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

In Brief In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and α-2-macroglobulin (α2M), 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 α2M 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 α2M 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. IMPLICATIONS: Antithrombin III-deficient neonates presenting for cardiac surgery have lower than expected levels of α2M, a significant inhibitor of thrombin during the neonatal period. Our data raise concern about the ability to adequately anticoagulate these neonates during cardiopulmonary bypass and question the meaning of the prolonged activated clotting times values often seen in these children.