Review Question - QID 101338

Protamine sulfate is a large, positively charged protein molecule that binds to negatively charged unfractionated heparin and may be used to reverse the effects of heparin.

While protamine sulfate is highly effective against unfractionated heparin, it is much less effective against low-molecular weight heparins (LMWH), such as enoxaparin (Lovenox). The lack of an effective antidote makes overanticoagulation with LMWH particularly dangerous.

Unfractionated and LMW heparin both work by binding to antithrombin III (ATIII) and enhancing ATIII's ability to inactivate factor Xa, thereby disrupting the coagulation cascade. Additionally, unfractionated heparin has a long pentasaccharide chain that allows it to bind to both antithrombin and thrombin itself, deactivating thrombin. LMWH's have a shorter pentasaccharide chain, making them unable to bind to both antithrombin and thrombin. Therefore, LMWH has greater activity against Factor Xa compared with thrombin, while unfractionated heparin has equal activity against both Factor Xa and thrombin.

A comprehensive list of antidotes can be found in the Medbullets topic "Poisons and Treatments" (Step 1).

Incorrect Answers:
Answer 1: Vitamin K and FFP are used to reverse the effects of warfarin.
Answer 2: According to Pai and Crowther, "Protamine sulfate is a specific and virtually complete reversal agent for UFH; however, it only partially neutralizes the anticoagulant effect of LMWH." Enoxaparin is a LMWH.
Answer 4: Bivalirudin is a direct thrombin inhibitor. Dialysis is used to reverse the effects of this anticoagulant.
Answer 5: Dabigatran is a direct thrombin inhibitor. Idarucizumab is a recently approved antidote which reverses the effects of dabigatran.