Clinical Exam Questions on Anemia & Pallor - Difficulty-Ranked Guide

HARD QUESTIONS (Show-stoppers - Examiners use these to separate good from excellent candidates)

1. "Classify anemia for me."

• Decreased production (hypoproliferative) - nutritional, marrow failure, EPO deficiency
• Increased destruction (hemolytic) - hereditary (spherocytosis, G6PD, thalassemia, sickle cell) or acquired (immune, microangiopathic, infections)
• Blood loss - acute or chronic

2. "How does hepcidin explain the difference between iron deficiency anemia and anemia of chronic disease?"

• Iron deficiency anemia: Low iron stores → HFE protein on hepatocytes senses low iron → hepcidin production falls → ferroportin is not blocked → maximum iron absorption from duodenum. Result: low ferritin, low serum iron, high TIBC, low transferrin saturation.
• Anemia of chronic disease (ACI/ACD): Chronic inflammation → IL-6 upregulates hepcidin production → hepcidin blocks ferroportin on enterocytes AND macrophages → iron is trapped in macrophages and cannot reach erythroid precursors → functional iron deficiency despite adequate iron stores. Result: low serum iron, LOW TIBC (distinguishing feature), normal or HIGH ferritin.

3. "What is the reticulocyte count telling you, and how do you use it to approach anemia?"

• High reticulocyte count (>2-3%): Bone marrow is responding appropriately → the problem is outside the marrow. Think blood loss or hemolysis. The marrow is working fine - something is destroying or losing the RBCs faster than they are being made.
• Low/normal reticulocyte count in the setting of anemia: Marrow is NOT responding → hypoproliferative state. Think nutritional deficiency (iron, B12, folate), aplastic anemia, myelophthisis, chronic disease, renal failure (EPO deficiency).

4. "Tell me the sequence of events in progressive iron deficiency."

1. Pre-latent (Storage depletion): Iron stores fall → serum ferritin drops below 12 µg/L → serum iron and Hb still normal. No anemia yet.
2. Latent (Iron-deficient erythropoiesis): Stores exhausted → serum iron falls, TIBC rises, transferrin saturation drops below 16% → protoporphyrin accumulates in red cells. MCV begins to fall. Still no frank anemia.
3. Iron deficiency anemia: Frank anemia appears → microcytic hypochromic picture, poikilocytosis, pencil cells, target cells in peripheral smear.

5. "What are the features that distinguish pernicious anemia from folate deficiency? How do you tell them apart?"

6. "What is hemolytic anemia? How do you distinguish intravascular from extravascular hemolysis?"

7. "What is the pathophysiology of splenomegaly in hemolytic anemia?"

MODERATE QUESTIONS (Standard expected knowledge)

8. "Where do you look for pallor and why those sites?"

1. Conjunctival pallor (lower palpebral conjunctiva) - Most reliable; the conjunctival vessels reflect tissue perfusion. Pull down the lower lid - pale pink or white = significant anemia (Hb usually <9-10 g/dL in studies)
2. Palmar crease pallor - Creases themselves become pale (normally remain pink even when palm is pale)
3. Nail bed pallor - Press on the nail, release, and the return of pink color is delayed or the bed looks pale
4. Tongue/buccal mucosa - Oral mucosa is normally deep pink
5. Skin (overall) - Less reliable due to skin tone variation

9. "What is the normal hemoglobin range and when do we define anemia?"

• Men: Hb < 13 g/dL
• Women (non-pregnant): Hb < 12 g/dL
• Pregnant women: Hb < 11 g/dL
• Children 6-59 months: Hb < 11 g/dL

10. "Enumerate the causes of microcytic hypochromic anemia." (Mnemonic: TAILS or SITS)

• Thalassemia
• Anemia of chronic disease (sometimes)
• Iron deficiency anemia
• Lead poisoning
• Sideroblastic anemia

11. "What are the causes of macrocytic anemia?"

• B12 deficiency: pernicious anemia, gastrectomy, ileal resection, Crohn's, fish tapeworm, vegan diet, bacterial overgrowth
• Folate deficiency: poor diet (alcoholism), pregnancy, malabsorption, drugs (methotrexate, trimethoprim, phenytoin, OCP)
• Drugs affecting DNA synthesis: hydroxyurea, azathioprine, chemotherapy

• Liver disease
• Alcohol (direct toxic effect on marrow, independent of folate)
• Hypothyroidism
• Reticulocytosis (reticulocytes are larger)
• Myelodysplastic syndrome

12. "What is the Coombs test and when do you use it?"

• Positive DAT = Autoimmune hemolytic anemia (AIHA), hemolytic transfusion reaction, drug-induced immune hemolysis, hemolytic disease of the newborn

13. "What specific features on history would help you find the cause of anemia?"

14. "What is the peripheral blood smear in iron deficiency anemia?"

• Microcytes (small RBCs)
• Hypochromia (increased central pallor >1/3 of cell diameter)
• Pencil/cigar-shaped cells (pencil poikilocytes)
• Target cells (codocytes) - occasionally
• Elliptocytes
• Anisocytosis (variation in size) and poikilocytosis (variation in shape) = increased RDW
• Low reticulocyte count (hypoproliferative)
• Platelets may be elevated (reactive thrombocytosis from iron deficiency)

15. "What are the lab findings in iron deficiency anemia vs anemia of chronic disease?"

EASY QUESTIONS (Scoring points - should be answered flawlessly)

16. "What is the most common cause of anemia worldwide?"

17. "What are the symptoms of anemia?"

• Fatigue, weakness, easy fatigability
• Dyspnea on exertion
• Palpitations
• Dizziness, lightheadedness
• Headache
• Poor concentration

• Glossitis, angular cheilitis, koilonychia (spoon nails) - IDA
• Jaundice, splenomegaly - hemolytic
• Neurological symptoms - B12
• Plummer-Vinson syndrome (dysphagia + IDA from esophageal webs) - IDA

18. "What are the signs specific to iron deficiency anemia?"

• Koilonychia (spoon-shaped nails)
• Angular cheilitis (cracks at corners of mouth)
• Glossitis (smooth, sore tongue)
• Pica (craving for non-food items - ice, dirt)
• Plummer-Vinson / Paterson-Kelly syndrome (post-cricoid dysphagia + IDA + esophageal webs)
• Pallor
• Hair loss

19. "What investigations would you order for a patient with suspected anemia?"

• Full blood count (CBC) - Hb, MCV, RDW, reticulocyte count
• Peripheral blood smear
• Serum iron, TIBC, ferritin (if microcytic)
• Serum B12 and folate (if macrocytic)

• LDH, haptoglobin, indirect bilirubin (hemolysis screen)
• Direct Coombs test (if immune hemolysis suspected)
• Hemoglobin electrophoresis (thalassemia/hemoglobinopathy)
• Reticulocyte count
• Bone marrow aspiration/biopsy (if aplastic anemia or infiltration suspected)
• Stool for occult blood (GI blood loss)
• Upper and lower GI endoscopy (IDA in adults)

20. "What is the treatment of iron deficiency anemia?"

1. Treat the underlying cause (most important - find the bleeding source)
2. Oral iron replacement: Ferrous sulfate 325 mg (65 mg elemental iron) three times daily, taken on an empty stomach with vitamin C to enhance absorption. Avoid taking with tea, milk, antacids.
3. Duration: 3 months after Hb normalizes to replenish stores
4. IV iron (ferric carboxymaltose, iron sucrose): if oral not tolerated, malabsorption, ongoing blood loss, or rapid repletion needed (e.g., late pregnancy, dialysis)
5. Blood transfusion: only if severely symptomatic (Hb <7 g/dL, or higher threshold if cardiac disease) - not first-line for chronic IDA

21. "What is the treatment of pernicious anemia?"

• Hydroxocobalamin (B12) IM injections: 1000 µg on alternate days for 2 weeks (loading doses), then 1000 µg every 3 months for life
• Oral high-dose B12 (1000-2000 µg/day) works even without intrinsic factor via passive diffusion - an alternative if injections not feasible
• Monitor potassium (hypokalemia can occur as marrow rapidly resumes erythropoiesis)
• Neurological recovery is slower than hematological; neurological damage may be permanent if longstanding

22. "What is aplastic anemia and what are its causes?"

• Idiopathic/Autoimmune (most common ~70%) - T-cell mediated destruction of stem cells
• Drugs: chloramphenicol, NSAIDs, sulfonamides, carbamazepine, gold
• Toxins: benzene, radiation
• Viral: hepatitis (non-A, non-B, non-C), EBV, CMV, HIV, parvovirus B19
• Inherited: Fanconi anemia (chromosome instability + skeletal anomalies + café-au-lait spots)
• PNH (paroxysmal nocturnal hemoglobinuria - can evolve to or from aplastic anemia)

BONUS: Hard Clinical Scenario Questions