Macrocytic and Normocytic Anemia Flashcards
what are the 2 forms of anemia with macrocytosis and which is more common?
megaloblastic anemia (most common)
non-megaloblastic anemia
what is characteristic of a megaloblast? where can it be seen? what is the cause?
changes seen in cytoplasm of maturing erythrocyte is not in sync - due to impaired DNA synthesis
see immature nucleus (chromatin remodeling still occurring) in mature cytoplasm (hemoglobin present)
erythroid precursor - need a bone marrow sample to identify megaloblast (will not see in blood smear)
how can you diagnose megaloblastic anemia from a peripheral blood smear, given that megaloblasts are only found in bone marrow?
megaloblasts (erythroid precursors) are caused by impaired DNA synthesis, which also impacts WBC maturation
can see hyper-segmented / hyper-lobular neutorphils
megaloblastic anemia is due to impaired DNA synthesis, and is usually acquired
what is the most common etiology?
problem: RNA synthesis proceeds generating cytoplasmic contents —> mature RBC are larger than normal
most common etiology is nutritional: B12 deficiency or folate deficiency
can also occur with certain medications (drugs that impair pyrimidine or purine synthesis)
hydroxyurea, methotrexate, azathioprine, and mycophenolate mofetil are all drugs (medications) that can cause what kind of anemia?
what do these drugs do?
medications that impair pyrimidine or purine synthesis can cause megaloblastic anemia
impair pyrimidine synthesis: hydroxyurea, methotrexate
impair purine synthesis: azathioprine, mycophenolate mofetil
What is the function of vitamin B12 and where does it come from? What is its relationship to anemia?
Vitamin B12 (cobalamin) - essential vitamin acquired in diet via animal products or fortified cereals but NOT PLANTS, body stores last 1-2+ years
required for:
1. synthesis of methionine from homocysteine (DNA synthesis)
2. synthesis of succinyl CoA form methylmalonyl CoA (TCA)
3. myelin synthesis
B12 (cobalamin) deficiency causes anemia (acquired megaloblastic)
*note that B12 deficiency can also cause neurological symptoms (via axonal demyelination) - muscle weakness, numbness, impaired vibration sense
what causes anemia in megalobastic anemia?
megaloblasts (defective erythroid precursors) undergo apoptosis in bone marrow
macrocytes are also fragile, rigid —> shortened life span of RBC
B12 deficiency can cause anemia. How can it be diagnosed?
specify for signs/symptoms, CBC, and peripheral smear
- signs of anemia with or without neurological injury (B12 needed for myelination)
- CBC: low Hgb/HCT, high MCV, low reticulocyte
- peripheral smear: hyper-segmented neutrophils
Increased homocysteine and increased methyl-malonyl CoA indicate a ____ deficiency
which may lead to what pathology?
B12 (cobalamin) deficiency, because it is required for:
1. homocysteine —> methionine (DNA synthesis)
- methylmalonyl CoA —> succinyl CoA (TCA)
B12 deficiency can cause anemia (acquired megaloblastic)
where do we get folate, and what is it required for?
what kind of anemia can folate deficiency cause?
folate: essential vitamin found in most foods, body stores last 2-4 months (less with alcohol use)
required for DNA synthesis (transfers one carbon units) - conversion of homocysteine to methionine, pyrimidine synthesis (dTMP), purine synthesis
folate deficiency (like B12) can cause acquired megaloblastic anemia
both folate and B12 deficiency result in what….?
but how do you distinguish?
both folate and B12 deficiency:
- increased homocysteine
- identical hematological abnormalities (hyper-segmented neutrophils)
- acquired megaloblastic anemia
ONLY B12:
- increased methyl-malonic acid (B12 needed to make succinyl Co-A)
- neurological symptoms associated with demyelination
in anemia with low reticulocytes, hyper segmented neutrophils indicate:
a. non-megaloblastic anemia
b. megaloblastic anemia
b. megaloblastic anemia: due to impaired DNA synthesis, most commonly caused by B12 or folate deficiency
myelodysplastic syndrome and cause
clonal disorder - low production (cytopenia) of non-megaloblastic macrocytic anemia
causes: excess alcohol use (with normal folate/B12), liver disease, splenectomy (causes increased RBC membrane)
what kind of anemia does this describe?
- macrocytic anemia (high MCV)
- low reticulocyte count
- low neutrophil count
- PMNs have abnormal cell morphology (dysplasia) and defective function - nuclear hypolobation or bilobed nucleus
myelodysplastic syndrome - non-megaloblastic macrocytic anemia
nuclear hypolobation - less lobules in granulocytes (bilobed nucleus is key marker)
when anemia is present (low Hgb/Hct), but reticulocytes are not increased, and MCV and RBC morphology are normal, what are the possible causes of the anemia? (3)
(this would be normocytic anemia, MCV is 80-100fL)
- chronic kidney disease is causing decrease in erythropoietin (EPO) —> less RBC are made
- early iron deficiency or anemia of chronic disease - ferritin will decrease before cell size/shape begin to change
- bone marrow failure (rare)
a rare event that could cause normocytic anemia (MCV is 80-100fL) is bone marrow (hematopoietic) failure, which can present as either only RBC count being low, or….
describe how this presents and is diagnosed
pancytopenia: all cell counts are decreased, bone marrow is hypocellular (“dry tap”) —> aplastic anemia
causes: chemicals/drugs, irradiation, autoimmunity
diagnosis is from low RBC, platelets, and WBCs —> anemia, thrombocytopenia, neutropenia
*requires biopsy because of “dry tap”
myelophisthic anemia
bone marrow has been invaded by a disease - most commonly metastatic cancer
causes normocytosis anemia (MCV is 80-100fL) via pancytopenia (all cell counts decreased)
what are the key features of normocytic anemia due to red cell aplasia? (3)
- anemia with very low (practically 0) reticulocyte count
- absence of erythroid precursors in bone marrow
- presumptive immune-mediated damage
the cause of primary pure red cell aplasia (normocytic anemia) is idiopathic, but what causes secondary pure red cell aplasia? (2 are particularly important)
- lymphocyte disorders (leukemia)
- autoimmune disorders (lupus)
- medications
important:
- infection by parvovirus B19
- thymoma (cancer) - can cause autoantibodies against RBC
how is parvovirus B19 related to development of anemia?
parvovirus B19: nonenveloped ssDNA virus, attacks RBC progenitors, transiently stopping erythropoiesis —> no antibodies, no CTL
however, in patients with hemolytic anemia (RBC lifespan is short), infection can cause aplastic crisis
parvovirus B19 is cause of secondary pure red cell aplasia - normocytic anemia
