Relationship between the anticoagulant and antithrombotic effects of heparin in experimental venous thrombosis.

The relationship between the antithrombotic and anticoagulant effects of heparin was assessed using venous thrombi in rabbits. Accretion of 125I-fibrinogen onto jugular vein thrombi was used to assess the antithrombotic effect of heparin, and the protamine sulfate titration test (heparin activity) and the activated partial thromboplastin time (APTT) were used to measure its anticoagulant effect. The effect of heparin on jugular vein bleeding times was also measured in a separate group of animals. Fibrinogen accretion was significantly lower with continuous infusion than with intermittent injection. Heparin, given by continuous infusion, produced marked inhibition of fibrinogen accretion (to less than 10% of control accretion) at an APTT value of between 75 and 80 sec (control 34 sec) and at a level of heparin activity of 0.4-0.5 U/ml. Infusion of cryoprecipitate reduced the effect of heparin on the APTT relative to its effect on heparin activity. In these cryoprecipitate-treated animals, marked inhibition of fibrinogen accretion occurred at a similar level of heparin activity (0.4-0.6 U/ml) but at a significantly lower APTT (35-50 sec) than in normal animals. On the other hand, there was a progressive increase in jugular vein bleeding time with both increasing APTT values and heparin levels in both groups of animals.

Heparin kinetics in venous thrombosis and pulmonary embolism.

The response to a standard dose of heparin was studied in 20 patients with venous thromboembolism. The heparin regimen consisted of intravenous injection of 70 units per kg, followed after 90 minutes by a maintenance dose of 400 units per kg per 24 hours given by continuous infusion. Plasma heparin activity and the activated partial thromboplastin time (APTT) were measured at intervals to determine clearance of the initial injection and the response to maintenance dose. Large inter-individual variations were found in the anticoagulant effect and these were due in part to differences in heparin clearance and in part to differences in the APTT response to given amounts of heparin (heparin effect index). The heparin half-life was 63 +/- 15 minutes when plasma heparin activities were used for this calculation and 84 +/- 71.5 minutes when the APTT was used. These results are similar to values previously reported in normal volunteers. Four of the 20 patients had pulmonary embolism and in these heparin half-life was significantly shortened (P less than 0.005).