Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass

Weike Tao, Donald J. Deyo, Robert L. Brunston, Roger A. Vertrees, Tonya L. Grochoske, Joseph B. Zwischenberger

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    To reduce the risks of protamine reactions after cardiopulmonary bypass (CPB), a heparin removal device (HRD) with plasma separation and poly-L- lysine (PLL) affinity adsorption was developed. To compare the efficacy of HRD with that of protamine, blood coagulation variables were evaluated in a swine model of CPB. Female Yorkshire swine were randomly divided into the HRD group (n = 6, weight 79.7 ± 7.0 kg) and the protamine group (n = 6, weight 79.3± 6.8 kg), and subjected to 60 min of right atrium-to-aortic, hypothermic (28°C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual lumen cannula in the HRD group. Blood flow was drained from the inferior vena cava, through the plasma separation chamber of the HRD where heparin was bound to PLL, and re-infused into the right atrium. The HRD run time was determined by an established mathematical model of first-order exponential depletion targeted to 90% heparin removal. In the protamine group, protamine was given in a 100 U heparin to 1 mg protamine ratio after CPB in a slow intravenous infusion. Hemodynamics, activated clotting time (ACT), activated partial thromboplastin time (APTT), and heparin concentration were obtained before, every 5 min during, and after the use of the HRD or before and after protamine administration, and 1 and 3 hours after HRD or protamine. Heparin concentration immediately after CPB was 4.90 ± 0.19 U/ml in the HRD group and 3.94 ± 0.63 U/ml in the protamine group, respectively (p > 0.05 between groups). The ACT was 994 ± 7 sec in the HRD group and 768 ± 55 sec in the protamine group, and APTT was greater than 150 sec in both groups (p > 0.05 between groups). In the HRD group, the HRD run time was determined to be 31.5 ± 2.4 min for the targeted 90% heparin removal, and the plasma heparin concentration followed first-order depletion kinetics. In the protamine group, the full dose of protamine was administered over 15 min. Immediately after the HRD run or protamine administration, plasma heparin concentration decreased to 0.48 ± 0.09 U/ml in the HRD group and 0.13 ± 0.02 U/ml in the protamine group (p < 0.01 between groups); likewise, ACT decreased to 188 ± 25 sec in the HRD group and 101 ± 5 in the protamine group (p < 0.01 between groups). The APTT was not significantly different between the groups at any time during the experiment. Plasma heparin concentration and ACT were not significantly different three hours after the HRD run or protamine administration. The authors conclude that the HRD is capable of predictable reversal of systemic heparinization after CPB, and is an alternative to achieve heparin clearance in subjects who may develop adverse reactions to protamine.

    Original languageEnglish (US)
    JournalASAIO Journal
    Volume43
    Issue number5
    StatePublished - Sep 1997

    Fingerprint

    Device Removal
    Protamines
    Cardiopulmonary Bypass
    Heparin
    Partial Thromboplastin Time
    Plasmas
    Thromboplastin
    Heart Atria

    ASJC Scopus subject areas

    • Biophysics
    • Bioengineering

    Cite this

    Tao, W., Deyo, D. J., Brunston, R. L., Vertrees, R. A., Grochoske, T. L., & Zwischenberger, J. B. (1997). Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass. ASAIO Journal, 43(5).

    Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass. / Tao, Weike; Deyo, Donald J.; Brunston, Robert L.; Vertrees, Roger A.; Grochoske, Tonya L.; Zwischenberger, Joseph B.

    In: ASAIO Journal, Vol. 43, No. 5, 09.1997.

    Research output: Contribution to journalArticle

    Tao, W, Deyo, DJ, Brunston, RL, Vertrees, RA, Grochoske, TL & Zwischenberger, JB 1997, 'Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass', ASAIO Journal, vol. 43, no. 5.
    Tao W, Deyo DJ, Brunston RL, Vertrees RA, Grochoske TL, Zwischenberger JB. Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass. ASAIO Journal. 1997 Sep;43(5).
    Tao, Weike ; Deyo, Donald J. ; Brunston, Robert L. ; Vertrees, Roger A. ; Grochoske, Tonya L. ; Zwischenberger, Joseph B. / Efficacy of a heparin removal device in comparison with protamine after hypothermic cardiopulmonary bypass. In: ASAIO Journal. 1997 ; Vol. 43, No. 5.
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    abstract = "To reduce the risks of protamine reactions after cardiopulmonary bypass (CPB), a heparin removal device (HRD) with plasma separation and poly-L- lysine (PLL) affinity adsorption was developed. To compare the efficacy of HRD with that of protamine, blood coagulation variables were evaluated in a swine model of CPB. Female Yorkshire swine were randomly divided into the HRD group (n = 6, weight 79.7 ± 7.0 kg) and the protamine group (n = 6, weight 79.3± 6.8 kg), and subjected to 60 min of right atrium-to-aortic, hypothermic (28°C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual lumen cannula in the HRD group. Blood flow was drained from the inferior vena cava, through the plasma separation chamber of the HRD where heparin was bound to PLL, and re-infused into the right atrium. The HRD run time was determined by an established mathematical model of first-order exponential depletion targeted to 90{\%} heparin removal. In the protamine group, protamine was given in a 100 U heparin to 1 mg protamine ratio after CPB in a slow intravenous infusion. Hemodynamics, activated clotting time (ACT), activated partial thromboplastin time (APTT), and heparin concentration were obtained before, every 5 min during, and after the use of the HRD or before and after protamine administration, and 1 and 3 hours after HRD or protamine. Heparin concentration immediately after CPB was 4.90 ± 0.19 U/ml in the HRD group and 3.94 ± 0.63 U/ml in the protamine group, respectively (p > 0.05 between groups). The ACT was 994 ± 7 sec in the HRD group and 768 ± 55 sec in the protamine group, and APTT was greater than 150 sec in both groups (p > 0.05 between groups). In the HRD group, the HRD run time was determined to be 31.5 ± 2.4 min for the targeted 90{\%} heparin removal, and the plasma heparin concentration followed first-order depletion kinetics. In the protamine group, the full dose of protamine was administered over 15 min. Immediately after the HRD run or protamine administration, plasma heparin concentration decreased to 0.48 ± 0.09 U/ml in the HRD group and 0.13 ± 0.02 U/ml in the protamine group (p < 0.01 between groups); likewise, ACT decreased to 188 ± 25 sec in the HRD group and 101 ± 5 in the protamine group (p < 0.01 between groups). The APTT was not significantly different between the groups at any time during the experiment. Plasma heparin concentration and ACT were not significantly different three hours after the HRD run or protamine administration. The authors conclude that the HRD is capable of predictable reversal of systemic heparinization after CPB, and is an alternative to achieve heparin clearance in subjects who may develop adverse reactions to protamine.",
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    N2 - To reduce the risks of protamine reactions after cardiopulmonary bypass (CPB), a heparin removal device (HRD) with plasma separation and poly-L- lysine (PLL) affinity adsorption was developed. To compare the efficacy of HRD with that of protamine, blood coagulation variables were evaluated in a swine model of CPB. Female Yorkshire swine were randomly divided into the HRD group (n = 6, weight 79.7 ± 7.0 kg) and the protamine group (n = 6, weight 79.3± 6.8 kg), and subjected to 60 min of right atrium-to-aortic, hypothermic (28°C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual lumen cannula in the HRD group. Blood flow was drained from the inferior vena cava, through the plasma separation chamber of the HRD where heparin was bound to PLL, and re-infused into the right atrium. The HRD run time was determined by an established mathematical model of first-order exponential depletion targeted to 90% heparin removal. In the protamine group, protamine was given in a 100 U heparin to 1 mg protamine ratio after CPB in a slow intravenous infusion. Hemodynamics, activated clotting time (ACT), activated partial thromboplastin time (APTT), and heparin concentration were obtained before, every 5 min during, and after the use of the HRD or before and after protamine administration, and 1 and 3 hours after HRD or protamine. Heparin concentration immediately after CPB was 4.90 ± 0.19 U/ml in the HRD group and 3.94 ± 0.63 U/ml in the protamine group, respectively (p > 0.05 between groups). The ACT was 994 ± 7 sec in the HRD group and 768 ± 55 sec in the protamine group, and APTT was greater than 150 sec in both groups (p > 0.05 between groups). In the HRD group, the HRD run time was determined to be 31.5 ± 2.4 min for the targeted 90% heparin removal, and the plasma heparin concentration followed first-order depletion kinetics. In the protamine group, the full dose of protamine was administered over 15 min. Immediately after the HRD run or protamine administration, plasma heparin concentration decreased to 0.48 ± 0.09 U/ml in the HRD group and 0.13 ± 0.02 U/ml in the protamine group (p < 0.01 between groups); likewise, ACT decreased to 188 ± 25 sec in the HRD group and 101 ± 5 in the protamine group (p < 0.01 between groups). The APTT was not significantly different between the groups at any time during the experiment. Plasma heparin concentration and ACT were not significantly different three hours after the HRD run or protamine administration. The authors conclude that the HRD is capable of predictable reversal of systemic heparinization after CPB, and is an alternative to achieve heparin clearance in subjects who may develop adverse reactions to protamine.

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