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.
III. Subjective findings
A. Complaints are related to tissue hypoxia and include the following:
1. Dyspnea on exertion that previously had not caused problems
2. Headaches
3. Tinnitus
4. Syncope
5. Dizziness
6. Fatigue, weakness
7. Sleep disturbance
8. Mood disturbance
9. Impaired concentration
10. Jaundice and hepatosplenomegaly
11. Neurologic manifestations
12. Increased frequency of angina pectoris
B. Dementia or intermittent claudication may be exacerbated.
C. Anorexia and weight loss
D. If anemia has developed very slowly, the patient may be asymptomatic.
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.
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:
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
V. Laboratory/diagnostic findings
A. Vitamin B12 deficiency is a megaloblastic anemia.
1. Macrocyte with MCV is usually 110 to 140 fL but may be in normal range if concurrent with iron deficiency or thalassemia.
2. RDW is increased.
B. Hct may be 10 to 15 ml/dl low.
C. Peripheral blood smears usually exhibit macro-ovalocytes, anisocytosis, and poikilocytosis with hypersegmented neutrophils present (more than four lobes, sometimes six lobes).
D. Reticulocyte count is usually reduced.
E. In severe cases, pancytopenia is present with WBC and platelet count reduced.
F. Serum folate is usually increased in vitamin B12 deficiency.
G. Decreased serum vitamin B12
1. Less than 100 pg/ml is symptomatic.
2. 170 to 240 pg/ml is borderline.
3. Greater than 240 pg/ml is normal.
H. Red cell folate is usually decreased in vitamin B12 deficiency.
I. Serum ferritin is increased.
J. Lactate dehydrogenase (LDH) may be elevated. (Often, it is mistakenly assumed that anemia is hemolytic.)
K. Consider ordering the following:
1. Anti-IF and anti–parietal cell antibodies (presence affirms deficiency)
2. Schilling’s test (used only when it is unclear why the patient is vitamin B12 deficient because of the expense of the test)
3. Gastric analysis for achlorhydria
L. Megaloblastosis of the bone marrow characteristically is present.
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
II. Incidence/predisposing factors
A. Vegans and strict vegetarians are at risk.
B. Major cause is malabsorption that results from diseases of the ileum or enteritis.
C. Blind loop syndrome
D. Drugs such as alcohol, anesthetics, metformin, nitrous oxide, and the antituberculosis drug para-aminosalicylic acid (PASA)
E. Hemodialysis
F. Fish tapeworm (Diphyllobothrium latum)
G. Because storage of vitamin B12 is normally high and body utilization is low, deficiency takes about 2 to 7 years to develop in the case of malabsorption.
H. Nutritional vitamin B12 deficiency is rare in the U.S.
III. Subjective findings
Same as in pernicious anemia (see preceding)
Full access? Get Clinical Tree
