Concentration-effect relationship for tranexamic acid inhibition of tissue plasminogen activator-induced fibrinolysis in vitro using the viscoelastic ClotPro® TPA-test.

Abstract

Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women. We performed an in vitro study of whole blood samples spiked with tranexamic acid from pregnant women in the first, second, and third trimester (n=20 per group) and from non-pregnant women (n=20). We performed ClotPro TPA-tests of whole blood sample and ClotPro EX-tests, FIB-tests, and TPA-tests. Clot lysis was inhibited in a concentration-dependent manner up to a tranexamic acid concentration of 6.25 mg L^-1. At tranexamic acid concentrations of 12.5 mg L^-1 and above, clot lysis was completely inhibited. The concentration-effect relationship of tranexamic acid did not differ in a clinically important manner in blood from pregnant women across all three trimesters or from non-pregnant controls. A median maximum lysis cut-off value of at9 least 16% (25-75th percentiles 15-18), a median clot lysis time of 3600 s (25-75th percentiles 3600-3600), or both was associated with a tranexamic acid concentration of least 12.5 mg L^-1. The ClotPro® TPA-test is sensitive in detecting inhibition of fibrinolysis by tranexamic acid in whole blood samples of pregnant and non-pregnant women. The concentration-effect relationship of tranexamic acid to inhibit fibrinolysis in whole blood did not differ for women in the first, second, and third trimester or for non-pregnant women.