Hematology Oncology · Year 2 · from Hematology Oncology
Case 1: Pernicious Anemia with Neurologic Manifestations
Patient Presentation
Demographics: 68-year-old female
Chief Complaint: Progressive fatigue, numbness in feet, and unsteady gait for 6 months
History of Present Illness: The patient reports gradually worsening fatigue and shortness of breath. Over the past 4 months, she has developed numbness and tingling in both feet that has progressed to involve her lower legs. She has noticed difficulty with balance and has fallen twice. Family members report she has become more forgetful. She has a history of vitiligo and hypothyroidism. She follows a regular diet including meat and dairy products.
Physical Examination:
- Vital signs: BP 118/72, HR 88, RR 18, Temp 36.8C
- General: Pale, elderly woman with mild lemon-yellow skin tinge
- HEENT: Scleral icterus, smooth beefy-red tongue (glossitis)
- Cardiac: II/VI systolic flow murmur
- Neurologic:
- Decreased vibration sense at ankles bilaterally
- Decreased proprioception in toes
- Positive Romberg sign
- Broad-based gait with positive heel-to-toe difficulty
- Deep tendon reflexes: 3+ at knees (brisk)
- Babinski sign positive bilaterally
Workup and Results
Complete Blood Count:
- WBC: 4,200/uL (low normal)
- Hemoglobin: 7.8 g/dL (severely low)
- MCV: 118 fL (markedly elevated)
- MCH: 38 pg (elevated)
- Platelets: 125,000/uL (low)
- Reticulocyte count: 0.5% (inappropriately low)
Peripheral Blood Smear:
- Macro-ovalocytes
- Hypersegmented neutrophils (6+ lobes seen)
- Anisocytosis and poikilocytosis
- Occasional nucleated red blood cells
Additional Labs:
- LDH: 1,850 U/L (markedly elevated)
- Indirect bilirubin: 2.4 mg/dL (elevated)
- Haptoglobin: 45 mg/dL (low normal)
- Vitamin B12: 82 pg/mL (severely low, normal 200-900)
- Folate: 15 ng/mL (normal)
- Methylmalonic acid (MMA): 3,200 nmol/L (markedly elevated)
- Homocysteine: 48 umol/L (elevated)
Immunologic Testing:
- Anti-intrinsic factor antibodies: Positive
- Anti-parietal cell antibodies: Positive
Clinical Image
Peripheral blood smear findings in megaloblastic anemia showing characteristic macro-ovalocytes and hypersegmented neutrophils with nuclear-cytoplasmic asynchrony.
Diagnosis
Pernicious Anemia with Subacute Combined Degeneration of the Spinal Cord
Diagnostic criteria met:
- Macrocytic anemia with MCV > 100 fL
- Low vitamin B12 with elevated MMA (confirms tissue deficiency)
- Positive anti-intrinsic factor antibodies (highly specific for pernicious anemia)
- Neurologic findings of posterior and lateral column involvement
- Associated autoimmune conditions (vitiligo, hypothyroidism)
Treatment Plan
- Urgent B12 replacement:
- Cyanocobalamin 1000 mcg IM daily x 7 days
- Then weekly x 4 weeks
- Then monthly maintenance indefinitely
- Monitoring during treatment:
- Watch for hypokalemia (potassium shifts into new RBCs)
- Reticulocyte count should peak at days 5-7
- Hemoglobin rises within 1-2 weeks
- Long-term care:
- Lifelong B12 replacement (cannot be cured)
- Upper endoscopy to screen for gastric carcinoma/carcinoid
- Monitor neurologic symptoms (may take 6+ months to improve, may be irreversible)
Teaching Points
- B12 deficiency causes neurologic damage that folate deficiency does not
- Subacute combined degeneration affects posterior columns (vibration, proprioception) and lateral columns (upper motor neuron signs)
- Neurologic manifestations can occur without significant anemia
- Elevated MMA distinguishes B12 deficiency from folate deficiency (both elevate homocysteine)
- Anti-intrinsic factor antibodies are highly specific (but not sensitive) for pernicious anemia
- The elevated LDH reflects ineffective erythropoiesis with intramedullary hemolysis
- Treatment must begin promptly to prevent irreversible neurologic damage