Antithrombin use during pediatric cardiac extracorporeal membrane oxygenation admission: insights from a national database

Abstract

<jats:sec><jats:title>Introduction:</jats:title><jats:p> The frequency of extracorporeal membrane oxygenation in pediatric patients continues to increase, especially in patients with complex congenital heart disease. Providing adequate anticoagulation is necessary for patients on extracorporeal membrane oxygenation and is achieved with adequate heparin administration. Antithrombin is administered to potentiate heparin’s effects. However, the efficacy of antithrombin supplementation is unclear and a clear clinical benefit has not been established. We present a large retrospective study examining the effects of antithrombin on pediatric patients receiving extracorporeal membrane oxygenation. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Data for this study were obtained from the Pediatric Health Information System and Pediatric Health Information System+ databases from 2004 to 2015. Pediatric patients receiving extracorporeal membrane oxygenation with a congenital heart disease diagnosis were included and divided into groups that did or did not utilize antithrombin. For all admissions, the following were captured: age of admission, gender, year of admission, length of stay, billed charges, inpatient mortality, the presence of specific congenital malformations of the heart, specific cardiac surgeries, and comorbidities. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> A total of 9,193 admissions were included and 865 (9.4%) utilized antithrombin. Between groups, there were significantly different frequencies of co-morbidities, cardiac lesion types and antithrombin usage over the study period. There were significantly lower odds in the antithrombin group of venous thrombosis. Antithrombin was not significantly associated with hemorrhage; however, antithrombin was associated with increased inpatient mortality and a decrease in length of stay and billed charges. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Antithrombin administration is associated with increased mortality, a shorter length of stay, and decreased billing cost. Recently, antithrombin usage has been decreasing—potentially due to the reported lack of clinical benefit. Together, these results reinforce that antithrombin may not be indicated for all pediatric extracorporeal membrane oxygenation patients. </jats:p></jats:sec>

Antithrombin III supplementation during neonatal and pediatric extracorporeal membrane oxygenation

“…A number of studies have found no association between AT3 administration and bleeding. Another analysis of PHIS data, focused on patients with cardiac lesions on ECMO, found no association between AT3 supplementation and bleeding but did find an association with increased inpatient mortality 16 . An analysis of respiratory pediatric and neonatal patients on ECMO ( N = 64) also found no association between AT3 administration and severe bleeding 23 .…”

“…Aiello et al, found reduced rates of venous thrombosis among the AT3‐supplemented cohort. Of note, Aiello et al, hypothesized that the reduced rates of thrombosis are potentially due to the AT3 cohort having shorter ECMO runs with increased mortality 16 . Stansfield et al, also found lower rates of mechanical clots among neonatal patients treated with AT3 7 .…”

“…Some adult studies also suggest that AT3 could reduce inflammation 28 . Further studies in children are needed to evaluate the potential benefits of AT3 supplementation 13,16,19 …”

“…An analysis of the US Pediatric Health Information System (PHIS) database found that AT3 supplementation for patients on cardiac‐indicated ECMO increased from 1% of admissions in 2004 to 9% in 2015. Utilization peaked in 2012 at 17% of admissions 16 . Another PHIS analysis of all ECMO admissions found that in 2012 52% of patients received AT3 17 .…”

Evaluation of the Safety and Efficacy of a Novel Thrombin Containing Combination Hemostatic Powder Using a Historical Control

“…Postoperative bleeding following cardiothoracic procedures remains an important concern with multiple avenues of investigation continuing to assess factors predisposing and potentially influencing the severity of this adverse event. Recent areas of interest include: development of new antifibrinolytic agents to reduce bleeding; 31 measurement of platelet function to reduce bleeding and mortality; 32 single or dual agent antiplatelet therapy to maximize bypass graft patency, but increase postoperative bleeding; 33 – 36 direct linkage of postoperative cardiac surgical bleeding with increased cost; 4 , 5 safe and efficacious use of postoperative fibrinogen concentrates; 37 , 38 role of patient blood management in reducing blood product transfusion and improving cardiac surgical outcomes; 39 , 40 transfusion reductions associated with the use of prothrombin complex concentrate; 41 , 42 morbidity associated with reoperation for bleeding following cardiac surgery; 3 , 43 , 44 methods of employing thromboelastometry (ROTEM) during cardiac surgery; 45 , 46 contribution of albumin/gelatin to postoperative bleeding; 47 – 49 advantages of anticoagulation management using thromboelastography (TEG) during cardiopulmonary bypass; 50 – 52 benefit of thrombin inhibitors for pediatric VAD anticoagulation; 53 , 54 reduction of postoperative blood loss using Unilastin as an antifibrinolytic agent; 55 , 56 and blood loss leading to multisystem organ failure and hematologic complications following LVAD insertion. 7 , 57 …”