Blood is very essential to maintain the optimum physiological functions of all the organ systems of the body. For this, the blood must be in a non-coagulated state or liquid state. Hemostasis is the process of maintaining blood in a liquid form, prevent excess loss of blood from trauma or disease by forming a hemostatic plug and removal of this plug when healing is complete. To balance the forces which cause blood to solidify or to remain fluid involves several interacting systems.
This process involves the following coagulation mechanisms.1
- Vascular constriction
- Platelet plug formation
- Blood clot formation as a result of blood coagulation
- Growth of fibrous tissue into the clot opening in the vessel
When the blood vessel ruptures, the wall of the vessel contracts immediately to reduce bleeding. This contraction is due to the nerve reflexes, local myogenic spasm and local humoral factors from the ruptured tissue and the blood platelet. A local vascular spasm or seizure lasts for many minutes during which the processes of platelet plugging and blood coagulation take place. Platelets release thromboxane A2 that is responsible for vascular constriction.
Formation of Platelet
Platelet plug is formed when the trauma to the blood vessel is very small or in case of minute damages that happen to the body everyday.
Mechanism of Platelet Plug Formation
Mechanism of platelet plug formation chiefly depends on the functioning of the platelets, which change their characteristics when they come in contact with the damaged vascular surface.
- begin to swell,
- assume irregular forms,
- become sticky for attachment,
- secrete adenosine diphosphate or their enzymes form thromboxane A2 and
- their contractile proteins contract and release granules containing active factors
The adenosine diphosphate and thromboxane A2 activate the nearby platelets. The stickiness of the platelets makes them adhere to the activated platelets, thus forming a platelet plug.2
The blood takes 15–20 seconds to begin the clot formation if the trauma is severe and 1–2 minutes to develop the clot if the trauma is less severe or minor.3
Mechanism of Blood Coagulation
It has been known that more than 50 important substances affect the coagulation process. Of these substances, some of them, which promote the coagulation process are called procoagulants and some of them, which inhibit the coagulation process are called anticoagulants. The blood clotting depends on the balance between the procoagulants and anticoagulants. The following steps are involved in the process of blood coagulation.
As a result of rupture to the blood vessels, a complex cascade of chemical reactions take place involving blood coagulation factors. This results in the formation of a complex, involving activated substances that are collectively called as prothrombin activator.
Prothrombin activator readily converts prothrombin to thrombin. The prothrombin activator in the presence of calcium ions converts prothrombin to thrombin. The thrombin causes polymerization of fibrinogen molecules into fibrin fibers within a span of 15–20 seconds. Platelets also play an important role in this conversion, as the prothrombin first attaches to prothrombin receptors on the platelets, which are already bound to the damaged tissue. This binding increases the formation of thrombin from prothrombin.
Thrombin in turn converts fibrinogen into fibrin fibers. These fibrin fibers entangle platelets, blood cells and plasma to form the clot. Thrombin is a protein enzyme with weak proteolytic properties. Thrombin acts on fibrinogen and removes the low molecular weight peptides forming fibrin monomer molecule. This fibrin monomer molecule has the capacity to polymerize with other fibrin monomer molecules forming fibrin, which then constitutes the reticulum of the clot.
The Blood Clot
The blood clot is composed of a meshwork of fibrin fibers, which run in all directions and enclose the blood cells, platelets and plasma.
Initiation of Coagulation: Formation of Prothrombin Activator
Initiation of blood coagulation is a complex mechanism and occurs when there is:
trauma to the vascular wall and adjacent tissues,
trauma to the blood, and
contact of the blood with damaged endothelial cells, collagen and other tissue elements outside the blood vessel
The above instances lead to the formation of prothrombin activator, which converts prothrombin to thrombin.
Prothrombin activator is usually formed in two ways.4
Extrinsic pathway, which begins with trauma to the vascular walls and surrounding tissues.
Intrinsic pathway, which begins in the blood itself.
In both the pathways, blood-clotting factors play a major role.
The following steps are involved in the extrinsic pathway.
The ruptured or traumatized tissue releases several factors called tissue factors or tissue thromboplastin, which are composed of phospholipids from the tissue membranes and lipoprotein complex (this acts as proteolytic enzymes).
The lipoprotein complex of the tissue factor combines with blood coagulation factor VII and in the presence of calcium ions it acts enzymatically on factor X to form activated factor X (Xa).
The activated factor X combines with tissue phospholipid or phospholipids released from the platelet along with factor V to form a complex called prothrombin activator. In the presence of calcium ions, prothrombin activator splits prothrombin to form thrombin within a few seconds and this is followed by the clotting process.
Intrinsic pathway begins with the trauma to the blood itself or exposure of the blood to collagen from a traumatized blood vessel wall.
Following are the steps involved in this pathway:
Trauma to the blood causes the activation of the factor XII and release of platelet phospholipids. Factor XII is disturbed when it comes in contact with collagen or a wettable surface. Now, factor XII takes a new configuration and is converted into proteolytic enzymes called activated factor XII. Simultaneously, blood trauma also damages the platelets, which releases platelet phospholipid, which contains the lipoprotein called platelet factor 3, required for clotting reactions.
Activated factor XII, enzymatically acts on factor XI to activate it. This reaction requires high molecular weight kininogen and is accelerated by prokallikrein.
The activated factor XI then enzymatically acts on Factor IX to activate it.
The activated factor IX then enzymatically with activated factor VIII, platelet phospholipid and factor 3 from traumatized platelets, activates factor X. Factor VIII is the factor which is not seen in persons who have classic hemophilia. Hence, it is called antihemophilic factor. Platelets are clotting factors, which are not seen in persons suffering from bleeding disease called thrombocytopenia.
This step is similar to the last step of the extrinsic pathway where the activated factor X combines with factor V and platelet or tissue phospholipids to form a complex called prothrombin activator. The prothrombin activator immediately converts prothrombin to thrombin, there by leading the clotting process.