-associated inhibitors targeted at factors IIa, Xa, or tissue factor/VIIa/Xa complex effectively reduce procoagulant activity on prosthetic grafts. The success of local application of antithrombotic agents in attenuating early fibrin formation suggests that this strategy could favorably influence acute graft patency, and we speculate these agents may improve long-term graft patency as well.

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