title: Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery.
abstract: The aim of this study was to systematically elucidate the effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass (CPB) surgery. Twenty-two patients undergoing CPB surgery were randomized to receive 100 mg/kg tranexamic acid or an equal volume of saline after anesthesia induction and prior to skin incision. Plasma levels of tissue plasminogen activator (t-PA) antigen and activity, crosslinked fibrin degradation products (D-dimer), alpha2-antiplasmin-plasmin complex, and plasminogen activator inhibitor-1 (PAI-1) antigen were measured. Blood samples were obtained after induction of anesthesia, before, during, and after CPB, at the end of surgery, and the next morning after surgery. Intraoperative and postoperative blood loss during 24 h after surgery was recorded. Patients' demographics were similar between the two groups. No patients suffered from thrombotic complications after surgery. In the tranexamic acid group, fibrinolytic activity and secondary fibrinolysis as measured by t-PA activity and D-dimer were markedly suppressed during CPB surgery (P=.042 and P=.015, respectively). Decreased fibrinolytic activity and fibrinolysis were accompanied by reduction of perioperative bleeding in the tranexamic acid group. We could also find a good positive correlation between the peak levels of t-PA activity and D-dimer (r(2)=.4203, P=.0011). No differences in the t-PA antigen, PAI-1 antigen release, and plasmin inhibition by alpha2-antiplasmin were apparent between the two groups. In a randomized, prospective trial of patients undergoing CPB surgery, we demonstrated that the synthetic antifibrinolytic drug tranexamic acid effectively suppresses fibrinolysis by inhibiting t-PA and plasmin activity with clear reduction of perioperative blood loss. While tranexamic acid had no effects on the other important fibrinolytic inhibitors like PAI-1 and alpha2-antiplasmin.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: S
authors.initials: S
authors.lastname: Gando
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: H
authors.initials: H
authors.lastname: Mashio
authors.forename: Y
authors.initials: Y
authors.lastname: Goda
authors.forename: H
authors.initials: H
authors.lastname: Kawahigashi
authors.forename: O
authors.initials: O
authors.lastname: Kemmotsu
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin; D005342:Fibrinolysis / Q000187:drug effects*; D006488:Hemostasis, Surgical; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014148:Tranexamic Acid / Q000008:administration & dosage*; D000979:alpha-2-Antiplasmin
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; D014148:Tranexamic Acid; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin