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Effect of Antithrombin Supplementation In Pediatric Cardiac Extracorporeal Membrane Oxygenation

Sunday, October 21, 2012: 9:00 AM
Room 210 (Morial Convention Center)
Jonathan W. Byrnes, Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, Christopher J. Swearingen, PhD, Pediatrics--Biostatistics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, Parthak Prodhan, MBBS, Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, Richard Fiser, MD, Pediatric Critical Care, Arkansas Children's Hospital, Little Rock, AR and Umesh Dyamenahalli, Pediatric Cardiology and Cardiac Critical Care, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR

Purpose

Recombinant antithrombin III (rATIII) is used as an adjunct to heparin in anticoagulation during extracorporeal membrane oxygenation (ECMO) based on physiologic rationale and studies in patients on cardiopulmonary bypass.  In February 2008 our institution began using rATIII as replacement for low antithrombin III (ATIII) levels (<70%) in patients supported with ECMO.  We hypothesize that rATIII administration will result in reductions in heparin infusion rates, increases in unfractionated heparin anti-Xa (UF anti-Xa) levels, and longer effective life of the extracorporeal circuit.

Methods

We collected clinically pertinent data on 40 consecutive cardiac patients who represented 46 ECMO deployments; each was supported more than 72 hours with venoarterial ECMO from January 1, 2007 through December 31, 2008. While on ECMO patients are monitored by measuring activated clotting time (ACT) and heparin levels along with platelet count, prothrombin time and fibrinogen. Blood concentration of ATIII was measured at least once daily as part of routine clinical care, and rATIII concentrate was supplemented for concentrations < 70%. We questioned what effect rATIII supplementation had upon anticoagulation and circuit survival. A reduction of greater than 10% in the heparin infusion rate with stable ACT range after ATIII supplementation within the treatment group was a primary outcome. Secondary outcomes were response of UF anti-Xa level in response to rATIII administration within the supplementation group and duration of circuit life in supplemented versus unsupplemented controls.

Results

No difference in heparin infusion rates was observed regardless whether rATIII was administered (p= 0.245) (Table 1). Unfractionated heparin anti-Xa levels were lower at the time of administration and were increased following rATIII supplementation (p < 0.001) within the supplemented group. There was however increased incidence of circuit failure in rATIII-supplemented group compared to the unsupplemented controls (p=0.018) (Figure 1). 

Conclusion

Heparin responsiveness is not altered by daily rATIII supplementation in our study population, although there was a statistically significant if not a clinically significant effect increase in UF anti-Xa levels. The supplementation of rATIII did not prolong ECMO circuit life. Further prospective studies are necessary to determine whether the routine administration of rATIII is warranted in patients supported on ECMO.

Table 1. Estimated Differences in Measures of Coagulation Based on Routine rATIII Replacement.

AT-III Treatment

No

Yes

P

Heparin Dose

31.0 (1.2)

30.4 (1.1)

0.665

10% Heparin Reduction

32.9%

38.4%

0.5215

20% Heparin Reduction

17.8%

29.3%

0.1061

Anti-Xa*

0.25 (0.02)

0.19 (0.02)

0.001

*Treatment effect modeled using Generalized Estimating Equation (GEE).

Estimated in 21 Patients over 221 Observations using Repeated Measures Linear Regression Adjusting for Age at ECMO Cannulation

Figure 1. Estimated Cumulative Incidence of Circuit Change by AT III Administration by Cox Regression Adjusting for Disease Group and Day of Life ECMO Started in 40 Patients with 74 Circuit Changes