Anti-Xa Directed Protocol for Anticoagulation Management in Children Supported With Extracorporeal Membrane Oxygenation

Abstract

The optimum heparin monitoring method during extracorporeal membrane oxygenation (ECMO) is unknown. We report a protocol utilizing only anti-factor Xa (anti-Xa) to manage anticoagulation in 22 consecutive ECMO patients. Anti-Xa was monitored with heparin titration every hour until goal 0.4-0.8 IU/ml. Once therapeutic, monitoring was progressively spaced up to every 6 hours. Patients received frequent antithrombin III (ATIII). Extracorporeal membrane oxygenation indications were as follows: 13 cardiorespiratory failures, eight extracorporeal cardiopulmonary resuscitations (ECPRs), and one pulmonary hypertension. Median weight was 4 kg, age 12.5 days, and ECMO duration 88 hours. Survival was 50%. Mean heparin dose was 38 ± 11 unit/kg/hr. Eight patients received no heparin for median 9 hours because of postoperative bleeding. Compared with prior activated clotting time (ACT) protocol, there were 20 fewer blood draws per day to manage anticoagulation, p < 0.001. Only 9% of the anti-Xa levels were outside therapeutic range versus 22% using ACT, p < 0.01. Six patients had bleeding complications, and seven had oxygenator change-out. Change-out was associated with blood product administration and bleeding but not with heparin-free period (p = 0.39). Survival to discharge was higher among those who did not require circuit/oxygenator change-outs, 4/7 versus 7/7 (p < 0.01). Anti-factor Xa-based ECMO heparin management protocol is feasible, decreases blood sampling and heparin infusion adjustments, and does not appear to increase complications.

Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO

“…Overall, there are limited studies evaluating anticoagulation management, antithrombin replacement, and outcomes for patients on ECMO. In a retrospective study of [84]. These observations are consistent with research conducted by Irby and colleagues who retrospectively analyzed 62 pediatric ECMO patients using daily anti-Xa measurements.…”

Anticoagulation during ECMO: The Past, Present and Future

“…In recent years, anti-factor Xa assay was evaluated as a possible replacement for ACT and aPTT tests. The current view is that anti factor Xa test might provide superior results in adjusting heparin doses that those given by ACT and aPTT [25,26].…”

Managing the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation Laboratories

“…In a cohort of 22 patients managed with anti-FXa compared with 10 ACT managed controls, patients managed with the revised protocol had almost 20 fewer blood draws per day, more results within the goal range (91% compared with 78%, p < 0.01) and less bleeding (27% compared with 50% in the ACT managed controls). 53 In addition, in a pediatric single center who implemented anti-FXa monitoring, a 0.01 unit/mL decrease in anti-FXa activity increased the odds for a circuit or oxygenator change by 5%. 54 In adults, lower levels of anti-FXa activity in VV ECMO patients was associated with a sevenfold increase in the odds of developing a deep venous thrombosis.…”