Anemia of chronic disease (ACD), 285.29
Folic acid deficiency, 281.2
Pernicious anemia, 281.0
Vitamin B12 deficiency, 281.1
Anemias, 285.9
Iron deficiency, 280.9
Thalassemia, 282.49
I. Definition of anemia
A. Reduction to below normal blood levels of erythrocytes, hemoglobin (Hgb), or volume of RBCs, caused by blood loss, impaired or failed bone marrow production, or hemolysis or destruction of RBCs
B. Inability of the blood to supply adequate oxygen for proper functioning of the body
C. Classified according to pathophysiologic basis, diminished production, accelerated loss of RBCs, or cell size
II. Incidence/predisposing factors
A. In a healthy person, about 1% of fully mature circulating RBCs are lost daily.
B. Anemia is common among the elderly.
1. Occurs in more than 33% of outpatients
2. Hgb and hematocrit (Hct) decrease slightly with age but remain in the normal adult range.
C. Anemia is a sign, not a diagnosis.
D. Adults residing at higher altitudes have normal values that are higher than those of adults residing at lower altitudes.
E. Plasma volume expansion in fluid-retaining states can mimic the appearance of anemia; conversely, states of dehydration can mimic the appearance of a normal Hct when the patient may actually be anemic.
IV. Physical examination findings
A. Skin and mucous membrane pallor
B. Tachycardia and increased pulse pressure (may be minimal if anemia is slow, progressive)
C. Systolic ejection murmurs
D. Venous hums
E. Peripheral edema
F. Retinal hemorrhages (flamelike) in severe anemia associated with thrombocytopenia
V. Laboratory/diagnostic findings
A. Initially, consider ordering the following:
1. CBC with differential or Hct with mean corpuscular volume (MCV)
2. Reticulocyte count (absolute)
3. Platelet count (or estimate of platelets on smear)
4. Wright-stained blood smear
5. Serum ferritin, serum iron, and total iron-binding capacity (TIBC)
VI. Evaluation/management
A. Diagnosis of the specific cause of anemia should be made before transfusion, if possible.
B. Evaluate Hgb and Hct against normal ranges of patient population.
C. Evaluate reticulocyte count:
1. Absolute reticulocyte count not elevated indicates anemia of marrow failure. This is the most common cause of anemia.
2. Elevated absolute reticulocyte count indicates erythropoietic response to anemia and probable blood loss or hemolysis.
D. Evaluate peripheral blood smear for characteristics.
E. Classify RBC indices according to size or MCV of erythrocytes.
2. Normocytosis is normal MCV (80 to 100 fL).
3. Macrocytosis is increased MCV (greater than 100 fL).
F. Classify RBCs by variation in size from normal red cell size using red cell indices in concert with red cell distribution width (RDW) rating.
1. Normal RDW is 11.5% to 14.5%.
2. Increased RDW may indicate anisocytosis resulting from a heterogeneous mix of cells or poikilocytosis from a variation in cell mix. The type of cell is then specified.
G. Consider bone marrow smear and biopsy. Interpretation requires a differential count of
1. Myeloid, lymphoid, erythroid series, and maturational characteristics
2. Iron stain
H. Specific studies are indicated to rule out specific disease processes.
1. Hgb electrophoresis (hemoglobinopathies, thalassemia syndromes)
2. Antiglobulin testing (hemolytic anemias)
3. Osmotic fragility test (hereditary spherocytosis)
4. Sucrose hemolysis test or acidified serum test (known as Ham’s test) (paroxysmal nocturnal hemoglobinuria)
5. Tests for RBC enzymes (hemolytic anemias, glucose-6-phosphate dehydrogenase [G6PD] deficiency, pyruvate kinase [PK] deficiency)
6. Serum iron and iron-binding capacity (iron deficiency anemia)
7. Folate and vitamin B12 measurements (megaloblastic anemias)
PERNICIOUS ANEMIA
I. Definition
A. A megaloblastic anemia
B. Caused by a lack of intrinsic factor produced by parietal cells of the gastric mucosa; this prevents vitamin B12 absorption, resulting in vitamin B12 deficiency
C. Autoimmune in origin
II. Incidence/predisposing factors
A. May be inherited as an autosomal recessive disorder
1. More common in people of northern European ancestry
2. Rare in African Americans and Asians
B. May be caused by atrophic gastritis, antibodies to gastric parietal cells, or autoimmune histamine-fast achlorhydria
C. Occurs in about 1% of people, usually adults older than age 60
D. Antibodies to intrinsic factor (IF) are detected in about 50% of patients with the disease.
E. The patient may have or develop other, associated autoimmune diseases including the following:
1. Immunoglobulin (Ig)A deficiency
2. Rheumatoid arthritis
4. Myxedema
5. Thyroiditis
6. Idiopathic adrenocortical insufficiency
7. Hypoparathyroidism
8. Agammaglobulinemia
9. Vitiligo
10. Tropical sprue
11. Celiac disease
12. Crohn’s disease
13. Ileum and small intestine infiltrate disorders
F. It takes approximately 3 years for liver stores of vitamin B12 to be depleted after absorption ceases.
G. Predisposition to gastric polyps and stomach cancer
III. Subjective findings
A. Weakness and tiredness
B. Bleeding gums
C. Nausea, appetite loss, and weight loss
D. Sore tongue in about 50% of patients
E. Tingling of hands and feet
F. Difficulty maintaining balance
G. Yellowish tinge to eyes and skin
H. Shortness of breath
I. Poor memory
J. Headache
K. Depression
IV. Physical examination findings
A. Patient is usually pale and may be mildly icteric.
B. Abnormal reflexes
C. Babinski’s sign is positive.
D. Romberg’s sign is positive.
E. Vibratory sensation and proprioception are lost or decreased in lower extremities.
F. Paresthesia and numbness of extremities
G. Ataxia
H. Sense of smell is lost or diminished.
I. Patient may exhibit loss of glossal papillae with tenderness (smooth tongue).
J. Depression or dementia may be present.
K. Splenomegaly
L. Tinnitus
M. Hepatomegaly
N. Tachycardia
O. Congestive heart failure
VI. Management
A. Parenteral vitamin B12, 100-1000 mcg subcutaneously daily for 7 days, then once a week for 1 month, then monthly for the remainder of life
B. Folic acid should not be given without vitamin B12 because of the potential for fulminant neurologic deficit.
C. Hypokalemia may coincide with the first week of vitamin B12 replacement.
D. CNS signs and symptoms are reversible if of short duration (less than 6 months), and if replacement therapy is initiated aggressively and promptly.
E. Endoscopy every 5 years even if asymptomatic (opinion varies in the literature)
VITAMIN B12 DEFICIENCY
I. Definition
A. A megaloblastic anemia caused by deficiency of vitamin B12
B. Usually results from a deficiency of hydrochloric acid or pancreatic enzymes that causes an inability to metabolize vitamin B12
III. Subjective findings
Same as in pernicious anemia (see preceding)
IV. Physical examination findings
Same as in pernicious anemia (see preceding)