Johns Hopkins All Children's Hospital, Johns Hopkins University School of Medicine St. Petersburg, Florida, United States
Abstract: Introduction / Objective Antithrombin III (AT-III) is a protease inhibitor that inhibits thrombin (factor IIa) and factor Xa, and to a lesser extent factors IXa, XIa, XIIa, tissue plasminogen activator, plasmin, and kallikrein. At low baseline levels, AT-III to thrombin binding occurs. However, when heparin binds to AT-III, thrombin inhibition is increased 2000- to 4000-fold, enabling anticoagulation for cardiopulmonary bypass (CPB). Normal AT-III activity is adult plasma is reported to range from 80% to 120%. Neonates and young pediatric patients have lower levels of AT-III, and adult levels are not typically reached until approximately 6 months to 1 year of age. Literature regarding the clinical utility in relation to the high cost of AT-III is limited; although lower antithrombin activity has been associated with lower heparin efficiency, increased thrombin generation, and larger total heparin doses during CPB. AT-III replacement has been described as part of protocols for extracorporeal life support (ECLS) and in adult CPB studies to increase heparin efficiency and minimize potential bleeding or transfusion rates. The objective of this study was to evaluate the clinical and financial impact of a standardized protocol for AT-III replacement in neonates and infants prior to congenital heart surgery.
Methods A retrospective review of AT-III medication orders and laboratory tests from April 2021 to April 2022 was performed following implementation of a standard ATIII perioperative management protocol. Multidisciplinary education was provided prior to protocol go-live on October 2021. Two cohorts of patients were evaluated: 1) pre-implementation (April 2021 to September 2021) and 2) post-implementation (November 2021 to April 2022). Patients were included if they were neonates, infants, had an AT-III order prior to cardiac surgery. Patients on extracorporeal life support (ECLS) were excluded. For statistical analysis the Wilcoxon Rank Sum test was performed.
Results Thirty-three patients were included: 18 in the pre-protocol and 15 in the post-protocol cohorts. The median (range) age was 7 (2-42) and 4 (2-152) days in the pre- and post-protocol cohorts, respectively. Following protocol implementation, AT-III medication doses and lab tests deemed to be unnecessary by the new protocol decreased by 46.9% (p=0.015) and 34.1% (p=0.007), respectively. This resulted in total cost savings of $42,376.44 per 100 patients: $38,479 (p=0.008) for AT-III medication doses and $3,905.56 (p=0.49) for AT-III levels. Heparin (units/kg) (median, range) requirements prior to CPB was not significant with 418.4 (100.3-537.6) and 384.6 (92.3-500) in the pre- and post-protocol cohorts (p=0.58), respectively. Blood product transfusions (fresh frozen plasma, packed red blood cells, platelets) and factor product administration were not significantly different between groups.
Conclusion The development and implementation of a standardized protocol for perioperative AT-III management reduced the number of unnecessary AT-III medication and lab orders, resulting in $42,376.44 cost savings per 100 patients. Clinical impact with regards to intra-operative heparin requirement, factor product utilization, and blood product administration were similar.
