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J Thorac Cardiovasc Surg 1994;107:1375-1376
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

Tranexamic acid after bypass: Too late to help?

Departments of Anesthesiology and Cardiothoracic Surgery
Hahnemann University
Philadelphia, PA 19102

To the Editor:

Øvrum and associates ¹ conclude that tranexamic acid is not necessary to reduce blood loss after coronary artery bypass operations. Under their usual protocol, in which they used prophylactic tranexamic acid after bypass, the authors encountered one woman who had thrombosis of both the grafts and the native arteries. This led them to abandon prophylactic tranexamic acid. Although they found a numerical (but not statistically significant) difference in the prevalence of myocardial infarctions (n = 200), ¹ other studies of synthetic antifibrinolytics with more objective definitions of myocardial infarction conducted by DelRossi ² and Horrow ^{3, 4} and their associates found no such suggestion. DelRossi and colleagues found myocardial infarction in 10 of 180 patients receiving placebo versus 4 of 170 patients receiving epsilon-aminocaproic acid; Horrow and coworkers found in two studies no myocardial infarctions in either placebo or treated groups comprising 38 and 160 patients, respectively.

Although Øvrum and associates state plainly in the discussion the limitations of their study, namely, its unblinded, sequential, retrospective design, they do not squarely address the specific circumstance which engenders bias: the anecdotal case of graft occlusion that led them to abandon prophylactic tranexamic acid. They subsequently collected data on the control group. These nonrandomized data thus suffer from extreme bias. A surgeon no longer administering a drug given to limit bleeding would naturally provide additional attention to hemostasis to subsequent patients whether on a conscious or subconscious basis.

The minimal effect of tranexamic acid demonstrated in the authors' study probably arises from several factors. First, the extreme bias provided by a sequential unblinded design after an anecdotal case remains unaffected by either the clinical homogeneity of the group populations or the similar perioperative data. Second, treatment by the same surgical team serves to intensify rather than compensate for this bias. Third, the ranges of blood loss demonstrate outliers in both groups, rendering suspect statistical tests that assume normally distributed data. The authors used Student's t test, which assumes normal distributions, to analyze the blood loss data; thus their conclusions must be questioned.

Fourth, because they waited until the completion of cardiopulmonary bypass to administer tranexamic acid, their study design did not provide blockade of plasmin receptors on platelets, which may account for a substantial part of the benefit provided by antifibrinolytics, whether synthetic or natural. ^{5, 6} Indeed, well-conducted studies of the synthetic antifibrinolytics administered after bypass demonstrate about 15% savings in blood loss ⁷ compared with the 30% savings when they are given before bypass. ^2-4 In agreement, Øvrum's group ¹ also find a 14% savings in blood loss with tranexamic acid given after bypass. Does this warrant the conclusion that the drug is not necessary to reduce blood loss or instead that authors gave the drug too late?

References

1. Øvrum E, Åm Holen E, Abdelnoor M, Øystese R, Ringdal M. Tranexamic acid (Cyklokapron) is not necessary to reduce blood loss after coronary artery bypass operations. J THORAC CARDIOVASC SURG 1993;105:78-83.[Abstract]
   
2. DelRossi AJ, Cernaianu AC, Botros S, Lemole GM, Moore R. Prophylactic treatment of postperfusion bleeding using EACA. Chest 1989;96:27-30.[Abstract/Free Full Text]
   
3. Horrow JC, Hlavacek J, Strong MD, et al. Prophylactic tranexamic acid decreases bleeding after cardiac operations. J THORAC CARDIOVASC SURG 1990;99:70-4.[Abstract]
   
4. Horrow JC, Van Riper DF, Strong MD, Brodsky I, Parmet JL. Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. Circulation 1991;84:2063-70.[Abstract/Free Full Text]
   
5. Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 1991;38:113-9.[Medline]
   
6. van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CRH. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1990;99:788-97.[Abstract]
   
7. Vander Salm TJ, Ansell JE, Okike ON, et al. The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: a double-blind randomized study. J THORAC CARDIOVASC SURG 1988;95:538-40.[Abstract]
   

This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael D. Strong Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Horrow, J. Articles by Van Riper, D. F. Search for Related Content PubMed PubMed Citation Articles by Horrow, J. Articles by Van Riper, D. F.