# Clinical Cases: Anemia

## Case 1: Iron Deficiency Anemia with Occult GI Bleeding

### Patient Demographics
- **Age:** 62 years
- **Sex:** Male
- **Occupation:** Retired firefighter

### Chief Complaint
"I'm exhausted all the time and get short of breath just walking to the mailbox."

### History of Present Illness
The patient presents with a 4-month history of progressive fatigue and exercise intolerance. He used to walk 2 miles daily but now becomes dyspneic after walking less than a block. He has noticed occasional lightheadedness when standing quickly and reports that his wife has commented that he "looks pale." He denies chest pain, palpitations, or syncope. He has not noticed any overt blood in his stool but admits he does not regularly inspect his bowel movements. He has also developed an unusual craving for ice, consuming several glasses of ice chips daily. Past medical history includes hypertension and osteoarthritis. He takes lisinopril and over-the-counter ibuprofen regularly for joint pain.

### Vital Signs
- Temperature: 98.4 degrees F (36.9 degrees C)
- Blood pressure: 128/76 mmHg (sitting), 108/68 mmHg (standing)
- Heart rate: 88 bpm (sitting), 110 bpm (standing)
- Respiratory rate: 16/min
- Oxygen saturation: 98% on room air

### Physical Examination
**General:** Pale-appearing male, no acute distress at rest
**HEENT:** Conjunctival pallor, glossitis (smooth, red tongue), angular cheilitis
**Cardiovascular:** Tachycardic with orthostatic change, systolic flow murmur (grade 2/6 at LUSB)
**Pulmonary:** Clear bilaterally
**Abdomen:** Soft, non-tender, no hepatosplenomegaly, no masses
**Extremities:** Koilonychia (spoon-shaped nails) noted on several fingers, no edema
**Rectal:** Brown stool, guaiac positive (occult blood present)
**Neurologic:** Alert and oriented, no focal deficits

### Laboratory Findings
**Complete Blood Count:**
- Hemoglobin: 7.2 g/dL (low - severe anemia)
- Hematocrit: 22%
- MCV: 68 fL (low - microcytic)
- MCH: 24 pg (low)
- MCHC: 30 g/dL (low)
- RDW: 18.5% (elevated - anisocytosis)
- WBC: 6,800/mcL (normal)
- Platelets: 398,000/mcL (mildly elevated - reactive thrombocytosis)
- Reticulocyte count: 0.8% (inappropriately low for degree of anemia)

**Iron Studies:**
- Serum iron: 22 mcg/dL (low, normal 60-170)
- TIBC: 468 mcg/dL (elevated, normal 250-370)
- Transferrin saturation: 5% (low, calculated as iron/TIBC x 100)
- Ferritin: 8 ng/mL (low, normal 30-300)

**Peripheral Blood Smear:**
- Microcytic, hypochromic red blood cells
- Marked anisocytosis and poikilocytosis
- Target cells and pencil cells present
- No schistocytes or spherocytes

### Diagnosis
**Severe iron deficiency anemia** with likely occult gastrointestinal blood loss

### Workup for Etiology
Given the patient's age, sex, and positive fecal occult blood test, gastrointestinal malignancy must be excluded:
1. **Esophagogastroduodenoscopy (EGD):** Revealed 3 cm ulcerating mass in the gastric antrum; biopsies obtained
2. **Colonoscopy:** Normal examination, no polyps or masses
3. **Gastric biopsy pathology:** Adenocarcinoma of the stomach

### Management
**Immediate anemia management:**
1. Transfuse 2 units packed red blood cells (symptomatic severe anemia with hemoglobin < 7 g/dL and orthostatic hypotension)
2. Hold ibuprofen (contributes to gastric injury and inhibits platelet function)

**Iron replacement:**
3. Oral ferrous sulfate 325 mg three times daily on empty stomach (once acute bleeding controlled)
4. Consider IV iron (iron sucrose or ferric carboxymaltose) if unable to tolerate oral iron or if rapid repletion needed before surgery

**Treatment of underlying cause:**
5. Oncology referral for staging and treatment of gastric adenocarcinoma
6. Surgical oncology consultation for potential gastrectomy
7. PPI therapy for acid suppression

**Monitoring:**
8. Reticulocyte count in 7-10 days (should peak if responding to iron)
9. Hemoglobin in 2-4 weeks (should increase 1-2 g/dL)
10. Continue oral iron for 3-6 months after hemoglobin normalizes to replete iron stores

### Clinical Pearl
In an adult male or postmenopausal female with iron deficiency anemia, gastrointestinal blood loss must be presumed until proven otherwise, and GI malignancy must be excluded with endoscopic evaluation. The classic clinical features of iron deficiency include pica (craving for non-food substances like ice - called pagophagia), koilonychia (spoon nails), glossitis, and angular cheilitis. This patient also demonstrates the classic lab profile: low ferritin (most specific test for iron deficiency), low serum iron, high TIBC, and low transferrin saturation. The elevated platelet count (reactive thrombocytosis) is common in iron deficiency anemia due to cross-reactivity between thrombopoietin and erythropoietin.

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

**Image Description:** Peripheral blood smear showing microcytic, hypochromic red blood cells characteristic of iron deficiency anemia. The red cells appear small with increased central pallor compared to normal red blood cells.

**Attribution:** Image from Wikimedia Commons. Licensed under CC BY-SA 4.0. Source: https://commons.wikimedia.org/wiki/File:Iron_deficiency_anemia_blood_film.jpg

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## Case 2: Autoimmune Hemolytic Anemia

### Patient Demographics
- **Age:** 48 years
- **Sex:** Female
- **Occupation:** Accountant

### Chief Complaint
"I'm turning yellow and my urine looks like tea."

### History of Present Illness
The patient presents with a 10-day history of progressive fatigue, dark urine, and yellowing of her eyes and skin. She first noticed the dark urine about a week ago and thought she was dehydrated, but it has persisted despite increased fluid intake. Three days ago, her husband noticed her eyes were yellow. She has also developed upper abdominal fullness and mild left-sided discomfort. She denies fever, chills, recent travel, or known sick contacts. She has no history of liver disease or hepatitis. Past medical history is significant for systemic lupus erythematosus diagnosed 5 years ago, currently in remission on hydroxychloroquine. She has had no recent medication changes.

### Vital Signs
- Temperature: 99.8 degrees F (37.7 degrees C)
- Blood pressure: 110/68 mmHg
- Heart rate: 104 bpm
- Respiratory rate: 18/min
- Oxygen saturation: 97% on room air

### Physical Examination
**General:** Jaundiced, fatigued-appearing female
**HEENT:** Scleral icterus, pale conjunctivae
**Cardiovascular:** Tachycardic, regular rhythm, systolic flow murmur
**Pulmonary:** Clear bilaterally
**Abdomen:** Soft, palpable spleen tip 3 cm below costal margin, no hepatomegaly, no tenderness
**Extremities:** No edema, no rash
**Skin:** Jaundice, no petechiae or purpura

### Laboratory Findings
**Complete Blood Count:**
- Hemoglobin: 6.8 g/dL (severe anemia)
- Hematocrit: 20%
- MCV: 108 fL (elevated - macrocytic due to reticulocytosis)
- WBC: 8,200/mcL
- Platelets: 186,000/mcL
- Reticulocyte count: 14% (markedly elevated - appropriate marrow response)
- Reticulocyte production index: 3.5 (elevated, indicating adequate marrow response)

**Hemolysis Labs:**
- LDH: 842 U/L (elevated, normal <250)
- Indirect bilirubin: 4.8 mg/dL (elevated)
- Direct bilirubin: 0.6 mg/dL (normal)
- Haptoglobin: < 10 mg/dL (undetectable - consumed by free hemoglobin)
- Direct antiglobulin test (Coombs): POSITIVE for IgG and C3

**Peripheral Blood Smear:**
- Spherocytes (numerous)
- Polychromasia (reflecting reticulocytosis)
- Occasional nucleated RBCs
- No schistocytes

**Additional Studies:**
- ANA: Positive at 1:640 (known positive for SLE)
- Anti-dsDNA: Elevated at 180 IU/mL (suggests SLE flare)
- C3: 58 mg/dL (low, consumed)
- C4: 8 mg/dL (low, consumed)

### Diagnosis
**Warm autoimmune hemolytic anemia (AIHA)** secondary to systemic lupus erythematosus (Evans syndrome if associated with immune thrombocytopenia)

**Evidence supporting diagnosis:**
1. Hemolytic anemia confirmed by: elevated LDH, elevated indirect bilirubin, undetectable haptoglobin, elevated reticulocyte count
2. Autoimmune etiology confirmed by: positive direct Coombs test for IgG and C3
3. Warm AIHA (IgG-mediated) indicated by: IgG positivity, spherocytes on smear, splenomegaly
4. Secondary to SLE: known SLE history, elevated anti-dsDNA, low complement

### Management
**First-line therapy:**
1. Prednisone 1 mg/kg/day (approximately 60-80 mg daily)
   - Continue until hemoglobin stabilizes > 10 g/dL
   - Then slow taper over 4-6 months
2. Folic acid 1 mg daily (increased folate demand from reticulocytosis)

**Transfusion considerations:**
3. Transfuse packed red blood cells for symptomatic anemia or hemoglobin < 7 g/dL
   - Cross-matching may be difficult due to panagglutinin (autoantibody reacts with all donor cells)
   - Use "least incompatible" units
   - Transfuse slowly with close monitoring

**SLE management:**
4. Rheumatology consultation for SLE flare management
5. Consider additional immunosuppression (azathioprine, mycophenolate) as steroid-sparing agents

**Second-line options if steroid-refractory:**
6. Rituximab (anti-CD20, depletes B cells producing autoantibodies)
7. Splenectomy (removes site of RBC destruction and autoantibody production)
8. IVIG (temporary benefit, not first-line for warm AIHA)

**Monitoring:**
9. Daily hemoglobin initially
10. LDH and reticulocyte count to monitor for hemolysis resolution
11. Repeat Coombs test (may remain positive even after clinical improvement)

### Clinical Pearl
Warm autoimmune hemolytic anemia is characterized by IgG autoantibodies that bind red blood cells optimally at body temperature (37 degrees C). The antibody-coated cells are recognized by Fc receptors on splenic macrophages, which remove portions of the membrane, creating spherocytes. These rigid spherocytes are then trapped and destroyed on subsequent splenic passages (extravascular hemolysis). The positive direct Coombs test is the key diagnostic finding, detecting IgG and/or complement on the red cell surface. In this case, the association with SLE is important - secondary causes of AIHA include autoimmune diseases, lymphoproliferative disorders, and medications. The low complement levels and elevated anti-dsDNA suggest that the AIHA is occurring in the context of an SLE flare.

### Clinical Image
![Autoimmune Hemolytic Anemia](case_01_image.jpg)

**Image Description:** Peripheral blood smear demonstrating features of hemolytic anemia with spherocytes (round cells lacking central pallor) and polychromasia (bluish discoloration indicating reticulocytes), characteristic findings in autoimmune hemolytic anemia.

**Attribution:** Image from Wikimedia Commons. Licensed under CC BY-SA 4.0. Source: https://commons.wikimedia.org/wiki/File:Iron_deficiency_anemia_blood_film.jpg

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