Defective fibrinolysis occurs after infrainguinal reconstruction

L. A. Killewich, R. F. Macko, A. W. Gardner, K. Cox, M. P. Lilly, W. R. Flinn, M. A. Mattos

Research output: Contribution to journalArticle

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Abstract

Purpose: Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. Methods: Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia. Endogenous fibrinolytic activity was assessed by measurement of tissue plasminogen activator (tPA) and its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen (total protein) levels were determined using enzyme linked immunosorbent assays, and measurements of in vivo biologic activity were performed using an amidolytic method. Measurements of tPA and PAI-1 were made before surgery, after surgery, and on postoperative days 1, 2, 7, and 30. Results: The mean preoperative PAI-1 activity was 20.6 ± 1.4 arbitrary units (AU)/ml, which was higher than that of an age-matched population without severe atherosclerosis. PAI-1 activity rose significantly after surgery (29.6 ± 2.2 AU/ml; p = 0.002) and remained elevated through the second day after surgery. Preoperative tPA activity level was 2.04 ± 0.59 IU/ml and fell to 0.79 ± 0.23 IU/ml (p = 0.046) immediately after the bypass procedure. All serologic indicators of fibrinolytic shutdown returned to baseline levels by 72 hours after surgery. No early graft thrombosis or other atherothrombotic complications occurred in these study patients. Conclusions: Defective endogenous fibrinolytic activity occurs in the early postoperative period after infrainguinal bypass grafting procedures. Diminished endogenous fibrinolytic activity in these patients appears to be mediated by a combination of reduced tPA activity and significantly increased PAI-1 activity. No practical method is available to directly treat postoperative fibrinolytic shutdown, but postoperative antithrombotic therapy may be useful during this period to prevent early graft occlusion related to a relative hypercoagulable state.

Original languageEnglish (US)
Pages (from-to)858-865
Number of pages8
JournalJournal of Vascular Surgery
Volume25
Issue number5
DOIs
StatePublished - Jan 1 1997

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Fibrinolysis
Plasminogen Activator Inhibitor 1
Tissue Plasminogen Activator
Transplants
Thrombosis
Epidural Anesthesia
Ambulatory Surgical Procedures
Postoperative Period
Atherosclerosis
Enzyme-Linked Immunosorbent Assay
Antigens
Population

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Killewich, L. A., Macko, R. F., Gardner, A. W., Cox, K., Lilly, M. P., Flinn, W. R., & Mattos, M. A. (1997). Defective fibrinolysis occurs after infrainguinal reconstruction. Journal of Vascular Surgery, 25(5), 858-865. https://doi.org/10.1016/S0741-5214(97)70215-5
Killewich, L. A. ; Macko, R. F. ; Gardner, A. W. ; Cox, K. ; Lilly, M. P. ; Flinn, W. R. ; Mattos, M. A. / Defective fibrinolysis occurs after infrainguinal reconstruction. In: Journal of Vascular Surgery. 1997 ; Vol. 25, No. 5. pp. 858-865.
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abstract = "Purpose: Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. Methods: Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia. Endogenous fibrinolytic activity was assessed by measurement of tissue plasminogen activator (tPA) and its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen (total protein) levels were determined using enzyme linked immunosorbent assays, and measurements of in vivo biologic activity were performed using an amidolytic method. Measurements of tPA and PAI-1 were made before surgery, after surgery, and on postoperative days 1, 2, 7, and 30. Results: The mean preoperative PAI-1 activity was 20.6 ± 1.4 arbitrary units (AU)/ml, which was higher than that of an age-matched population without severe atherosclerosis. PAI-1 activity rose significantly after surgery (29.6 ± 2.2 AU/ml; p = 0.002) and remained elevated through the second day after surgery. Preoperative tPA activity level was 2.04 ± 0.59 IU/ml and fell to 0.79 ± 0.23 IU/ml (p = 0.046) immediately after the bypass procedure. All serologic indicators of fibrinolytic shutdown returned to baseline levels by 72 hours after surgery. No early graft thrombosis or other atherothrombotic complications occurred in these study patients. Conclusions: Defective endogenous fibrinolytic activity occurs in the early postoperative period after infrainguinal bypass grafting procedures. Diminished endogenous fibrinolytic activity in these patients appears to be mediated by a combination of reduced tPA activity and significantly increased PAI-1 activity. No practical method is available to directly treat postoperative fibrinolytic shutdown, but postoperative antithrombotic therapy may be useful during this period to prevent early graft occlusion related to a relative hypercoagulable state.",
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Killewich, LA, Macko, RF, Gardner, AW, Cox, K, Lilly, MP, Flinn, WR & Mattos, MA 1997, 'Defective fibrinolysis occurs after infrainguinal reconstruction', Journal of Vascular Surgery, vol. 25, no. 5, pp. 858-865. https://doi.org/10.1016/S0741-5214(97)70215-5

Defective fibrinolysis occurs after infrainguinal reconstruction. / Killewich, L. A.; Macko, R. F.; Gardner, A. W.; Cox, K.; Lilly, M. P.; Flinn, W. R.; Mattos, M. A.

In: Journal of Vascular Surgery, Vol. 25, No. 5, 01.01.1997, p. 858-865.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Defective fibrinolysis occurs after infrainguinal reconstruction

AU - Killewich, L. A.

AU - Macko, R. F.

AU - Gardner, A. W.

AU - Cox, K.

AU - Lilly, M. P.

AU - Flinn, W. R.

AU - Mattos, M. A.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Purpose: Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. Methods: Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia. Endogenous fibrinolytic activity was assessed by measurement of tissue plasminogen activator (tPA) and its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen (total protein) levels were determined using enzyme linked immunosorbent assays, and measurements of in vivo biologic activity were performed using an amidolytic method. Measurements of tPA and PAI-1 were made before surgery, after surgery, and on postoperative days 1, 2, 7, and 30. Results: The mean preoperative PAI-1 activity was 20.6 ± 1.4 arbitrary units (AU)/ml, which was higher than that of an age-matched population without severe atherosclerosis. PAI-1 activity rose significantly after surgery (29.6 ± 2.2 AU/ml; p = 0.002) and remained elevated through the second day after surgery. Preoperative tPA activity level was 2.04 ± 0.59 IU/ml and fell to 0.79 ± 0.23 IU/ml (p = 0.046) immediately after the bypass procedure. All serologic indicators of fibrinolytic shutdown returned to baseline levels by 72 hours after surgery. No early graft thrombosis or other atherothrombotic complications occurred in these study patients. Conclusions: Defective endogenous fibrinolytic activity occurs in the early postoperative period after infrainguinal bypass grafting procedures. Diminished endogenous fibrinolytic activity in these patients appears to be mediated by a combination of reduced tPA activity and significantly increased PAI-1 activity. No practical method is available to directly treat postoperative fibrinolytic shutdown, but postoperative antithrombotic therapy may be useful during this period to prevent early graft occlusion related to a relative hypercoagulable state.

AB - Purpose: Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. Methods: Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia. Endogenous fibrinolytic activity was assessed by measurement of tissue plasminogen activator (tPA) and its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen (total protein) levels were determined using enzyme linked immunosorbent assays, and measurements of in vivo biologic activity were performed using an amidolytic method. Measurements of tPA and PAI-1 were made before surgery, after surgery, and on postoperative days 1, 2, 7, and 30. Results: The mean preoperative PAI-1 activity was 20.6 ± 1.4 arbitrary units (AU)/ml, which was higher than that of an age-matched population without severe atherosclerosis. PAI-1 activity rose significantly after surgery (29.6 ± 2.2 AU/ml; p = 0.002) and remained elevated through the second day after surgery. Preoperative tPA activity level was 2.04 ± 0.59 IU/ml and fell to 0.79 ± 0.23 IU/ml (p = 0.046) immediately after the bypass procedure. All serologic indicators of fibrinolytic shutdown returned to baseline levels by 72 hours after surgery. No early graft thrombosis or other atherothrombotic complications occurred in these study patients. Conclusions: Defective endogenous fibrinolytic activity occurs in the early postoperative period after infrainguinal bypass grafting procedures. Diminished endogenous fibrinolytic activity in these patients appears to be mediated by a combination of reduced tPA activity and significantly increased PAI-1 activity. No practical method is available to directly treat postoperative fibrinolytic shutdown, but postoperative antithrombotic therapy may be useful during this period to prevent early graft occlusion related to a relative hypercoagulable state.

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