Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support

Abstract

Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between individuals. Population pharmacokinetic/pharmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes.

Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions

“…The vast majority of studies where anti-FXa has been used for titrating UFH dose in ECMO report a target value of 0.3 to 0.7 IU/mL, 10,13 but higher ranges (lower limit: 0.4-0.5 IU/mL; upper limit: 0.8 IU/mL) have also been proposed. 7,11,44 Lower ranges (0.2-0.4 IU/mL) have been proposed as well. 45 The range 0.3 to 0.7 IU/mL, proposed by the Extracorporeal Life Support Organization 46 in 2014, simply reflects the range traditionally considered adequate for UFH treatment and prevention of venous thrombosis.…”

“…At least, this measure should be implemented with AT activity assessment, and a (functional) measure of the substrates contribution to clot formation after thrombin generation (platelet count/function and fibrinogen). To this respect, coupling the anti-FXa with another plasma-based test like the aPTT seems unreasonable, given (1) the poor or absent correlation between anti-FXa and aPTT 7,57 and (2) the lack of measure of platelet contribution in both tests. For partially different reasons, even a strategy based on anti-FXa plus ACT does not seem rationale: again, there is poor concordance between the two tests 45,57 ; the ACT is sensitive to fibrinogen levels and platelet count/function, but cannot discriminate different sources of coagulopathy.…”

“…(3) reaction time using viscoelastic tests (VETs) at 1.5-2.0 Â the upper limit of the normal range 5,7,8 ; and (4) antifactor Xa (anti-FXa) activity between 0.3 and 0.7 IU/mL. 6,9,10 In recent years, anticoagulation strategies based on anti-FXa have gained widespread consensus, with different studies advocating their superiority compared with other available options, and claiming better outcomes or at least a lower need for administration of allogeneic blood products.…”

Interference in the anti‐Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support

“…Heparin is difficult to monitor in these patients for a variety of reasons including low antithrombin levels, low coagulation factor levels, lupus inhibitors, hemolysis, and icterus. The activated clotting time has been used for ECLS unfractionated heparin monitoring, but has been called into question due to its lack of correlation with heparin dose, anti‐Xa heparin activity, partial thromboplastin time (PTT), bleeding, or circuit thrombosis . The PTT has also been used to monitor unfractionated heparin during ECLS, but it has been reported to show high levels of discordance with anti‐Xa heparin activity assays, due to low or high coagulation factor levels, lupus inhibitors, contact factor deficiencies, and other causes …”

“…The activated clotting time has been used for ECLS unfractionated heparin monitoring, but has been called into question due to its lack of correlation with heparin dose, anti-Xa heparin activity, partial thromboplastin time (PTT), bleeding, or circuit thrombosis. [1][2][3][4][5][6] The PTT has also been used to monitor unfractionated heparin during ECLS, but it | 881 KHAN ANd CHANdLER has been reported to show high levels of discordance with anti-Xa heparin activity assays, due to low or high coagulation factor levels, lupus inhibitors, contact factor deficiencies, and other causes. [7][8][9][10] Anti-Xa heparin activity assays are becoming a standard approach for monitoring heparin during ECLS.…”