Protocol of Hirsh and Raschke for the Reversal of Antithrombotic Effect of Low Molecular Weight Heparin (LMWH) Using Protamine Sulfate

 

LMWH after subcutaneous injection:

(1) show a peak anti-Xa activity at 4 hours (3 to 5)

(2) show an elimination half-life of 3 to 6 hours.

 

Thus at 8 hours after administration about half of the activity should be present (4 hours to peak, then one half-life).

 

If protamine sulfate is given to neutralize the LMWH the pararmeters to consider are:

(1) number of hours since LMWH given

(2) number of units of anti-Xa activity given (1 mg enoxaparin = 100 units anti-Xa activity, 1 mg dalteparin is 156 units of anti-Xa activity).

Time Since LMWH Admnistration	Dose of Protamine Sulfate
<= 8 hours, first dose protamine	1 mg per 100 units anti-Xa activity
<= 8 hours, second dose protamine for continued bleeding	0.5 mg per 100 units of anti-Xa activity
> 8 hours	“smaller dose”

 

Synthetic protamine variants may be more effective but have not been approved for clinical use.