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An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis
  1. Anne Godier1,2,3,
  2. Kiran Parmar3,
  3. Karuna Manandhar3,
  4. Beverley J Hunt3,4
  1. 1Department of Anesthesia and Critical Care, Fondation Ophtalmologique Rothschild, Paris, France
  2. 2Faculté de Pharmacie, INSERM UMR-S1140, Université Paris Descartes, Paris, France
  3. 3Department of Thrombosis and Vascular Biology, Rayne Institute, London, UK
  4. 4Thrombosis and Haemostasis Centre, Guy's and St Thomas's NHS Foundation Trusts, and King's College, London, UK
  1. Correspondence to Dr Anne Godier, Service d'Anesthésie-Réanimation, Fondation Adolphe de Rothschild, 25 rue Manin, Paris 75019, France; agodier{at}fo-rothschild.fr

Abstract

Aims 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.

  • FIBRINOLYSIS
  • FIBRINOGEN
  • BLEEDING DISORDERS
  • HAEMOSTASIS
  • COAGULATION

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Footnotes

  • This work has been presented to the International Society of Thrombosis and Haemostasis in Amsterdam.

  • Handling editor Mary Frances McMullin

  • Contributors AG participated in the design of the study, performed whole blood experiments, analysed results, made the figures and wrote the manuscript. KP provided samples, performed laboratory plasma assays, discussed data results and critically read the manuscript. KM participated in data analysis and provided critical revisions to the manuscript. BJH conceived the study, analysed results and provided critical revisions to the manuscript. The final version was approved by all authors.

  • Funding This paper was supported by a grant from the Société française d'Anesthésie Réanimation. TEG devices and TEG reagents were kindly provided by Haemonetics Corporation, Braintree, MA, USA.

  • Competing interests None declared.

  • Ethics approval National Research Ethics Service Committee London—City and East UK (protocol number: 12/LO/0128).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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