title: An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis.
abstract: OBJECTIVE
  Acute traumatic coagulopathy is characterised by fibrinolysis and low fibrinogen. It is unclear how much fibrinogenolysis contributes to reduce fibrinogen levels. The study aim was to: investigate in vitro the effects of tissue-plasminogen activator (t-PA) and tranexamic acid (TXA) on coagulation and fibrinolysis.
  
  
  METHODS
  Whole blood was spiked with varying t-PA concentrations. Clauss fibrinogen levels and thrombelastography (TEG, Haemonetics) were performed, including functional fibrinogen level (FLEV). TXA effects were assessed using four TXA concentrations. Recorded parameters from kaolin activated TEG included maximal amplitude (MA), clot strength (G), percentage lysis (LY). Plasmin-antiplasmin complex (PAP), endogenous thrombin potential (ETP), prothrombin fragment 1+2 (PF1+2), factor V and factor VIII levels were all measured.
  
  
  RESULTS
  t-PA induced fibrinolysis: it increased PAP and LY, but decreased MA and G. t-PA induced fibrinogenolysis, with a concentration-dependant decrease in fibrinogen from 2.7 (2.6-3.1) to 0.8 (0.8-0.9) g/L with 60 nM t-PA. FLEV and fibrinogen levels were well correlated. High t-PA doses increased PF1+2, decreased ETP of 19% and FVIII of 63% but not FV. TXA had no effect on plasmin generation as evidenced by no change in PAP. It corrected LY, MA and G and partly protected fibrinogen against fibrinogenolysis: 0.03 mg/mL TXA reduced the fibrinogen fall induced by t-PA 20 nM from 43% to 14%. TXA halved the FVIII fall and increased ETP.
  
  
  CONCLUSIONS
  t-PA induced plasminogen activation and fibrinogenolysis in a concentration-dependant manner. TXA did not affect plasmin activation but reduced fibrinogenolysis. These results suggest that TXA given early in bleeding patients may prevent fibrinogenolysis.
authors.affiliation: Department of Anesthesia and Critical Care, Fondation Ophtalmologique Rothschild, Paris, France.|Faculté de Pharmacie, INSERM UMR-S1140, Université Paris Descartes, Paris, France.|Department of Thrombosis and Vascular Biology, Rayne Institute, London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Godier
authors.affiliation: Department of Thrombosis and Vascular Biology, Rayne Institute, London, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Parmar
authors.affiliation: Department of Thrombosis and Vascular Biology, Rayne Institute, London, UK.
authors.forename: Karuna
authors.initials: K
authors.lastname: Manandhar
authors.affiliation: Department of Thrombosis and Vascular Biology, Rayne Institute, London, UK.|Thrombosis and Haemostasis Centre, Guy's and St Thomas's NHS Foundation Trusts, and King's College, London, UK.
authors.forename: Beverley J
authors.initials: BJ
authors.lastname: Hunt
mesh_terms: D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology*
chemical_list: D000933:Antifibrinolytic Agents; D005343:Fibrinolytic Agents; D014148:Tranexamic Acid; D010959:Tissue Plasminogen Activator
keywords: BLEEDING DISORDERS; COAGULATION; FIBRINOGEN; FIBRINOLYSIS; HAEMOSTASIS