ALTERED HEPARIN PHARMACODYNAMICS IN PATIENTS WITH PULMONARY-EMBOLISM

Heparin clearance and pharmacodynamic response were examined in 12 patients being treated for deep venous thrombosis (DVT, 6 patients) or pulmonary embolism (PE, 6 patients). A loading dose of 70 units/kg was administered to DVT patients and 100 units/kg to PE patients followed by an initial infusion rate of 15 or 25 units/kg/h for DVT or PE patients, respectively. Heparin clearance was determined at 4, 12, and 24 h after initiating heparin therapy. The mean heparin clearance in the DVT group was 2,164 +/- 1,024 ml/h at 4 h, 2,591 +/- 1,239 ml/h at 12 h, and 2,795 +/- 1,863 m/h at 24 h. The PE patients had clearances of 1,775 +/- 494, 2,004 +/- 321, and 2,843 +/- 1,000 ml/h at 4, 12, and 24 h, respectively. The difference between the two groups was not statistically significant (p > 0.50). The activated partial thromboplastin time (aPTT) was used as a measure of heparin effect. The maximum effect (E(MAX)) and concentration required to attain 50% of the maximum effect (EC50) Were determined for each group using the Lineweaver-Burke linearization method. The mean E(MAX) and EC50 for the DVT patients were 130 +/- 40.99 s and 1.01 +/- 0.70 units/ml, respectively. For the PE patients, the mean E(MAX) was 418 +/- 200 s and the mean EC50 was 4.32 +/- 2.81 units/ml. The difference between both groups for each parameter was statistically significant (p < 0.05). The results of the present study indicate that PE patients do not have a higher clearance than DVT patients; however, PE patients do have a lower sensitivity to heparin at higher concentrations than DVT patients. This supports the concept that comparable heparin doses can be used for anticoagulation at the lower aPTT range, but in the higher range of aPTTs, higher doses are required to treat PE patients compared to DVT patients.