Hematopoietic Drugs

Chapter 17 Hematopoietic Drugs

I. General Considerations

A. Causes of anemia

1. Failure to produce sufficient red blood cells (RBCs)

2. Inadequate synthesis of hemoglobin

3. Destruction of RBCs

4. Bleeding

Iron deficiency due to bleeding is the most common cause of anemia

B. Classification by mean corpuscular volume (MCV)

1. Different conditions may lead to the development of the various types of anemia (Table 17-1)

2. Microcytic

a. Smaller than normal RBCs and decreased MCV (<80 µm³)

Table 17-1 Etiology of Anemia

Types of Anemia	Specific Cause/Pathophysiology
Microcytic Anemia
Iron deficiency anemia	Increased need (e.g., growth, pregnancy, menstruation) Blood loss (e.g., gastrointestinal bleeding) Inadequate dietary intake Malabsorption
Anemia of chronic disease	Chronic infection, cancer, or liver disease Failure of increase in red blood cell production due to sequestration of iron in reticuloendothelial system in the bone marrow
Thalassemia	Hereditary disorder characterized by decreased globin chain production
Megaloblastic Anemia
Folic acid deficiency anemia	Inadequate dietary intake Increased need during pregnancy Interference with utilization by other drugs (phenytoin, primidone, and phenobarbital; oral contraceptives; isoniazid) Malabsorption syndromes (e.g., high rates of cell turnover as in hemolytic anemia or alcoholism, or poor liver function)
Vitamin B₁₂ deficiency anemia	Pernicious anemia (lack of intrinsic factor [IF]), which may occur following gastrectomy Lack of receptors for IF-vitamin B₁₂ complex in ileum Fish tapeworm infestations Crohn’s disease/ileotomy
Normocytic Anemia
Anemia due to bone marrow failure	Myelofibrosis and multiple myeloma: direct effects Myelosuppressive chemotherapy Deficiency of hematopoietic growth factors and hormones (as in chronic renal failure) Aplastic anemia

Microcytic anemia; MCV less than 80 µm³

b. Iron deficiency, anemia of chronic disease, and thalassemia (α and β) result in small RBCs with insufficient hemoglobin (microcytic hypochromic anemia)

Microcytic anemia is most commonly due to iron deficiency.

3. Macrocytic

a. Larger than normal RBCs and increased MCV (>100 µm³)

Macrocytic anemia; MCV greater than 100 µm³

b. Both folic acid deficiency and vitamin B₁₂ deficiency cause impaired production and nuclear maturation of erythroid precursors (macrocytic hyperchromic or megaloblastic anemia).

• Problems also occur with nuclear maturation of other hematopoietic elements (e.g., neutrophils).

Macrocytic anemia due to folic acid and/or vitamin B₁₂ deficiency.

4. Normocytic

a. Normal sized RBCs and normal MCV (80−100 µm³)

b. Causes include:

(1) Renal failure

• Decreased synthesis of erythropoietin (EPO)

(2) Aplastic anemia

• Suppression of hematopoiesis

(3) Acute/chronic blood loss

(4) Hemolytic anemia

• Destruction of RBCs

(5) Early stages of iron deficiency and anemia of chronic disease

• Both are normocytic before they are microcytic

Normocytic anemia due to: decreased EPO; aplastic anemia; blood loss; hemolytic anemia.

C. Agents used to treat anemia (Box 17-1)

II. Minerals

• Iron

A. Role of iron

1. Requirement for the synthesis of hemoglobin and myoglobin

2. Cofactor in many enzymes (e.g., cytochromes in the liver)

B. Causes of iron deficiency (see Table 17-2)

C. Clinical use

1. Treatment and prevention of iron deficiency anemia

2. Preparations

a. Oral preparations

• Preferred

TABLE 17-2 Causes of Iron Deficiency Anemia

Classification	Causes	Discussion
Blood loss	Gastrointestinal loss	Meckel’s diverticulum (older children) PUD (most common cause adult men) Gastritis (e.g., NSAID) Hookworm infestation Polyps/colorectal cancer (most common cause in adults >50-yrs-old); positive stool for blood.
	Menorrhagia	Most common cause in women <50-yrs-old
Increased utilization	Pregnancy/lactation	Daily iron requirement in pregnancy is 3.4 mg and 2.5-3.0 mg in lactation Net loss of 500 mg of iron if not on iron supplements
	Infants/children	Iron required for tissue growth and expansion of blood volume
Decreased intake	Prematurity Infants/children	Loss of iron each day fetus is not in utero Blood loss from phlebotomy Most common cause of iron deficiency in young children
	Elderly	Restricted diets with little meat (lack of heme iron)
Decreased absorption	Celiac sprue	Absence of villous surface in the duodenum
Intravascular hemolysis	Microangiopathic hemolytic anemia	Chronic loss of Hb in urine leads to iron deficiency