Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions

Abstract

Choices for monitoring of unfractionated heparin (UFH) anticoagulation in extracorporeal membrane oxygenation (ECMO) patients include activated clotting time, activated partial thromboplastin time, reaction times of viscoelastic tests, and anti-factor Xa activity (between 0.3 and 0.7 IU/mL). Recent studies propose the anti-factor Xa to be the gold standard for monitoring UFH anticoagulation in ECMO. However, many extraneous factors combined question the utility of anti-factor Xa as the sole method of monitoring of UFH effects in ECMO. Anti-factor Xa is a chromogenic assay, which may be biased by the frequently elevated values of bilirubin and free hemoglobin in ECMO patients. The test may alternatively underestimate UFH effects in cases of low antithrombin values. More importantly, the anti-factor Xa assay is a plasma-based test which does not take into account the role of platelets and fibrinogen in forming a stable clot. Thrombocytopenia and platelet dysfunction are common features in ECMO patients, and underestimating their role may lead to over-anticoagulation, should only anti-factor Xa guiding be used to adjust the UFH dose. Conversely, fibrinogen is an acute phase protein, and some patients may experience high levels of fibrinogen during the ECMO course. In this case, an UFH monitoring based on anti-factor Xa is insensitive to this condition, although it may potentially be associated with thrombotic complications. Finally, the generally suggested range of 0.3 to 0.7 IU/mL is a somewhat arbitrary estimate, based on the desired range for treating and preventing thrombotic events in non-ECMO patients. In conclusion, anti-factor Xa may offer useful information on the real effects of UFH only when combined with a whole blood test capable of assessing the relative contribution of platelets and fibrinogen to clot formation.

Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure

“…In recent years, more centres integrated anti-Xa levels alongside ACT or PTT in their routine coagulation monitoring during ECMO support following promising results mainly in paediatric populations and better reflection of heparin concentrations [30][31][32][33]. Since inflammation can influence ACT measurements [34] the ECMO centres of the current study also utilize anti-Xa levels alongside thromboelastography and single clotting factor analysis where coagulation state is uncertain, and PTT or ACT seems out of line with heparin dosing.…”

Activated Clotting Time (ACT) for Monitoring of Low-Dose Heparin: Performance Characteristics in Healthy Adults and Critically Ill Patients

“…ACT is a whole blood-based measurement technique that has no exclusive sensitivity to UFH and is not capable to differentiate between affecting variables. 16 However, using iSTAT Alinity and Hemochron Signature Elite, the effect of temperature is excluded, because analyzers perform a standardized sample warm-up to 37 C. Moreover, both instruments feature a protection system to measure a defined sample volume. The influence of viscotic factors including platelet count, fibrinogen level and extreme hematocrit values is predicted for the Hemochron system.…”

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

“…Two trends have emerged for prophylactic or therapeutic concentrations (anti-Xa up to 1.5 IU/mL). First, with TEG, anti-Xa levels and R and K parameters (clot initiation) seemed to correlate, while an inverse correlation between anti-Xa levels and α angle and MA is observed (fibrin polymerization), sometimes leading to a 'flat line' with the highest anti-Xa levels [109][110][111][112]. Second, fewer data are available for ROTEM, but there seems to be a correlation only between anti-Xa levels and CT parameter from the INTEM assay (clot initiation) [112][113][114].…”