Antithrombotic activity of recombinant tick anticoagulant peptide and heparin in a rabbit model of venous thrombosis.

Abstract:

:An in vivo rabbit model of venous thrombosis which includes physiological blood flow was used to compare the efficacy of the potent and specific factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) with standard heparin in the prevention of venous thrombus formation. In anesthetized rabbits, an autologous thrombus was induced with thrombin in a jugular vein and the increase in thrombus size was determined by measuring the accretion of intravenously injected [125I]fibrin(ogen) onto the developing thrombus. The effects of rTAP on hemostasis were monitored by changes in APTT values and template bleeding times. Inhibition of thrombus formation by an intravenous bolus followed by infusion of either rTAP or heparin exhibited a dose-response relationship with an IC50 of 0.9 micrograms/kg/min and 0.12 units/kg/min, respectively. At the IC50 doses, both rTAP and heparin inhibited fibrin(ogen) deposition without any significant effect on APTT or bleeding times. Bleeding times were modestly elevated at the fully efficacious doses of rTAP and heparin. Significant changes in APTT (1.9 +/- 0.3 fold over baseline) were only evident at the highest dose of rTAP while heparin caused a significant dose-dependent increase from 1.3 +/- 0.2 to greater than 4.2 +/- 0.6 fold over baseline. Therefore, in this rabbit model of venous thrombosis, specific inhibition of factor Xa by rTAP is an effective antithrombotic mechanism that does not require changes in systemic hemostatic parameters.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Fioravanti C,Burkholder D,Francis B,Siegl PK,Gibson RE

doi

10.1016/0049-3848(93)90200-8

subject

Has Abstract

pub_date

1993-08-15 00:00:00

pages

317-24

issue

4

eissn

0049-3848

issn

1879-2472

pii

0049-3848(93)90200-8

journal_volume

71

pub_type

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