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Introduction

Haemostasis is a process that prevents excessive blood loss in the body. There are three primary mechanisms employed to control bleeding, vascular spasm, platelet plug, and blood clotting. This brief paper describes the mechanisms of haemostasis.

Vascular Spasm

Vascular spasm occurs when a blood vessel is punctured. The smooth muscle surrounding the vessel contracts and pinches off blood supply to the area. This mechanism can be seen as the ‘first-aid’ system of the body and it can hold for minutes to hours. The exact cause of vascular spasm is not understood, but may be related to damaged nerve endings in the muscle itself and from reflexes set up by pain receptors¹.

Platelet Plug Formation

Platelet plug formation is a more complex process than vascular spasm, and it occurs in three phases:

Platelet adhesion - The first phase begins when platelets detect damage to a blood vessel and begin to adhere to the exposed surfaces.

Platelet release reaction - Once stuck to a site of damage, the platelets begin to change. Firstly they create extensions so that they can contact each other, and then they release their contents. There are two types of chemical packages (granules) held within the cytoplasm of platelets: alpha granules that contain clotting factors, growth factors, and fibroblasts; and dense granules that contain ADP, ATP, Calcium ions, and Serotonin. Other components are also present within the platelet that aids its work. Nearby platelets are stimulated into action by the release of ADP and Thromboxane A2 (a prostaglandin found within platelets). Thromboxane and Serotonin act to cause vasoconstriction.

Platelet aggregation - The ADP acts to make the nearby platelets sticky and adhere to the other recruited platelets, and when the collection is large enough it creates a platelet plug stopping the loss of blood through holes in small vessels.

Blood Clotting

Clotting or Coagulation is the most complex haemostatic process. The aim of the process is to turn liquid blood into a gel. The gel is called a clot and is composed of protein fibres called fibrin in which the formed elements of blood are trapped. The gel effectively forms a cap over a wound.

Clotting involves several substances called clotting factors; these are typically numbered from one to thirteen using Roman numerals. The clotting factors act upon each other to create a cascade of interactions that ultimately results in clot formation.

The clotting process occurs with a positive feedback mechanism: once a clot is formed it continues to expand and external factors are required to hold it in check.

Clotting occurs in three stages. The first stage can occur via two distinct pathways, intrinsic or extrinsic, and results in the formation of the enzyme prothrombinase. This phase can be described as a cascade of interactions between clotting factors (refer to figure 1).

The extrinsic pathway occurs quickly and involves fewer steps than the intrinsic pathway. It is so named because it requires the release of Tissue Factor (TF) from outside the blood vessels through tissue trauma, in order to form prothrombinase. The intrinsic pathway occurs more slowly and uses activators within the blood to reach prothrombinase.

In the second stage of the process, prothrombin is catalysed by prothrombinase and calcium ions to the enzyme thrombin.

In stage three, thrombin converts fibrinogen to loose fibrin threads. Fibrin stabilising factor (XIII), also activated by thrombin, aids with the strengthening and stabilisation of fibrin. Two positive feedback effects are brought about by thrombin: it accelerates the formation of prothrombinase and it activates platelets stimulating their activity.

Vitamin K is a key factor required for the formation of several clotting factors (II, VII, IX, and X). Two recently recognised coagulation proteins involved in the clotting cascade, C and S, are also vitamin K dependent. They inactivate factors V, and VIII and can stimulate fibrinolysis².

The clot that caps a broken area stops the blood loss, and in addition the fibrin within the clot contracts and aids in pulling the broken ends of the blood vessel back together. Once the ends are retracted tissue repair can take place.

Keeping the clot local

The positive feedback mechanism associated with clotting could continue unchecked leading to a larger and larger clot, but it is desirable to keep the clot localised. Clot formation is held in check by fibrin, it has the ability to absorb and inactivate up to 90% of the thrombin formed from prothrombin. This stops the spread of the clot and helps to keep it localised.

Another mechanism for localising clots is blood circulation. Some of the clotting factors are carried away in the blood and the concentration is reduced. Other agents carried by the blood act as antagonist to the clotting factors. These include: prostacyclin, produced by endothelial and white blood cells; anticoagulants, antithrombin III, protein C, alpha-2-macroglobulin, alpha-1-antitrypsin, and heparin¹.

Stopping and removing clots

Clots can form many times a day throughout the body, even when it is not necessary for a clot to form. Unnecessary clots can block impede the flow of blood it vital organs. The fibrinolytic system prevents clots from getting too large and acts to dissolves clots once damaged vessels have been repaired.

Fibrinolysis is the process of dissolving a clot, by removing the fibrin within it. All clots are created with a built in time bomb: plasminogen. Plasminogen is activated by factors circulating in the blood and present in endothelial tissue. In its active form it becomes plasmin or fibrinolysin which is capable of digesting fibrin fibres and inactivating certain clotting factors.

Despite these mechanisms homeostatic imbalances can occur and clots can form. Atheroscloritic plaque, trauma, or infection can roughen the insides of blood vessels and attract the adhesion of platelets. Clotting in an unbroken vessel is called thrombosis and the clot itself is called a thrombus. If the clot breaks free and is transported it is called and embolus. The embolus can become lodged in a vital organ such as the lungs or vessels servicing the brain and death may result.

A number of coagulation defects can and do exist; some of them include Haemophilia, Von Willebrand’s Disease, Disseminated Intravascular Coagulation, and Acquired Circulating Anticoagulants².

Conclusion

The mechanisms the body uses to protect itself from the loss of blood are very sophisticated. However, if large ruptures occur, medical treatment is necessary.

References

Tortora, G.J., Grabowski, S.R., Principles of Anatomy and Physiology - 8^th Edition, Harper Collins, NY, 1996.

Willis Hurst, J (Ed.), Medicine for the Practicing Physician – 3^rd Edition, Butterworth-Heinemann, USA, 1992.