Clot-dissolving system

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

Figure 12.11 (a) The fibrinolytic system, in which tPA proteolytically converts the zymogen plasminogen into active plasmin, which in turn degrades the fibrin strands, thus dissolving the clot. tPA and plasminogen both bind to the surface of fibrin strands (b), thus ensuring rapid and efficient activation of the thrombolytic process... 

The role of the fibrinolytic system is to dissolve any clots that are formed within the intact vascular system and so restrict clot formation to the site of injury. The digestion of the fibrin and hence its lysis is catalysed by the proteolytic enzyme, plasmin, another serine proteinase. Plasmin is formed from the inactive precursor, plasminogen, by the activity of yet other proteolytic enzymes, urokinase, streptokinase and tissue plasminogen activator (tPA) which are also serine proteinases. These enzymes only hydrolyse plasminogen that is bound to the fibrin. Any plasmin that escapes into the general circulation is inactivated by binding to a serpin (Box 17.2). 

A fibrinolytic system reverses thrombosis and thereby maintains hemostasis. Fibrinolytic enzymes and other factors work in concert to dissolve the clot using a series of rather nonspecific proteases that act locally by digesting the fibrin deposited at the site... 

Why do we have the intrinsic pathway when the tissue factor pathway provides rapid clot formation The answer seems to be that the tissue factor pathway is needed immediately after injury but that it is turned off quickly by the anticoagulation systems of the body. As a result the protease plasmin begins to dissolve (lyse) the clot within a few hours. The intrinsic pathway is apparently needed to maintain the clot for a longer period.514... 

The coagulation system regulates fibrin clot formation, whereas the fibrinolytic system dissolves the polymerized clot and restores blood flow. As a regnlatory mechanism to maintain blood flow, the fibrinolytic system removes fibrin deposits and prevents formation of unnecessary fibrin clots. It also contributes to the localized repair of damaged endothelium. 

The blood is the body s main transport system. Although the transport and delivery of oxygen to the cells of the tissues is carried out by specialized cells, other vital components such as nutrients, metabolites, electrolytes, and hormones, are all carried in the noncellular fraction of the blood, the plasma Some components, such as glucose, are dissolved in the plasma others, for example, lipids and steroid hormones, are bound to carrier proteins for transport. The osmotic pressure of the plasma proteins regulates the distribution of water between the blood and the tissues. Plasma proteins in conjunction with platelets maintain the integrity of the circulatory system through the process of clotting. 

Normally, newly formed blood clots (fibrin) are dissolved by the actions of the fibrinolytic system, the purpose of which is the removal of unwanted clots without damaging the integrity of the vascular system. This system works via a relatively nonspecific protease enzyme called plasmin, the function of which is to digest fibrin (the very last step of the coagulation cascade) (Fig. 31.1). The lack of substrate specificity of plasmin is illustrated by the fact that it degrades fibrin clots as well as some plasma proteins and coagulation factors. 

Acute myocardial infarction can be limited by streptokinase which dissolves fresh clots and opens the artery, but muscle death and necrosis causes a mechanical defect. Subsequent infarcts cause further muscle death and ultimately lead to defective ventricular function and cardiac failure. There is the need for simple alarm systems to detect acute myocardial infarction and less traumatic invasive procedures to dissolve the clot and dilate the artery immediately. Coronary arteries ramify and branch in 3-dimensional space and the present generation of balloon catheters for percutaneous transluminal coronary angioplasty carries a small but definite risk. New, non-traumatic guidewires, low profile dilatation systems and more powerful dilatation balloons which will not rupture the artery are needed. 

The Proteolytic Emyme System of Plasma (Plaemin and Plasminogen), It has long been known that fibrin clots commonly dissolve after a few hours or days, even in the complete absence of bacterial contaminatioiL It was inferred that this lytic action was due to an enssrme. 

Oxygent only functions to carry gases to and from tissues it cannot clot or perform any of the immune-system functions that blood does. Still, the substitute has several advantages over real blood. Oxygent has a shelf life of more than a year. Oxygent also eliminates many of the risks associated with blood transfusions. Because the substitute can dissolve larger amounts of oxygen than real blood can, smaller amounts of the mixture are needed. 

---