Monday, May 20, 2013

Protamine Sulfate for LMWH

There is much discussion lately regarding new reversal strategies of oral anticoagulants that are rapidly growing in popularity.  While the data to support the use of agents like PCC and aPCCs are limited, our clinical experience is also lacking.  So-called ‘old school’ reversal agents, though infrequently used, still have a place for patients who receive parenteral anticoagulation. 

Protamine sulfate, our favorite salmon sperm derived drug, was (and still is) our go to reversal drug for heparin products.  The clinical experience with protamine for reversing heparin in cardiac surgery patients is extensive.  The effectiveness of protamine for reversing the effects of low molecular weight heparins is regarded as incomplete.  Since the mechanism of protamine relies on its positive charge and the large molecular weight of unfractionated heparin and its net negative charge, LMWHs by definition provide a smaller target that is less strongly attracted to protamine. While it is suggested to utilize protamine for LMWH reversal, other strategies such as PCC may be a consideration since the effects of protamine may be short lived due to its 7 minute half-life. [Am. J. Hematol, 2012; 87:S119–S126, CHEST, 2012;141(Supp.2): e24S-e43S]

The dosing of protamine for LMWHs is significantly less complicated than UFH.  Dosing recommendations are 1 mg of protamine for every 100 anti-Xa units of LMWH (Enoxaparin 1mg = 100 anti-Xa units) administered over the previous 8 hours with a maximum protamine dose of 50 mg. If it has been greater than 8 hours since the last LMWH dose, the dose of protamine decreases to 0.5 mg for every 100 anti-Xa units of LMWH. [CHEST, 2012;141(Supp.2): e24S-e43S]

Dosing of protamine is quite critical since protamine itself can paradoxically illicit anticoagulant effects through reduction in the rate of Factor V activation.  The problems with protamine do not stop there. Rapid administration can cause profound hypotension and bradycardia, pulmonary vasoconstriction, transient neutropenia, and although highly the highly warned risk to patients who’ve previously received NPH insulin (the “p” is for protamine, neutral protamine Hagedorn) developing anaphylactic reactions, the risk is about 1%.
Importantly protamine will not work with fondaparinux or any other anticoagulant (parenteral or oral) that is not technically a heparin. [Journal of Pharmacy Practice
23(3) 217-225]

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