title: Low preoperative antithrombin activity causes reduced response to heparin in adult but not in infant cardiac-surgical patients.
abstract: We evaluated the interaction of preoperative antithrombin (AT) activity and intraoperative response to heparin in cardiac surgery. Heparin anticoagulation is essential during cardiopulmonary bypass (CPB). Heparin itself has no anticoagulant properties, however it causes a conformational change of the physiologic plasma inhibitor AT that converts this slow-acting serine protease inhibitor into a fast acting one. Thus, adequate AT activity is a prerequisite for sufficient heparin anticoagulation. AT activity is reduced by long-term heparin therapy. This prospective, observational study investigated 1516 consecutive cardiac-surgical patients (1304 patients >1 yr (Group A) and 212 patients < or = 1 yr (Group I)). AT activity was measured the day before surgery by a chromogenic substrate assay. The celite-activated activated clotting time (ACT) was used to guide intraoperative heparin administration. Heparin sensitivity was calculated and the postoperative blood loss and perioperative blood requirement was recorded. Infant patients had significantly less preoperative AT activity compared with older patients: 84 (33)% vs 97 (17)%, median (interquartile range) (P < 0. 05). The subgroup of patients aged <1 mo (n = 64) demonstrated a preoperative AT activity of 56 (27)% as compared with 90 (23)% in infant patients between one month and one year (n = 148). In adult patients, preoperative AT activity depended predominantly on preoperative heparin treatment: 62% of the patients with an AT activity <80% were pretreated with heparin. Five minutes after heparin but before CPB the ACT was 587 (334) s in Group A patients with AT activity > or = 80%, and 516 (232) in patients with AT activity < or = 80% (P < 0.05). The target ACT of 480 s was achieved in 70% of patients with normal AT activity in Group A compared with only 54% of patients with AT activity <80% (P < 0.05). In Group A patients with decreased AT activity, 18% demonstrated an inadequate ACT response-defined as ACT <400 s-to the first bolus injection of heparin. In Group I, preoperative AT activity did not influence the ACT response (ACT 5 min after heparin: 846 [447] s in patients with AT activity > or = 80% vs 1000 [364] s in patients with decreased AT activity). The heparin sensitivity was 2.4 (1.1) s/unit heparin/kg compared with 1.5 (0.8) s/unit heparin/KG in group A (P < 0.05). These results suggest that preoperative diminished AT activity causes reduced response to heparin in adult but not in infant patients. Infant patients demonstrate a higher heparin sensitivity despite lower preoperative AT activity. Measurement of preoperative AT activity identifies adult patients at risk of reduced sensitivity to heparin.
  
  
  CONCLUSIONS
  In patients less than one year of age, low antithrombin (AT) activity is caused by the immature coagulation system. Despite low AT activity, these young patients demonstrate a normal or increased response to heparin anticoagulation before cardiopulmonary bypass (CPB). In contrast, in patients older than one year of age and adult patients decreased preoperative AT activity is mainly caused by preoperative heparin therapy and causes insufficient response to heparin anticoagulation with a standard heparin dosage. Measurement of preoperative AT activity identifies patients at risk of inadequate anticoagulation during CPB.
authors.affiliation: Department of Anesthesiology, German Heart Center, Munich, Germany. dietrich@dhm.mhn.de
authors.forename: W
authors.initials: W
authors.lastname: Dietrich
authors.forename: S
authors.initials: S
authors.lastname: Braun
authors.forename: M
authors.initials: M
authors.lastname: Spannagl
authors.forename: J A
authors.initials: JA
authors.lastname: Richter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood*; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000502:physiology*; D006348:Cardiac Surgical Procedures; D002648:Child; D002675:Child, Preschool; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D011300:Preoperative Care; D011446:Prospective Studies; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006493:Heparin