Anticoagulants

• Anti-thrombin III is a serine protease inhibitor that inhibits multiple coagulation factors
• Prostacyclin, a metabolite of arachidonic acid, is synthesized by COX-2 in endothelial cells and inhibits platelet aggregation
• Protein C is activated when thrombin forms a complex with thrombomodulin

  
• The thrombin/thrombomodulin complex coverts inactive Protein C to the active Protein C protease (APC)
• Activate Protein C and Protein S (cofactor) degrade clotting factors Va and VIIIa
• Heparin is a glycosaminoglycan of alternating D-glucuronic acid and N-acetyl-D-glucosamine residues found in the secretory granules of mast cells
• Heparin binds to anti-thrombin III and enhances the affinity for activated clotting factors by 1000x, terminating their activity
• Heparin does not cross the placenta and is the anticoagulant of choice during pregnancy
• Heparin has an immediate onset of action when given IV
• Heparin must be monitored using Activated Partial Thromboplastin Time (aPTT or PTT)
• PTT measures the intrinsic coagulation pathway
• Heparin can rapidly be reversed by the IV infusion of protamine sulfate
• Heparin-Induced Thrombocytopenia (HIT) occurs in 1-5% of patients 5-10 days after heparin administration
• HIT is caused by antibodies that develop against heparin in complex with platelet factor 4. They bind and activate the platelets leading to thrombosis and eventually thrombocytopenia when platelets are depleted
• HIT is treated by IV argatroban or bivalirudin
• Warfarin may precipitate venous limb gangrene or skin necrosis in patients with HIT
• Adverse effects of heparin include osteoporosis and Type 4 RTA
• Enoxaparin is a low molecular weight heparin
• Enoxaprin primarily works by inhibiting factor Xa but still retains some ability to inhibit thrombin
• Compared to heparin, enoxaparin has more predictable pharmacokinetics and does not require routine laboratory monitoring
• HIT is less common with enoxaparin than heparin
• Enoxaparin is administered subcutaneously
• Enoxaparin is often used as a "bridge" to an oral anticoagulant
• Enoxaparin has a longer half life than heparin
• Unlike heparin, enoxaparin is not readily reversible by protamine sulfate
• Fondaparinux has anti-factor Xa activity only because it is too short to bridge antithrombin to thrombin
• Fondaparinux is not readily reversible by protamine sulfate
• Apixaban is a direct oral anticoagulant
• All factor Xa inhibitors have "xa" in the name
• Apixaban does not require lab monitoring
• Apixaban is used as stroke prophylaxis in non-valvular AFib pts
• Apixaban is contraindicated in pts w/ mechanical heart valves or valvular AFib
• Apixaban has a lower risk for bleeding than warfarin
• Andexanet alfa is the reversal agent for Apixaban
• Prothrombin complex concentrate (PCC) is the standard of care for exsanguinating hemorrhage secondary to excess Factor Xa inhibitors
• Dabigatran is an orally available direct thrombin inhibitor
• The bleeding risk for dabigatran is a little higher than Factor Xa inhibitors
• The reversal agent for dabigatran is idarucizumab
• Dabigatran is predominantly cleared by the kidneys, so it is avoided in patients with renal impairment
• Argatroban is administered IV as the preferred agent for HIT with acute thrombosis