Pathology · Year 2 · from Pathology
Case 1: Anemia Workup - Using the CBC and Peripheral Smear
Patient Demographics
- Age: 45 years
- Sex: Female
- Occupation: Elementary school teacher
Chief Complaint
"I've been feeling exhausted and short of breath when I climb stairs."
History of Present Illness
A 45-year-old woman presents with progressive fatigue over 6 months. She initially attributed her tiredness to work stress but now notes she becomes short of breath walking up one flight of stairs. She reports occasional palpitations and lightheadedness. Her diet is unremarkable; she is not vegetarian. She has heavy menstrual periods (menorrhagia) lasting 7-8 days with frequent pad changes. She denies blood in stool, black stools, hematuria, or easy bruising. She has tried taking iron supplements intermittently but stopped due to constipation.
Past Medical History
- Uterine fibroids (diagnosed 3 years ago)
- Menorrhagia
- No prior surgeries
Medications
- Ibuprofen PRN for menstrual cramps
- Multivitamin (intermittent)
Physical Examination
- Vital Signs: BP 118/72 mmHg, HR 98 bpm, RR 18/min
- General: Pale-appearing female, no acute distress
- HEENT: Pale conjunctivae; smooth, atrophic tongue (glossitis); angular cheilitis at mouth corners
- Cardiovascular: Tachycardic, regular rhythm, II/VI systolic flow murmur at LUSB
- Nails: Koilonychia (spoon-shaped nails)
- Abdomen: Soft, non-tender, no hepatosplenomegaly
Laboratory Workup
Complete Blood Count (CBC):
| Parameter | Result | Reference Range | Interpretation |
|---|---|---|---|
| Hemoglobin | 8.2 g/dL | 12-16 g/dL | Low (anemia) |
| Hematocrit | 26% | 36-46% | Low |
| RBC Count | 3.8 million/mcL | 4.0-5.5 million/mcL | Low |
| MCV | 68 fL | 80-100 fL | Low (microcytic) |
| MCH | 22 pg | 27-33 pg | Low (hypochromic) |
| MCHC | 28 g/dL | 32-36 g/dL | Low |
| RDW | 18.5% | 11.5-14.5% | Elevated (anisocytosis) |
| WBC | 6,800/mcL | 4,500-11,000 | Normal |
| Platelets | 425,000/mcL | 150,000-400,000 | Mildly elevated (reactive) |
Peripheral Blood Smear Findings:
- Microcytosis: RBCs smaller than lymphocyte nuclei
- Hypochromia: Increased central pallor (>1/3 of cell diameter)
- Anisocytosis: Variation in RBC size (correlates with elevated RDW)
- Poikilocytosis: Abnormal shapes including:
- Pencil cells (elongated elliptocytes)
- Target cells (occasional)
- Thrombocytosis: Increased platelets (reactive to iron deficiency)
Systematic Approach to Anemia
Step 1: Classify by MCV
- MCV 68 fL = Microcytic anemia (MCV < 80 fL)
- Differential for microcytic anemia:
- Iron deficiency (most common worldwide)
- Thalassemia
- Anemia of chronic disease (can be microcytic)
- Sideroblastic anemia
- Lead poisoning
Step 2: Order Iron Studies
Iron Studies:
| Test | Result | Reference | Interpretation |
|---|---|---|---|
| Serum Iron | 25 mcg/dL | 60-170 mcg/dL | Low |
| TIBC | 450 mcg/dL | 250-370 mcg/dL | High |
| Transferrin Saturation | 6% | 20-50% | Very Low |
| Ferritin | 8 ng/mL | 12-150 ng/mL | Low (diagnostic) |
Iron Studies Interpretation:
| Condition | Iron | TIBC | Ferritin | Saturation |
|---|---|---|---|---|
| Iron Deficiency | Low | High | Low | Low |
| Anemia of Chronic Disease | Low | Low-Normal | Normal-High | Low |
| Thalassemia Trait | Normal | Normal | Normal | Normal |
| Sideroblastic Anemia | High | Normal | High | High |
Ferritin is the KEY differentiator:
- Ferritin < 15 ng/mL is essentially diagnostic of iron deficiency
- Ferritin is an acute phase reactant - can be falsely normal/elevated with inflammation
- If inflammatory disease suspected, ferritin < 100 ng/mL with low transferrin saturation suggests iron deficiency
Diagnosis
Iron Deficiency Anemia secondary to chronic blood loss (menorrhagia)
Additional Workup
- Reticulocyte count: 0.8% (low for degree of anemia - inadequate marrow response due to iron deficiency)
- Pelvic ultrasound: Multiple uterine fibroids, largest 5 cm
Why RDW is Elevated in Iron Deficiency
- RDW (Red Cell Distribution Width) measures variation in RBC size
- In iron deficiency: Mixed population of older normal-sized cells and newer microcytic cells
- This creates anisocytosis (elevated RDW)
- In contrast: Thalassemia trait has uniformly small cells with NORMAL RDW (helps differentiate)
Clinical Findings Explained
| Finding | Pathophysiology |
|---|---|
| Glossitis (smooth tongue) | Rapidly dividing epithelial cells affected by iron deficiency |
| Angular cheilitis | Epithelial changes at mouth corners |
| Koilonychia (spoon nails) | Abnormal nail growth without adequate iron |
| Flow murmur | Hyperdynamic circulation compensating for anemia |
| Reactive thrombocytosis | Thrombopoietin cross-reacts with erythropoietin pathway |
Treatment
1. Iron Replacement:
- Ferrous sulfate 325 mg PO three times daily (65 mg elemental iron per tablet)
- Take on empty stomach for best absorption (if tolerated)
- Take with vitamin C (orange juice) to enhance absorption
- Avoid taking with calcium, antacids, or proton pump inhibitors
2. Address Underlying Cause:
- Gynecology referral for fibroid management
- Consider GnRH agonists, hormonal therapy, or surgical options
- If GI blood loss suspected (especially in males or postmenopausal women): upper and lower endoscopy
3. Monitoring:
- Reticulocyte count in 1 week (should increase, indicating marrow response)
- Hemoglobin in 2-4 weeks (should increase 1-2 g/dL)
- Continue iron for 3-6 months AFTER hemoglobin normalizes to replete stores
- Recheck ferritin to confirm stores replete (goal > 50-100 ng/mL)
If Oral Iron Not Tolerated or Ineffective:
- IV iron (iron sucrose, ferric carboxymaltose, ferumoxytol)
- Consider if malabsorption (celiac disease, gastric bypass)
- Consider if ongoing losses exceed oral replacement capacity
Clinical Pearl
The peripheral blood smear in iron deficiency shows microcytic, hypochromic red cells with increased central pallor, pencil cells, and elevated RDW reflecting anisocytosis. Ferritin is the most useful single test for diagnosing iron deficiency, but remember it's an acute phase reactant. The combination of low ferritin (<15), low serum iron, HIGH TIBC, and low transferrin saturation confirms iron deficiency. Always investigate the source of blood loss - in premenopausal women, menorrhagia is the most common cause; in men and postmenopausal women, GI blood loss must be excluded with endoscopy. The reticulocyte count should rise within 5-7 days of starting iron, and hemoglobin should increase by 1-2 g/dL within 2-4 weeks.
Clinical Image
Peripheral blood smear demonstrating microcytic, hypochromic red blood cells characteristic of iron deficiency anemia. Note the increased central pallor (hypochromia) and the presence of pencil cells (elongated elliptocytes).
Image Source: Wikimedia Commons - "Iron deficiency anemia blood smear" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Iron_deficiency_anemia_blood_smear.jpg