Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease.

Abstract

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), 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 alpha2M 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 alpha2M 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.

• Authors: Nina A Guzzetta, Bruce E Miller, Kathy Todd, Fania Szlam, Renee H Moore, Keith K Brosius, Elizabeth C Wilson, Anna M Cohen, Steven R Tosone
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 103 Issue 5 Pg. 1131-8 (Nov 2006) ISSN: 1526-7598 [Electronic] United States
• PMID: 17056945 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antithrombins
• Heparin
• Thrombin

Topics

• Antithrombins (pharmacology, therapeutic use)
• Blood Coagulation (drug effects, physiology)
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Female
• Heart Defects, Congenital (blood, drug therapy, epidemiology)
• Heparin (pharmacology, therapeutic use)
• Humans
• Infant
• Infant, Newborn
• Male
• Platelet Count
• Prospective Studies
• Thrombin (antagonists & inhibitors)