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Chapter: Medical Physiology: Hemostasis and Blood Coagulation

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Conditions That Cause Excessive Bleeding in Human Beings

Excessive bleeding can result from deficiency of any one of the many blood-clotting factors.

Conditions That Cause Excessive Bleeding in Human Beings

Excessive bleeding can result from deficiency of any one of the many blood-clotting factors. Three particu-lar types of bleeding tendencies that have been studied to the greatest extent are discussed here: bleeding caused by (1) vitamin K deficiency, (2) hemophilia, and (3) thrombocytopenia (platelet deficiency).

Decreased Prothrombin, Factor VII, Factor IX, and Factor X Caused by Vitamin K Deficiency

With few exceptions, almost all the blood-clotting factors are formed by the liver. Therefore, diseases of the liver such as hepatitis,cirrhosis, and acute yellowatrophy can sometimes depress the clotting system sogreatly that the patient develops a severe tendency to bleed.

Another cause of depressed formation of clotting factors by the liver is vitamin K deficiency. Vitamin K is necessary for liver formation of five of the impor-tant clotting factors: prothrombinFactor VIIFactorIX, Factor X, and protein C. In the absence of vitaminK, subsequent insufficiency of these coagulation factors in the blood can lead to serious bleeding ten-dencies.

Vitamin K is continually synthesized in the intes-tinal tract by bacteria, so that vitamin K deficiency seldom occurs in the normal person as a result of vitamin K absence from the diet (except in neonates before they establish their intestinal bacterial flora). However, in gastrointestinal disease, vitamin K defi-ciency often occurs as a result of poor absorption of fats from the gastrointestinal tract. The reason is that vitamin K is fat-soluble and ordinarily is absorbed into the blood along with the fats.

One of the most prevalent causes of vitamin K defi-ciency is failure of the liver to secrete bile into the gas-trointestinal tract (which occurs either as a result of obstruction of the bile ducts or as a result of liver disease). Lack of bile prevents adequate fat digestion and absorption and, therefore, depresses vitamin K absorption as well. Thus, liver disease often causes decreased production of prothrombin and some other clotting factors both because of poor vitamin K absorption and because of the diseased liver cells. Because of this, vitamin K is injected into all surgical patients with liver disease or with obstructed bile ducts before performing the surgical procedure. Ordinarily, if vitamin K is given to a deficient patient 4 to 8 hours before the operation and the liver parenchymal cells are at least one-half normal in function, sufficient clotting factors will be produced to prevent excessive bleeding during the operation.

Hemophilia

Hemophilia is a bleeding disease that occurs almost exclusively in males. In 85 per cent of cases, it is caused by an abnormality or deficiency of Factor VIII; this type of hemophilia is called hemophilia A or classichemophilia. About 1 of every 10,000 males in theUnited States has classic hemophilia. In the other 15 per cent of hemophilia patients, the bleeding tendency is caused by deficiency of Factor IX. Both of these factors are transmitted genetically by way of the female chromosome. Therefore, almost never will a woman have hemophilia because at least one of her two X chromosomes will have the appropriate genes. If one of her X chromosomes is deficient, she will be a hemophilia carrier, transmitting the disease to half of her male offspring and transmitting the carrier state to half of her female offspring.

The bleeding trait in hemophilia can have various degrees of severity, depending on the character of the genetic deficiency. Bleeding usually does not occur except after trauma, but in some patients, the degree of trauma required to cause severe and prolonged bleeding may be so mild that it is hardly noticeable. For instance, bleeding can often last for days after extraction of a tooth.

Factor VIII has two active components, a large com-ponent with a molecular weight in the millions and a smaller component with a molecular weight of about 230,000. The smaller component is most important in the intrinsic pathway for clotting, and it is deficiency of this part of Factor VIII that causes classic hemo-philia. Another bleeding disease with somewhat dif-ferent characteristics, called von Willebrand’s disease, results from loss of the large component.

When a person with classic hemophilia experiences severe prolonged bleeding, almost the only therapy that is truly effective is injection of purified Factor VIII. The cost of Factor VIII is high, and its availabil-ity is limited because it can be gathered only from human blood and only in extremely small quantities.

Thrombocytopenia

Thrombocytopenia means the presence of very low numbers of platelets in the circulating blood. People with thrombocytopenia have a tendency to bleed, as do hemophiliacs, except that the bleeding is usually from many small venules or capillaries, rather than from larger vessels as in hemophilia. As a result, small punctate hemorrhages occur throughout all the body tissues. The skin of such a person displays many small, purplish blotches, giving the disease the name throm-bocytopenic purpura. As stated earlier, platelets areespecially important for repair of minute breaks in capillaries and other small vessels.

Ordinarily, bleeding will not occur until the number of platelets in the blood falls below 50,000/ml, rather than the normal 150,000 to 300,000. Levels as low as 10,000/ml are frequently lethal.

Even without making specific platelet counts in the blood, sometimes one can suspect the existence of thrombocytopenia if the person’s blood fails to retract, because, as pointed out earlier, clot retraction is nor-mally dependent on release of multiple coagulation factors from the large numbers of platelets entrapped in the fibrin mesh of the clot.

Most people with thrombocytopenia have the disease known as idiopathic thrombocytopenia, which means thrombocytopenia of unknown cause. In most of these people, it has been discovered that for unknown reasons, specific antibodies have formed and react against the platelets themselves to destroy them. Relief from bleeding for 1 to 4 days can often be effected in a patient with thrombocytopenia by giving fresh whole blood transfusions that contain large numbers of platelets. Also, splenectomy is often helpful, sometimes effecting almost complete cure because the spleen normally removes large numbers of platelets from the blood.

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