Factors associated with errors in the heparin dose response test: recommendations to improve individualized heparin management in cardiopulmonary bypass

Perfusion. 2021 Jul;36(5):513-523. doi: 10.1177/0267659120952977. Epub 2020 Sep 10.


Background: A critical aspect of cardiopulmonary bypass (CPB) is to achieve full anticoagulation to prevent thrombosis and consumptive coagulation without using excessive amount of heparin. This can be achieved with heparin dose response (HDR) test in vitro to calculate an individualized heparin bolus to reach a target activated clotting time (ACT) and heparin concentration. However, we often observe that the measured ACT (mACT) with the calculated heparin bolus gives significant errors, both positive (mACT is higher than expected) and negative (mACT is lower), from expected ACT (eACT).

Methods: We performed a retrospective study of 250 patients who underwent cardiac surgery to attain an error distribution of the mACT from eACT with calculated heparin bolus. In addition, it is aimed to identify possible patterns of baseline ACT (bACT), calculated heparin concentration (CHC) and HDR slope that are associated with the significant positive and negative errors.

Results: We found that individualized heparin bolus by HDR test is consistently underestimated while it gave a significant number of positive and negative errors. Further analysis indicates that significant negative errors correlate with high bACT and slope and low CHC while significant positive errors with low bACT and slope and high CHC.

Conclusion: The mACT can be substantially different from eACT. The accuracy of the HDR test appears to be dependent upon bACT, slope, and CHC. Based on our analysis, we provide several recommendations and a flow chart to improve the quality of individualized heparin management on CPB.

Keywords: anticoagulation; cardiopulmonary bypass; expected vs measured activated clotting time; heparin dose response test; individualized heparin management.

MeSH terms

  • Anticoagulants / therapeutic use
  • Cardiopulmonary Bypass*
  • Heparin* / therapeutic use
  • Humans
  • Retrospective Studies
  • Whole Blood Coagulation Time


  • Anticoagulants
  • Heparin