INABILITY OF THE ACTIVATED PARTIAL THROMBOPLASTIN TIME TO PREDICT HEPARIN LEVELS - TIME TO REASSESS GUIDELINES FOR HEPARIN ASSAYS

Background: In treating venous thromboembolic disorders, patient outco mes appear to correlate with heparin levels. Due to pharmacokinetic an d pharmacodynamic variations, a relationship between heparin dose and level cannot be reliably predicted in individual patients. Some patien ts have low heparin levels despite therapeutic activated partial throm boplastin times (aPTTs), which may increase their risk for recurrent t hromboembolism. Patients with high heparin requirements appear to have fewer bleeding episodes with heparin level-guided therapy. The aPTT d oes not reliably correlate with heparin blood concentrations or antith rombotic effects. Consequently, heparin therapy monitored with heparin levels may be more effective and safer. Objectives: To prospectively determine whether (1) the aPTT therapeutic range adequately predicts h eparin levels in 38 patients used to establish the therapeutic aPTT ra nge as is currently recommended and (2) whether 3 paired sets of aPTT- antifactor Xa levels provide the basis for using aPTTs to predict subs equent heparin levels in individual patients (n=27) receiving intraven ous heparin for coronary artery disease or venous thromboembolic disea se. Results: In the therapeutic aPTT range established, the R-2 value for the relationship was 0.4. Prediction intervals were wide. For an a PTT of 60 seconds, the 95% prediction interval estimates were heparin levels of 0.05 to 1.0 U/mL. In individual patients, the aPTT-antifacto r Xa relationship had an average R-2 value of 0.75. There was no consi stent relationship between the aPTT and antifactor Xa level in a signi ficant number of patients. Conclusions: The aPTT does not appear to be a useful surrogate for heparin levels. These findings suggest that th e current recommendations on the use of heparin levels should be expan ded.