Thursday, April 12, 2007

Inhibiting Blood Clots: Anticoagulants

 
There are several naturally occurring blood clot inhibitors. The most important is antithrombin. As the name implies, antithrombin blocks the activity of thrombin and this prevents the formation of fibrin and clotting networks. It makes sense that blood clotting has to be terminated because otherwise it would grow and block the vein cutting off blood supply.

Antithrombin III, the main antithrombin activity, is a protein that binds to thrombin in the presence of an oligosaccharide called heparin. Heparin is a glycosaminoglycan (GAG) which means that it’s formed by stringing together amino sugars (glycosamines). There are seven different kins of GAG’s in humans and heparin is one of them. The repeat unit in heparin is a sulfated glucosamine plus a sulfated iduronic acid residue [Monday’s Molecule 320].

The heparin oligosaccharide is bound to a very specific protein to form heparin proteoglycan. The physiologically important oligosaccharide is called heparan sulfate. It is found on the surface of normal endothelial cells and it is this molecule that binds antithrombin III.

The combination of antithrobin III-heparin+thrombin blocks processing of fibrinogen and prevents clotting. This is why patients are treated with heparin to prevent blood clotting or to dissolve blood clots that have formed during pulmonary embolisms, strokes, or clotting in leg veins. Heparin can also be used to coat medical equipment to prevent clotting on exposed surfaces. Heparin is an anticoagulant.

A different inhibitory mechanism is initiated when thrombin binds to a membrane protein called thrombomodulin. Thrombomodulin is a glycoprotein [Glycoproteins] found on the surface of normal endothelial cells.

The thrombin:thrombomodulin complex activates Protein C, which combines with Protein S to form a protease. Activated Protein C (APC) degrades Factors Va and VIIIa. These are the two factors required for activation of Factor X in extrinsic and intrinsic activation respectively [Blood Clotting: Intrinsic Activity, Blood Clotting: Extrinsic Activity and Platelet Activation]. Thus, degradation of these factors prevents further activation of prothrombin and clotting activity ceases.

6 comments :

  1. I actually had this one too except I had to go to a morning lab.

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  2. That's okay. I'm sure you'll get another one very soon.

    I really enjoyed our lunch, by the way. Maybe we could do it again sometime even if you don't figure out Monday's molecule!

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  3. Apparently, I'm not the only BCH kid who reads your blog. There is at least one lurker...

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  4. This Cardiology Patient Page will focus on medical treatment of blood clots that can cause critical illness by blocking the blood supply to the heart, ...

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  5. Great blog. Anticoagulants are a great way to prevent blood clots. Blood clots are a serious concern. In fact, Blood clots, DVTS and PE, are the leading cause of preventable deaths in a hospital. Before you enter a hospital, your risk factors for developing a blood clot must be assessed and the preventative steps assessed. Medication, compression stockings, and other methods may be necessary. In many cases, a blood clot that develops in a hospital is a product of medical malpractice.

    For more information on blood clots, see my blog at
    http://www.rosemanlaw.net/blog.html

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