During ECMO the dose–response relationship disappears when heparin is monitored by ACT but it is preserved by anti-Xa activity

Extracorporeal membrane oxygenation (ECMO) has become standard supportive therapy during critical cardiorespiratory situations. Anticoagulation is mandatory to prevent obstruction of the circuit. The optimal heparin infusion rate is estimated for each patient according to a dose–response relationship that is usually measured with the activated clotting time (ACT). Preliminary data suggests that ACT gives a wrong estimate of this relationship so we compared it to anti-Xa activity during heparin infusion. We performed an observational prospective cohort study on 65 consecutive patients treated with ECMO and unfractionated heparin between January 2014 and April 2015 in the intensive care unit of the Rangueil University Hospital in Toulouse, France. ACT was measured with Hemocron ® Low Range for a target 180–220 s. Anti-Xa activity was measured for a target 0.2–0.4 UI/mL with STA-Liquid anti-Xa on the STAR ® coagulometer. The dose–response relationship and risk of over and under dosage were analyzed on the first 5 days of treatment divided each in 2 periods of 12 h. This dose–response relationship over time was studied with a generalized mixed effects model. The study protocol was approved by our institutional ethics and research committee (no. 11-0214). ACT results are independent ( P  = 0.55) of the daily amount of heparin administered (IU/kg/day) while anti-Xa activity results show a clear quadratic dose–response relationship ( P P  = 0.82) while anti-Xa activity shows that this risk diminishes over time ( P P  = 0.05). The risk of underdosage is less pronounced with ACT than with anti-Xa activity. This study confirms that ACT gives a wrong estimate of the dose–response relationship during ECMO. The amount of heparin administered is independent of ACT results. These results challenge ACT as the reference method for adjusting heparin infusion rates during ECMO ( Fig. 1 ).