18. Describe the two pathways involved in the initiation of blood coagulation: Difference between revisions

Haemostasis is the body’s response to stop bleedings after endothelial damage. It consists of three steps:

** Dissolving the blood clot

Most of the components involved in haemostasis are found in the blood. The first are the platelets. The second are the coagulation factors. The coagulation factors are proteins in the plasma that are involved in haemostasis. There are many coagulation factors. They travel in the blood in an inactive state. Most of them have two names, one which is just a roman numeral, and one which is their real name. Some coagulation factors are referred to by their roman number and some are referred to by their real name. Almost all of them are synthesized in the liver.

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''A protein in an inactive state is usually given an “-ogen” suffix. As an example, the inactive form of plasmin is plasminogen, and the inactive form of fibrin is fibrinogen.''

When there is endothelial damage the first priority is to “plug” the hole. This is the goal of primary haemostasis.

This platelet plug isn’t very stable; it can loosen easily. To ensure that the platelet plug is stable enough to remain until the endothelial damage has been repaired, we must “secure” the plug in place. This is where secondary haemostasis comes in.

Secondary haemostasis is the process of stabilizing the platelet plug by forming a mesh of a protein called ''fibrin''. This process is complicated.

The coagulation cascade is (somewhat arbitrarily) divided into two main pathways; the extrinsic pathway and the intrinsic pathway, both of which end in the ''common'' pathway. The final point of the extrinsic and intrinsic pathways is the activated factor X, which is also the beginning of the common pathway.

The intrinsic pathway, also called the ''contact activation pathway'' begins when the blood touches a negatively charged surface, such as collagen or glass. Glass is obviously not present in the body, but collagen is a major component of subendothelial tissues. As such, when endothelium is damaged, the blood is exposed to collagen, and so the intrinsic pathway initiates.

When blood touches the collagen or glass factor XII will be activated, turning into its activated form XIIa. Activated factor XII (XIIa) will activate factor XI. Activated factor XI (XIa) will activate factor IX. Activated factor IX (IXa) will, together with factor VIII activate factor X.

A protein called ''tissue factor'' (TF) is also present in subendothelial tissue. When the endothelium of a vessel is damaged the underlying TF will be exposed to blood, which initiates the extrinsic pathway. Factor VII will bind to tissue factor and become activated. VIIa activates factor IX and factor X.

Activated factor X (Xa) will activate factor II, converting it from prothrombin to thrombin. Thrombin will activate factor I, converting it from fibrinogen to fibrin. Thrombin also activates factor XIII.

''The coagulation system is described as divided into the intrinsic and extrinsic pathways as a result of how the coagulation cascade acts in the laboratory (in vitro), not in the body (in vivo). The intrinsic pathway is initiated when blood comes in contact with glass, and the pathway was described according to what happened to the blood after this contact. The extrinsic pathway is initiated when blood comes in contact with thromboplastin, a mixture of tissue factor and phospholipids.The model depicted here is old and outdated; we now know that the two systems are not redundant in vivo but are both needed. In the body, tissue damage initiates the extrinsic pathway, which generates a small amount of thrombin but also activates the "intrinsic" pathway, which in turn generates a lot of thrombin. Also, deficiency of some factors in the intrinsic pathway doesn’t cause a defect in haemostasis (but rather in immunity).''

Fibrinolysis is the process where the blood clot is broken down. This process is activated simultaneously as the coagulation cascade, and both processes occur simultaneously. This is to prevent the blood clot from growing too large and occluding the whole blood vessel. Fibrinolysis is also involved in removing the blood clot completely after the damage to the blood vessel has been repaired.

The formed blood clot contains a lot of plasminogen. A few days after the blood clot has been formed and the bleeding has stopped will the endothelium secrete tissue plasminogen activator. This protein activates the plasminogen, which is contained in the blood clot, converting it into plasmin. Plasmin then dissolves the clot.

In some cases, the blood clots aren’t broken down by fibrinolysis but instead ''organized''. This means that they’re slowly replaced by connective tissue formed by a type of cell called the ''fibroblast''.

The body is constantly in a balance between procoagulation and anticoagulation. Both of these processes occur simultaneously and in a balance, so that neither too many (or too large) nor too few blood clots are formed. The term ''thrombosis'' refers to when a blood clot is too large and completely obstructs a blood vessel. This can be very dangerous and is the basis of heart attacks and strokes, among other diseases.

Coumarins are used to treat people who are at risk for ''thrombosis''.

There are multiple tests we can perform on the blood to determine the function of the different parts of haemostasis.

The problem with prothrombin time is that the result varies significantly from lab to lab, depending on equipment and substrates used. To overcome this the result of the measurement needs to be normalized. This is done by inserting the prothrombin time into an equation, which gives you the ''international normalized ratio'' (INR). The INR is therefore a measurement of the prothrombin time, but it is standardized so that differences between laboratories doesn’t influence the result.

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|Bleeding time

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Many diseases of haemostasis exist, both congenital and acquired. Here are the most important ones and which parameter they affect:

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|Thrombocytopaenia