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.
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.
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 fibrinogen and VWF receptors. If the break is small, this platelet plug may be adequate to seal the break.
Coagulation reactions 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.
In addition to an actual 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. Other examples include turbulent blood flow or damage to endothelium from an immunological cause.
Excessive activation of the blood coagulation reactions can results from stasis of blood flow in the veins of an immobilized or post-operative patient. The slow flow leads to the accumulation of activated clotting factors and tends to prevent their normal inactivation by the inhibitors described above. The handout discusses this further.
The most dramatic example of hypercoagulability is disseminated intravascular coagulation, which can have many causes. As mentioned on a earlier page, certain serious, systemic inflections can trigger this state. 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, leading to widespread hemorrhage. It is very easy for the sequence to fatal. Treatment involves reducing the tendency of the blood to clot with a drug such as heparin, while replacing the lost platelets and clotting factors.
One cause of inadequate clotting is thrombocytopenia, which is discussed on the handout.
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.