Anemia is a deficiency of red blood cells in the bloodstream. Anemias are generally classified as caused by blood loss, inadequate red cell formation by the bone marrow, and abnormal destruction of the red cells. Anemia caused by acute or chronic blood loss results from the inability of the bone marrow to make new cells as fast as they are depleted from the body. In acute massive bleeding, the red blood cells have a normal appearance, and are simply reduced in number. Chronic, slow bleeding leads to iron deficiency anemia, due to a deficiency in iron stores needed for hemoglobin production. This deficiency results in red blood cells that are both smaller and more pale than they are normally.
Abnormal destruction of red cells (the hemolytic anemias) leads to a shorter than normal red cell survival. Two more common causes of hereditary hemolytic anemias are sickle-cell disease and Cooley anemia (thalassemia), in which defective hemoglobin in the red cells causes morphologic changes that make them more susceptible to destruction. In autoimmune hemolytic anemia, the person manufactures antibodies that attach to the red cell membranes, and cause premature destruction in the spleen, and sometimes in the bloodstream.
Anemias caused by bone marrow failure include aplastic anemia, in which the bone marrow produces inadequate numbers of all types of blood cells, and red cell aplasia, in which the bone marrow selectively produces fewer red blood cells. In pernicious anemia red cells are produced in the bone marrow, but lack of vitamin BNM leads to defective DNA synthesis and the cells do not mature normally. In this hereditary disease, the stomach fails to produce "intrinsic factor," which is necessary for the normal absorption of vitamin BNM from the small intestine.
In some persons, the concentration of red cells and of hemoglobin in the blood may be abnormally increased, rather than decreased, resulting in polycythemia. This is usually caused by an increased production of red cells by the bone marrow, either spontaneously or in response to low oxygen concentrations such as that occurring at high altitude. In some cases, the high concentration of red cells may be caused by a decreased volume of plasma.
Deficiency of circulating granulocytes, with poor resistance to infection, may occur in many diseases. In general, if fewer than 1,000 neutrophils exist for every cubic millimeter of blood, the chance of severe infection is greatly increased. One common cause is the use of chemotherapy and X rays in the treatment of malignant diseases.
A great increase in bone marrow production of abnormal leukocytes may occur for unknown reasons, resulting in the diseases known as leukemias. These diseases range from chronic lymphocytic leukemia, in which patients may live for many years, to acute leukemias, often causing death within months. The abnormal leukocytes tend to accumulate and crowd out normal cells, allowing infections and bleeding problems to develop. Advances in treatment over the last several years have produced a significant number of cures, with the highest percentage of cures in childhood leukemia.
When the number of platelets severely decreases, there is danger of bleeding. Perhaps the most common cause of platelet deficiency, or thrombocytopenia, is an autoimmune disease in which the body produces antibodies that attach to the platelets and cause their premature destruction. Platelet deficiency is also found in such diseases as aplastic anemia, in which all the normal bone marrow cells are decreased. Severe infections, numerous medications, and bone marrow involvement by leukemias and other cancers may also cause thrombocytopenia. When platelet counts become severely depressed, platelet transfusions may be used to temporarily increase the counts.
Lymphomas and Multiple Myeloma
In certain malignant disorders of blood cells, proliferation of the abnormal cells occurs mainly within tissues such as lymph nodes and bone marrow, with less involvement of the circulating blood. Non-Hodgkins lymphomas and Hodgkin's disease cause enlarged lymph glands, whereas multiple myeloma affects the bone marrow and produces painful bone lesions. Excellent responses can be obtained with chemotherapy in many of these disorders.
Deficiencies of one or more of the plasma coagulation factors may also cause abnormal bleeding. The best-known such bleeding disorder is hemophilia, in which a hereditary deficiency of factor VIII exists. This sex-linked genetic disorder can cause life-threatening bleeding, usually in males. Von Willebrand's disease is a hereditary bleeding disorder of varying severity that occurs in both males and females, involving abnormalities of both factor VIII and platelets. Genetically engineered preparations of injectable factor VIII have dramatically decreased the need for blood transfusions in these patients.
More common than abnormal bleeding, however, is abnormal clotting in the blood vessels, known as thromboembolic disease. Arteries may be involved, as occurs with heart attacks and strokes, or veins may be involved, as occurs with phlebitis. Causes include excesses of one or more of the plasma clotting factors, deficiencies of one of the fibrinolytic or other circulating inhibitory factors, and complex interactions of platelets with lipids in the blood vessel walls. There has been significant progress in recent years in the treatment of these disorders with drugs that inhibit both the coagulation system and platelet aggregation, leading to improved survival and quality of life.