A 45-year-old woman with pernicious anemia is started on intramuscular vitamin B12 therapy. Which of the following is NOT a recognized hematologic or neurologic complication that may develop if B12 deficiency is left untreated?
A. Peripheral neuropathy with demyelination of sensory nerves
B. Optic atrophy and central scotoma from optic nerve demyelination
C. Subacute combined degeneration of the spinal cord with posterior column involvement
D. Acute hemolytic anemia with positive direct Coombs test
Explanation
Neurologic and Hematologic Complications of B12 Deficiency
Key Point
Vitamin B12 deficiency causes two distinct pathologic processes: (1) megaloblastic anemia from impaired DNA synthesis, and (2) demyelinating neuropathy from impaired myelin synthesis. Hemolytic anemia is NOT a complication of B12 deficiency.
Recognized Neurologic Complications
Table
Complication
Pathophysiology
Clinical Features
Subacute combined degeneration (SCD)
Demyelination of posterior columns and lateral corticospinal tracts
B12 deficiency causes megaloblastic (non-hemolytic) anemia, not hemolytic anemia. The mechanism is impaired DNA synthesis leading to ineffective erythropoiesis, not immune-mediated RBC destruction.
Clinical Pearl
The anemia of B12 deficiency is characterized by:
Low reticulocyte count (inappropriately low for degree of anemia)
Elevated LDH and indirect bilirubin (from intramedullary hemolysis, not peripheral hemolysis)
Negative direct Coombs test (no antibodies against RBC surface antigens)
Do not confuse B12 deficiency with folate deficiency. Folate deficiency causes megaloblastic anemia but does NOT cause neurologic complications (no demyelination). B12 deficiency causes BOTH anemia and neuropathy.
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