Conversion From Activated Clotting Time to Anti-Xa Heparin Activity Assay for Heparin Monitoring During Extracorporeal Membrane Oxygenation*

Abstract

Objectives: Anticoagulation with unfractionated heparin remains the most common therapy used to prevent circuit thrombosis during extracorporeal membrane oxygenation, but no consensus exists on the optimal method or targets for heparin monitoring. From 2015 to 2018, we switched from monitoring heparin during extracorporeal membrane oxygenation using activated clotting times to anti-Xa heparin activity assays. This study describes the transition from activated clotting time to anti-Xa heparin activity assay monitoring and the associated clinical changes. Design: Retrospective analysis at single institution. Setting: Referral Children’s Hospital. Patients: A total of 145 pediatric patients over 152 extracorporeal membrane oxygenation runs using 206 extracorporeal membrane oxygenation circuits. Interventions: Anticoagulation protocol quality improvement. Measurements and Main Results: From 2015 to 2018, heparin monitoring during extracorporeal membrane oxygenation changed from hourly activated clotting time to anti-Xa heparin activity assay every 6 hours with an associated 75% reduction in the circuit changes per extracorporeal membrane oxygenation day. Over the 4 years, patients with an average anti-Xa heparin activity assay of at least 0.25 U/mL showed a 59% reduction in circuit changes per extracorporeal membrane oxygenation day compared with less than 0.15 U/mL. In addition to its association with reduced circuit changes, anti-Xa heparin activity assay monitoring was also associated with reduced heparin dose changes per day from 11 ± 4 to 2 ± 1 (p < 0.001), smaller heparin dose changes (less variation in dose), and reduced diagnostic phlebotomy volumes from 41 ± 6 to 25 ± 11 mL/day (p < 0.001). The number of patients with reported bleeding decreased from 69% using activated clotting time to 51% (p = 0.03). Transfusion rates did not change. Conclusions: Over 4 years, we replaced the activated clotting time assay with the anti-Xa heparin activity assay for heparin monitoring during extracorporeal membrane oxygenation. Minimum anti-Xa heparin activity assay levels of 0.25 U/mL were associated with reduced circuit changes. Further studies are needed to determine the optimum anti-Xa heparin activity assay therapeutic range during extracorporeal membrane oxygenation.

Carnitine deficiency among hospitalized pediatric patients: A retrospective study of critically ill patients receiving extracorporeal membrane oxygenation therapy

“…Pediatric ECMO occurs more often in younger children; the average age of children receiving ECMO 1 month. 29 In the ECMO cohort, female patients were overrepresented (60.5%; n = 49/81). This is not expected to significantly impact the observed outcomes, as there are no known gender‐specific differences in carnitine metabolism.…”

“…ECMO patients were skewed to younger patients compared with the non‐ECMO cohort. Pediatric ECMO occurs more often in younger children; the average age of children receiving ECMO 1 month 29 . In the ECMO cohort, female patients were overrepresented (60.5%; n = 49/81).…”

Venovenous Extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe ARDS: A systematic review and meta-analysis of the literature

“…51 Two studies from 2016, and 2017 described 46.7% and 50% bleeding rates respectively, while the five papers from 2018-2021 recorded 10-24.3% bleeding rates. Anti-Xaguided anticoagulation may offer favourable bleeding profiles, 68 however, this could not be statistically evaluated here and definitions of bleeding were not standardised. Higher blood flow rate devices were associated with reduced haemorrhage and haemolysis (21% vs 6%, p=0.045) and (27% vs 6%, p=0.01) respectively in SUPERNOVA, 69 and the same inverse relationship -bleeding: (30% vs 6%, p=0.04), and haemolysis: (28% vs 0% ,p=0.03) 46 49 were documented by Augy et al 46 Rotary pumps may exert increased blood trauma at lower blood flows (particularly<1L.min-1), [70][71][72] causing shear stress and loss of high molecular weight von Willebrand factor multimers.…”

Diagnostic Modalities in Critical Care: Point-of-Care Approach

“…The main disadvantage is poor correlation with anti-Xa measures of heparin activity, or heparin concentration in general [ 103 ] and, especially during haemodilution or hypothermia, both present during cardiopulmonary bypass. During ECMO, the anti-Xa guided heparin dosing resulted in less circuit clotting and resulted in a significant reduction of costs [ 104 ]. Thrombocytopenia, anaemia, presence of platelet inhibitors and membrane receptor antagonists, low antithrombin levels, severe hypofibrinogenaemia, and low temperature can also influence the accuracy of ACT POC diagnostics [ 105 ].…”