Clot Formation




In the previous page we examined the activation of platelets and briefly mentioned the blood coagulation reactions, which result in the conversion of fibrinogen to fibrin. Now let us pull all this together by following a typical sequence of events following a break in the wall of a blood vessel.

Intact Endothelium

The thin, single layer of cells than line a blood vessel is called the endothelium. (The walls of the smallest vessels, the capillaries, are comprised of the endothelium alone.) When the endothelium is intact and healthy, a clot, of course, should not form. A number of factors keep a clot from forming under these circumstances.

Platelet Plug Starts to Form

A break in the endothelium allows platelets to contact collagen and the other factors that activate platelets (see previous page). Platelets begin adhering to one another and the subendothelial tissue via glycoprotein IIb/IIIa and VWF receptors. If the break is small, this platelet plug may be adequate to seal the break.

Coagulation Reactions Begin at Surface of Platelet

Coagulation reactions now begin occuring more rapidly since tissue factor is exposed and the surface of activated platelets provides the environment for the activation of the cascade that ultimately converts prothrombin to thrombin. The developing clot consists of interlaced fibrin fibrils and activated platelets.

Hypercoagulability

In addition to an accidental break in the endothelium, various other situations can lead inappropriately to activated platelets. Injury to the endothelium, in general, tends to activate platelets. An important example here is a developing atherosclerotic plaque in an artery. Other examples include turbulent blood flow or damage to the endothelium from an immunological cause.

Slow flow can also lead to inappropriate clotting. The slow flow leads to the accumulation of activated clotting factors and tends to prevent their normal inactivation by the inhibitors described above. A particularly important case is atrial fibrillation, which is common in elderly patients. The atria of the heart do not rhythmically contract, which causes the atria to become stretched with areas of poor flow. This is dangerous because a clot forming in the left atrium can travel to the brain and cause a stroke.

Stasis of blood flow of blood in leg veins in an immobilized or post-operative patient can cause excessive activation of the blood coagulation reactions. When the clot breaks free, it is termed a venous thromboembolism.

The most dramatic example of hypercoagulability is disseminated intravascular coagulation, which can have many causes. As mentioned on a previous page, it might arise from sepsis, which is a systemic infection accompanied by damage to organs. It has the characteristics of a general, systemic inflammatory problem. Also, trauma, in general, potentially can lead to disseminated intravascular coagulation. Cancer can be another cause, probably through the entry of tissue factor into the blood. In all cases, many small clots form, blocking blood flow to widespread areas of the body. But since this is so widespread, it depletes platelets and clotting factors. Serious hemorrhaging can result. It is very easy for the sequence to fatal.

Coagulation Deficits

One cause of inadequate clotting is thrombocytopenia, which is discussed on the lecture outline.

Impaired clotting can be genetic due to lack of certain clotting factors (e.g. hemophilia) or lack of VWF. Or it can be due to impaired synthesis of clotting factors for other reasons. Vitamin K deficiency, which is required for the synthesis of several clotting factors, can be important here. Newborn infants, for example, may not have enough vitamin K.



Quick Quiz

Fill in Answer Correct False Correct Answer
What, is the term for a clot that has broken loose and is traveling in the blood?
If a thrombus blocks blood flow to an area, what term refers to the resulting necrotic area?
If a dying patient infected with the Ebola virus begins bleeding profusely, what is the term for the condition causing this?
What does heparan proteoglycan activate?
Name a protein that a cancer cell might carry into the blood, leading to a fatal hypercoagulation of the blood.
Name the vitamin necessary for the synthesis of several clotting factors, including thrombin.

(Spelling must be correct)
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