Pharmacodynamics of Unfractionated Heparin During and After a Hemodialysis Session

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.

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.

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

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)