Efficacy and Monitoring of Heparin Therapy in Experimental Venous Thrombosis

Abstract

Opinions differ regarding the most effective means of administering heparin therapy. We have compared 1) the effectiveness of continuous intravenous infusion with intermittent intravenous injection and 2) the relative effectiveness of using heparin level and activated partial thromboplastin time (APTT) for monitoring heparin in experimental venous thrombi in rabbits. Thrombus extension was quantitated by measuring the net accretion of 125I rabbit fibrinogen onto non-radioactive experimental venous thrombi over a 10 hour period. Fifty-four animals received heparin and 30 controls received saline. Heparin was administered by 1) continuous infusion in the following doses: a) initial bolus 200 U/kg followed by 400 U/kg infused in 10 hrs (full dose), b) 3/4 of full dose and c) ½ of fulldose; 2) by intermittent intravenous injection of a) 200 U/kg, b) 150 U/kg and c) 100 U/kg 4 hourly. All 3 continuous intravenous regimens showed significantly less accretion than the control animals, however, of the intermittent regimens only the full dose regimen showed significantly less accretion than the controls. Continuous heparin in both full dose and 3/4 dose showed significantly less accretion than the corresponding intermittent intravenous heparin regimens. The antithrombotic effect of heparin was reflected by both the heparin level and the APTT. The experiments were repeated with continuous intravenous heparin following infusion of cryoprecipitate into rabbits. This shortened the pre-heparin APTT and reduced the post-heparin APTT rise. Optimal suppression of thrombus extension in both normal and cryoprecipitate treated rabbits was obtained when APTT was maintained at approximately twice pre-treatment level.