Garcia DA, Baglin TP, Weitz JI, et al.9 A black box warning exists for protamine regarding these hypersensitivity reactions and caution is advised. Additionally, men who have a history of vasectomies may also be at increased risk for these reactions, although newer evidence suggests that may not be true.
Anaphylactoid reactions, hypotension, flushing, and pulmonary edema are more likely with larger doses or rapid administration. Hypersensitivity reactions to protamine sulfate have been discovered in patients who are allergic or have sensitivities to fish and other protamine containing medications such as NPH insulin. 7, 8 Because protamine can exhibit a weak anticoagulant effect at higher doses within a short period of time, excessive protamine dosing to reverse heparin or LMWH can paradoxically result in an increased risk of bleeding. Regardless of the heparin or LMWH dosage, the maximum recommended protamine dose is 50 mg. 1, 2 Enoxaparin (Lovenox®)Įnoxaparin reversal is determined based on the following table: 1 Time Since Enoxaparin DoseĠ.5 mg protamine for every 1 mg enoxaparinĭepending on dose received and renal function, protamine reversal may not be necessary due to enoxaparin metabolismĭalteparin reversal is determined based on the following table: 2 Time Since Enoxaparin Doseġ mg protamine for every 100 units dalteparinĠ.5 mg protamine for every 100 units dalteparinĭepending on dose received and renal function, protamine reversal may not be necessary due to dalteparin metabolism It is estimated that protamine will reverse up to about 60% to 75% of anti-Xa activity. 1, 2įor both enoxaparin and dalteparin, protamine does not provide a complete reversal of anti-Xa activity. 6 If a second dose is given, it is recommended to administer 0.5 mg of protamine per 1 mg of enoxaparin or 100 units of dalteparin. In patients with elevated LMWH anti-Xa assays 2 to 4 hours after protamine administration, a second dose of protamine to achieve complete reversal may be considered. The 7 minute half-life of protamine and the prolonged LMWH half-life lend themselves to consideration of redosing due to LMWH rebound. The half-lives of LMWH are longer than UFH, ranging from 4-7 hours.
Enoxaparin antidote full#
Taking that into consideration, if reversal is necessary within 8 hours of receiving a LMWH, a full dose of protamine should be administered. 3, 5, 6 Similar to UFH, protamine dosing for LMWH reversal is dependent on the timing of LMWH administration relative to need for reversal.
One milligram (mg) of protamine sulfate will neutralize approximately 100 anti-Xa units of a LMWH. 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. 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).
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