Published in:
01-12-2020 | COVID-19 | Letter
Use of multiple laboratory tests including anti-factor Xa to optimally manage anticoagulation during ECMO
Published in: Critical Care | Issue 1/2020
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We read with great interest the recent article by Chlebowski et al., who recommend the use of multiple laboratory tests including anti-factor Xa (anti-Xa) to optimally manage anticoagulation during ECMO [1]. Anti-Xa directly measures heparin inhibition of factor Xa and is increasingly used to measure heparin effect, especially in pediatric patients [1]. Anti-Xa assay correlates better with unfractionated heparin (UFH) concentration than with activated clotting time (ACT) or activated partial thromboplastin time (aPTT) [2, 3]. The major criticism made of using anti-Xa in isolation to titrate heparin for anticoagulation is that while it is a direct measure of heparin effect, it does not represent the overall hemostatic state of the patient [1]. For example, a patient who before heparin therapy is highly prothrombotic may still be prothrombotic with what is considered to be a therapeutic effect of heparin based on anti-Xa levels [1]. We would like to make some comments. Prior to the COVID-19 pandemic, we routinely used anticoagulation for veno-arterial ECMO (VA-ECMO), but not for veno-venous ECMO (VV-ECMO) [4]. We have found the situation to be totally different in COVID-19 patients treated with VV-ECMO. We have needed to use very high doses of heparin, from 20,000 IU up to 50,000 IU, and despite those high doses, we have had several cases of thrombosis. In an attempt to avoid both bleeding and thrombosis, we have started monitoring anticoagulation in these patients with both anti-Xa and aPTT. If the anti-Xa level is within the reference range (0.3–0.7 IU/ml) but the aPTT is low, we increase the UFH, aiming for an aPTT between 50 and 70 s (according to a sliding scale). On the other hand, if the aPTT is between 50 and 70 s, but the anti-Xa is greater than 1 IU/ml, we reduce the UFH (again according to a sliding scale). By adjusting the UFH dose on the basis of a combination of two different measurements, we have aimed to improve our anticoagulation strategy and potentially reduce bleeding and thrombosis. Obviously, to confirm this, we would need to perform a randomized controlled trial. A sliding scale for UFH is easy to obtain whereas it is somewhat more difficult for anti-Xa. With this in mind, we have included our sliding scale for anti-Xa at the end of this letter (adapted from a sliding scale from the literature (Table 1) [5]).
Table 1
Adjustment of unfractionated heparin dose during ECMO according to anti-Xa activity and body weight. 20,000 IU UFH + 44 cc NaCl 0.9%
|
Anti-Xa activity
|
Bolus
|
Variation
|
55–64 kg
|
65–74 kg
|
75–84 kg
|
85–94 kg
|
95–104 kg
|
105–114 kg
|
115–124 kg
|
|---|---|---|---|---|---|---|---|---|---|
|
< 0.2
|
26 U/kg
|
↑96 U/kg/h
|
↑0.6 cc/h
|
↑0.7 cc/h
|
↑0.8 cc/h
|
↑0.9 cc/h
|
↑1 cc/h
|
↑1.1 cc/h
|
↑1.2 cc/h
|
|
0.20–0.29
|
No
|
↑48 U/kg/h
|
↑0.3 cc/h
|
↑0.3 cc/h
|
↑0.4 cc/h
|
↑0.4 cc/h
|
↑0.5 cc/h
|
↑0.6 cc/h
|
↑0.7 cc/h
|
|
0.30–0.70
|
No
|
||||||||
|
0.71–0.80
|
No
|
↓24 U/kg/h
|
↓0.1 cc/h
|
↓0.1 cc/h
|
↓0.2 cc/h
|
↓0.2 cc/h
|
↓0.2 cc/h
|
↓0.3 cc/h
|
↓0.3 cc/h
|
|
0.81–0.99
|
No
|
↓48 U/kg/h
|
↓0.3 cc/h
|
↓0.3 cc/h
|
↓0.4 cc/h
|
↓0.4 cc/h
|
↓0.5 cc/h
|
↓0.6 cc/h
|
↓0.7 cc/h
|
|
> 1
|
No
|
↓96 U/kg/h
|
↓0.6 cc/h
|
↓0.7 cc/h
|
↓0.8 cc/h
|
↓0.9 cc/h
|
↓1.0 cc/h
|
↓1.1 cc/h
|
↓1.2 cc/h
|