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BACKGROUND: Antifibrinolytics are widely used in cardiac surgery to reduce bleeding. Allogeneic blood transfusion, even in primary cardiac operations with low blood loss, is still high. In the present study we evaluated the impact of tranexamic acid compared to aprotinin on the transfusion incidence in cardiac surgical patients with low risk of bleeding.

METHODS: This prospective, randomized, double-blind study included 220 patients undergoing primary coronary artery revascularization (coronary artery bypass grafting [CABG]) or aortic valve replacement (AVR). Randomized in blocks of 20, patients received either tranexamic acid (approximately 6 g) or full-dose aprotinin (approximately 5–6 x 10⁶ Kallikrein Inhibiting Units). Transfusion was guided by a strict transfusion algorithm. Molecular markers of hemostasis were determined to assess differences in the mode of action of the two drugs. Primary end-points were the incidence of allogeneic red cell transfusion and 24-h postoperative blood loss. Data were analyzed according to the intention-to-treat principle and compared using the ² and Mann-Whitney U-test.

RESULTS: Two-hundred-twenty patients were enrolled (CABG: 134, AVR: 86). In the aprotinin Group 47% of patients received allogeneic blood during the hospital stay as compared to 61% in the tranexamic acid group (P = 0.036). Aprotinin conferred a 23% reduction in allogeneic transfusion risk (RR 0.77, 95% CI 0.53–0.88). Overall, no significant difference in postoperative bleeding was observed, although 24-h blood loss was reduced in aprotinin-treated CABG patients (500, 350–750 mL vs 650, 475–875 mL (median, 25th–75th percentile); P = 0.039). Despite the lower transfusion rate, the hemoglobin concentration on the first postoperative day was higher in the aprotinin group (11.3, 9.9–12.1 vs 10.6, 9.9–11.6 mg/dL; P = 0.023). The fibrinolytic activity at the end of operation determined by D-Dimer was comparable in both groups. (0.15, 0.11–0.17 mg/L [aprotinin] versus 0.18, 0.12–0.24 mg/L [tranexamic acid]). The activated partial thromboplastin time was prolonged up to 4 h postoperatively in the aprotinin group, while the heparin requirement was reduced: 19% of the patients in the aprotinin group and 45% in the tranexamic acid group received at least one additional bolus heparin during cardiopulmonary bypass (P < 0.001). Troponin T levels postoperatively and on postoperative day 1 were significantly higher in the tranexamic acid group (P = 0.017). No differences in renal, cardiac, or mortality outcomes were observed.

CONCLUSION: Considering the rate of transfusion of red blood cells, tranexamic acid was slightly inferior in patients undergoing CABG, but there was no difference in patients receiving AVR. Tranexamic acid seems to be less effective in operations with increased bleeding such as CABG. Clinical benefit depends on specific patient and institution characteristics (ClinicalTrials.gov NCT00396760).

The Origin of Species
Written by Charles Darwin

Perhaps the most readable and accessible of the great works of scientific imagination, The Origin of Species sold out on the day it was published in 1859. Theologians quickly labeled Charles Darwin the most dangerous man in England, and, as the Saturday Review noted, the uproar over the book quickly "passed beyond the bounds of the study and lecture-room into the drawing-room and the public street." Yet, after reading it, Darwin's friend and colleague T. H. Huxley had a different reaction: "How extremely stupid not to have thought of that."
Based largely on Darwin's experience as a naturalist while on a five-year voyage aboard H.M.S. Beagle, The Origin of Species set forth a theory of evolution and natural selection that challenged contemporary beliefs about divine providence and the immutability of species. A landmark contribution to philosophical and scientific thought, this edition also includes an introductory historical sketch and a glossary Darwin later added to the original text.

Charles Darwin grew up considered, by his own account, "a very ordinary boy, rather below the common standard of intellect." A quirk of fate kept him from the career his father had deemed appropriate--that of a country parson--when a botanist recommended Darwin for an appointment as a naturalist aboard H.M.S. Beagle from 1831 to 1836. Darwin is also the author of the five-volume work Zoology of the Voyage of the Beagle (1839) and The Descent of Man (1871).


From the Trade Paperback edition.