Heparin Monitoring on ECMO: Xa vs aPTT

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Colin McCloskey
EM Intensivist at University Hospitals Cleveland Medical Center

The Pre-brief

A 56 year old male presents after acute myocardial infarction with cardiogenic shock. Despite stenting the culprit lesion and initiation of multiple inopressors, the patient’s condition continues to deteriorate. The decision is made to cannulate for veno-arterial (V-A) ECMO. After cannulation is completed, the bedside nurse asks how you will monitor heparin anticoagulation.

“Do you want me to follow aPTTs or Xa’s?”

I authored an earlier post on the nuances of monitoring heparin anticoagulation for patients on ECMO. ELSO recognizes this but offers no recommendation on which test of heparin anticoagulation should be used for patients on ECMO. My practice is to use Anti-Xa levels for daily monitoring, but ACT, aPTT and TEG all are reasonable options. Evidence is scarce.

Recently, Kulig and colleagues published a study comparing adult V-A ECMO patients receiving unfractionated heparin for anticoagulation monitored with the aPTT versus the anti-Xa assay.

This retrospective cohort study was undertaken at a single academic medical center between 2010-2019. This was a before (aPTT) and after (anti-Xa) cohort following a protocol change at the institution. V-V ECMO, pregnant patients, and those who were cannulated at other institutions were excluded from the analysis.

The primary outcome was heparin rate required to achieve the target anticoagulation goal and time until that assay goal was reached. Secondary outcomes of note included what percentage of time patients were above-, below- and at-goal, as well as in-hospital mortality. Safety outcomes included a number of circuit changes, number of thrombotic events and administration of blood products.

Forty-two patients were enrolled, with 29 utilizing aPTT and 12 utilizing anti-Xa levels. The groups had a significant difference baseline, with the aPTT group having a higher starting heparin rate. Though not statistically significant, the aPTT group also had longer ECMO run times (95 vs 75 hrs). 

The results of the primary and secondary endpoints of note are listed below.

Despite starting at a higher heparin rate, the aPTT group took longer to reach their assay target than the anti-Xa group. Significantly, the aPTT group also spent a longer percentage of time above goal range.

Due to low event rates, safety outcomes were described but not statistically analyzed. However, at a glance there were more clotting events and greater blood product administration in the aPTT group. 

This is not a randomized controlled study. It is a retrospective chart review with a before and after design that included 41 patients. Indication for ECMO, cannulation configuration, comorbid organ failures are not reported. All may confound the findings. Further, to my reading, the aPTT target range was correlated to anti-Xa ranges of 0.3-0.7. Thus, the study was aPTT correlating to a goal anti-Xa versus a goal anti-Xa alone. 

This study does give us more data on a contentious topic of discussion on ECMO rounds. I read the results to support my current practice of using anti-Xa, as it may reduce heparin dose requirements as well as quicken time to therapeutic anticoagulation. Like everything in ECMO, higher quality studies with large sample sizes are needed.

The Debrief

  • ACT, anti-Xa, aPTT, and TEG are all viable but flawed monitoring options for heparin anticoagulation. 
  • In this before and after chart review, anti-Xa levels led to less heparin exposure and more time in a therapeutic range than aPTT driven anticoagulation
  • More robust study designs with greater sample sizes are needed to improve our understanding of which monitoring test to use in ECMO patients


  1. Prime, B. ECLS Circuit. “ELSO Anticoagulation Guideline.” (2014).

  2. Kulig, C. E., Schomer, K. J., Black, H. B., & Dager, W. E. (2021). Activated Partial Thromboplastin Time Versus Anti-Factor Xa Monitoring of Heparin Anticoagulation in Adult Venoarterial Extracorporeal Membrane Oxygenation Patients. ASAIO Journal, 67(4), 411-415.


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