Definition

Anemia is defined by the World Health Organization as hemoglobin (Hb)

<13 g/dL (<130 g/L; <8.07 mmol/L) in men or <12 g/dL (<120 g/L; <7.45
mmol/L) in women

Anemia is a group of diseases characterized by a decrease in either Hb or

circulating red blood cells (RBCs), resulting in reduced oxygen-carrying
capacity of the blood

classification
Anemia can be classified on the basis of the morphology of the RBCs,
etiology, or pathophysiology

I. Morphology
Macrocytic anemias

Megaloblastic anemias
Vitamin B 12 deficiency
Folic acid deficiency anemia
Microcytic hypochromic anemias
Iron-deficiency anemia

Genetic anomaly
Sickle cell anemia

Thalassemia
Other hemoglobinopathies (abnormal hemoglobins)
Normocytic anemias
Recent blood loss
Hemolysis
Bone marrow failure
Anemia of chronic disease : Renal failure , Endocrine disorders Myelodysplastic anemias

II. Etiology
Deficiency

Iron
Vitamin B12
Folic acid
Pyridoxine
Central, caused by impaired bone marrow function
Anemia of chronic disease
Anemia of the elderly
Malignant bone marrow disorders
Peripheral

Bleeding (hemorrhage)
Hemolysis (hemolytic anemias)

III. Pathophysiology
Excessive blood loss : Recent hemorrhage;
ulcer; Gastritis; Hemorrhoids

Trauma;

Peptic

Chronic hemorrhage : Vaginal bleeding; Peptic ulcer; Intestinal parasites; Aspirin and
other nonsteroidal antiinflammatory agents
Excessive RBC destruction : Extracorpuscular (outside the cell) factors (RBC
antibodies; Drugs; Physical trauma to RBC (artificial valves); Excessive sequestration
in the spleen); Intracorpuscular factors (Heredity; Disorders of hemoglobin synthesis)
Inadequate production of mature RBCs : Deficiency of nutrients (B 12, folic acid, iron,
protein); Deficiency of erythroblasts(Aplastic anemia; Isolated (often transient);
erythroblastopenia; Folic acid antagonists; Antibodies)

Conditions with infiltration of bone

marrow: Lymphoma; Leukemia;
Endocrine abnormalities:
insufficiency

Myelofibrosis;

Hypothyroidism;

Carcinoma

Adrenal insufficiency;

Pituitary

Chronic renal disease

Chronic inflammatory disease : Granulomatous diseases; Collagen vascular diseases

Hepatic disease

Epidemiology
In the United States approximately 3.5 million Americans have anemia
based on self-reported data from the National Center for Health
Statistics. It is estimated that millions of people are unaware they have
anemia, making it one of the most underdiagnosed conditions in the
United States. Iron deficiency is considered to be the leading cause of
anemia worldwide, accounting for as many as 50% of cases

Data from the National Health and Nutrition Examination Survey

(NHANES) indicates the prevalence of IDA in young children and women
of childbearing age is 1.2% and 4.5%, respectively. 2 The normal ranges for
Hb and Hct are so wide that a patient may lose up to 15% of RBC mass
and still have a Hct within the normal range. Therefore, iron deficiency
may precede the appearance of anemia.

Clinical Presentation of Anemia

General

Patients may be asymptomatic or have vague complaints

Patients with vitamin B 12 deficiency may develop neurologic consequences
In ACD, signs and symptoms of the underlying disorder often overshadow those of the anemia
Symptoms
Decreased exercise tolerance

Fatigue
Dizziness

Irritability
Weakness
Palpitations
Vertigo
Shortness of breath
Chest pain
Neurologic symptoms in vitamin B 12 deficiency

Clinical Presentation of Anemia

Signs
Tachycardia
Pale appearance (most prominent in conjunctivae)

Decreased mental acuity

Increased intensity of some cardiac valvular murmurs
Diminished vibratory sense or gait abnormality in vitamin B 12 deficiency
Laboratory Tests
Hb, hematocrit (Hct), and RBC indices may remain normal early in the disease and then decrease as the anemia progresses
Serum iron is low in IDA and ACD
Ferritin levels are low in IDA and normal to increased in ACD
TIBC is high in IDA and is low or normal in ACD

Mean cell volume is elevated in vitamin B 12 deficiency and folate deficiency

Vitamin B12 and folate levels are low in their respective types of anemia
Homocysteine is elevated in vitamin B 12 deficiency and folate deficiency
Methylmalonic acid is elevated in vitamin B 12 deficiency
Other Diagnostic Tests
Schilling test may help uncover intrinsic factor deficiency
Bone marrow testing with iron staining can indicate low iron levels in IDA and adequate stores in ACD

Goal
The severity and cause of IDA determines the approach to treatment. Treatment is focused on
replenishing iron stores. Because iron deficiency can be an early sign of other illnesses,
treatment of the underlying disease may aid in the correction of iron deficiency.
Primary prevention of IDA in infants, children, and adolescents is the most appropriate goal
because delays in mental and motor development are potentially irreversible
The goals of treatment for vitamin B12 deficiency include reversal of hematologic
manifestations, replacement of body stores, and prevention or resolution of neurologic
manifestations
Therapy for folic acid deficiency consists of administration of exogenous folic acid to induce
hematologic remission, replace body stores, and resolve signs and symptoms
Treatment of ACD depends on the underlying etiology

Patients with anemia of critical illness require the necessary substrates of iron, folic acid, and
vitamin B12 for RBC production. Parenteral iron is generally preferred in this population
because patients often are undergoing enteral therapy or because of concerns regarding
inadequate iron absorption. The disadvantage of parenteral therapy is the theoretical risk of
infection.

Treatment
Dietary Supplementation and Oral Iron Preparations
Parenteral Iron Therapy
Transfusions

Evaluation of Therapeutic Outcomes

A positive response to a trial of oral iron therapy results in a modest reticulocytosis in a few
days, with an increase in Hb around 2 weeks with continued rapid rise in Hb. As the Hb level
approaches normal, the rate of increase slows progressively. A Hb response of <2 g/dL (<20
g/L; <1.24 mmol/L) over a 3-week period warrants further evaluation. Hb should reach a
normal level after 2 months of therapy and often sooner. 10 If the patient does not develop
reticulocytosis, reevaluation of the diagnosis or iron replacement therapy is necessary.
Iron therapy should continue for a period sufficient for complete restoration of iron stores.
Serum ferritin concentrations should return to the normal range prior to discontinuation of
iron. The time interval required to accomplish this goal varies, although at least 6 to 12
months of therapy usually is warranted. Patients with negative iron balances caused by
bleeding may require iron replacement therapy for only 1 month after correction of the
underlying lesion, whereas patients with recurrent negative balances may require long -term
treatment with as little as 30 to 60 mg of elemental iron daily.

When large amounts of parenteral iron are administered, by either total dose infusion or
multiple intramuscular or intravenous doses, the patient's iron status should be closely
monitored. Patients receiving regular intravenous iron should be monitored for clinical or
laboratory evidence of iron toxicity or overload. Iron overload may be indicated by abnormal
hepatic function tests, serum ferritin >800 ng/mL (>800 g/L), or transferrin saturation >50%.
Serum ferritin and transferrin saturation should be measured in the first week after doses of
100 to 200 mg and 2 weeks after larger intravenous iron doses. Hb and Hct should be
measured weekly, and serum iron and ferritin levels should be measured at least monthly.
Serum iron values can be obtained reliably 48 hours after intravenous dosing.

Most patients respond rapidly to vitamin B12 therapy. The typical patient
will experience an improvement in strength and well-being within a few
days. Bone marrow begins to become normoblastic in 2 to 3 days.
Reticulocytosis is evident in 3 to 5 days. Hb begins to rise after the first
week and should normalize in 1 to 2 months. CBC count and serum
cobalamin levels usually are drawn 1 to 2 months after initiation of
therapy and 3 to 6 months thereafter for surveillance monitoring.
Homocysteine and MMA levels should be repeated 2 to 3 months after
initiation of replacement therapy to evaluate for normalization of levels,
although levels begin to decrease in 1 to 2 weeks. Neuropsychiatric signs
and symptoms can be reversible if treated early. If permanent neurologic
damage has resulted, progression should cease with replacement
therapy. Slow response to therapy or failure to observe normalization of
laboratory results may suggest the presence of an additional abnormality
such as iron deficiency, thalassemia trait, infection, malignancy,
nonadherence, or misdiagnosis.

Symptomatic improvement, as evidenced by increased alertness and

appetite, often occur early during the course of treatment.
Reticulocytosis begins in the first week. Hct begins to rise within 2 weeks
and should reach normal levels within 2 months. MCV initially increases
because of an increase in reticulocytes but gradually decreases to normal.