The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: A double-blind randomized study

Salm, Thomas J. Vander; Ansell, Jack; Okike, O. N.; Marsicano, Thomas H.; Lew, Robert A.; Stephenson, Wendy P.; Rooney, Kathy

doi:10.1016/s0022-5223(19)35778-2

Cited by 135 publications

(15 citation statements)

References 4 publications

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“…No hemostatic salutary effect accompanied desmopressin for elective procedures in children [4] or adult aortocoronary bypass grafting [5,6]. Lysine analog plasmin-plasminogen inhibitors (antifibrinolytics) also have provided varied results [7,8,9,10,11,12,13]. Several trials of the lysine analog E-aminocaproic acid were neither randomized nor blinded [7][8][9]111.…”

Section: Introductionmentioning

confidence: 99%

Effect of tranexamic acid on platelet ADP during extracorporeal circulation

1991

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Seventeen adults received the antifibrinolytic drug tranexamic acid during cardiac surgery utilizing extracorporeal circulation (ECC). In 8 patients, drug administration began prior to skin incision (pre-ECC); infusions commenced after ECC and protamine administration in another 9 patients (post-ECC). Compared with the post-ECC group, the pre-ECC group exhibited less bleeding via mediastinal drains (420 vs. 655 mL/12 h median, P = 0.024), decreased frequency of the presence (greater than or equal to 10 micrograms/mL) of fibrin split products (P less than 0.05), and greater platelet dense granule content of adenosine diphosphate after surgery (15.47 vs. 4.05 nmoles/mg protein median, P = 0.021). Follow-up in vitro study of tranexamic acid inhibition of plasmin-induced platelet activation utilizing normal human platelet rich plasma and porcine plasmin revealed a 13-fold lower concentration of tranexamic acid for 50% inhibition when plasmin was preincubated with the drug (1.2 micrograms/mL, 95% CI = 1.13-1.60 micrograms/mL) compared to when platelet rich plasma was preincubated with the drug (16 micrograms/mL, 95% CI = 7.3-99. micrograms/mL). Plasmin inactivated with tranexamic acid retained its ability to inhibit thrombin-induced platelet activation, thus suggesting that tranexamic acid inhibits plasmin's catalytic activity and not its binding to platelets. Both clot lysis and platelet dysfunction may contribute to bleeding after ECC. Tranexamic acid blocks plasmin-induced partial platelet activation during ECC, thus preserving platelet function and promoting hemostasis after ECC.

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Section: Introductionmentioning

confidence: 99%

Effect of tranexamic acid on platelet ADP during extracorporeal circulation

1991

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“…The present study agrees in part with the findings of a recent report which showed that patients treated with EACA had only modest reductions in blood loss as compared to a placebo group. 22 In a separate study, EACA decreased intraoperative bleeding in patients undergoing cardiac surgery, but was not effective during the subsequent 24 hours. 23 DelRossi and colleagues12 demonstrated that prophylactic treatment with EACA was effective in reducing postoperative blood loss after CPB surgery.…”

Section: Discussionmentioning

confidence: 96%

Tranexamic Acid Reduces Bleeding After Cardiopulmonary Bypass When Compared to Epsilon Aminocaproic Acid and Placebo

et al. 1997

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“…This rise in plasma levels of plasmin may lead to cleavage of GPIb or to proteolysis of von Willebrand proteins as suggested by in vitro studies (1). The importance of reversing the fibrinolysis that occurs with cardiopulmonary bypass and heparin administration has been underscored by studies in which bleeding tendencies were reversed or at least decreased using plasmin inhibitors such as aprotinin (6,5) or e-aminocaproic acid (38). For example, aprotinin administration prior to bypass has been shown to prevent the formation of FDP and the consumption of a 2 -antiplasmin activity (6).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Heparin on Fibrinolytic Activity and Platelet Function

Upchurch¹,

Valeri²,

Khuri³

et al. 1995

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Heparin, a polyanionic glycosaminoglycan, is used routinely prior to the induction of cardiopulmonary bypass. Earlier observations in our laboratory suggested that the postoperative bleeding which occurs, despite neutralization of heparin with prdtamine, is secondary to hypothermia and dilutional anemia during bypass. An additional, potential mechanism for excessive bleeding following cardiopulmonary bypass is that heparin activates the fibrinolytic system, which may, in turn, adversely affect hemostasis. To understand better the effects of heparin administration on the fibrinolytic system in vivo, we simulated the anticoagulant regimen of cardiopulmonary bypass by administering increasing doses of intravenous heparin to five adult baboons over 60 minutes. We measured fibrinolytic parameters serially following heparinization, and demonstrated that heparin induces activation of the fibrinolytic system. We showed that the fibrinolytic system was activated in vivo as evidenced by an increase in plasmin activity and immunoreactive plasmin light chain, as well as an increase in immunoreactive fibrinogen fragment E in yjtro. These results demonstrate that the fibrinolytic system is activated in vivo by the administration of heparin during cardiopulmonary bypass. These data suggest that, despite administration of a neutralizing agent such as protamine, heparin may contribute to postoperative bleeding complications following cardiopulmonary bypass surgery owing principally to its longer-lived effects on the fibrinolytic system.

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The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: A double-blind randomized study

Cited by 135 publications

References 4 publications

Effect of tranexamic acid on platelet ADP during extracorporeal circulation

Effect of tranexamic acid on platelet ADP during extracorporeal circulation

Tranexamic Acid Reduces Bleeding After Cardiopulmonary Bypass When Compared to Epsilon Aminocaproic Acid and Placebo

The Effect of Heparin on Fibrinolytic Activity and Platelet Function

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