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.
du Breuil et al. discuss the use of heparin vs LMWH, stating that use of outpatient LMWH is as safe and effective as inpatient unfractionated heparin for treatment of venous thromboembolism.
Lee et al. compared oral anticoagulation and LMWH in cancer patients to prevent VTE. They found that dalteparin, a LMWH, was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. LMWH is therefore generally preferred over warfarin for prevention of VTE in patients with cancer.
A comprehensive list of antidotes can be found in the Medbullets topic "Poisons and Treatments" (Step 1).
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. No specific antidote exists for the reversal of this anticoagulant.
du Breuil AL, Umland EM. Outpatient management of anticoagulation therapy. Am Fam Physician. 2007 Apr 1;75(7):1031-42. Review.
PMID:17427618 (Link to Abstract)
Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53.
PMID:12853587 (Link to Abstract)
Pai M, Crowther MA. Neutralization of heparin activity. Handb Exp Pharmacol. 2012;(207):265-77. Review.
PMID:22566228 (Link to Abstract)