Format

Send to

Choose Destination
J Am Coll Cardiol. 1996 Dec;28(7):1858-65.

Selective inhibition of factor Xa is more efficient than factor VIIa-tissue factor complex blockade at facilitating coronary thrombolysis in the canine model.

Author information

1
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.

Abstract

OBJECTIVES:

We determined the effect of adjunctive inhibition of the extrinsic coagulation pathway by factor VIIa-tissue factor complex inhibitors, DEGR VIIa and tissue factor pathway inhibitor (TFPI), and the selective factor Xa inhibitor, tick anticoagulant peptide (TAP), after thrombolytic therapy with tissue-type plasminogen activator (t-PA) in a canine model of electrically induced coronary thrombosis.

BACKGROUND:

Ongoing thrombin generation is considered an important component of the heightened thrombin activity associated with thrombolytic therapy and may be responsible for reperfusion failure and reocclusion.

METHODS:

Forty-two dogs with electrically induced coronary thrombus undergoing thrombolysis with t-PA (1 mg/kg over 20 min) were randomly assigned to one of the following adjunctive regimens: TAP (30 micrograms/kg body weight per min for 90 min, n = 10); TFPI (100 to 150 micrograms/kg per min for 90 min, n = 10); DEGR VIIa (1- to 2-mg/kg bolus, n = 10) and saline control (n = 12). The dogs were observed for 120 min after thrombolysis for reocclusion.

RESULTS:

All three active study agents accelerated the time to reperfusion by an average of 12 min (all p < 0.05). Duration of reflow was greatest with TAP (117 +/- 8 min, p < 0.05 compared with saline control), whereas DEGR VIIa and TFPI did not prolong the duration of reflow. Reocclusion rates were similar among control, DEGR VIIa and TFPI groups (70%, 78% and 67%, respectively). Tick anticoagulant peptide reduced the occurrence of reocclusion (0%, p < 0.05 compared with saline control).

CONCLUSIONS:

In this experimental model, during systematic blockade of various extrinsic coagulation pathway proteins, we demonstrated that whereas acceleration of thrombolysis occurs with factor VIIa-tissue factor complex inhibition, optimal enhancement of thrombolysis was achieved through specific factor Xa blockade.

PMID:
8962577
DOI:
10.1016/S0735-1097(96)00401-9
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center