Abstract
As a medical student I, along with my classmates, learned the coagulation cascade. Later, in 1968 when I passed my internal medicine boards and was on my way to becoming a cardiologist, I thought that was the last I had to remember that complicated series of events and the drugs used to alter coagulation. Little did I know at that time how important coagulation and anti‐coagulation would become for cardiovascular patients. Copyright © 2010 Wiley Periodicals, Inc.
Introduction
Most modern cardiologists are “thrombo‐cardiologists” since we have responsibility for patients in atrial fibrillation, patients with prosthetic valve disease, and patients with acute coronary syndromes and other aspects of ischemic heart disease requiring anti‐coagulation such as patients with intra‐coronary stents and those with multiple high‐risk factors.
As multiple agents evolve, I have found it somewhat difficult to remember the general mode of action of these agents. I suspect that some of you have the same problem. Thus, I have put together a simple list of the anti‐coagulants, anti‐platelet agents, and thrombolytic agents that are commonly used (or will be commonly used) and have summarized their mode of action briefly. I did this so I could have a list in one place that I could refer to easily.
Anticoagulants
Indirect Thrombin Inhibitors
Unfractionated Heparin—Inactivates thrombin by binding to antithrombin 111 (prevents fibrin formation and inhibits thrombin‐induced activation of platelets and of factors V and V111).
Low Molecular Weight Heparin (Lovenox) —Inactivates factor Xa Lovenox.
Fondiparinux (Arixtra)—Synthetic pentascccharide that causes an antithrombin 111‐mediated indirect factor Xa selective inhibition that exerts its anti‐thrombotic effect by inhibiting thrombin generation and therefore fibrin formation.
Direct Thrombin Inhibitors
Lepirudin (Refludan) Recombinant Hirudin—Highly specific inhibitor of the thrombogenic activity of thrombin, independent of antithrombin 111.
Bivalarudin (Hirulog, Angiomax)—Specific and reversible direct thrombin inhibitor binding to circulating and clot‐bound thrombin.
Argatroban (Argatroban)—Directly binds to the thrombin‐active site and does not require the co‐factor antithrombin 111 for anti‐thrombotic activity—Often used in heparin‐induced thrombocytopenia (HIT).
Dabigatran (Pradaxa)—This is a new agent, not yet approved in the US which binds directly to thrombin and blocks its interaction with its substrates.
Vitamin K‐Dependent Coagulation Inhibitor
Warfarin (Coumadin)—Inhibits vitamin K‐dependent coagulation factor synthesis (11,V11, IX, X, Protein C and S).
Antiplatelets Agents
Thromboxane A2 Blocker
Aspirin—Irreversibly blocks the formation of thromboxane A2 in platelets, inhibiting platelet aggre‐ gation.
Thienopyridine
Clopidogrel (Plavix)—A PRO drug; anti‐aggregetory activity is caused by a metabolite generated in the liver by a cytochrome P450‐dependent pathway. It is an ADP‐sensitive agent that inhibits the binding of ADP to its platelet receptors and decreases platelet activation. It inhibits ADP‐induced platelet‐fibrinogen binding.
Ticlopidine (Ticlid)—Not a PRO drug; interferes with platelet membrane function by inhibiting ADP‐induced platelet –fibrinogen binding and subsequent platelet‐platelet interaction which is irreversible for the life of the platelet.
Prasagrel (Efient)—A PRO drug in which the metabolite, like other thienopyridines, binds irreversibly to the platelet P2Y12 receptor, inhibiting ADP‐mediated platelet activation and aggregation.
Non‐Thienopyridine
Ticagrelor (Brilinta)—Note a PRO drug; reversible oral P2Y12 receptor antagonist which acts directly on the P2Y12 receptor to inhibit platelet activation by ADP.
Adenosine Uptake Inhibitor
Dipyridamole (Persantine)—Inhibits the uptake of adenosine into platelets, endothelial cells, and erythrocytes which acts on the platelet A2 receptor and inhibits platelet aggregation.
Glycoprotein 2b3a Receptor Blocker
Abciximab (ReoPro)—Fab fragment of the chimeric monoclonal antibody 7E3. It binds to the GP 2b3a receptor on the platelet membrane and inhibits this final step in platelet aggregation.
Tirofiban (Aggrastat)—Non‐peptide reversible antagonist of the platelet GP 2b3a receptor and inhibits platelet aggregation.
Eptifibatide (Integrillin)—Binds to the GP 2b3a receptor and inhibits platelet aggregation.
Thrombolytics
Plasminogen Activators
Streptokinase—Forms a complex in the plasma with plasminogen which activates plasminogen through cleavage to produce plasmin which breaks down the major constituent of blood clots, fibrin.
Recombinant Thrombolytics
Tissue Plasminogen Activator (Alteplase, Tenecteplase, Reteplase)—Activates plasminogen to produce plasmin which promotes clot lysis.
There you have it—a list that I think will be useful to me and hopefully useful to you.