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PEDIATRIC ANESTHESIA

Clinical Measures of Heparin’s Effect and Thrombin Inhibitor Levels in Pediatric Patients with Congenital Heart Disease

Nina A. Guzzetta, MD^*, Bruce E. Miller, MD^*, Kathy Todd, RN, BA, CCRC, Fania Szlam, MMSc^*, Renee H. Moore, MS, Keith K. Brosius, MD^*, Elizabeth C. Wilson, MD^*, Anna M. Cohen, MD^*, and Steven R. Tosone, MD^*

From the *Department of Anesthesiology, Emory University School of Medicine; Cardiac Research Department, Children’s Healthcare of Atlanta at Egleston; and Department of Biostatistics, Emory University, Atlanta, Georgia.

Address correspondence and reprint requests to Nina A. Guzzetta, MD, Department of Anesthesiology, Children’s Healthcare of Atlanta at Egleston, 1405 Clifton Road, N.E., Atlanta, GA 30322. Address e-mail to nina_guzzetta{at}emoryhealthcare.org.

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and -2-macroglobulin (2M), and several clinical tests of heparin’s effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1–3 mo, 3–6 mo, 6–12 mo, 12–24 mo, and >10 yr. Baseline ATIII, HCII, and 2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose–response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin’s effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of 2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.

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