Download pdf - Anemias Pharmacotherapy

7/17/2019 Anemias Pharmacotherapy

http://slidepdf.com/reader/full/anemias-pharmacotherapy 1/27



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; <7.45mmol/L) in women

Anemia is a group of diseases characterized by a decrease in either Hb orcirculating red blood cells (RBCs), resulting in reduced oxygen-carrying

capacity of the blood

Definition



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

classification



Macrocytic anemiasMegaloblastic anemias

Vitamin B 12 deficiency

Folic acid deficiency anemia

Microcytic hypochromic anemias

Iron-deficiency anemiaGenetic 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

I. Morphology





DeficiencyIron

Vitamin B 12

Folic acid

PyridoxineCentral, caused by impaired bone marrow function

Anemia of chronic disease

Anemia of the elderly

Malignant bone marrow disordersPeripheral

Bleeding (hemorrhage)

Hemolysis (hemolytic anemias)

II. Etiology







Excessive blood loss : Recent hemorrhage; Trauma; Pepticulcer; Gastritis; Hemorrhoids

Chronic hemorrhage : Vaginal bleeding; Peptic ulcer; Intestinal parasites; Aspirin andother nonsteroidal antiinflammatory agents

Excessive RBC destruction : Extracorpuscular (outside the cell) factors (RBCantibodies; 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 bonemarrow : Lymphoma; Leukemia; Myelofibrosis; Carcinoma

Endocrine abnormalities : Hypothyroidism; Adrenal insufficiency; PituitaryinsufficiencyChronic renal disease

Chronic inflammatory disease : Granulomatous diseases; Collagen vascular diseases

Hepatic disease

III. Pathophysiology



In the United States approximately 3.5 million Americans have anemiabased on self-reported data from the National Center for HealthStatistics. It is estimated that millions of people are unaware they haveanemia, making it one of the most underdiagnosed conditions in theUnited States. Iron deficiency is considered to be the leading cause ofanemia 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 womenof childbearing age is 1.2% and 4.5%, respectively. 2 The normal ranges forHb and Hct are so wide that a patient may lose up to 15% of RBC massand still have a Hct within the normal range. Therefore, iron deficiency

may precede the appearance of anemia.

Epidemiology



GeneralPatients 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



SignsTachycardia

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 B 12 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

Clinical Presentation of Anemia







The severity and cause of IDA determines the approach to treatment. Treatment is focused onreplenishing 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 goalbecause delays in mental and motor development are potentially irreversible

The goals of treatment for vitamin B12 deficiency include reversal of hematologicmanifestations, replacement of body stores, and prevention or resolution of neurologicmanifestations

Therapy for folic acid deficiency consists of administration of exogenous folic acid to inducehematologic 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, andvitamin B12 for RBC production. Parenteral iron is generally preferred in this populationbecause patients often are undergoing enteral therapy or because of concerns regardinginadequate iron absorption. The disadvantage of parenteral therapy is the theoretical risk ofinfection.

Goal



Dietary Supplementation and Oral Iron PreparationsParenteral Iron Therapy

Transfusions

Treatment

















A positive response to a trial of oral iron therapy results in a modest reticulocytosis in a fewdays, with an increase in Hb around 2 weeks with continued rapid rise in Hb. As the Hb levelapproaches normal, the rate of increase slows progressively. A Hb response of <2 g/dL (<20g/L; <1.24 mmol/L) over a 3-week period warrants further evaluation. Hb should reach anormal level after 2 months of therapy and often sooner. 10 If the patient does not developreticulocytosis, 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 ofiron. The time interval required to accomplish this goal varies, although at least 6 to 12months of therapy usually is warranted. Patients with negative iron balances caused bybleeding may require iron replacement therapy for only 1 month after correction of theunderlying lesion, whereas patients with recurrent negative balances may require long-termtreatment 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 ormultiple intramuscular or intravenous doses, the patient's iron status should be closelymonitored. Patients receiving regular intravenous iron should be monitored for clinical orlaboratory 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 of100 to 200 mg and 2 weeks after larger intravenous iron doses. Hb and Hct should bemeasured 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.

Evaluation of Therapeutic Outcomes



Most patients respond rapidly to vitamin B12 therapy. The typical patientwill experience an improvement in strength and well-being within a fewdays. 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 firstweek and should normalize in 1 to 2 months. CBC count and serumcobalamin levels usually are drawn 1 to 2 months after initiation oftherapy and 3 to 6 months thereafter for surveillance monitoring.Homocysteine and MMA levels should be repeated 2 to 3 months afterinitiation of replacement therapy to evaluate for normalization of levels,although levels begin to decrease in 1 to 2 weeks. Neuropsychiatric signsand symptoms can be reversible if treated early. If permanent neurologicdamage has resulted, progression should cease with replacementtherapy. Slow response to therapy or failure to observe normalization oflaboratory results may suggest the presence of an additional abnormalitysuch as iron deficiency, thalassemia trait, infection, malignancy,nonadherence, or misdiagnosis.



Symptomatic improvement, as evidenced by increased alertness andappetite, often occur early during the course of treatment.Reticulocytosis begins in the first week. Hct begins to rise within 2 weeksand should reach normal levels within 2 months. MCV initially increasesbecause of an increase in reticulocytes but gradually decreases to normal.

