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Blood clotting (hemostasis) is an important protective mechanism of the body. It seals wounds – for example after an injury – stops the bleeding and starts the healing process.
The process takes place in two phases. Primary (cellular) hemostasis serves to quickly stop bleeding and minimize blood loss. The injured cells of the endothelium – a thin layer of cells on the inner wall of the blood vessels – and the underlying layer of cells emit signals (messengers) which enable the blood platelets (thrombocytes) to accumulate in the region of the injured blood vessel, forming a plug that provisionally seals the wound. Secondary (plasmatic) hemostasis, coagulation, is initiated at the same time.
This process is controlled by a signaling cascade consisting of 13 coagulation factors which interact and activate each other (see figure). At the end of the coagulation cascade, fibrinogen is converted into fibrin. A network of fibrin fibers reinforces wound closure; platelets and other blood cells get caught in this network and form a blood clot (thrombus). Finally, platelets and the endothelium release growth factors which control the wound-healing process. At the end of this process, the fibrin network is dissolved by enzymes in the blood plasma.
There are two separate clotting pathways, the intrinsic and extrinsic. These eventually join together to form the common pathway.
The Intrinsic pathway
The Extrinsic pathway
Begins in the vessel wall. Damaged endothelial cells will release factor III (tissue factor), and the greater the amount of damage, the more is released.
This combines with calcium, and activates factor VII and turns it into factor VIIa.
The Common Pathway
Note that – once activated, thrombin can act as a ‘catalyst’ in other areas of the cascade to speed up the process:
The extrinsic pathway produces thrombin very quickly, but in small amounts, the intrinsic pathway produces a large amount of thrombin, but takes a while to get going.
In a healthy person's body, a fine balance is maintained between procoagulant and anticoagulant factors, so that coagulation only begins in order to heal injuries; otherwise the blood remains fluid, and small blood clots are immediately dissolved.
Some of this main Regulators are:
Protein C (Factor C)
Prostacyclin (PGI2)TFPI – Tissue factor pathway inhibitor – this is a protein that directly inhibits Xa – even when present at very low concentrations. It is important in regulating the clotting cascade.
Antithrombin-III – this is am enzymes found circulating in the blood that binds to thrombin, thus preventing its action. It is crucial for the action of heparin!
Plasmin will remove and inactivate thrombin. About 85-90% of the thrombin produced is inactivated in this way.
The signaling cascade of blood coagulation is a suitable target for treating diseases involving dysregulated blood clotting or the absence of clotting. In the treatment of hemophilia, for example, a clotting factor (factor VIII or factor IX) is replaced if it is deficient or missing; on the other hand, certain coagulation factors can be inhibited in order to prevent and treat thrombosis.
Prothrombin complex concentrate, cryoprecipitate and fresh frozen plasma are commonly used coagulation factor products. Recombinant activated human factor VII is increasingly popular in the treatment of major bleeding.
Tranexamic acid and aminocaproic acid inhibit fibrinolysis, and lead to reduced bleeding rate.
Antiplatelet drug and Anticoagulant
Anti-platelet agents include aspirin, dipyridamole, ticlopidine, clopidogrel, ticagrelor and prasugrel; the parenteral glycoprotein IIb/IIIa inhibitors are used during angioplasty. Of the anticoagulants, warfarin (and related coumarins) and heparin are the most commonly used. Warfarin affects the vitamin K-dependent clotting factors (II, VII, IX,X) and protein C and protein S, whereas heparin and related compounds increase the action of antithrombin on thrombin and factor Xa. Other drugs like Lepirudin, rivaroxaban, dabigatran,apixaban can also be use.
Read Our other article about Anticoagulants (Warfarin & Heparin Complications) at : http://www.medrx22.com/1/post/2014/04/hematological-complications-of-heparin-warfarin-therapy.html
Nigel Key, Michael Makris, et al (2009). Practical Hemostasis and Thrombosis. Wiley-Blackwell. p. 2. ISBN 978-1-4051-8460-1
Jump up^ Pallister CJ and Watson MS (2010). Haematology. Scion Publishing. pp. 334–336.ISBN 1-904842-39-9.