Antithrombin supplementation in adult patients receiving extracorporeal membrane oxygenation

Abstract

Introduction: Extracorporeal membrane oxygenation is associated with an increased risk of thrombosis and hemorrhage. Acquired antithrombin deficiency often occurs in patients receiving extracorporeal membrane oxygenation, necessitating supplementation to restore adequate anticoagulation. Criteria for antithrombin supplementation in adult extracorporeal membrane oxygenation patients are not well defined. Methods: In this retrospective observational study, adult patients receiving antithrombin supplementation while supported on extracorporeal membrane oxygenation were evaluated. Antithrombin was supplemented when anti-Xa levels were subtherapeutic with unfractionated heparin infusion rates of 15-20 units/kg/h and measured antithrombin activity <50%. Patients were evaluated for changes in degree of anticoagulation and signs of bleeding 24 hours pre- and post-antithrombin supplementation. Results: A total of 14 patients received antithrombin supplementation while on extracorporeal membrane oxygenation. The median percentage of time therapeutic anti-Xa levels were maintained was 0% (0-43%) and 40% (9-84%) in the pre-antithrombin and post-antithrombin groups, respectively (p = 0.13). No difference was observed in the number of patients attaining a single therapeutic anti-Xa level (pre-antithrombin = 6, post-antithrombin = 13; p = 0.37) or unfractionated heparin infusion rate (pre-antithrombin = 7.35 (1.95-10.71) units/kg/h, post-antithrombin = 6.81 (3.45-12.58) units/kg/h; p = 0.33). Thirteen patients (92%) achieved an antithrombin activity at goal following supplementation. Antithrombin activity was maintained within goal range 52% of the time during the replacement period. Four bleeding events occurred pre-antithrombin and 10 events post-antithrombin administration (p = 0.26) with significantly more platelets administered post-antithrombin (pre-antithrombin = 0.5 units, post-antithrombin = 4.5 units; p = 0.01). Conclusion: Therapeutic anticoagulation occurred more frequently following antithrombin supplementation; however, this difference was not statistically significant. More bleeding events occurred following antithrombin supplementation while observing an increase in platelet transfusions.

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation

“…One concern about supplementing AT in the presence of large doses of heparin is increased risk of bleeding. 41 After March 2, the AT activity level was obtained in the authors' center and AT supplementation using continuous infusion plasma was recommended because of the lack of commercial AT recombinant product in China. The effect of plasma therapy was unsatisfactory at 200-to-400 mL/d, and most patients had a low AT level during ECMO support.…”

“…While antithrombin is frequently exogenously supplemented to restore therapeutic anticoagulation, when antithrombin activity is deficient, this practice varies widely among institutions. One concern about supplementing antithrombin in the presence of large doses of heparin was increased risk of bleeding 42 . After March 2 nd , 2020, antithrombin activity level was obtained in our center and antithrombin supplementation using continuous infusion plasma was recommended due to the lack of commercial antithrombin recombinant product in China.…”

COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review

“…Anti-inflammatory functions of AT are partly mediated through inhibition of thrombin that reduces platelet activation, neutrophil-endothelial cell interactions, and endothelial upregulations [25]. In patients on ECMO, acquired AT deficiency is a result of hemodilution, blood coagulation activation, and consumption due to the use of UFH [61]. The binding of AT to UFH competes with the binding of AT to endothelial GAGs, thus increasing the likelihood of inflammation-related complications.…”

Platelet Count and Function during Pediatric Extracorporeal Membrane Oxygenation

“…Studies on replacement of AT, however, have noted mixed results, with some finding increased bleeding or no effect on heparin dosing or outcome. 32,33 Thus this practice remains controversial and confusing. [34][35][36] ELSO acknowledges this uncertainty and suggests considering replacing AT in infants and children with escalating UFH requirements and confirmed low AT activity.…”