7/25/23, 12:58 PM Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session - American Journal of Kidney Diseases

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ORIGINAL INVESTIGATION DIALYSIS | VOLUME 51, ISSUE 5, P789-795, MAY 2008

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Pharmacodynamics of Unfractionated Heparin During and After a

Hemodialysis Session
Philippe Brunet, MD   • Nicolas Simon, MD • Adriana Opris, MD • ... Henri Portugal, PharmD •
Bertrand Dussol, MD • Yvon Berland, MD • Show all authors DOI: https://doi.org/10.1053/j.ajkd.2007.12.040

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Background
Anti-Xa activity is used as a clinical guide to anticoagulation with heparin, but heparin dosing
regimens for hemodialysis were established before anti-Xa assays were developed; thus, the
optimal regimen for heparin dosing was not determined. The aim is to confirm the interesting
characteristics of unfractionated heparin pharmacokinetics for hemodialysis anticoagulation, provide
insight into the hemorrhagic risk of hemodialysis patients, and determine the dose of unfractionated
heparin and its adequate mode of administration.

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7/25/23, 12:58 PM Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session - American Journal of Kidney Diseases

Study Design
Cross-sectional study of the pharmacokinetics of unfractionated heparin performed during and after
a 4-hour midweek hemodialysis session.

Setting & Participants

35 long-term hemodialysis patients at the Sainte-Marguerite Unit of the Marseille University
Hospital, Marseille, France.
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Predictor
Hemodialysis anticoagulation with continuous unfractionated heparin infusion at a dose of 50
IU/kg/session (25 IU/kg/h during the first hour, 12.5 IU/kg during the second and third hours, and
stop during the last hour).

Outcome & Measurements

Anti-Xa activity was monitored during the 10 hours after the beginning of the hemodialysis session.
Levels of 0.3 to 0.7 IU/mL are considered sufficient for anticoagulation. Pharmacokinetics was
determined by using a population approach (nonlinear mixed-effects modeling). The final model and
corresponding parameter values (including interindividual and residual variability) were used to
simulate 1,000 replicates.

Results
No case of clotting was recorded. A pharmacokinetic model with 1 compartment and first-order
elimination best fitted the data. Terminal half-life was 54 minutes. Median anti-Xa activities were
0.55 IU/mL at peak, 0.25 IU/mL at end of the 4-hour session, and less than 0.1 IU/mL at 90 minutes
after the session. We simulated a continuous infusion of the dose of 50 IU/kg for 1, 2, 3, and 4
hours. Peak values were 1.1, 0.8, 0.6, and 0.5 IU/mL, respectively. Values at the end of the session
were 0.12, 0.18, 0.3, and 0.5 IU/mL, respectively. Values became less than 0.1 IU/mL at 15, 60,
105, and 120 minutes after the session, respectively.

Limitations
Interindividual variability in unfractionated heparin pharmacokinetics.

Conclusions

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7/25/23, 12:58 PM Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session - American Journal of Kidney Diseases

Unfractionated heparin administered by means of a 3-hour continuous infusion for hemodialysis

anticoagulation provided an efficient and safe effect that quickly disappeared after the end of the
session.

Index Words
Anticoagulation • anti-Xa • heparin • hemodialysis • population pharmacokinetics •
nonlinear mixed effects modeling (NONMEM)   

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Article info
Publication history
Accepted: December 26, 2007
Received: May 30, 2007

Identification

DOI: https://doi.org/10.1053/j.ajkd.2007.12.040

Copyright
© 2008 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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7/25/23, 12:58 PM Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session - American Journal of Kidney Diseases

Linked Article
Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session: The
Impact of the Administered Dose
American Journal of Kidney Diseases, Vol. 52, Issue 4
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