Reduction of bleeding after heart operations through the prophylactic use of epsilon- aminocaproic acid Thomas J. Vander Salm, MDa, Shubjeet Kaur, MDb,

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Presentation transcript:

Reduction of bleeding after heart operations through the prophylactic use of epsilon- aminocaproic acid Thomas J. Vander Salm, MDa, Shubjeet Kaur, MDb, Robert A. Lancey, MDa, Okike N. Okike, MDa, A.Thomas Pezzella, MDa, Russell F. Stahl, MDa, Lisa Leone, BSNa, Jian-Ming Li, MDa, C.Robert Valeri, MDc, Alan D. Michelson, MDd The Journal of Thoracic and Cardiovascular Surgery Volume 112, Issue 4, Pages 1098-1107 (October 1996) DOI: 10.1016/S0022-5223(96)70112-5 Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 1 Platelet surface expression of GPIb (von Willebrand factor receptor) did not change significantly during or after CPB, irrespective of whether patients received EACA (closed circles) or placebo (open circles). Platelet surface GPIb was determined at indicated time points by whole blood flow cytometry with monoclonal antibody 6D1. PRE-OP, Preoperative; HEPARIN, 5 minutes after initial heparin administration; 45 MIN CPB, 45 minutes into CPB; PROTAMINE, 5 minutes after protamine administration; 2 H POST, 2 hours after skin closure. Data are mean ± standard error of the mean; n = 13 patients for EACA and n = 10 patients for placebo. Actual preoperative values (mean flourescence ± standard error of the mean) were 33.8 ± 2.4 in EACA group and 37.0 ± 1.8 in placebo group. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 2 Platelet surface expression of the GPIIb-IIIa complex (fibrinogen receptor) did not change significantly during or after CPB, irrespective of whether patients received EACA (closed circles) or placebo (open circles). Platelet surface GPIIb-IIIa complex was determined at indicated time points (see Fig. 1) by whole blood flow cytometry with monoclonal antibody 7E3. Data are mean ± standard error of the mean; n = 13 patients for EACA and n = 9 patients for placebo. Actual preoperative values (mean flourescence ± standard error of the mean) were 24.2 ± 1.5 in EACA group and 20.2 ± 0.9 in placebo group. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 3 Irrespective of whether patients received EACA (closed symbols) or placebo (open symbols), platelets circulated during and after CPB with little bound fibrinogen (circles), and platelets were normally reactive to combination of ADP and epinephrine (ADP/epi), as determined by ability to bind fibrinogen to GPIIb-IIIa complex (squares). Fibrinogen binding to platelet surface GPIIb-IIIa complex was determined at indicated time points (see Fig. 1) by whole blood flow cytometry with monoclonal antibody F26. F26 binding to preoperative samples incubated with 20 mmol/L ADP and 20 mmol/L epinephrine was defined as 100%. Data are mean ± standard error of the mean; n = 12 patients for EACA and n = 7 patients for placebo. Preoperative fibrinogen binding to platelet surface GPIIb-IIIa complex in absence of agonist (mean flourescence ± standard error of the mean) was 5.8 ± 2.3 in EACA group, and 4.5 ± 1.3 in placebo group. Binding with ADP/epi agonist was 39.7 ± 8.3 in EACA group and 58.5 ± 13.9 in placebo group. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 4 Platelet surface expression of P-selectin (reflecting granule secretion) was minimal whether patients received EACA (closed circles) or placebo (open circles). Platelet surface P-selectin was determined at indicated time points (see Fig. 1) by whole blood flow cytometry with monoclonal antibody S12. S12 binding to preoperative samples incubated with 2 U/ml thrombin was defined as 100%. Data are mean ± standard error of the mean; n = 12 patients for EACA and n = 9 patients for placebo. Preoperative values (mean flourescence ± standard error of the mean) were 2.7 ± 0.4 in EACA group and 2.6 ± 1.8 in placebo group. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 5 Euglobulin clot lysis time, assay of fibrinolytic activity, was significantly longer, indicating less fibrinolysis in patients receiving EACA (closed circles) than in control patients (open circles). Time points as given in Fig. 1. Data are mean ± standard error of the mean; n = 14 patients for EACA and n = 11 patients for placebo. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 6 Administration of EACA inhibited fibrinolysis, as evidenced by obliteration of CPB-associated increase in circulating plasma d-dimer. Time points as given in Fig. 1. Data are mean ± standard error of the mean; n = 14 patients for EACA and n = 10 patients for placebo. The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 7 Plasma fibrinogen levels decreased during CPB, irrespective of whether patients received EACA (closed circles) or placebo (open circles). Time points as given in Fig. 1. Data are mean ± standard error of the mean; n = 14 patients for EACA and n = 12 patients for placebo. Actual preoperative values (± standard error of the mean) were 405.3 ± 33.9 mg/dl (EACA) and 313.8 ± 36.6 mg/dl (placebo). The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 8 Plasma antiplasmin levels decreased during CPB, irrespective of whether patients received EACA (closed circles) or (open circles). Time points as given in Fig. 1. Data are mean ± standard error of the mean; n = 14 patients for EACA and n = 12 patients for placebo. Actual preoperative values (percentage of mean values in normal volunteers ± standard error of the mean) were 92.3% ± 4.5% (EACA) and 85.0% ± 2.5% (placebo). The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions

Fig. 9 Plasma antithrombin III levels decreased during CPB, irrespective of whether patients received EACA (closed circles) or placebo (open circles). Time points as given in Fig. 1. Data are mean ± standard error of the mean; n = 10 patients for EACA and n = 7 patients for placebo. Actual preoperative values (percentage of mean values in normal volunteers ± standard error of the mean) were 94.2% ± 7.1% (EACA) and 85.1% ± 3.3% (placebo). The Journal of Thoracic and Cardiovascular Surgery 1996 112, 1098-1107DOI: (10.1016/S0022-5223(96)70112-5) Copyright © 1996 Mosby, Inc. Terms and Conditions