PREVENTION OF BLOOD COAGULATION
1. What are some preventatives against coagulation in the normal vascular system?
2. How does heparin prevent intravascular clotting?
3. What is the significance of mast cells? Why are there great numbers of them in the lung?
4.
How do chelating agents prevent clotting in withdrawn blood?In addition to procoagulants in the blood, there are also anticoagulants. Their presence balances and prevents coagulation that might otherwise occur because of small amounts of the procoagulants normally present. Also, when blood is withdrawn for analytical purposes or for storage, anticoagulants are added to the blood containers to prevent coagulation.
Prevention in normal circulation
The formation of thrombin occurs through a series of chemical reactions, so it is normal to have a small amount of thrombin in the circulation. The thrombin that is present could cause the conversion of fibrinogen (a normal plasma protein) to fibrin except that another protein, antithrombin III, blocks the action of thrombin on fibrinogen and also inactivates the thrombin that it binds.
In addition to antithrombin III action, coagulation in the normal vascular system is prevented by the smoothness of the endothelium. This prevents contact activation of factor XII, which is involved in the activation of factor IX in the intrinsic system (see Figure 3-16). Also, a monomolecular layer of protein (net-negative charge) is absorbed to the surface of the endothelium that repels clotting factors and platelets. When endothelial damage occurs, both the smoothness and the protein layer are lost at the damaged site.
Heparin, an anticoagulant, is produced,by mast cells that reside in the pericapillary connective tissues. Mast cells are particularly abundant in the lungs because of the vulnerability of the lungs to emboli, which are clots that have broken loose from their original site and flow freely in the blood. The plasma concentration of heparin is normally low.
The effectiveness of heparin in preventing normal intravascular clotting depends on its combining with antithrombin III to form a complex that removes not only thrombin but also factors IX, X, XI, and XII.Because of the biological potency of thrombin, there are mechanisms that limit the rate and extent of thrombin generation around sites of vascular damage. One of these, the anticoagulant protein C pathway, involves the high-affinity binding of thrombin to thrombomodulin (TM), a membrane protein of endothelial and peripheral blood cells. When bound to TM, thrombin loses its ability to activate platelets and to clot fibrinogen and becomes an activator of protein C. Activated protein C destroys the activity of factors Va and VIIIa (thrombin modified FV and FVIII), which are cofactors in the prothrombinase and tenase complexes, respectively (see Figure 3-15).
Prevention in Withdrawn Blood
It is often desirable to prevent blood coagulation when blood is withdrawn from an animal for later examination and analysis. Anticoagulants are used for this purpose. Chelating agents are used most frequently; they bind the calcium ions so that they are not available for the coagulation process. Trisodium citrate, sodium oxalate, or ethylenediamine-tetraacetic acid (sodium EDTA, disodium salt) is added in an appropriate quantity to the collection container and mixed with the withdrawn blood. Heparin is also available commercially and can be used to prevent coagulation of withdrawn blood. It is also used to prevent coagulation of blood in the body in certain disease conditions that predispose to clot formation.
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