Anticoagulants, Fibrinolytics, Antiplatelet

Anticoagulants
1. Unfractionated Heparin
-activates antithrombin III --> degrade thrombin and Xa
-nonspecific binding --> unpredictable and monitor with PTT, Xa assay, platelet count
-prevent progression of existing clots (venous thrombosis, embolism, MI)
-HIT-IgG attack AT III and factor IV complexes-->vascular damage-->thrombocytopenia
-Protamine

2. LMWH
-smaller molecule and more predictable
-degrade thrombin and Xa (more specific for Xa)
-DVT
-monitoring in larger and pregnant patients

3. Fondaparinux
-factor Xa
-DVT and pulmonary embolism

4. Direct Factor Xa Inhibitors (Rivaroxaban CYP3A4/5, Apixaban)
-reversible inhibition of free and bound Xa
-DVT and pulmonary embolism
-nonvalvular atrial fibrillation
-prothrombin complexes

5. Direct Thrombin Inhibitors (Argatroban CYP3A4/5, Dabigatran, Bivalirudin)
-bind to active site of thrombin to prevent fibrinogen --> fibrin and activation of factors V, VIII, XIII

6. Warfarin CYP2C9
-block VKORC1
-inhibit factors X, IX, VII, II, and Protein C and S
-full-thrombotic effect not achieved for several days --> need bridging therapy
-PT and INR monitoring
-bleeding, thrombosis, purple toe syndrome
-contradicted in pregnancy (nasal hypoplasia, hemorrhage, CNS abnormalities)
-Vitamin K, plasma, prothrombin complexes

Fibrinolytics
1. Streptokinase
-binds to plasminogen-->plasmin-->systemic lytic state
-systemic lytic stage-->hemostatic plugs-->concurrent use of heparin increases risk of hemorrhage
2. Alteplase
-activate plasmin in presence of fibrin
3. Tenecteplase
-activate plasmin in presence of fibrin
4. Reteplase
-activate plasmin in presence of fibrin

Antiplatelets
1. Aspirin
-block COX1-->inhibit TXA2
-MI, ischemic stroke, transient ischemic episodes (adjunctive in revascularization)

2. ADP Receptor Antagonist (Clopidogrel CYP2C19, Prasugrel, Ticagrelor)
-P2Y12 receptor inhibitor-->no fibrinogen cross-linking
-STEMI and stent placement
-bleeding, thrombocytpenia

3. Glycoprotein IIb/IIIa Inhibitors (Abciximab, Eptifibatide, Tirofiban)
-fibrinogen cannot bind
-prevention of PCI, STEMI
-used in conjunction with heparin and aspirin
-bleeding