RBC Clinical Cases
Learning objectives
- LO 1Pick out the symptoms and history clues that matter in a patient with anemia.
- LO 2Build a differential diagnosis for each case.
- LO 3Choose the right lab tests for a suspected disease and interpret the results.
- LO 4Describe the smear and marrow findings that support the diagnosis.
- LO 5Turn lab results into a treatment and follow-up plan.
MAPThe two cases at a glance
In-house exam
This session is formative: expect the exam to give a short history and a lab panel and ask for the next test, the diagnosis, the mechanism behind an odd lab (e.g., high LDH in B12 deficiency), or the treatment and its duration.
LO 1Symptoms and history
Q1. What symptoms suggest anemia in these patients?
- Fatigue for months
- Exertional dyspnea: stopped exercising because she gets "winded"; can no longer walk from the Metro to the office without resting
- Exam: pallor; tachycardia with exertion
Trap
Both patients have Hb 7.8 yet still walk around: slow-onset anemia is compensated. The speed of the drop, not the number, drives symptoms.
Q2. What history should you take, and what does each answer tell you?
| Ask about | Why | Case 1 | Case 2 |
|---|---|---|---|
| Menstrual / pregnancy history | Size of blood loss; iron use by pregnancy and lactation | Heavy: 6–8 tampons/24 h for 3–4 days; never pregnant | Hysterectomy for fibroids; 7 pregnancies, 5 children |
| GI bleeding | Occult loss | No blood or dark stools | None |
| Diet | Iron intake; strict vegetarians often iron deficient; pica | Poor diet; embarrassing cravings (pica) | "Healthy," not vegetarian |
| Medications | Many drugs cause anemia by different mechanisms | Motrin monthly (NSAID → GI blood loss) | Rare Tylenol |
| Family history | Inherited hemoglobinopathy | Almost every female relative anemic; anemic as a child | — |
| Surgical history | Absorption sites removed or bypassed | — | Gastric bypass 9 months ago |
| Other symptoms | Clues to a cause | No dark urine; no rash or joint pain | 85 lb weight loss; numb, tingling feet at night |
High yield
- Dark urine → hemoglobinuria / bilirubin → hemolysis.
- Rash or joint pain → autoimmune disease (lupus, RA) → autoimmune hemolytic anemia.
- Pica / pagophagia (ice) → strongly suggests iron deficiency.
- Numbness and tingling → B12 deficiency.
Memory tool
"Bleed, Eat, Take, Inherit, Cut, Show": Bleeding (menses, pregnancies, GI), Eating (diet, pica), Taking (medications), Inherited (family history), Cut (surgery), Show (other symptoms).
Analogy — timing as a clue
Anemia found before her first period points to something she was born with (hemoglobinopathy). Anemia only after menarche can still be iron deficiency, with or without an inherited trait.
ApplyLO 1 application questions
A1Why ask how many tampons a patient uses in 24 hours?
A2Which single history item in Case 2 most changes the differential?
LO 2Building the differential
Q1. What is the differential for Case 1 (microcytic, family history)?
| Option | For | Against |
|---|---|---|
| Iron deficiency (menstrual loss) | Heavy menses, NSAIDs, poor diet, pica; MCV 62, RDW high, RBC count low, ferritin 2 | — |
| α-thalassemia trait | Family history of anemia in females; African American | Would give uniform small cells (normal RDW), normal/high RBC count, normal iron studies |
| Sickle cell disease | African American | No pain crises; would be normocytic and hemolytic |
| Sickle cell trait | African American | Doesn't cause anemia |
Diagnosis: iron deficiency anemia due to menstrual blood loss (an α-thal trait may also be present).
Trap
α-thalassemia trait has a normal Hb electrophoresis. A normal electrophoresis does not rule it out.
Q2. What is the differential for Case 2 (borderline MCV, neuropathy, bypass)?
| Option | Evidence |
|---|---|
| Iron deficiency alone | Bypass skips the duodenum; past fibroids and pregnancies. But MCV is not low and she has neuropathy |
| B12 deficiency alone | Neuropathy, pancytopenia, low retics, B12 112. But ferritin borderline (20) and MCV only 100 |
| B12 + iron deficiency | Mixed big and small cells average to MCV 100 with a high RDW |
| Hemolysis | LDH high, haptoglobin low, but bilirubin normal and retics low → not peripheral hemolysis |
Diagnosis: possible combined B12 and iron deficiency after bariatric surgery.
High yield
A normal MCV with a high RDW can hide two opposite problems: small iron-deficient cells + large B12-deficient cells.
ApplyLO 2 application questions
A1Microcytic anemia with RDW 13%, RBC count 5.6 million and normal ferritin. Top diagnosis?
A2Why is hemolysis unlikely in Case 2 despite high LDH and low haptoglobin?
LO 3Choosing and reading the labs
Q1. Which labs do you order, and why?
| Test | What it tells you |
|---|---|
| CBC | Degree of anemia; other cell lines (marrow capacity); MCV (size); RDW (size variation); RBC number |
| Reticulocyte count | Red cell production rate → production problem vs destruction/loss problem |
| Plasma iron | Iron intake over the past 24–48 h; not a reliable measure of stores |
| TIBC | Transferrin binding capacity; indirectly reflects total body iron (↑ when iron-poor) |
| Transferrin saturation | Mostly recent intake; not reliable for stores |
| Ferritin | Fairly accurate indirect measure of total body iron stores; but an acute phase reactant (falsely ↑ in infection, inflammation, tissue damage) |
| Peripheral smear | Shape, size, other cells |
| LDH | Released with cell destruction or rapid turnover (hemolysis) |
| Haptoglobin | Binds free Hb → very low or undetectable in hemolysis |
| Basic metabolic panel | Creatinine: renal insufficiency → ↓ EPO → anemia. K⁺ may rise with rapid hemolysis |
| Bilirubin | Total may rise; the indirect fraction rises in hemolysis |
| Hb electrophoresis | Hemoglobinopathies (sickle, β-thal). Normal in α-thal trait |
| B12, folate | Megaloblastic causes; add when neuro symptoms or surgery suggest it |
In-house exam
Know which iron test reflects stores (ferritin; TIBC indirectly) versus recent intake (plasma iron, transferrin saturation). Hemolysis tests (LDH, haptoglobin, bilirubin) are low-yield in Case 1 because nothing suggested hemolysis.
Q2. How do the two cases' labs compare?
| Test (normal) | Case 1 | Case 2 |
|---|---|---|
| WBC (4.0–10.8) | 5.7 | 2.2 ↓ |
| RBC (4.2–5.5) | 2.86 ↓ | 2.86 ↓ |
| Hb (12.5–16.5) | 7.8 ↓ | 7.8 ↓ |
| Hct (37.5–49.5) | 22.3 ↓ | 22.3 ↓ |
| MCV (81–100) | 62 ↓ | 100 (upper limit) |
| MCH (27–31) | 25.3 ↓ | 25.3 ↓ |
| RDW (11.5–15.5) | 19.1 ↑ | 17.1 ↑ |
| Platelets (150–400) | 426 ↑ | 145 ↓ |
| Retics | 3% (low for this anemia) | 0.5% ↓ |
| Plasma iron (35–175) | 25 ↓ | 40 |
| TIBC (300–360) | 371 ↑ | 360 |
| Transferrin sat (15–50) | 30 | 40 |
| Ferritin (20–350) | 2 ↓↓ | 20 (low-normal) |
| LDH (135–240) | 157 | 535 ↑ |
| Haptoglobin (30–250) | 80 | 15 ↓ |
| BMP / creatinine | Normal | Normal; bilirubin normal |
| B12 (211–911) | — | 112 ↓ |
| Folate (2.8–14.0) | — | 15.4 |
High yield — reading the CBC
- Mild thrombocytosis is common in iron deficiency.
- Microcytosis with a low RBC count → iron deficiency; normal/high RBC count → thalassemia.
- High RDW in iron deficiency because cell size tracks recent iron supply; thal trait cells are uniformly small.
- Low retics + low platelets + low WBC → production problem (Case 2).
Trap
Case 1's transferrin saturation is normal despite profound iron deficiency: saturation reflects recent intake. Trust the ferritin.
Q3. Why are LDH high and haptoglobin low in Case 2 if she isn't hemolyzing?
Ineffective erythropoiesis. B12 deficiency stops precursors from maturing; they die inside the marrow (intramedullary destruction) and release their contents → ↑ LDH, ↓ haptoglobin, and pancytopenia.
ApplyLO 3 application questions
A1A patient with rheumatoid arthritis flare has ferritin 180 and low serum iron. Does the ferritin rule out iron deficiency?
A2Why check creatinine in an anemia work-up?
LO 4Smear and marrow findings
Q1. What do you look for on a peripheral smear?
- Poikilocytosis: variation in shape (normal resting shape = biconcave disc; shape depends on environment, metabolic status and age)
- Anisocytosis: variation in size
- White cells and platelets: number and morphology
| Normal RBC | Value |
|---|---|
| Diameter | 7.5–8.7 µm |
| Average volume | 90 fL |
| Surface area | 136 µm² |
| Spare membrane | Allows MCV up to 150 fL or squeezing to 2.8 µm |
| Lifespan | 100–120 days; travels ≈175 miles |
Memory tool
An-isocytosis = "not the same" (an + iso) size. Poikilocytosis = "varied" (poikilos) shape.
Q2. What did each case's smear show?
Case 1 · iron deficiency
- Microcytic, hypochromic
- Anisocytosis and poikilocytosis; pencil cells
- Lymphocyte (arrow) for size
Case 2 · mixed picture
- Big and small cells together (dimorphic)
- MCV averages out to "normal"; RDW high
Case 2 · neutrophil
- Hypersegmented → B12 deficiency
Q3. Which smear shapes point to which diagnoses?
| Shape | Think |
|---|---|
| Pencil cells, small pale cells | Iron deficiency |
| Oval macrocytes + hypersegmented neutrophils | B12 / folate deficiency |
| Spherocytes | Hereditary spherocytosis, warm AIHA |
| Schistocytes | Intravascular (microangiopathic) hemolysis |
| Target cells | β-thalassemia, hemoglobinopathies |
| Teardrop cells | Marrow infiltration / fibrosis |
| Sickle cells | Sickle cell disease |
Q4. What would the marrow show?
- Iron deficiency: absent iron stores (Prussian blue)
- B12 deficiency: hypercellular, megaloblastic precursors in all lines, ↑ apoptosis (ineffective erythropoiesis)
- Marrow biopsy is usually not needed when blood tests explain the anemia
ApplyLO 4 application questions
A1Smear shows two red cell populations, one small and pale and one large and oval. What combination?
LO 5Treatment and follow-up
Q1. How should Case 1 be treated, and for how long?
- Oral iron: ferrous sulfate 300 mg at least twice daily (transfusion and IV iron not needed for a stable patient absorbing normally)
- Duration: until Hb and Hct are normal and ferritin >50 (or simply until ferritin >50)
- If she also has α-thal trait, Hb, Hct and MCV may always stay slightly low, so don't chase a "normal" MCV
- Monitoring: CBC and ferritin every 4–6 months while she menstruates, restarting iron before anemia returns; keep ferritin ≈50 or higher
In-house exam
Answer choices on duration: "until Hb/Hct normal" is wrong (stores not refilled); "until MCV normal" is wrong (may never normalize with α-thal trait). Correct: until ferritin >50.
Q2. How should Case 2 be treated, and for how long?
- Both nutrients: either parenteral B12 + IV iron, or high-dose oral B12 on an empty stomach + parenteral iron
- Why parenteral iron: bypass skips the duodenum, the main site of iron absorption
- Why parenteral or high-dose B12: bypass impairs release and absorption of food-bound B12; high doses can be absorbed passively
- Duration: B12 lifelong (anatomy won't change); iron by monitoring, replace when ferritin falls below 50
Trap
Giving only oral iron and B12 after a bypass fails: the absorption sites are bypassed. Giving iron alone would leave the neuropathy progressing.
Step 1
Post-bariatric deficiencies: iron, B12, folate, thiamine, vitamin D/calcium, copper. Copper deficiency can mimic B12 deficiency (myelopathy + anemia).
ApplyLO 5 application questions
A1Case 1's Hb normalizes after 8 weeks of oral iron; ferritin is 18. Stop?
A2How long will Case 2 need B12?
IDSmear ID
Image 1 — smear
Image 2 — smear
Image 3 — neutrophil
Image 4 — smear
Image 5 — smear
Image 6 — smear
MCQExam-style questions
1A 30-year-old woman has 2 months of unsteady gait and numb legs. Eight years ago she had her terminal ileum resected for severe Crohn disease. She has mild spastic weakness and decreased pinprick, vibration and fine touch in all limbs. Deficiency of which is most likely?
2A 16-year-old boy is evaluated for jaundice. Liver enzymes are normal, direct Coombs is negative, MCHC is increased, and RBC osmotic fragility is increased. Which cell is most likely on the smear?
3A 46-year-old woman with advanced kidney disease from analgesic use has fatigue. Hb 8.8, MCV 82, ferritin 262, normal folate, transferrin saturation 22%, LDH 62. Most likely cause of her anemia?
4An 18-year-old woman with sickle cell disease has right upper quadrant pain after a fatty meal; ultrasound shows gallstones. Underlying cause?
5A 60-year-old man has 4 months of weakness, tingling hands and feet, irritability and forgetfulness; spasticity, hyperreflexia and absent vibration sense. Labs: megaloblastic anemia, antiparietal cell antibodies, ↑ MMA and ↑ homocysteine. Synthesis of which amino acid is impaired?
6A 20-year-old with heavy menses has Hb 7.8, MCV 62, RDW 19, iron 25, TIBC 371, ferritin 2. What is the best treatment?
7For the patient in question 6, when should iron be stopped?
8Nine months after gastric bypass, a woman has pancytopenia, low retics, B12 112, LDH 535, haptoglobin 15 and normal bilirubin. Why are LDH and haptoglobin abnormal?
9For the patient in question 8 (B12 and iron deficiency after bypass), which regimen is most appropriate?
10A microcytic patient's Hb electrophoresis is normal. Which diagnosis is still possible?
11Which iron study best reflects total body iron stores?
12A young woman with anemia reports joint pains and a facial rash. Which type of anemia does this history raise?
!Numbers that differ between in-house and Step 1
| Item | In-house | Step 1 / board review |
|---|---|---|
| MCV reference range | 81–100 fL (lab range in cases) | 80–100 fL |
| Iron treatment endpoint | Ferritin >50 | Continue ≈3 months after Hb normalizes to refill stores |
| B12 after bypass | Parenteral, or high-dose oral on an empty stomach; lifelong | Same |
| Ovalocytes | Notes link ovalocytes to iron deficiency | Macro-ovalocytes = megaloblastic; elongated pencil cells/elliptocytes = iron deficiency |
| Normal RBC diameter | 7.5–8.7 µm | ≈7–8 µm |