RT Journal Article
SR Electronic
T1 An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 154
OP 161
DO 10.1136/jclinpath-2016-203854
VO 70
IS 2
A1 Godier, Anne
A1 Parmar, Kiran
A1 Manandhar, Karuna
A1 Hunt, Beverley J
YR 2017
UL http://jcp.bmj.com/content/70/2/154.abstract
AB 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.