Heparin clearance profiles after systemic anticoagulation using a heparin removal device system

Weike Tao, Jon D. Callahan, Roger A. Vertrees, Robert L. Brunston, Donald J. Deyo, James C. Mcrea, Joseph B. Zwischenberger

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85% heparin removal for different body weights at 700 ml/min and 1400 ml/min extracorpurea HRDS blood flow. With an HRDS flow of 700 ml, 85% of total body hepaorin removal cannot be achieved within 30 min for subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85% heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 10) model of 60-min, hypothermic (28°C) cardiopulmonary bypass (CPB). Animals were given 300 U/ kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-factor Xa assays was 4.40 ± 1.08 U/ml in the 700 ml/min group and 4.78 ± 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (81.4 ± 3.7 kg) was significantly higher than that in the 700 ml/min group (67.2 ± 2.2 kg) (p < 0.05), with the actually achieved HRDS flow 658.5 ± 20.8 and 1437.4 ± 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85% heparin clearance was over 40 min, whereas in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 ± 3.7% heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 ± 2.5% (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin removal.

Original languageEnglish (US)
Pages (from-to)922-926
Number of pages5
JournalASAIO Journal
Volume43
Issue number6
StatePublished - Nov 1997

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Device Removal
Heparin
Plasmas
Animals
Body Weight
Cardiopulmonary Bypass

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering

Cite this

Tao, W., Callahan, J. D., Vertrees, R. A., Brunston, R. L., Deyo, D. J., Mcrea, J. C., & Zwischenberger, J. B. (1997). Heparin clearance profiles after systemic anticoagulation using a heparin removal device system. ASAIO Journal, 43(6), 922-926.

Heparin clearance profiles after systemic anticoagulation using a heparin removal device system. / Tao, Weike; Callahan, Jon D.; Vertrees, Roger A.; Brunston, Robert L.; Deyo, Donald J.; Mcrea, James C.; Zwischenberger, Joseph B.

In: ASAIO Journal, Vol. 43, No. 6, 11.1997, p. 922-926.

Research output: Contribution to journalArticle

Tao, W, Callahan, JD, Vertrees, RA, Brunston, RL, Deyo, DJ, Mcrea, JC & Zwischenberger, JB 1997, 'Heparin clearance profiles after systemic anticoagulation using a heparin removal device system', ASAIO Journal, vol. 43, no. 6, pp. 922-926.
Tao W, Callahan JD, Vertrees RA, Brunston RL, Deyo DJ, Mcrea JC et al. Heparin clearance profiles after systemic anticoagulation using a heparin removal device system. ASAIO Journal. 1997 Nov;43(6):922-926.
Tao, Weike ; Callahan, Jon D. ; Vertrees, Roger A. ; Brunston, Robert L. ; Deyo, Donald J. ; Mcrea, James C. ; Zwischenberger, Joseph B. / Heparin clearance profiles after systemic anticoagulation using a heparin removal device system. In: ASAIO Journal. 1997 ; Vol. 43, No. 6. pp. 922-926.
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abstract = "An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85{\%} heparin removal for different body weights at 700 ml/min and 1400 ml/min extracorpurea HRDS blood flow. With an HRDS flow of 700 ml, 85{\%} of total body hepaorin removal cannot be achieved within 30 min for subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85{\%} heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 10) model of 60-min, hypothermic (28°C) cardiopulmonary bypass (CPB). Animals were given 300 U/ kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-factor Xa assays was 4.40 ± 1.08 U/ml in the 700 ml/min group and 4.78 ± 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (81.4 ± 3.7 kg) was significantly higher than that in the 700 ml/min group (67.2 ± 2.2 kg) (p < 0.05), with the actually achieved HRDS flow 658.5 ± 20.8 and 1437.4 ± 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85{\%} heparin clearance was over 40 min, whereas in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 ± 3.7{\%} heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 ± 2.5{\%} (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin removal.",
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AU - Callahan, Jon D.

AU - Vertrees, Roger A.

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AU - Mcrea, James C.

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N2 - An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85% heparin removal for different body weights at 700 ml/min and 1400 ml/min extracorpurea HRDS blood flow. With an HRDS flow of 700 ml, 85% of total body hepaorin removal cannot be achieved within 30 min for subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85% heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 10) model of 60-min, hypothermic (28°C) cardiopulmonary bypass (CPB). Animals were given 300 U/ kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-factor Xa assays was 4.40 ± 1.08 U/ml in the 700 ml/min group and 4.78 ± 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (81.4 ± 3.7 kg) was significantly higher than that in the 700 ml/min group (67.2 ± 2.2 kg) (p < 0.05), with the actually achieved HRDS flow 658.5 ± 20.8 and 1437.4 ± 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85% heparin clearance was over 40 min, whereas in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 ± 3.7% heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 ± 2.5% (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin removal.

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