final B4L42;bleeding disorders 28-1.pdf

42 Bleeding disorders ILOs By the end of this lecture, students will be able to 1. Describe the types of bleeding disorders 2. Correlate the role of coagulation factors and platelets with different disorders 3. Describe the causes of increased coagulability Abnormalities of Haemostasis may occur res...

42 Bleeding disorders ILOs By the end of this lecture, students will be able to 1. Describe the types of bleeding disorders 2. Correlate the role of coagulation factors and platelets with different disorders 3. Describe the causes of increased coagulability Abnormalities of Haemostasis may occur resulting from deficiency of platelets or coagulation factors, and in this case will cause bleeding tendency, or because of overactivity of the coagulation cascade and hence cause thrombosis. Bleeding tendency § Excessive bleeding can result from a deficiency of any one of the many coagulation factors or platelets. Bleeding tendencies can be either congenital or acquired. I. Coagulation factor defects i. Congenital bleeding disorders 1. Hemophilia Hemophilia is a bleeding disease that occurs almost exclusively in males. In 85 percent of cases, it is caused by an abnormality or deficiency of Factor VIII; this type of hemophilia is called hemophilia A or classic hemophilia. In 15 percent of hemophilia patients, the bleeding tendency is caused by a deficiency of Factor IX ( haemophilia B). Genetic transmission: Both factors are transmitted genetically by way of the female chromosome. Therefore, rarely 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. Clinical picture: 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 the extraction of a tooth. Treatment: The disease can be treated with factor VIII-rich preparations made from plasma, or, more recently, factor VIII produced by recombinant DNA techniques. 2. Von Willebrand factor deficiency likewise causes a bleeding disorder (von Willebrand disease) by reducing platelet adhesion and by lowering plasma factor VIII. The condition can be congenital or acquired. Page 1 of 3 ii. Acquired bleeding disorder 1. Vitamin K deficiency, One of the most prevalent causes of vitamin K deficiency is failure of the liver to secrete bile into the gastrointestinal 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. Reduction of gut flora due to excessive use of antibiotics may be another cause of vitamin K deficiency. When vitamin K is depressed, the formation of the clotting factors (II,VII,IX,X)is greatly impaired and may cause a significant bleeding tendency. 2. Liver disease, with few exceptions, almost all the blood-clotting factors are formed by the liver. Therefore, diseases of the liver such as hepatitis or cirrhosis can sometimes depress the clotting system that the patient develops a severe tendency to bleed. II. Platelet defects Thrombocytopenia Thrombocytopenia means the presence of very low numbers of platelets in the circulating blood. People with thrombocytopenia tend to bleed, as do hemophiliacs, except that the bleeding is usually from 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 thrombocytopenic purpura. As stated earlier, platelets are especially important for repair of minute breaks in capillaries and other small vessels. Bleeding will occur when the number of platelets in the blood falls below 50,000/μl. Idiopathic Thrombocytopenia, which means thrombocytopenia of unknown cause. In most cases, specific antibodies form and react against the platelets themselves to destroy them. Relief from bleeding for 1 to 4 days can often be affected 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 § Thrombosis Formation of clots inside blood vessels is called thrombosis to distinguish it from the normal extravascular clotting of blood. Thromboses are a major medical problem and may occur on the following conditions: 1. Sluggish blood flow: because the slow flow permits activated clotting factors to accumulate instead of being washed away. 2. When the intima is damaged by atherosclerotic plaques, and over areas of damage to the endocardium. 3. Congenital absence of protein C; leads to uncontrolled intravascular coagulation and, in general, death in infancy. If this condition is diagnosed and treatment is instituted, the coagulation defect disappears. Page 2 of 3 4. Resistance to activated protein C is another cause of thrombosis, and this condition is common. 5. Mutations in protein S and antithrombin III may increase the incidence of thrombosis. The thrombi frequently occlude the arterial supply to the organs and pieces of the thrombus sometimes break off (emboli) and travel in the bloodstream to distant sites, damaging other organs. A common example is pulmonary embolism, where thrombi from the leg veins break off into emboli that travel and occlude the pulmonary artery or its branches, which could be fatal. Page 3 of 3