title: Early heparin administration attenuates tissue factor-mediated thrombin generation during simulated cardiopulmonary bypass.
abstract: BACKGROUND
  We tested the hypothesis that heparin administration prior to the emergence of tissue factor (TF) would increase plasma TF pathway inhibitor (TFPI) and attenuate TF-mediated thrombin generation during simulated cardiopulmonary bypass (CPB).
  
  
  METHODS
  Human blood was recirculated for 120 minutes using an oxygenator and roller pump. Four groups were examined: control group (heparin 3.75 U/mL, in donor blood, n = 7), rTF group (heparin + recombinant TF 1000 pg/mL, in donor blood, n = 7), TFPI boost group (heparin, in preheparinized donor blood, n = 8), and rTF + TFPI boost group (heparin + rTF, in preheparinized blood, n = 7). In the two TFPI boost groups, 50 U/kg of heparin was given to the donors intravenously five minutes before donation to boost plasma TFPI levels. Total plasma TFPI, thrombin-antithrombin complex, and prothrombin fragment F1+2 levels were measured before and during CPB.
  
  
  RESULTS
  Preheparinization increased total plasma TFPI levels by a factor of 8.0. Administration of rTF significantly enhanced the generation of F1+2 (p = 0.0002). The heparin-induced TFPI elevation reduced both thrombin-antithrombin complex and F1+2 to control levels in rTF + TFPI boost group (p = 0.0158 for thrombin-antithrombin complex, p < 0.0001 for F1+2 ). F1+2 levels were at all times lower than control levels in TFPI boost group (p < 0.0001).
  
  
  CONCLUSIONS
  Heparin-induced TFPI elevation attenuates TF-mediated thrombin generation. Early heparin administration prior to the emergence of plasma TF may represent a novel strategy for controlling thrombin generation by the extrinsic coagulation pathway during CPB.
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Morizumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: Kanji
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Goto
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.forename: Masakazu
authors.initials: M
authors.lastname: Abe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Muneaki
authors.initials: M
authors.lastname: Matsubara
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Sakakibara
mesh_terms: D000990:Antithrombin III; D001777:Blood Coagulation / Q000502:physiology; D002315:Cardiopulmonary Bypass; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D010447:Peptide Hydrolases / Q000097:blood; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; C046193:antithrombin III-protease complex; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III; D006493:Heparin; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin