The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery.
Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis. We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg x kg(-1) x h(-1) infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting.


CONCLUSIONS
In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting.
Slaughter
T F
TF
Department of Anesthesiology, Duke University Medical Center and the Durham Veteran's Affairs Medical Center, North Carolina 27710, USA.
Faghih
F
F
Greenberg
C S
CS
Leslie
J B
JB
Sladen
R N
RN
D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000990:Antithrombin III / Q000032:analysis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D005337:Fibrin / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D011183:Postoperative Complications; D011446:Prospective Studies; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects
D000933:Antifibrinolytic Agents; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005337:Fibrin; D010447:Peptide Hydrolases; D013917:Thrombin; D015119:Aminocaproic Acid