Establishing a new target range for unfractionated heparin for acute coronary syndromes.

INTRODUCTION

The target activated partial thromboplastin time (aPTT) range of 1.5 to 2.5 times the control value or 45 to 75 seconds recommended by the ACC/AHA for patients receiving unfractionated heparin (UFH) for acute coronary syndromes (ACS) is vulnerable to variation in test reagents. Rather than use the standard target aPTT range, it has been recommended that each institution establish its own target aPTT range based upon anti-factor Xa heparin levels. As a quality assurance project, we evaluated our institution's therapeutic aPTT range by examining the correlation between aPTTs and anti-factor Xa heparin levels and established a new target aPTT range with a new thromboplastin reagent based upon the therapeutic anti-factor Xa heparin levels.

METHODS

Sixty-two plasma samples from 26 consecutive patients receiving UFH for ACS were analyzed. Plasma aPTTs measured with a thromboplastin reagent and a new thromboplastin reagent and anti-factor Xa heparin levels were obtained on each plasma sample. Linear regression analysis was performed to establish a new target aPTT range from corresponding therapeutic anti-factor Xa heparin levels.

RESULTS

Thirty-two percent of patients with our institution's target range aPTTs of 61 to 100 seconds had anti-factor Xa heparin levels below 0.35 to 0.7 U/mL while 68% of patients had therapeutic anti-factor Xa heparin levels (positive predictive value = 68%). When the same blood was tested with a new thromboplastin reagent lot, only 9% of patients with target range aPTTs had anti-factor Xa heparin levels below 0.35 U/mL while 91% of patients had therapeutic anti-factor Xa heparin levels (positive predictive value = 91%). The Pearson correlation coefficient ( r ) for the new thromboplastin reagent lot was 0.93. The target aPTT range established with the new thromboplastin reagent lot was 61 to 100 seconds.

CONCLUSION

Monitoring aPTTs without standardizing the thromboplastin reagent may not adequately reflect therapeutic heparin levels. Despite apparently target aPTTs, patients treated with UFH may be under-anticoagulated. Our new anti-Xa-adjusted target aPTT range shows an increase in the positive predictive value of aPTTs. Large-scale clinical studies are needed to determine the optimal anti-factor Xa range for ACS patients treated with UFH, with further refinements if glycoprotein IIb/IIIa inhibitors are concomitantly used and to show a benefit in clinical outcomes for monitoring plasma heparin levels with anti-factor Xa heparin levels. Institutional standardization of the aPTT is necessary to ensure optimal patient care when changing thromboplastin reagents.