Heparin Kinetics in venons Thrombosis and Pulmonary Embolism

Patients with venous thromboembolism differ considerably in their heparin response and requirements. We have investigated the mechanism for, and practical consequence of this variation in 20 patients with proven venous thromboembolism (VTE). A standard i/v heparin dose 70 U/kg bolus followed 90 min later by 400 U/kg/24 hrs. by continuous infusion was given. Blood was drawn pre heparin and 15, 45 and 90 min post bolus and then during maintenance infusion for the following tests: heparin tolerance, activated partial thromboplastin time (APTT), heparin level. In addition heparin recovery and clearance were calculated. There were large inter-individual variations in the anticoagulant response to heparin which was due in part to differences in rates of heparin inactivation and clearance and in part to marked differences in the APTT response to heparin. For example, the heparin level at 15 min post bolus varied from 0.2 U to 0.9 U and during maintenance from 0.0 U to 0.5 U. The APTT varied from 45 to 200 sees, at 15 min and 38 to 96 sees during maintenance infusion. In addition the APTT prolongation over the pre-treatment APTT varied up to 9 fold between patients for a given heparin concentration. There was a marked and significant difference in heparin half life between patients with venous thrombosis (70±17 min) and pulmonary embolism (PE) (38±1 min) p < 0.005. This rapid clearance in PE may be due to release of antiheparin activity from platelets which interact with thrombin onto the surface of the embolus. The results suggest that the heparin dose should be individualized in VTE and that larger doses should be initially given to patients with PE.