Key Points
- To determine whether recombinant tissue factor pathway inhibitor (rTFPI) reduces early local procoagulant activity and acute thrombosis following balloon-induced carotid artery injury.
- Bilateral carotid artery injury was induced via balloon hyperinflation in anesthetized pigs assigned to untreated controls (n=16), 24-hour intravenous rTFPI (0.5 mg/kg bolus plus 25 µg/kg/min, n=14), or 24-hour unfractionated heparin (100 U/kg/h, n=19).
- Accumulation of radiolabeled autologous platelets and fibrin deposition on injured vessel walls were quantified over 24 hours.
- Factor Xa generation was assayed via chromogenic substrate S-2222 at 24 hours, alongside measurement of tissue factor protein induction.
- Platelet accumulation decreased significantly with rTFPI (0.6x10^6/cm^2) compared with controls (2.5x10^6/cm^2, P=0.0004), and fibrin deposition was also reduced (269±266 µg/cm^2 vs 2389±1673 µg/cm^2, P=0.04).
- Factor Xa activity on injured arterial segments was lower with rTFPI (0.14±0.13 OD) than with heparin (0.29±0.18 OD) and controls (0.47±0.24 OD, P=0.0007).
- Arteries treated with rTFPI exhibited a 4-fold lower induction of tissue factor protein compared with untreated controls (P=0.0002).
Structured PICO
Does rTFPI reduce procoagulant activity and thrombosis in pigs with balloon-induced arterial injury?
PPopulation49 anesthetized pigs with balloon-induced vascular injury in both carotid arteries
IInterventionIntravenous infusion of recombinant tissue factor pathway inhibitor (rTFPI) for 24 hours (0.5 mg/kg bolus and 25 microg/kg/min)
CComparatorNo anticoagulant (control) or intravenous infusion of unfractionated heparin (100 U/kg/h)
OOutcomeAccumulation of radiolabeled autologous platelets over 24 hourssurrogate
In a porcine angioplasty model, rTFPI significantly attenuated procoagulant activity, platelet accumulation, and tissue factor upregulation at the site of balloon-induced arterial injury.