Correspondence  |   July 2003
About Dosage Schemes and Safety of Tranexamic Acid in Cardiac Surgery
Author Notes
  • Policlinico di Monza, Monza, Italy.
Article Information
Correspondence   |   July 2003
About Dosage Schemes and Safety of Tranexamic Acid in Cardiac Surgery
Anesthesiology 7 2003, Vol.99, 236. doi:
Anesthesiology 7 2003, Vol.99, 236. doi:
To the Editor:—
Dowd et al.  1 have provided important information about the pharmacokinetics of tranexamic acid (TA) in cardiac surgery with cardiopulmonary bypass. Particularly, they demonstrated the necessity of a continuous infusion of TA to obtain stable therapeutic concentrations. Then, they proposed two different dosage schemes in low- and high-risk patients for bleeding, to obtain TA plasma concentrations of 334 μm and 800 μm, respectively. Considering the patients with low-risk for bleeding, they recommended a loading dose of 12.5 mg/kg (or greater) over 30 min, a continuous infusion of 6.5 mg · kg−1· hr−1, and 1 mg/kg (or greater) added to the priming, whereas in patients with high-risk for bleeding they proposed doses about 2.5 higher.
My group published various studies 2–4 proposing an original pharmacologic protocol for TA that seem very similar to that proposed by Down et al.  For patients with low-risk for bleeding; that is, a loading dose of 1 g over 20 min before sternotomy (and not 1 g, 20 min before sternotomy, as erroneously reported in the work of my group cited by Dowd et al.  5), followed by a continuous infusion of 400 mg/h, and 500 mg added to pump priming. We also applied the same protocol in high-risk patients for bleeding, obtaining a significant reduction of blood loss and allogeneic transfusions. 4,5 One criticism of the study of Dowd et al.  is that the need to increase the doses of TA in this type of patient requires further clinical demonstrations, particularly considering (as the same authors report) that TA plasma concentrations of about 200 μm completely inhibit fibrinolysis.
Concerning the administration of TA after surgery, I agree with Dowd et al.  regarding benefits in the postoperative period depending on intraoperative dosing techniques, but I do not understand why the authors claim that the efficacy of prolonged TA administration in the postoperative period is an open question. In reality, the authors, applying their pharmacokinetic model to our TA protocol, confirmed the conclusions of our study. 5 Our intraoperative TA dosage scheme guarantees therapeutic concentrations for about 12 h, rendering unnecessary postoperative infusion of the drug.
It also seems that the potential thrombotic risk intrinsic to antifibrinolytic drugs is underestimated by Down et al.  I particularly disagree with their statement, “TA appears to be a very safe medication…. Thus our attempt to avoid excessive TA concentrations may not be necessary.”1 An extensive literature search showed cases of thrombosis following the use of hemostatic drugs such as ϵ-aminocaproic acid, aprotinin, and TA, but it would be sufficient to cite a recent case report 6 describing two fatal cases of thrombosis after the use of ϵ-aminocaproic acid (very similar to TA with a potency 10 times lower) in cardiac surgical patients operated on with deep hypothermic circulatory arrest, wherein postmortem laboratory analysis revealed the presence of Factor V Leiden. Because it is impossible to identify patients with a preoperative prothrombotic state, it is appropriate to use the minimal effective doses of hemostatic drugs to avoid amplifying these thrombotic complications. Furthermore, the same authors’ group reported in a previous study 7 three cases of stroke in cardiac surgical patients with known peripheral vascular disease, treated intraoperatively with high doses of TA. One would speculate that high concentrations of TA facilitated the formation of a thrombus in the presence of blood flow reductions in a diseased vessel.
In conclusion, only large, prospective, blinded studies will establish the real safety and efficacy of the various doses of tranexamic acid in cardiac surgery. Currently, caution is required when using a hemostatic drug.
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Fanashawe MP, Shore-Lesserson L, Reich DL: Two cases of fatal thrombosis after aminocaproic acid therapy and deep hypothermic circulatory arrest. A nesthesiology 2001; 95: 1525–7Fanashawe, MP Shore-Lesserson, L Reich, DL
Karski JM, Teasdale SJ, Norman P, Carroll J, Van Kessel K, Wong P, Glynn MF: Prevention of bleeding after cardiopulmonary bypass with high-dose transexamic acid. J Thorac Cardiovasc Surg 1995; 110: 835–42Karski, JM Teasdale, SJ Norman, P Carroll, J Van Kessel, K Wong, P Glynn, MF