![]() In patients with elevated aPTTs as a result of heparin after protamine administration, a second dose of protamine may be considered. 3, 5, 6 Consideration to measure the activated partial thromboplastin time (aPTT) after protamine administration may be warranted. The half-life of protamine, about 7 minutes, is significantly shorter than UFH. For patients on heparin infusions, due to the half-life of heparin, the amount of heparin administered over the previous 2 hours should be utilized to calculate a protamine dose. ![]() Administration of full dose protamine is indicated in patients who need reversal less than 60 minutes after bolus administration. As more time elapses from heparin administration, less protamine is necessary to reverse the anticoagulant effects. 3, 5 Due to the half-life of heparin (~90 minutes), timing of protamine administration in patients is dependent upon timing of heparin exposure. One milligram (mg) of protamine sulfate will neutralize approximately 100 units of UFH. This calculator determines a neutralizing dose of protamine to reverse both UFH and LMWH in the non-surgical setting based on the anticoagulant to be reversed, the anticoagulant dose, and the time that the anticoagulant was last given. It is not appropriate for pediatric patients or for an operating room setting (such as cardiovascular surgery). 3, 4 This calculator is intended to dose protamine in adults patients on a medicine floor and in the ICU. Thus, careful choice of an anticoagulant agent and laboratory monitoring where appropriate are needed to minimize risk of bleeding complications.Protamine sulfate, a derivative of fish sperm, is commonly used for the reversal of anticoagulation effect of unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Newer anticoagulant agents generally lack specific antidotes. The new direct thrombin inhibitors (e.g., lepirudin, bivalirudin, argatroban) also have no specific antidote. For example, protamine sulfate reverses only about 60% of the anti-factor Xa activity of low-molecular-weight heparin, has negligible effects on danaparoid (a mixture of anticoagulant glycosaminoglycans used to treat heparin-induced thrombocytopenia) and fondaparinux (a novel synthetic antithrombin-binding pentasaccharide with exclusive anti-factor Xa activity approved in the United States for antithrombotic prophylaxis following orthopedic surgery). ![]() A growing problem arises from the increasing use of new anticoagulants that lack specific antidotes. However, vitamin K only begins to reverse warfarin's anticoagulant effect by four to six hours, so urgent situations additionally require blood products, such as plasma (fresh frozen or cryosupermatant plasma), prothrombin complex concentrates, or, possibly, recombinant factor VIIa. Specific "antidotes" exist for the "classic" anticoagulant agents: protamine sulfate for UFH, and vitamin K for warfarin. We reviewed the literature to determine what strategies are available to reverse anticoagulation caused by older agents, such as warfarin or unfractionated heparin (UFH), as well as newer agents, for example, low-molecular-weight heparin, danaparoid, fondaparinux, lepirudin, and argatroban. Reversal of pharmacologic anticoagulation is an issue that arises when an anticoagulated patient has major bleeding or when a patient on chronic anticoagulant therapy requires urgent reversal of anticoagulation, for example, for surgery.
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