Background

The practice of calculating doses of heparin based on weight is flawed. The volume of distribution of heparin has been shown to approximate the blood volume, not body weight.1,2,3

It seems logical to calculate the dose of heparin based on the blood volume, but the heparin concentration does not predict the activated clotting time.4

Di Biase et al. and Bruce et. al. 5,6 showed that an activated clotted time (ACT) >300 seconds during CA-AF prevents thrombus and silent cerebral ischemia (SCI). They showed that an ACT < 300 seconds during the procedure, and no administration of heparin bolus before transseptal catheterization are related to major thromboembolic complications such as silent cerebral infarct.

While protamine is used to neutralize heparin, it has anticoagulant properties that are attributed to an interaction with platelet function, interference with coagulation factors, and stimulation of clot breakdown.7 If given alone, it increases the ACT, so there is no need to withhold the dose that will completely reverse heparin. If too much is given, there is a danger of increasing the ACT with consequent bleeding.

How can we overcome these diverse problems?

by measuring the ACT before and after heparin, it is possible to determine the individual patient heparin:ACT dose-response relationship.

If an ACT device with a linear response (Such as the i-Stat or the MedtronicACTPlus) is used, the ACT correlates with the heparin concentration. This allows adjustments to the ACT throughout the procedure, and gives an estimate of the active heparin concentration at any time, allowing estimation of the appropriate dose of protamine for heparin reversal.

This approach is a modification of that proposed for cardiac surgical procedures by Bull in 1975. (his approach was based on body weight)

Citations

1. Heparin Pharmacokinetics and Pharmacodynamics. Robert J. Kandrotas Clin. Pharmacokinet. 22 (5): 359-374, 1992)

2. Kandrotas RJ, Gal P, Douglas JB, Deterding J. Heparin phar- macokinetics during hemodialysis. Therapeutic Drug Moni- toring 11: 674-679, 1989

3. Kandrotas RJ, Gal P, Douglas JB, Deterding J. Pharmacokinetics and pharmacodynamics of heparin during hemodialysis: in- terpatient and intrapatient variability. Pharmacotherapy 10: 349-356, 1990a.

4.Heparin monitoring during cardiac surgery . Part 1 : validation of whole-blood heparin concentration and activated clotting time. Raymond1PD, Ray MJ, Callen SN and Marsh NA. Perfusion 2003; 18: 269¡/ 276)

5.Bruce CJ, Friedman PA, Narayan O, Munger TM, Hammill SC, Packer DL, Asirvatham SJ. Early heparinization decreases the incidence of left atrial thrombi detected by intracardiac echocardiography during radiofrequency ablation for atrial fibrillation. J Interv Card Electrophysiol. 2008; 22:211–219.

6. Biase L Di, Gaita F, Toso E, et al. Does periprocedural anticoagulation management of atrial fibrillation affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging in patients undergoing radiofrequency atrial fibrillation ablation with o. Hear Rhythm. 2014;11(5):791-798. doi:10.1016/j.hrthm.2014.03.003

7. C. Boer1, M. I. Meesters, D. Veerhoek and A. B. A. Vonk

Anticoagulant and side-effects of protamine in cardiac surgery a narrative review. British Journal of Anaesthesia. 2008; 120 (5): 914 927

8. Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975;69(5):685-689. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1127967.