title: Monitoring high-dose heparinization during cardiopulmonary by-pass--a comparison between prothrombinase-induced clotting time (PiCT) and two chromogenic anti-factor Xa activity assays.
abstract: Heparinization requires monitoring, but optimal methods for measuring the anticoagulant effects of heparin remain to be determined. We compared prothrombinase-induced clotting time (PiCT) and two chromogenic anti-factor Xa activity (anti-Xa) assays in monitoring high-dose heparinization during cardiopulmonary by-pass (CPB). Heparin effects were serially measured with PiCT and two anti-Xa assays in 100 patients. Antithrombin and protein C activities were measured preoperatively, and antithrombin activity was measured during CPB. Activation of coagulation was assessed with measurements of prothrombin fragment F1+2, soluble fibrin complexes, and D-dimer before, during, and after CPB. During CPB mean ranges of PiCT and of anti-Xa heparin levels measured with (anti-Xa A) and without (anti-Xa B) dextran sulfate and antithrombin supplementation were 5.0-5.2, 4.7-5.0, and 4.5-4.9 IU/ml, respectively. There was poor agreement between PiCT and anti-Xa and between the two anti-Xa assays (r = 0.32-0.65 and broad limits of agreement). Patients with low preoperative antithrombin or protein C levels had lower PiCT (p = 0.028 and p = 0.01) and anti-Xa A (both p<0.001) levels during CPB than others. Patients with the lowest heparin activities during CPB (lowest deciles of PiCT and anti-Xa A) had higher subsequent F1+2 after CPB (p = 0.002 and p = 0.02), and patients with high heparin levels required fewer transfusions of packed red blood cells than others. In conclusion, in the challenging setting of CPB there is poor agreement between anti-Xa assays and PiCT. However, coagulation-based PiCT could provide an alternative to the chromogenic anti-Xa assays. Higher heparin levels during CPB were confirmed to associate with reduced transfusion requirements.
authors.affiliation: Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Helsinki, Finland. peter.raivio@hus.fi
authors.forename: Peter
authors.initials: P
authors.lastname: Raivio
authors.forename: Anne
authors.initials: A
authors.lastname: Kuitunen
authors.forename: Jari
authors.initials: J
authors.lastname: Petäjä
authors.forename: Sorella
authors.initials: S
authors.lastname: Ilveskero
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods*; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D002863:Chromogenic Compounds; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D016903:Drug Monitoring / Q000379:methods*; D017707:Erythrocyte Transfusion; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000295:instrumentation*; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D011486:Protein C; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005337:Fibrin; D006493:Heparin; D013925:Thromboplastin; D015951:Factor Xa