Agents Used in Anemias - Sweatman 03.17.15

Question 1

What is the most common cause of chronic anemia? Describe the associated symptoms.

Answer 1

• Iron deficiency
• Symptoms:
  1. Pallor, fatigue, dizziness, exertional dyspnea
  2. Generalized symptoms of tissue hypoxia
  3. CV adaptations: tachycardia, increased cardiac output, vasodilation -> can worsen condition of pts with underlying CVD

Question 2

Briefly describe how iron deficiency causes microcytic hypochromic anemia.

Answer 2

• Hemoglobin (Hb) = iron-protoporphyrin + globin
• Hb reversibly binds oxygen, providing mechanism for delivery of O2 from lungs to other tissues -> w/o adequate iron, small Hb-deficienyt erythrocytes formed

Question 3

Where does the iron needed to support hematopoiesis come from?

Answer 3

• Mostly reclaimed from catalysis of hemoglobin in senescent or damaged erythrocytes
• Dietary requirements: small and easily fulfilled by variety of foods

Question 4

How much iron is lost from the body each day?

Answer 4

Normally, only a small amount

Question 5

Patients with an unexplained iron deficiency anemia should be evaluated for…?

Answer 5

• Occult gastrointestinal bleed
• In men and postmenopausal women, the most common site of blood loss is the GI tract

Question 6

What types of people might have iron requirements that exceed normal dietary supplies?

Answer 6

• Growing children and pregnant or menstruating women
• Might devo iron deficiency

Question 7

What two drugs are used for oral iron therapy?

Answer 7

• Ferrous iron is most efficiently absorbed, and only ferrous salts should be given:
  1. Ferrous sulfate
  2. Ferrous gluconate
• Both are inexpensive and recommended for the tx of most pts.

Question 8

How much oral iron should be given daily? Why? How long should treatment be continued?

Answer 8

• 50–100 mg of iron can be incorporated into Hb daily, and 25% of oral iron given as ferrous salt absorbed, so 200–400 mg of elemental iron should be given daily to correct iron deficiency most rapidly
• Pts unable to tolerate lg doses of iron can be given lower daily doses, which results in slower, but still complete correction of iron deficiency
• Tx continued for 3–6 months after correction of cause of iron loss -> corrects the anemia and replenishes iron stores

Question 9

What are the toxic effects of oral iron therapy?

Answer 9

• Nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea
  1. Usually dose-related and can often be overcome by lowering daily dose of iron or by taking tablets immediately after or with meals
• Some pts have less severe GI AEs with one iron salt than another and benefit from changing preparations
• Pts develop black stools, which may obscure dx of continued GI blood loss

Question 10

Why would you use parenteral iron therapy? Provide some examples.

Answer 10

• For those unable to tolerate oral dosing
• Pts w/extensive chronic anemia not maintained w/oral iron alone
  1. Advanced chronic renal disease requiring hemodialysis and treatment with erythropoietin
  2. Various postgastrectomy conditions
  3. Previous small bowel resection
  4. Inflam bowel disease involving prox sm bowel
  5. Malabsorption syndromes

Question 11

What is the problem with parenteral administration of ferric iron? How is this resolved?

Answer 11

• Parenteral admin of inorganic free ferric iron produces serious dose-dependent toxicity
  1. Severely limits dose that can be administered
• Solution: iron dextran (IV & IM), a sodium ferric gluconate complex [Ferriecit]

Question 12

What are the toxic effects of parenteral iron therapy?

Answer 12

• IV Iron dextran therapy: headache, light-headedness, fever, arthralgias, N/V, back pain, flushing, urticaria, bronchospasm
  1. Anaphylaxis & death w/high mol. wt. products (RARELY) -> small test dose always given (hx of allergy and prev exposure add’l risk factors)
• Other preps less likely to cause hypersensitivity rxns
• Pts monitored for iron overload b/c bypass absorptive regulatory processes governing oral absorption
  1. Iron stores estimated via serum concentrations of ferritin and the transferrin saturation (ratio of total serum iron concentration to TIBC)

Question 13

What does acute iron toxicity look like in young children?

Answer 13

• Iron tablets look like candy, and as few as 10 tablets can be fatal to a child
• Causes necrotizing gastroenteritis
  1. Vomiting & abdominal pain
  2. Bloody diarrhea
  3. Shock, lethargy & dyspnea
  4. Initial improvement often followed by severe metabolic acidosis, coma, and death

Question 14

What does detoxification for iron toxicity look like?

Answer 14

• Whole bowel irrigation: activated charcoal does NOT bind – INEFFECTIVE
• Deferoxamine [Desferal], IV iron-chelating compound

1. Doesn’t effectively chelate other trace metals
2. Excreted in urine and bile -> red urine
3. Tachycardia, hypotension, and shock
4. Could add to CV collapse caused by iron toxicity
5. Abdominal discomfort, N/V, and diarrhea, which may add to symptoms of acute iron toxicity

Question 15

Describe chronic iron overload and its treatment.

Answer 15

• Hemochromatosis: excess iron deposited in heart, liver, pancreas, and other organs -> can lead to organ failure and death

1. Most commonly inherited excessive iron absorption
2. Pts who receive many RBC transfusions over a long period of time (e.g., pts w/thalassemia major)

• Best tx for chronic iron overload in absence of anemia intermittent phlebotomy (1 unit blood removed e/week)

Question 16

What is Vitamin B12? What is the most common cause of its deficiency, and what are the 3 main symptoms?

Answer 16

• Vit B12 (cobalamin) a cofactor for several essential biochemical reaction
  1. Deficiency leads to 1) megaloblastic anemia, 2) GI symptoms, & 3) neurologic abnormalities
• Deficiency due to inadequate supply in diet unusual
  1. Deficiency in adults—especially older adults—due to inadequate absorption is a relatively common and easily treated disorder

Question 17

What symptoms are associated with Vitamin B12 deficiency?

Answer 17

• Megaloblastic macrocytic anemia

1. Associated mild or moderate leukopenia or thrombocytopenia (or both)
2. Characteristic hypercellular bone marrow with accumulation of megaloblastic erythroid and other precursor cells

• Neurologic syndrome
  1. Paresthesia in peripheral nerves, weakness that progresses to spasticity, ataxia, CNS dysfunctions
  2. Correction of deficiency stops progression of neurologic disease, but may not fully reverse symptoms that have been present for months
• NOTE: occasional pts have few, if any hematologic abnormalities

Question 18

What are the common and rare causes of Vitamin B12 deficiency?

Answer 18

• Common
  1. Pernicious anemia
  2. Partial or total gastrectomy and other conditions that affect distal ileum: malabsorption syndromes, IBS, and sm bowel resection
• Rare
  1. Bacterial overgrowth of small bowel
  2. Chronic pancreatitis
  3. Thyroid disease
  4. Children: secondary to congenital deficiency of IF or to defects of receptor sites for B12-IF complex located in the distal ileum

Question 19

Why is B12 deficiency frequently treated parenterally? How is it available for tx (what 2 forms)?

Answer 19

• B/c most cases caused by malabsorption, parenteral injections required for therapy
• For pts with potentially reversible diseases, underlying disease treated after initial tx w/parenteral B12 (most pts do not have curable syndromes and require lifelong tx)
• Available as cyanocobalamin or hydroxocobalamin
  1. Hydroxocobalamin is preferred b/c more highly protein-bound, and remains longer in circulation

Question 20

Why is folic acid important?

Answer 20

• Reduced forms of folic acid are required for essential biochemical reactions
• Provides precursors for the synthesis of amino acids, purines, and DNA
• Deficiency not uncommon, and easily corrected by admin of folic acid

Question 21

Who might be deficient in folic acid?

Answer 21

• Often found in alcoholics and those w/liver disease: poor diet and diminished hepatic storage of folates
• Pregnant women and pts with hemolytic anemia have increased requirements and may become folic acid (FA)-deficient, esp. if their diets are marginal
  1. Evidence implicates maternal FA deficiency in fetal neural tube defects, e.g., spina bifida
• Pts with malabsorption syndromes also frequently develop folic acid deficiency
• Renal dialysis removes folate from the plasma; supplementation needed

Question 22

Describe oral folic acid therapy.

Answer 22

• Oral absorption high, even in pts w/malabsorption syn
  1. 1 mg orally daily can reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores in almost all pts
  2. Continue therapy until underlying cause of the deficiency is removed or corrected
  3. Continue indefinitely for pts w/malabsorption or dietary inadequacy
• Supplementation should be considered in high-risk patients, including pregnant women, pts with alcohol dependence, hemolytic anemia, liver disease, certain
  skin diseases, and pts on renal dialysis