Anemia is a decline in the concentration of hemoglobin resulting in a reduction of the oxygen-carrying capacity of the blood. Patients with anemia may be asymptomatic initially, but the lack of oxygen eventually results in fatigue, lethargy, shortness of breath, headache, edema, and tachycardia. Clinical complications of anemia arise when the hemoglobin concentration falls below 7 to 7.9 g/dL (70-79 g/L or 4.34-4.9 mmol/L) and include cardiovascular sequelae and hypoxia. Common causes of anemia include blood loss, decreased production of red blood cells (RBCs), increased destruction of RBCs, or a combination of these factors. Comorbid conditions increase the risk of anemia, particularly in cancer patients receiving chemotherapy and chronic kidney disease (CKD) patients. Factors leading to hypo-productive anemia are: nutritional (such as iron, vitamin B12, and folic acid), cancer, and CKD. Patients with immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to these chronic inflammatory conditions is termed anemia of chronic disease. Management of the anemia is determined by the underlying cause. Drug therapy is key in the management of anemia secondary to decreased production of RBCs and will be the focus of this chapter.
Erythropoiesis is a process that starts with a pluripotent stem cell in the bone marrow that eventually differentiates into an erythroid colony-forming unit (CFU-E). The development of these cells depends on stimulation from appropriate growth factors, primarily erythropoietin. Other cytokines involved include granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin-3. Eventually, the CFU-Es differentiate into reticulocytes and cross from the bone marrow in the peripheral blood. Finally, these reticulocytes mature into erythrocytes after 1 to 2 days in the bloodstream. Throughout this process, the cells gradually accumulate more hemoglobin and lose their nuclei. The following are areas that disrupt this process:
Deficiencies in nutrients such as folic acid and vitamin B12 hinder the process of erythrocyte maturation. Folic acid and vitamin B12 are required for the formation of DNA. Poor diet can be a contributor to the vitamin deficiencies. Patients with pernicious anemia are not able to absorb vitamin B12 from the gastrointestinal tract.
Iron is another vital nutrient in the development of erythrocytes. Iron deficiency decreases hemoglobin synthesis and ultimately RBCs production. Iron deficiency may result from inadequate dietary intake or overutilization of iron.
Patients with cancer may suffer from anemia caused by chemotherapy, radiation therapy, or tumor effects. Chemotherapy may cause destruction of proliferating stem cells, thereby decreasing erythrocyte production and decreasing the life span of RBCs. Radiation fields including bone marrow may decrease RBC production. Tumors can cause anemia via hemorrhage, replacing normal bone marrow with malignant cells, and/or releasing cytokines that decrease erythropoietin production or decrease the body's ability to respond to erythropoietin.
CKD patients develop anemia because deficiency of erythropoietin, which is primarily produced in the kidneys.
Anemia of chronic disease patients has a diminished production of erythropoietin ...