Anti-Xa assay is superior to ACT or aPTT for heparin monitoring in ECMO

Heparin titration based on anti-factor Xa assays may result in fewer hemorrhagic complications, less blood product transfusion, and increased ECMO circuit life.

The activated clotting time (ACT) has been used since the beginning of ECMO to measure and titrate anticoagulation with UNFH. The ACT is a widely available test that can be done at the bedside within minutes. It provides a measure of time in seconds necessary for whole blood to clot. However, the ACT does not provide detailed information regarding clotting. A prolonged ACT can be due to coagulopathy, excessive anticoagulation, thrombocytopenia, or any combination of these factors.

The activated partial thromboplastin time (aPTT) has a long history of being used to monitor and titrate therapy with UNFH. In a study of pediatric ECMO patients, the use of the aPTT versus the ACT led to decreased hemorrhagic complications, but a secondary increase in thrombotic complications. [1] There is evidence that aPTT levels are not as reliable in neonatal and pediatric patients as compared to adult patients. [2,3] In addition, aPTT can become unreliable in critical illness, as acute phase reactants such as C-reactive protein (CRP) and factor VIII affect the measurement of aPTT. Elevated CRP levels can falsely prolong aPTT levels, and elevated factor VIII levels can falsely decrease the aPTT. [4] The aPTT is currently the test of choice to monitor therapy with intravenous DTIs.

The anti-factor Xa assay has become the gold standard for monitoring therapy with UNFH. This assay measures the effect rather than the quantity of UNFH. Measurement of the anti-factor Xa assay can be done with or without the addition of antithrombin. For patients with antithrombin deficiency, the addition of antithrombin can artificially increase the anti-factor Xa assay. In a study of pediatric ECMO patients, an anticoagulation laboratory protocol that used anti-factor Xa assays to titrate UNFH was associated with fewer hemorrhagic complications, less blood product transfusion, and increased circuit life. [5]

The evidence regarding the use and monitoring of ECMO anticoagulation continues to evolve. The Extracorporeal Life Support Organization (ELSO) has developed guidelines regarding ECMO anticoagulation. [6]

References

[1] Maul TM, Wolff EL, Kuch BA, Rosendorff A, Morell VO, Wearden PD. Activated partial thromboplastin time is a better trending tool in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med 2012

[2] Chan AK, Black L, Ing C, Brandao LR, Williams S. Utility of aPTT in monitoring unfractionated heparin in children. Thrombosis Research 2008

[3] Ignjatovic V, Furmedge J, Newall F, et al. Age-related differences in heparin response. Thrombosis Research 2006

[4] Teruya J. Coagulation Tests Affected by Acute Phase Reactants Such as CRP and Factor VIII. Paper presented at: International Conference on Hematology and Blood Disorders; September 23 - 25, 2013; Research Triangle Park, NC USA.

[5] Northrop MS, Sidonio RF, Phillips SE, et al. The use of an extracorporeal membrane oxygenation anticoagulation laboratory protocol is associated with decreased blood product use, decreased hemorrhagic complications, and increased circuit life. Pediatr Crit Care Med 2015

[6] Extracorporeal Life Support Organization (ELSO). Guidelines for ECMO anticoagulation.