These multiple effects are mediated via complement activation, histamine release, thromboxane and nitric oxide production, and antibody formation. Fortunately, the hypotension is generally mild and short lived. Most reports of anaphylaxis have been observed in patients previously exposed to protamine through NPH insulin or previous heparin reversal. Though skin testing may be helpful in identifying patients at risk, false negatives occur and it is impractical in the emergency department setting. The incidence of anaphylactic reactions was 11 of 1150 consecutive patients receiving protamine for CV surgery in a study by Gupta et al.
Protamine is contraindicated in any patient known to be hypersensitive to the drug.
Protamine should be used with caution in patients who have previously received protamine or protamine-containing insulins such as NPH as they may be at increased risk of developing anaphylaxis. A dosing ratio of 1-milligram protamine for every 100 units of heparin remaining in the patient is the usual rule. Unfortunately, it is near impossible to know exactly how much heparin is remaining in the patient at the time of presentation, especially since heparin serum concentrations decline rapidly due to its short half-life. Generally, the 1 mg for every 100 units heparin should be used if heparin was given with in a few minutes of presentation. If 30 minutes to 1 hour have elapsed, 0.5 mg per 100 units heparin should be used.