Anemias Pharmacotherapy

  • View

  • Download

Embed Size (px)



Text of Anemias Pharmacotherapy

  • Anemia is defined by the World Health Organization as hemoglobin (Hb)
  • Anemia can be classified on the basis of the morphology of the RBCs, etiology, or pathophysiology


  • Macrocytic anemias

    Megaloblastic anemias

    Vitamin B12 deficiency

    Folic acid deficiency anemia

    Microcytic hypochromic anemias

    Iron-deficiency anemia

    Genetic anomaly

    Sickle cell anemia


    Other hemoglobinopathies (abnormal hemoglobins)

    Normocytic anemias

    Recent blood loss


    Bone marrow failure

    Anemia of chronic disease : Renal failure , Endocrine disorders Myelodysplastic anemias

    I. Morphology

  • Deficiency


    Vitamin B12

    Folic acid


    Central, caused by impaired bone marrow function

    Anemia of chronic disease

    Anemia of the elderly

    Malignant bone marrow disorders


    Bleeding (hemorrhage)

    Hemolysis (hemolytic anemias)

    II. Etiology

  • Excessive blood loss : Recent hemorrhage; Trauma; Peptic ulcer; Gastritis; Hemorrhoids

    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 (B12, 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; Myelofibrosis; Carcinoma

    Endocrine abnormalities: Hypothyroidism; Adrenal insufficiency; Pituitary insufficiency

    Chronic renal disease

    Chronic inflammatory disease : Granulomatous diseases; Collagen vascular diseases

    Hepatic disease

    III. Pathophysiology

  • 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.


  • General

    Patients may be asymptomatic or have vague complaints

    Patients with vitamin B12 deficiency may develop neurologic consequences

    In ACD, signs and symptoms of the underlying disorder often overshadow those of the anemia


    Decreased exercise tolerance







    Shortness of breath

    Chest pain

    Neurologic symptoms in vitamin B12 deficiency

    Clinical Presentation of Anemia

  • Signs


    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 B12 deficiency and folate deficiency

    Vitamin B12 and folate levels are low in their respective types of anemia

    Homocysteine is elevated in vitamin B12 deficiency and folate deficiency

    Methylmalonic acid is elevated in vitamin B12 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

    Clinical Presentation of Anemia

  • 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.


  • Dietary Supplementation and Oral Iron Preparations

    Parenteral Iron Therapy



  • 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
  • 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.