Correlation between activated clotting time and anti-xa activity in patients undergoing cardiac surgery requiring cardiopulmonary bypass

Introduction Anticoagulation for cardiopulmonary bypass (CPB) has historically involved the use of heparin as the anticoagulant of choice. Activated clotting time (ACT) is considered the gold standard for determining adequate level of anticoagulation before and during CPB. Recent guidelines suggest ACT > 480 seconds during CPB; however, initial validation studies were done on much older generations of bypass circuits in animal models and results have not been replicated in more recent clinical studies. ACT is also a measure of whole blood clotting and does not necessarily reflect degree of heparin activity. Newer studies have shown poor correlation between ACT and anti-Xa activity levels, the latter considered the gold standard for monitoring heparin activity. We sought to quantify the correlation between two point-of-care ACT instruments with the laboratory based anti-Xa activity assay for patients undergoing cardiac surgery requiring CPB at various time points during surgery. Methods 50 patients undergoing cardiac surgery requiring CPB were consented and enrolled. Blood samples were taken from each patient to examine the correlation between two ACT point-of-care instruments, Hemochron and i-STAT, and that of anti-Xa activity at various points during surgery. These timepoints were at baseline, after initial heparin bolus prior to initiating bypass, during CPB, and after protamine reversal of heparin. Pearson's correlation coefficient (r) was calculated for each set of comparisons. Results We obtained a total of 542 comparisons between ACT values and anti-Xa activity. There was poor correlation between both ACT instruments and anti-Xa activity after the initial bolus of heparin prior to bypass (r = 0.27 and 0.15), with correlations worsening on bypass (r = 0.11 and 0.04). i-STAT generally correlated better with anti-Xa activity and the two ACT instruments generally correlated well with each other (r = 0.88, all timepoints), except while on CPB (r = 0.11, CPB only). There was greater than 16-fold difference seen in heparin activity between patient samples when ACT > 400, with anti-Xa activity ranging from 0.78 to 16.10 U/mL. The average ACT (i-STAT) after protamine reversal was 22 seconds lower than baseline; however, average post-protamine anti-Xa activity was 0.77 U/mL. Discussion Our results suggest perhaps excessive and/or suboptimal anticoagulation in some patients during CPB and inadequate reversal of heparin post-bypass despite ACT values normalizing. Using ACT alone as a point-of-care tool may be inadequate in determining the optimal level of anticoagulation during bypass and reversal of heparin in patients undergoing cardiac surgery requiring CPB.