Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study.

Mouhamed Djahoum Moussa,Antoine Lamer,Osama Abou-Arab,Valentin Foulon,Annabelle Dupont,Guillaume Leroy,Guillaume Schurtz,Guillaume Gantois,Emmanuel Jeanpierre,Jérôme Soquet,Emmanuel Robin,Sophie Susen,Alain Duhamel,André Vincentelli,Julien Labreuche,Natacha Rousse,Caroline Brandt,Vincent Liu

doi:10.3390/jcm10102158

Abstract

Background: We aimed to investigate the relationship between anti-activated Factor X (anti-FXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We further investigated their association with serious bleeding and thrombotic complications. Methods: This retrospective single-center study included 265 adults supported by VA-ECMO for refractory cardiogenic shock from January 2015 to June 2019. The concordance of anti-FXa and aPTT and their correlations were assessed in 1699 paired samples. Their independent associations with serious bleeding or thrombotic complications were also analysed in multivariate analysis. Results: The concordance rate of aPTT with anti-FXa values was 50.7%, with 39.3% subtherapeutic aPTT values. However, anti-FXa and aPTT remained associated (β = 0.43 (95% CI 0.4–0.45) 10−2 IU/mL, p < 0.001), with a significant modulation by several biological co-variables. There was no association between anti-FXa nor aPTT values with serious bleeding or with thrombotic complications. Conclusion: During VA-ECMO, although anti-FXa and aPTT were significantly associated, their values were highly discordant with marked sub-therapeutic aPTT values. These results should favour the use of anti-FXa. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy.

Highlights

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a lifesaving therapy in refractory cardiogenic shock with an exponential increase in use over the last few decades
If activated clotting time (ACT) was shown to be irrelevant for anticoagulation monitoring in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as compared to anti-FXa and activated Partial Thromboplastin Time (aPTT) after the cannulation procedure [11,12], there is no clear evidence of the superiority of the anti-FXa assay over aPTT when excluding pre-analytical characteristics
Based on our results and considering the evidence available in the literature, we propose the use of anti-FXa rather than aPTT, bearing in mind that anti-FXa remains the least used test for monitoring unfractionated heparin (UFH) under ECMO worldwide [15]

Summary

Introduction

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a lifesaving therapy in refractory cardiogenic shock with an exponential increase in use over the last few decades. If ACT was shown to be irrelevant for anticoagulation monitoring in VA-ECMO as compared to anti-FXa and aPTT after the cannulation procedure [11,12], there is no clear evidence of the superiority of the anti-FXa assay over aPTT when excluding pre-analytical characteristics Their ability to reflect the sole heparin intrinsic activity can be questioned knowing that both anti-FXa (to a lesser extent) and aPTT may be susceptible to several biological factors unrelated to UFH therapy and to analytical limits. We aimed to investigate the relationship between anti-activated Factor X (antiFXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support We further investigated their association with serious bleeding and thrombotic complications. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy

Objectives

Methods

Conclusion