# Clinical Cases: Anemia Overview and Iron Deficiency

## Case 1: Iron Deficiency Anemia in a Young Woman

### Patient Presentation
**Demographics:** 28-year-old female

**Chief Complaint:** Progressive fatigue and shortness of breath over 4 months

**History of Present Illness:**
The patient reports gradually worsening fatigue that has begun to affect her work performance. She notes dyspnea on exertion when climbing stairs, which was not present previously. She also reports occasional pica, specifically craving ice (pagophagia). She has heavy menstrual periods lasting 7-8 days with frequent pad changes. She denies any melena, hematochezia, or hematemesis. Her diet consists mostly of vegetables with limited red meat intake.

**Physical Examination:**
- Vital signs: BP 108/68, HR 98, RR 18, Temp 36.8C
- General: Pale-appearing young woman, appears fatigued
- HEENT: Conjunctival pallor, glossitis with smooth tongue, angular cheilitis
- Cardiac: Tachycardic, II/VI systolic flow murmur at left sternal border
- Abdomen: Soft, non-tender, no hepatosplenomegaly
- Extremities: Koilonychia (spoon-shaped nails) noted bilaterally
- Neurologic: Normal

### Workup and Results

**Complete Blood Count:**
- WBC: 6,800/uL (normal)
- Hemoglobin: 8.2 g/dL (low, normal 12-16)
- Hematocrit: 25%
- MCV: 68 fL (low, normal 80-100)
- MCH: 24 pg (low)
- MCHC: 30 g/dL (low)
- RDW: 18% (elevated)
- Platelets: 420,000/uL (mildly elevated)
- Reticulocyte count: 0.8% (inappropriately low)

**Iron Studies:**
- Serum iron: 25 mcg/dL (low, normal 60-170)
- Total iron-binding capacity (TIBC): 480 mcg/dL (elevated, normal 250-370)
- Transferrin saturation: 5% (low, normal 20-50%)
- Ferritin: 8 ng/mL (low, normal 12-150)

**Peripheral Blood Smear:**
- Hypochromic, microcytic red blood cells
- Increased central pallor
- Anisocytosis and poikilocytosis
- Pencil cells present
- No target cells or basophilic stippling

### Clinical Image

![Iron Deficiency Anemia Blood Smear](case_01_image.jpg)

*Peripheral blood smear showing hypochromic, microcytic red blood cells with increased central pallor characteristic of iron deficiency anemia. Image source: Wikimedia Commons, Dr Graham Beards. License: CC BY-SA 3.0*

### Diagnosis
**Iron Deficiency Anemia secondary to Menorrhagia**

Diagnostic criteria met:
- Microcytic anemia (MCV < 80 fL)
- Low ferritin (< 30 ng/mL) - most sensitive single test
- Low serum iron with elevated TIBC
- Transferrin saturation < 20%
- Elevated RDW reflecting anisocytosis
- Clinical features: pagophagia, koilonychia, glossitis

### Treatment Plan
1. **Identify and address underlying cause:**
   - Gynecology referral for evaluation of menorrhagia
   - Consider hormonal management to reduce menstrual blood loss

2. **Oral iron replacement:**
   - Ferrous sulfate 325 mg (65 mg elemental iron) three times daily
   - Take on empty stomach if tolerated; with food if GI side effects occur
   - Take with vitamin C to enhance absorption
   - Avoid concurrent intake of calcium, tea, or coffee

3. **Monitoring:**
   - Reticulocyte count in 5-7 days (should increase)
   - CBC every 4 weeks until hemoglobin normalizes
   - Continue iron for 3-6 months after hemoglobin normalizes to replenish stores
   - Check ferritin to confirm store repletion (goal > 50 ng/mL)

### Teaching Points
1. Iron deficiency anemia is the most common cause of anemia worldwide
2. Ferritin is the most sensitive single test for iron deficiency; values < 30 ng/mL are diagnostic
3. Low serum iron with elevated TIBC produces a low transferrin saturation (< 20%)
4. Clinical features include pagophagia (ice craving), koilonychia (spoon nails), glossitis, and angular cheilitis
5. Always identify the source of iron loss - in premenopausal women, menorrhagia is most common; in postmenopausal women and men, GI bleeding must be excluded
6. The reticulocyte count is inappropriately low, indicating a production problem rather than hemolysis

---

## Case 2: Anemia of Chronic Disease

### Patient Presentation
**Demographics:** 58-year-old male

**Chief Complaint:** Fatigue and mild dyspnea on exertion for 2 months

**History of Present Illness:**
The patient has a 10-year history of rheumatoid arthritis requiring methotrexate and adalimumab. He reports progressive fatigue that has worsened despite good control of his joint symptoms. He denies any bleeding symptoms, melena, or hematochezia. His diet is well-balanced, and he takes folic acid supplementation as prescribed.

**Physical Examination:**
- Vital signs: BP 128/78, HR 82, RR 16, Temp 37.0C
- General: Mildly pale, no acute distress
- HEENT: Mild conjunctival pallor, no glossitis
- Cardiac: Regular rhythm, no murmurs
- Extremities: Mild synovial thickening at MCPs bilaterally, no active synovitis
- Abdomen: No hepatosplenomegaly

### Workup and Results

**Complete Blood Count:**
- WBC: 7,200/uL (normal)
- Hemoglobin: 10.8 g/dL (low)
- MCV: 88 fL (normal)
- RDW: 14% (normal)
- Platelets: 380,000/uL
- Reticulocyte count: 1.0%

**Iron Studies:**
- Serum iron: 40 mcg/dL (low)
- TIBC: 220 mcg/dL (low to normal)
- Transferrin saturation: 18% (low-normal)
- Ferritin: 280 ng/mL (elevated)

**Additional Labs:**
- ESR: 45 mm/hr (elevated)
- CRP: 2.8 mg/dL (elevated)
- B12: 450 pg/mL (normal)
- Folate: 12 ng/mL (normal)

### Diagnosis
**Anemia of Chronic Disease (Anemia of Inflammation)**

Key distinguishing features from iron deficiency:
- Normal or elevated ferritin (vs. low in iron deficiency)
- Low or normal TIBC (vs. elevated in iron deficiency)
- Underlying inflammatory condition present
- Normocytic anemia (can be mildly microcytic)

### Treatment Plan
1. **Primary treatment:**
   - Optimize treatment of underlying rheumatoid arthritis
   - Iron supplementation is NOT indicated (stores are adequate)

2. **If symptomatic anemia despite disease control:**
   - Consider erythropoiesis-stimulating agents (ESAs)
   - Target hemoglobin of 10-11 g/dL to minimize symptoms

3. **Monitoring:**
   - Follow hemoglobin with disease activity
   - Reassess if anemia worsens or becomes more severe

### Teaching Points
1. Anemia of chronic disease is the second most common cause of anemia worldwide
2. The pathophysiology involves hepcidin-mediated iron sequestration in macrophages
3. Key laboratory distinction: ferritin is normal/elevated (vs. low in iron deficiency)
4. TIBC is low/normal (vs. elevated in iron deficiency)
5. Treatment focuses on the underlying inflammatory condition, not iron replacement
6. Iron therapy is ineffective and potentially harmful due to hepcidin-mediated absorption block

---

## Case 3: Combined Iron Deficiency and Anemia of Chronic Disease

### Patient Presentation
**Demographics:** 62-year-old female

**Chief Complaint:** Progressive fatigue and weakness over 6 weeks

**History of Present Illness:**
The patient has a history of Crohn's disease involving the terminal ileum, currently on vedolizumab. She reports increasing fatigue and has noticed darker stools over the past month. She has had two disease flares requiring hospitalization in the past year.

**Physical Examination:**
- Vital signs: BP 100/62, HR 102, RR 18, Temp 37.2C
- General: Pale, fatigued-appearing
- HEENT: Conjunctival pallor, angular cheilitis
- Cardiac: Tachycardic, II/VI systolic ejection murmur
- Abdomen: Mild right lower quadrant tenderness, no masses

### Workup and Results

**Complete Blood Count:**
- Hemoglobin: 8.0 g/dL
- MCV: 76 fL (low)
- RDW: 17% (elevated)
- Platelets: 450,000/uL

**Iron Studies:**
- Serum iron: 30 mcg/dL (low)
- TIBC: 280 mcg/dL (normal)
- Transferrin saturation: 11% (low)
- Ferritin: 55 ng/mL (intermediate - neither clearly low nor elevated)

**Additional Studies:**
- Soluble transferrin receptor: 4.2 mg/L (elevated, normal < 2.5)
- sTfR/log ferritin ratio: 2.4 (> 2 suggests iron deficiency)
- CRP: 18 mg/L (elevated)

### Diagnosis
**Combined Iron Deficiency Anemia and Anemia of Chronic Disease**

The intermediate ferritin (30-100 ng/mL range) in setting of inflammation creates diagnostic uncertainty. The elevated soluble transferrin receptor and sTfR/log ferritin ratio > 2 confirm superimposed true iron deficiency.

### Treatment Plan
1. **Address both problems:**
   - IV iron (ferric carboxymaltose or iron sucrose) - preferred over oral due to:
     - Terminal ileum disease causing malabsorption
     - Ongoing inflammation blocking oral absorption
   - Optimize Crohn's disease management

2. **GI evaluation:**
   - Colonoscopy to evaluate disease activity and exclude other bleeding sources

3. **Monitoring:**
   - Check hemoglobin in 2-4 weeks after IV iron
   - Repeat ferritin 8-12 weeks after infusion

### Teaching Points
1. Combined iron deficiency and ACD commonly coexist, especially in inflammatory bowel disease
2. Ferritin between 30-100 ng/mL in inflammatory states is diagnostically challenging
3. Soluble transferrin receptor (sTfR) is elevated in iron deficiency but normal in ACD
4. The sTfR/log ferritin ratio > 2 suggests true iron deficiency even in inflammation
5. IV iron is preferred when oral absorption is compromised (malabsorption, active inflammation)
6. Both the underlying inflammation AND the iron deficiency must be addressed