Conditions for considering protamine sulfate therapy - all of the following:
(1) excessive dose of dalteparin.
(2) clinical bleeding
(3) unable to wait for the dalteparin effect to wear off on its own
The terminal half-life of dalteparin sodium is:
(1) 2-3 hours after intravenous administration in normal patients
(2) 3-5 hours after subcutaneous administration in normal patients
(3) 4-8 hours after intravenous administration in patients with renal failure
Initial dosing of protamine sulfate:
(1) 1 mg protamine for each 100 IU anti-Factor Xa activity of dalteparin
(2) slow intravenous infusion of a 1% solution (1 gram protamine sulfate per dL infusate)
Monitoring:
(1) Although the PDR states that the aPTT can be used to monitor the response to protamine sulfate, it is generally reported that the aPTT is unreliable for monitoring the effects of low molecular weight heparin. This is stated previously on page 2764.
(2) The activity of dalteparin therapy should be monitored with levels of activated Factor X (Factor Xa).
(3) The anti-Factor Xa activity usually does not correct completely with protamine sulfate. The maximum correction is in the order of 60-75%.
A second infusion of 0.5 mg protamine sulfate for each 100 IU anti-Factor Xa activity can be given in 2-4 hours if the patient has not responded. Since this interval is about one-half life for dalteparin, I am not sure if the estimate of residual anti-Factor Xa activity should be decreased by half, or if the lower dose of protamine compensates for this.
Cautions with protamine therapy:
(1) Do not give excessive protamine sulfate.
(2) Adverse reactions may occur with infusion of protamine sulfate, as described in the previous section.
