Macrocytic/Megaloblastic Anemia

reticulocyte < 100,000 uL

B12/folic acid deficiency drugs

Compare and contrast the morphological characteristics of megaloblasts and normoblasts.

Megaloblasts are large cells with increased RNA per DNA unit. Their nuclear chromatin appears loose and less mature than the nuclear chromatin of normoblasts at the same stage of maturation.

Characterize the peripheral blood morphology of megaloblastic anemia.

RBCs are macrocytic and normochromic. Depending on the degree of anemia, the MCV may range from 100-160 fL. The MCH is elevated but the MCHC is normal. Red cell inclusions such as Howell-Jolly bodies and basophilic stippling are frequently present. Hypersegmented neutrophils are seen in the peripheral smear in 98% of cases.

List other causes of macrocytic nonmegaloblastic anemias.

The most common causes of macrocytic anemia are chronic liver disease and alcoholism. Macrocytosis has also been reported in patients taking immunosuppressive drugs as well as arsenic and chlordane intoxification.

List the causes of vitamin B12 and folate deficiencies.

Vitamin B12 deficiency can be caused by dietary deficiency, malabsorption, or pernicious anemia. The main cause of folic acid deficiency is decreased dietary intake. Other causes are malabsorption, increased requirement, and drug-induced folate deficiencies.

peripheral blood smear w/ target cells =

liver disease

Define megaloblastic anemia.

Megaloblastic anemia is a subgroup of macrocytic anemia characterized by defective nuclear maturation caused by impairs DNA synthesis. This defect is manifested by the presence of megaloblasts (large and abnormal red cell precursors) in the bone marrow and macro-ovalocytes in the peripheral blood.

Compare and contrast the treatment for vitamin B12 and folate deficiencies.

Most people with a vitamin B12 deficiency require lifelong vitamin therapy. Cyanocobalamin and hydroxocobalamin are the two therapeutic forms of vitamin B12. The recommended therapeutic dose to treat folate deficiency is 1-5 mg/day for two to three weeks. Lifelong therapy is not required because it is usually possible to treat folate deficiency within a short period of time.

acute megaloblastic anemia

NO toxicity severe illness complicated by dialysis, exposure to weak folate antagonists, TPN w/ out folate replacement

Identify the bone marrow morphology of megaloblastic anemia.

Patients with megaloblastic anemia have a hypercellular bone marrow. The myeloid-to-erythroid (M:E) ratio is decreased and may be as low as 1:1 to 1:3.

Describe pernicious anemia, including the pathophysiology and clinical and laboratory findings.

Pernicious anemia is the most common cause of vitamin B12 deficiency. It is a chronic disease caused by the deficiency of intrinsic factor (IF). Patients with pernicious anemia have all the signs and symptoms of megaloblastic anemia, as well as fever, loss of appetite, and glossitis (sore tongue).

Describe the Schilling test as a diagnostic tool for pernicious anemia.

The Schilling test evaluates the pathophysiology of vitamin B12 malabsorption. part 1: patient given small amount of radioactive B12 orally, then a flushing dose 2 hours later; amount of radioactive B12 is then measured in a 24-hour urine collection part 2: test is repeated with addition of IF to the oral dose to determine if malabsorption is caused by the lack of IF

Evaluate laboratory tests used for the diagnosis of megaloblastic anemia.

The most common laboratory screening tests and results that are used in the diagnosis of megaloblastic anemias are low hemoglobin level, elevated MCV, and peripheral smear morphology (such as macro-ovalocytes and hypersegmented neutrophils).

megaloblastic anemia

characterized by impaired DNA synth - asynchrony in nuclear-cytoplasmic maturation - megaloblastic cells (hallmark) - ineffective myelopoiesis --> anemia leucopenia and thrombocytopenia (pancyopenia) - intramedullary hemolysis and cell death

causes of megaloblastic anemia

folic acid def B12 def inborn errors of B12/folate metabolism drugs interfere w/ DNA synth congenital dyserythropoietic anemias dysplastic marrow syndromes

reticulocyte > 100,000 uL

hemolytic anemia w/ retic increase

folate deficiency clinical features

indistinguishable form B12 def peripheral neuritis maybe neural tube defects in fetus

peripheral blood findings in megaloblastic anemia

macro ovalocytes Howell-jolly body Basophilic stippling low WBC low platelets (w/ pancytopenia) hypersegmentation of granulocytes (>5 lobes) low retic count - ineffective erythropoiesis

parietal cell and IF AB positive =

pernicious anemia

mechanisms of macrocytosis

reticulocytes MCV 103-126 membrane changes of RBC interference w/ DNA synthesis

Using the peripheral blood findings, differentiate the anemia of liver disease from a megaloblastic anemia caused by vitamin B12 or folate deficiency.

- In macrocytic, normoblastic anemias, the MCV is more than 100 fL but not as high as in megaloboastic anemias (where the MCV is more than 110 fL). - The red cells on the peripheral blood smear appear large and round, but not oval. - The neutrophils are not hypersegmented. - The bone marrow is normocellular or hypercellular with erythroid hyperplasia.

B12 deficiency clinical features

1. anemia w/ mild jaundice 2. GI sx 3. neuro 4. skin/hair pigment changes (aging) 5. skeletal (osteoporosis)

causes of B12 deficiency

1. decreased intake 2. impaired absorption - gastric abnorm

causes of folate deficiency

1. decreased intake 2. impaired absorption 3. increased requirement 4. drugs/toxins

causes of macrocytosis

1. interference w/ DNA synthesis 2. increased membrane surface 3. reticulocytosis 4. alcohol

pernicious anemia

B12 def (most common) megalobalstic anemia w/ pancytopenia neuro disease (post/lat column axonal degen)

hypersegmented PMN =

B12/folate deficiency

homocysteine increased =

B12/folic acid deficiency