Activated Partial Thromboplastin Time and Anti-IIa Monitoring in Argatroban Anticoagulation in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation

Abstract

Unfractionated heparin has long been considered the standard anticoagulation in ECMO, despite some pitfalls such as heparin resistance, heparin induced thrombocytopenia (HIT), etc Recently, some centres started to increasingly use argatroban for this purpose, typically using activated partial thromboplastin time (aPTT) for its monitoring. Direct monitoring of the efficacy of argatroban using Anti-IIa is not yet an established method, although it might be more appropriate as it targets the same pathway.An observational study was performed in adult veno-venous ECMO patients hospitalized with SARS-CoV-2 infection anticoagulated with argatroban to an aPTT target of 40-60 s and Anti-IIa target of 0.4-0.6 µg/mL. Bleeding and thrombotic complications were monitored.Forty-four VV ECMO patients were included, with an overall hospital mortality of approx. 50%. No life-threatening thrombotic events were recorded. The risk of bleeding complications significantly increased with aPTT above 52.7 s and with Anti-IIa values over 0.78 µg/mL. Using the above cut-offs for both the aPTT and Anti-IIa and their combination, the negative predictive value for bleeding was approximately 90%.It seems that the generally recommended limits for Anti-IIa of 1.5 µg/mL may be high. However, further data are needed to confirm lower limits.Trial Registration:retrospectively registered in ClinicalTrials.gov, NCT06038682.

Keywords: Anti-IIa; activated partial thromboplastin time (aPTT); anticoagulation; argatroban; extracorporeal oxygenation (ECMO); monitoring.

Figure 1.

aPTT and Anti-IIa Distribution According to Bleeding Complications. The Distribution of aPTT (Seconds, Left) and Anti-IIa (µg/mL, Right) Values According to Bleeding events.

Figure 2.

The Absolute risks of the Occurrence of Bleeding Complications in Individual Categories. Deciles are Shown for aPTT (Seconds, Top) and Anti-IIa (µg/mL, bottom). The Whiskers Indicate the 95% Confidence Intervals of the Absolute Risks Determined Using the Clopper-Pearson Method.

Figure 3.

Forest Plots Indicating the Risk Ratios of Bleeding Complications. Deciles were Used for aPTT (Seconds, Top) and Anti-IIa (µg/mL, Bottom) Containing the Low Cut-off of the Target Range as a Reference.