Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis

Andras Gruber, Stephen R. Hanson, Andrew B. Kelly, Betty S. Yan, Nils Bang, John H. Griffin, Laurence A. Harker

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Activated protein C (APC) is an antithrombotic enzyme. The therapeutic potential of infused human recombinant APC (rAPC) was studied in a primate model of platelet-dependent thrombosis. Eight baboons with chronic femoral arteriovenous shunts received rAPC infusions for 1 hour. The shunts were extended with 5-cm long, 4-mm-i.d. thrombogenic Dacron graft segments for the time of infusion. The plasma level of the enzyme, the blood flow in the shunt, and the deposition of indium-111-labeled platelets and iodine-125 fibrinogen on the graft were measured. The influence of rAPC infused at doses of 0.25 and 1.0 mg/kg-hr was compared with the effects of control infusions of saline. Five of eight control grafts occluded within 60 minutes, whereas there was no change in the blood flow during rAPC infusion. Deposition of platelets was inhibited by 13±10% and by 42±13% (mean±SEM) after 30 minutes of infusion at the two doses, which gave rise to circulating rAPC plasma concentrations of 0.4 and 1.9 mg/l, respectively. Both doses significantly inhibited fibrin deposition in the graft. Circulating plasma markers of thrombus formation and of fibrinolysis did not increase significantly during rAPC infusion; measurements of bleeding time were also within normal limits. Thus, rAPC, like human plasma-derived APC, inhibited thrombus formation without impairing primary hemostasis.

Original languageEnglish (US)
Pages (from-to)578-585
Number of pages8
JournalCirculation
Volume82
Issue number2
StatePublished - Aug 1990
Externally publishedYes

Fingerprint

Protein C
Recombinant Proteins
Primates
Thrombosis
Transplants
Blood Platelets
Indium
Bleeding Time
Polyethylene Terephthalates
Papio
Fibrinolysis
Enzymes
Thigh
Hemostasis
Fibrin
Iodine
Fibrinogen
Therapeutics

Keywords

  • Fibrinolysis
  • Grafts
  • Platelets

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Gruber, A., Hanson, S. R., Kelly, A. B., Yan, B. S., Bang, N., Griffin, J. H., & Harker, L. A. (1990). Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. Circulation, 82(2), 578-585.

Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. / Gruber, Andras; Hanson, Stephen R.; Kelly, Andrew B.; Yan, Betty S.; Bang, Nils; Griffin, John H.; Harker, Laurence A.

In: Circulation, Vol. 82, No. 2, 08.1990, p. 578-585.

Research output: Contribution to journalArticle

Gruber, A, Hanson, SR, Kelly, AB, Yan, BS, Bang, N, Griffin, JH & Harker, LA 1990, 'Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis', Circulation, vol. 82, no. 2, pp. 578-585.
Gruber, Andras ; Hanson, Stephen R. ; Kelly, Andrew B. ; Yan, Betty S. ; Bang, Nils ; Griffin, John H. ; Harker, Laurence A. / Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. In: Circulation. 1990 ; Vol. 82, No. 2. pp. 578-585.
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