The Use of Recombinant Antithrombin III in Pediatric and Neonatal ECMO Patients

Abstract

A retrospective review of 77 pediatric and neonatal extracorporeal membranous oxygenation (ECMO) patients who received recombinant antithrombin III (ATIII) for ATIII activity greater than 80% was conducted. Anticoagulation management was per institutional protocol. An ATIII activity greater than 80% was targeted. Diagnosis, reason for ECMO cannulation, blood product usage, heparin dosing, ATIII activity and doses, thrombotic and bleeding complications, hours on ECMO, and mortality were recorded. We calculated patient-level summary statistics and assessed differences between groups using χ tests (categorical variables) and Wilcoxon rank sum tests (continuous variables). Hierarchical generalized linear models were developed to model bleeding and thrombotic complications. The majority (n = 75) received venoarterial ECMO and had cardiac diagnoses (n = 62). Antithrombin III activity was below 80% for an average of 5.2 hours per patient. Antithrombin III activity less than 80% was not associated with thrombotic complications (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.97-1.06, p = 0.86). Antithrombin III activity greater than 80% was not associated with bleeding complications (OR = 1.06, 95% CI = 1.01-1.11, p = 0.44). Duration of ECMO was an independent predictor of thrombotic complications (OR = 1.08, 95% CI = 1.02-1.11, p = 0.02). There were no independent predictors of bleeding complications. Antithrombin III activity correlated with anti Xa activity (r = 0.367, p < 0.001) but not with other measures of anticoagulation or with heparin dose (r = 0.16, p = 0.165). ATIII activity was not associated with bleeding, thrombosis, or heparin dose. Antithrombin III activity was associated with anti Xa activity but not with traditional measures of anticoagulation. Antithrombin III replacement for an activity less than 80% did not increase bleeding.

Coagulation and Bleeding Management in Pediatric Extracorporeal Membrane Oxygenation: Clinical Scenarios and Review

“…When evaluating the administration of one vial of AT (1,000 U; averaging 241 U/kg) Ryerson et al also reported no adverse events, though it is important to note that heparin dose was decreased by 50% at the time of administration (18). Other studies have confirmed lack of bleeding complications associated with AT treatment (20). Tighter control of anticoagulation with AT replacement is also reported; however, this did not affect the longevity of the ECMO circuit (17).…”

Anticoagulation in Neonatal ECMO: An Enigma Despite a Lot of Effort!

“…Another problem is heparin resistance related to reliance on ATIII levels which are lower in critically ill children and neonates and UFH's inability to inhibit factor Xa bound to platelets (56). Evidence suggests that ATIII activity often decreases over time in children on ECMO (57–60). Many centers routinely replace ATIII in an attempt to maximize heparin effect.…”

“…ATIII can be supplemented by transfusion of fresh frozen plasma or by infusing ATIII concentrates. But, ATIII concentrates are expensive and studies in the neonatal and pediatric population have found mixed results when ATIII supplementation is utilized (57–60). A recent large observational report (including 5,360 neonates) found that ECMO patients supplemented with ATIII had an increased number of thrombotic and hemorrhagic events and longer hospital length of stay with no difference in mortality (61).…”

Description of Bivalirudin Use for Anticoagulation in Pediatric Patients on Mechanical Circulatory Support

“…Heparin requires endogenous antithrombin III (AT3) to be effective; however, serum AT3 levels have been noted to be naturally low in neonatal populations and may also be low in those undergoing ECMO. 4,5 AT3 may be supplemented with either fresh frozen plasma or recombinant antithrombin products. 6,7 This practice is not standardized, may provide inconsistent anticoagulation results, and significantly increases the cost of heparin therapy.…”