Clinical signs and symptoms include inflammation of the tongue, lips or mucous membranes of the mouth and spooned nails. In its advanced state, it is described as a microcytic hypochromic anemia. Laboratory tests used to diagnose iron deficiency anemia include a low hemoglobin, low hematocrit, low MCV, low serum iron, elevated total iron binding capacity (TIBC), low reticulocyte count, low ferritin, elevated RDW and elevated erythrocyte sedimentation rate. Not all of these tests may be available due to cost restraint. The MCV is the key test to examine once a low hemoglobin and low hematocrit are identified.
Once underlying causes of iron deficiency anemia are identified and addressed, oral iron therapy is preferred, however a multivitamin may be better tolerated. Absorption is best on an empty stomach, but may cause gastric upset (Blackwell, 2001). Remember that the goal of pharmacological intervention is to increase the deficient body components while avoiding a negative impact on the total dietary intake of the patient.
Anemia of chronic and inflammatory diseases
Anemia of chronic and inflammatory diseases develops as a result of an extended infection or inflammation. The anemia usually manifests itself in a similar manner to iron deficiency anemia. While the physical signs and symptoms are the same as iron deficiency, anemia of chronic and inflammatory diseases is a normochromic-normocytic anemia. In anemia of chronic and inflammatory diseases, the lab results are below normal ranges for hemoglobin, hematocrit, serum iron and TIBC. However, the MCV and ferritin are usually normal. The changes in lab test
Table 6. Anemias According to RBC Indices
| Normocytic1, Normochromic2, Anemia •Iron Deficiency (early stages) •Anemia of Chronic and Inflammatory Diseases •Acute Blood Loss •Pernicious Anemia ( about 40% of cases) | |
| Microcytic3, Hypochromic4 Anemia •Iron Deficiency (advanced) | |
| Microcytic3 Normochromic1 Anemia • Renal Disease due to loss of erythropoietin | |
| Macrocytic5, Normochromic1 Anemia •Vitamin B12 / Pernicious Anemia •Folic Acid Deficiency/Megaloblastic Anemia |
Key:
1 Normocytic - normal RBC size
2 Normochromic - normal color (normal hemoglobin content)
3 Microcytic - smaller than normal RBC size
4 Hypochromic - less than normal color (
5 Macrocytic - larger than normal RBC size
results are either related to redistribution of iron stores or impaired utilization. A multivitamin supplement with iron or oral iron therapy may be ordered, however, should be carefully monitored for expected outcomes. In cases of true anemia of chronic and inflammatory diseases, the lab values will not improve until the underlying condition resolves.
Other characteristics of anemia of chronic and inflammatory diseases may include slow involuntary weight loss and hypoalbuminemia. Weight loss occurs despite efforts to increase caloric intake. Certain chronic infections and inflammatory diseases cause several changes in the blood cell production system. These include a slightly shortened red blood cell life span and an isolation of iron in inflammatory cells (macrophages) that result in a decrease in the amount of iron available to make RBC. In the presence of these effects, a low-to-moderate grade anemia develops.
Conditions associated with the anemia of chronic and inflammatory diseases include the following:
•Advanced age
•AIDS
•Chronic Bacterial Endocarditis
•Chronic Renal Failure
•Congestive Heart Failure
•Crohn's Disease
•Juvenile Rheumatoid Arthritis
•Osteomyelitis
•Rheumatic fever
•Ulcerative Colitis
Macrocytic anemias
The metabolic interrelationship between folate and vitamin B12 may explain why a single deficiency of either leads to the same hematological changes. The most common cause of macrocytic anemia is megaloblastic anemia due to impaired DNA synthesis. Vitamin B12 and folate coenzymes are required for thymidylate and purine synthesis. A deficiency of either or both nutrients retards DNA synthesis that triggers dyspoiesis (abnormal rate of RBC maturation in bone marrow) and pancytopenia (decrease in the production of RBC). While the macrocytic RBC is the hallmark of macrocytic anemia, other rapidly dividing cells are affected. Other physiological changes may include, sore tongue due to glossitis or atrophy of tongue, skin changes, and flattening of intestinal villi (Guyton, 2006).
RNA synthesis is unaffected by a deficiency of folate or vitamin B12 but, there is a build up of cytoplasmic components in a slowly dividing cell making the RBC larger than normal. The primary defect in DNA synthesis caused by folate or vitamin B12 deficiency is a depletion of thymidine triphosphate (dTTP). This leads to retarded mitosis and nuclear maturation. The RBC have shortened life spans and reduced capacity to carry hemoglobin. Iron is stored as serum iron or ferritin rather than in hemoglobin (Guyton, 2006).
The first sign of inadequate folic acid intake is a decrease in serum folate concentration followed by a decrease in erythrocyte folate concentration and a rise in homocysteine levels. When folate supply to the bone marrow becomes rate limiting for erythropoiesis, macrocytic cells are produced. Macrocytic anemia is not evident in the early stages of folate deficiency because of the 120-day lifespan of normal erythrocytes.
When dietary vitamin B12 is deficient, the body cannot convert N5methyl THF to the active form of folate, tetrahydrofolate (THF). Without adequate vitamin B12, folate is trapped in an unusable form (Guyton, 2006). When dietary folate is deficient, the same problems occur because there are inadequate amounts of THF needed for the cascade of reactions required for DNA synthesis (Guyton, 2006). A B12 deficiency will eventually cause a folate deficiency because folate cannot be converted into an active form without vitamin B12 (Bostom, 1996).
One of the earliest clinical signs of both folate and vitamin B12 deficiency is hyper-segmentation of > 5 percent of neutrophils. Hyper-segmentation may also occur in uremia, myeloproliferative disorders, myelofibrosis and as a congenital lesion in 1% of the population. More testing is required to differentiate between megaloblastic and pernicious anemia.
The abnormal RBC cannot conform to the size of small capillaries. Instead, they fracture and hemolyze, thus shortening their lifespan. The macrocytic RBC has a reduced capacity to carry hemoglobin. Dietary iron is absorbed by the body and stored as serum iron or ferritin rather than in hemoglobin. Once the folate and/or vitamin B12 deficiency is treated through dietary supplements, the iron stores from the serum iron and ferritin will shift back to the RBC and the hemoglobin and hematocrit will return to normal levels. Homocysteine levels may or may not return to normal