Anticoagulants Flashcards
What are the four broad classes of anticoagulants?
Heparin/LMWH/Fondaparinux, Warfarin, Direct Factor X Inhibitors, Thrombin Inhibitors
Mechanism of unfractionated Heparin
Binds and activates antithrombin III, which degrades factor II, IX, X. Unfractionated heparin also has a binding site for thrombin (factor II), bringing it in close proximity with antithrombin III to allow for effective degradation.
Molecular structure of unfractionated Heparin
A glycosaminoglycan (GAG) consisting of 30-50 monosaccharide units. Has a 5-saccharide binding site for antithrombin III as well as a separate binding site for thrombin.
Administration and monitoring of Heparin
IV or subcutaneous administration. Monitored using aPTT since the factors inhibited by Heparin are part of the intrinsic pathway.
Clinical uses of Heparin
Prevention of clotting during CV intervention/surgery and in patients with heart valves, treatment of very severe/acute thrombosis, dialysis, extracorporeal membrane oxygenation (ECMO, aka life support).
CAD/IHD: Inpatient (acute, stop clot formation)
Mechanism of LMWH
Binds and activates antithrombin III, but cannot bind thrombin as well. Antithrombin III thus can only inhibit factor X, resulting in lower anti-clotting activity than unfractionated Heparin
Molecular structure of LMWH
A glycosaminoglycan (GAG) consisting of <20 monosaccharide units. Has a 5-saccharide binding site for antithrombin III
Administration and monitoring of LMWH
Subcutaneous administration. 0.1-0.3 units for prophylaxis and 1.0-2.0 units for treatment. Drug monitoring is not needed since LMWH has lower activity than Heparin (thus a higher therapeutic index).
Clinical uses of LMWH
Treatment of thrombolytic diseases, prophylaxis post-surgery to prevent clotting, prophylaxis and treatment of acute venous thromboembolism (AVT, includes DVT and PE)
CAD/IHD: Inpatient (acute, stop clot formation)
What are the pros/cons of using Heparin vs LMWH and Fondaparinux?
Heparin has higher actvity than LMWH and fondaparinux. Heparin also has a shorter half life, meaning that its effects will quickly be stopped upon cessation. As a result, heparin is more useful in acute settings, and is usually used during surgical operations and in in-patient settings. The longer half-life of LMWH and fondaparinux is more useful in out-patient settings, where it can be used to treat chronic illnesses and for prophylaxis.
Mechanism and Molecular Structure of Fondaparinux
Fondaparinux is the isolated 5-saccharide binding site of unfractionated Heparin. Thus, it can only bind antithrombin III and only has anti-factor X activity. However, the small size of the molecule allows it to have an extremely long half-life.
Administration and monitoring of Fondaparinux
Subcutaneous administration. Drug monitoring is not needed since Fondaparinux has lower activity than Heparin (thus a higher therapeutic index).
Clinical uses of Fondaparinux
Treatment of thrombolytic diseases, prophylaxis post-surgery to prevent clotting, prophylaxis and treatment of acute venous thromboembolism (AVT, includes DVT and PE)
CAD/IHD: Inpatient
Mechanism of Warfarin (Coumadin)
Inhibits Vit K reductase, which normally reduces Vit K epoxide to reduced Vit K. Reduced Vit K is converted to Vit K epoxide during gamma-carboxylation of factor II, IX, X, VII. Thus, inhibition of Vit K reductase prevents the proper function of these clotting factors.
Clinical uses of Warfarin (Coumadin)
Prevent thromboembolism in patients with Afib or prosthetic valves, treat recurring venous thromboembolism (VT), long term anti-coagulation treatment
CAD/IHD: Outpatient
Administration and monitoring of Warfarin (Coumadin)
Oral or intravenous administration. Requires drug monitoring via prothrombin time (PT, goal of INR 2-3) due to its low therapeutic index. PT is used since Warfarin inhibits extrinsic pathway factors, including factor VII.
