Heparin pharmacokinetics: increased requirements in pulmonary embolism

Heparin disappearance after injection and plasma levels during continuous infusion were studied in normal subjects and patients with thrombophlebitis, pulmonary embolism, renal failure, and liver failure. Heparin removal in normal subjects after 75 u/kg was nearly linear with a clearance of 0.64 ml/min/kg, SD +/- 0.11. Clearance varied inversely with dose. Heparin clearance in pulmonary embolism (0.80 ml/min/kg +/- 0.23) was significantly accelerated compared both to normals (P less than 0.005) and to thrombophlebitis patients (0.55 ml/min/kg +/- 0.19, P less than 0.01); the disappearance was more curvilinear in thrombophlebitis and pulmonary embolism than in normal subjects (P less than 0.025). Continuous infusion heparin requirements were greater in pulmonary embolism than in thrombophlebitis, in accordance with pharmacokinetic predictions. The pattern and rate of disappearance in renal disease was similar to normal subjects; in liver disease clearance was accelerated (0.86 ml/min/kg +/- 0.28) and disappearance curvilinear. Because of accelerated clearance, the initial dose of heparin in pulmonary embolism should be greater (25 u/kg/h) than in thrombophlebitis (10-15 u/kg/h). Variability within patient groups necessitates some laboratory control of dosage.