Macrocytic Anemia Flashcards
Reticulocyte Production Index
RPI less than 2 indicates that the patient’s bone marrow is not making enough reticulocytes
RPI over 3 indicates that the marrow is responding appropriately to the anemia and making enough
Macrocytosis
MCV > 100
Usually Associated with Hypoproduction
30 - 50 percent patients may not be anemic
Result of:
Lipid deposition on cell membrane
Altered nuclear growth in presence of normal hemoglobin and cytoplasmic development
DDx of Macrocytosis
Folate/B12 deficiency Chronic Liver Disease Alcoholism Chemotherapy Reticulocytosis Myelodysplastic Idiopathic Distance runners Hypothyroidism Hyperlipidemia
Evaluation of Macrocytosis
History
Physical
Rule Out a False Macrocytosis
Cold agglutinins: RBC clumping
Hyperglycemia: Hyperosmolarity
Leukocytosis: WBC counted as RBC
Ask about Alcohol History Reticulocyte Count B12 / Folate: look for hypersegmented neutrophils Thyroid Studies: if clinically indicated Liver Associated Enzymes
Causes of Anemia
- Due to Decreased RBC Production
- Due to Increased RBC Destruction
- Blood Loss
Normal RDW and High MCV
Aplastic Anemia
Myelodysplasia
Alcohol
High RDW and High MCV
B12/Folate
Autoimmune hemolysis
Cold Agglutinins
Macrocytosis: Drugs Associated
- Chemotherapy
- Purine Antagonists: Acyclovir
3. Altered Folate Metabolism Oral Contraceptives Anticonvulsants Triamterene Sulfonamides Pentamidine
- Cobalamin Malabsorption
Colchicine
Neomycin - Impaired Cobalamin utilization: Nitrous Oxide
Alcohol
Vast Majority of Alcoholics have Macrocytosis
Does NOT Require B12 or Folate Deficiency
Though Often Present
Unclear Etiology
Important to Delineate Drinking History
Megaloblastic Anemia
Vitamin B12 and Folate Deficiency
Anemia
Macrocytes
Hypersegmented Neutrophils: neutrophil with > 5 segments
Presence of Macroovalocytes: egg - shaped cells
Megaloblastic Anemia:Diagnosis
Red cell changes are not seen in all vitamin deficient patients
MCV usually > 110 though > 130 more specific
Look at RDW and cell morphology
Serum folate levels may be misleading
Alcohol lowers the folate levels
Correcting serum folate can be seen after a meal
Determine the cause of the deficiency
Ie. Pernicious anemia, Malabsorption, Diet
Diagnosing Vitamin Deficiencies
Serum cobalamin (B12) 300 pg/ml: Normal
Serum folate concentrations
If Folate is >4ng/ml then not folate deficient
If Folate is
Cobalamin Deficiency (B12)
2–5 years for cobalamin deficiency to manifest clinically
Most Commonly Due to Inadequate Diet
Can Be Precipitated by: Malabsorption Surgery to GI tract Pancreatic exocrine insufficiency Autoantibodies to parietal cells/Intrinsic Factor Pernicious Anemia Infections Genetic Factors
A serum cobalamin assay is initial diagnostic test
Variation and accuracy limited
Cobalamin Deficiency (B12): Adjunctive Tests
Methylmalonic Acid (MMA) Homocysteine Both are elevated in Cobalamin deficiency
If homocysteine only elevated = folate deficiency because not involved in MMA conversion to succinyl-CoA via B12
May see elevation of Homocysteine with: Folate or pyridoxine deficiency Renal insufficiency Hypovolemia Hypothyroidism Congenital metabolic defects Neurodegenerative disease Malignancy Medications
Megaloblastic Anemia: Peripheral Smear and BM Aspirate
Peripheral Smear
•Increased mean corpuscular volume (MCV)
•Nuclear hypersegmentation neutrophils (PMNs)
One PMN with six lobes or 5% with five lobes
•Thrombocytopenia
Bone Marrow Aspirate
•General increase in cellularity of all three major hematopoietic elements
•Abnormal erythropoiesis—megaloblasts
•Abnormal leukopoiesis—giant metamyelocytes and “band” forms (pathognomonic), hypersegmented PMNs
•Abnormal megakaryocytopoiesis
