Patients who have previously received protamine sulfate–containing insulin, who have undergone vasectomy, or who have a known allergy to fish are at increased risk of having preformed antibodies against protamine and suffering allergic reactions; these patients can be pretreated with corticosteroids and antihistamines.⁵

Low molecular weight heparin, like unfractionated heparin, anticoagulates by activating the antithrombin III complex, which in turn inactivates factor Xa. Low molecular weight heparin, however, has a plasma half-life that is 2 to 4 times as long as unfractionated heparin, which allows for dosing once or twice a day. Enoxaparin, dalteparin, and ardeparin are the most widely available of the low molecular weight heparin products. These preparations cause less bleeding than unfractionated heparin.

Protamine will neutralize the antithrombin effect of low molecular weight heparin but incompletely reverses factor Xa inhibition. In the event of clinically significant bleeding, 1 mg of protamine will neutralize 1 mg of enoxaparin and 100 units of dalteparin,³ given within 8 hours of low molecular weight heparin administration.

A second dose of 0.5 mg protamine sulfate per 1 mg of enoxaparin should be administered if the bleeding continues. Smaller doses of protamine sulfate can be given if the time since low molecular weight heparin administration exceeds 8 hours.⁵

Aspirin irreversibly blocks cyclooxygenase, a platelet enzyme that catalyzes the conversion of arachidonic acid to thromboxane A2 and promotes prostacyclin synthesis, which results in vasodilation and the inhibition of platelet aggregation. Aspirin’s antiplatelet effect lasts for the life span of the platelet, about 10 days. Upper gastrointestinal irritation is the most commonly seen side effect of aspirin therapy, while life-threatening gastrointestinal bleeding is uncommon.

Management of acute aspirin-induced hemorrhage requires the transfusion of enough normal platelets to increase the platelet count by 50,000/mcL. Because of the irreversible effect of aspirin on platelets, the coagulopathy might last for 4 to 5 days following discontinuation of aspirin therapy, and platelet transfusions may have to be repeated daily.

Other nonsteroidal anti-inflammatory agents (NSAIDs) reversibly inhibit patelet cyclooxygenase. This inhibition of platelet aggregation typically lasts less than 24 hours, with the exception of piroxicam, which has a half-life of 2 days. Because of the relatively short half-life, platelet dysfunction caused by NSAID use will usually resolve within 1 day of stopping use.

Clopidogrel and ticlopidine selectively inhibit platelet aggregation induced by ADP. Both agents carry a rare risk of TTP, even after as little as 2 weeks of therapy. Should quick reversal of these agents be required, the physician should consider platelet transfusion.³