Blood clotting is an essential and potentially lethal process of life - Essay Example

Blood clotting is an essential and yet potentially lethal process of life Clotting is the solidification of blood in a process known as coagulation.When the body is injured it responds rapidly to stop the bleeding and repair the damage. The blood that oozes out is exposed to the air and after a while the blood clots. The platelets present in the blood come into action to seal the leak by forming a clot. A blood clot consists of a plug of platelets entangled in a network of insoluble fibrin. The clot seals the wound to prevent excessive blood loss while at the same time preventing foreign invasive particles from entering the bloodstream (ThinkQuest, 2001). Though blood clotting is an essential process, not all blood clotting is desirable. The normal blood clotting system is defensive and is essential, intended to prevent blood loss, a normal process called hemostasis. At other times, the body aggressively over-responds when there is not really a danger of blood loss, a disease process called thrombosis. In heart attacks and strokes, damage inside a blood vessel, often caused by cholesterol deposits, can trigger the same molecular reactions and produce an undesirable clot, called a thrombus. Unlike a normal clot, thrombi cut off essential blood flow to vital organs such as heart, lungs, brain, kidneys etc. It is a pathologic condition that occurs when the body forms arterial or venous blood clots that are excessively large and obstruct blood flow. The blood clots can also detach from the vascular wall and travel in the blood (Steriti). If we look at the process of blood clotting, during an injury, it can be seen that, the damaged tissues secrets an enzyme called thrombokinase and blood platelets in the bloodstream. The key players in clot-building system are the proteins thrombin and fibrin, and special blood cells, the platelets. Numerous blood platelets gather around the wound and then adhere to the tissue below the vessel surface (Delude, 2004).The clump of platelets forms a plug that begins to prevent blood loss. Platelet aggregators cause platelets to clump together (aggregate). They also cause the blood vessels to contract (vasoconstrict) to reduce blood loss. Platelet aggregators include adenosine diphosphate (ADP), thromboxane A2, and serotonin (5-HT).Coagulants, such as fibrin, bind the platelets together to form a permanent plug (clot) that seals the leak (Steriti). Fibrinogen is a blood plasma protein produced by the liver that plays an important role in blood coagulation. Fibrinogen circulates in the bloodstream, but does not interact with other blood proteins. At the site of the injury, however, fibrinogen encounters thrombin, which activates the fibrinogen, transforming it into fibrin. Fibrin is formed from fibrinogen in a complex series of reactions called the coagulation cascade. The enzymes that comprise the coagulation system are called coagulation factors, which are numbered in the order that they were discovered. They include Factor XII, Factor XI, Factor IX, Factor X, Factor VII and Factor V. The activation of the coagulation factors results in the formation of thrombin which acts as a cofactor for the conversion of fibrinogen into fibrin (Steriti). Fibrinogen deficiency is a very rare inherited bleeding disorder. There are three kinds of fibrinogen deficiency: afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia. This disorder affects men and women in equal numbers. In some cases it can also cause serious bleeding or thrombosis. (Canadian Hemophilia Society, 2004) This meshwork stops blood loss, but allows some blood to pass through to the tissues, providing nourishment while the wound is under repair. After the leak has been sealed with a blood clot, the body responds with another set of chemical messengers that oppose the actions of these chemicals. These include Platelet aggregation inhibitors and vasodilators, such as nitric oxide and prostacyclin (which is also known as prostaglandin I2, PGI2). The blood clotting system is quite complex. In the healthy body a balance is created between the opposing chemicals (coagulants versus anti-coagulants, vasodilators versus vasoconstrictors, and platelet aggregators versus platelet aggregator inhibitors). Fibrinogen also participates in the cellular phase of coagulation, acting to promote platelet aggregation, which may lead to diminished blood flow and delivery of oxygen to the body. Fibrinogen can also cause blood platelets to bind together, initiating abnormal arterial blood clots (Steriti). At the molecular level, the system works essentially the same whether a clot forms in response to an injury to prevent blood loss (hemostasis) or in a misguided response (thrombosis) to a misinterpreted threat, such as arterial plaque. Thrombosis is any unwarranted response, in the absence of imminent blood loss that blocks a blood vessel. Even while a clot forms, other molecules begin to dissolve it, a counter-process called fibrinolysis. The cast of characters for this biological drama includes plasmin, its precursor plasminogen, and plasminogen activators, such as t-PA. Plasminogen flows ubiquitously through the circulatory system but, like fibrinogen, does not interact with other molecules until activated. In fibrinolysis, the presence of fibrin in a clot alerts the plasminogen activator protein t-PA to its upcoming role. When plasminogen encounters t-PA near the clot, the plasminogen is converted into plasmin. Plasmin snips apart the fibrin mesh supporting the clot. As fibrin degrades, the platelets are removed and the clot dissolves. To prevent the natural fibrinolytic activity from happening too quickly, molecular inhibitors normally slow down the activation of plasmin, allowing the clot to linger as long as it is needed. When the inhibitors, for either genetic or environmental (lifestyle) reasons, get out of balance and overpower the plasmin activation, fibrinolysis cannot function normally. Such an imbalance can lead to the thrombi that cause heart attacks and strokes. When renegade clots form in the coronary arteries, they overwhelm the natural fibrinolytic process (Delude, 2004). Cigarette smoking can dramatically increase the plasma fibrinogen levels. Experts think that raised fibrinogen levels contribute to the increased risk of coronary heart disease in heavy smokers. A sedentary lifestyle may also contribute to increased fibrinogen levels. However, it has been suggested that excessive physical stress or psychological stress may cause an increase in fibrinogen by activating the fibrinolytic clotting system. Defective platelet function or thrombocytopenia can cause bleeding problems but clinically important bleeding only occurs when the abnormalities are severe. However, as fibrinogen is susceptible to genetic drift, congenital abnormalities of fibrinogen exist commonly and are passed on to the future generations. Hemostasis is a complex balance between thrombosis and bleeding that is coordinated through a number of interacting proteins. Mutations in a number of the genes encoding these proteins have been identified and it is now clear that hereditary factors contribute significantly to thromboembolic disease (Clericuzio, 2002). Two types of congenital abnormalities of fibrinogen exist: afibrinogenemia and dysfibrinogenemia. Afibrinogenemia is a quantitative deficiency that results in bleeding diatheses. The term hypofibrinogenemia refers to a less severe fibrinogen deficiency. Dysfibrinogenemia is marked by functional abnormalities of fibrinogen that may result in either bleeding or thrombosis. The bleeding symptoms associated with the inherited platelet disorders are mucocutaneous, whereas haemarthrosis and intracerebral haemorrhage are rare. Deficiency of membrane receptor GPIIb-IIIa (Glanzmann’s thrombastenia) is inherited as an autosomal recessive bleeding disease, affected individuals having intermittent and minor bleeding problems (Dahlback, 2005). In conclusion, the blood clotting system is a good example of how the body usually maintains a delicate balance between opposing actions. While hemostasis is a defensive maneuver, thrombosis is a biological mistake. Fibrinogen levels are one of the most important factors responsible for coronary heart disease and might influence management of other risk factors. References Canadian Hemophilia Society (2004) Fibrinogen Or Factor I Deficiency – An Inherited Bleeding Disorder [online]. Available from: [Accessed 25 November 2005]. Clericuzio, C.L. (2002) Genetic Considerations in Thrombotic Disorders [online]. Available from: [Accessed 22 November 2005] Dahlback, B. (2005) Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases Journal of Internal Medicine; 257: p 209–223. Delude, C (2004) Clot Busters!! - Discovery of Thrombolytic Therapy for Heart Attack & Stroke [online]. FASEB. Available from: [Accessed 26 November 2005]. Steriti, R. (n.d) Thrombosis Prevention[online]. Available from: [Accessed 26 November 2005]. ThinkQuest (2001) Blood The river of life [online]. Available from: [Accessed 26 November 2005]. Read More