Progressive intermittent claudication is associated with impaired fibrinolysis

L. A. Killewich, Andrew Gardner, R. P. Macko, D. J. Hanna, A. P. Goldberg, D. K. Cox, W. R. Flinn

Research output: Contribution to journalArticle

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Abstract

Purpose: Acute complications of atherosclerosis such as stroke and myocardial infarction are mused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). Methods: The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance ≤200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean ± SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls. Results: Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC (p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication (p = 0.001). Conclusions: All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis.

Original languageEnglish (US)
Pages (from-to)645-650
Number of pages6
JournalJournal of Vascular Surgery
Volume27
Issue number4
DOIs
StatePublished - Jan 1 1998

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Intermittent Claudication
Fibrinolysis
Peripheral Arterial Disease
Plasminogen Activator Inhibitor 1
Walking
Antigens
Serum
Immunosorbents
Tissue Plasminogen Activator
Enzymes
Disease Progression
Atherosclerosis
Thrombosis
Stroke
Myocardial Infarction

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Killewich, L. A., Gardner, A., Macko, R. P., Hanna, D. J., Goldberg, A. P., Cox, D. K., & Flinn, W. R. (1998). Progressive intermittent claudication is associated with impaired fibrinolysis. Journal of Vascular Surgery, 27(4), 645-650. https://doi.org/10.1016/S0741-5214(98)70229-0
Killewich, L. A. ; Gardner, Andrew ; Macko, R. P. ; Hanna, D. J. ; Goldberg, A. P. ; Cox, D. K. ; Flinn, W. R. / Progressive intermittent claudication is associated with impaired fibrinolysis. In: Journal of Vascular Surgery. 1998 ; Vol. 27, No. 4. pp. 645-650.
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Killewich, LA, Gardner, A, Macko, RP, Hanna, DJ, Goldberg, AP, Cox, DK & Flinn, WR 1998, 'Progressive intermittent claudication is associated with impaired fibrinolysis', Journal of Vascular Surgery, vol. 27, no. 4, pp. 645-650. https://doi.org/10.1016/S0741-5214(98)70229-0

Progressive intermittent claudication is associated with impaired fibrinolysis. / Killewich, L. A.; Gardner, Andrew; Macko, R. P.; Hanna, D. J.; Goldberg, A. P.; Cox, D. K.; Flinn, W. R.

In: Journal of Vascular Surgery, Vol. 27, No. 4, 01.01.1998, p. 645-650.

Research output: Contribution to journalArticle

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T1 - Progressive intermittent claudication is associated with impaired fibrinolysis

AU - Killewich, L. A.

AU - Gardner, Andrew

AU - Macko, R. P.

AU - Hanna, D. J.

AU - Goldberg, A. P.

AU - Cox, D. K.

AU - Flinn, W. R.

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N2 - Purpose: Acute complications of atherosclerosis such as stroke and myocardial infarction are mused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). Methods: The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance ≤200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean ± SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls. Results: Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC (p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication (p = 0.001). Conclusions: All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis.

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