A 27-year-old woman of Chinese descent has been told she has had mild anemia since childhood. Three days after starting nitrofurantoin for a urinary infection, she becomes jaundiced. Results: Hb 7.2 g/dL [72 g/L] (usually about 9.5 g/dL [95 g/L]), RBC 4.80 × 10^6/µL [4.80 × 10^12/L], MCV 60 fL, reticulocytes 9%, ferritin 110 ng/mL [110 µg/L] (reference 15-150 ng/mL) and DAT negative. After incubation with brilliant cresyl blue, many red cells show fine, evenly spaced inclusions. HPLC shows a very early-eluting (fast) peak of 11%, Hb A2 1.4% (reference 2.0-3.3%) and Hb F 0.8%. Which disorder best explains all of these findings?

Hb H disease (alpha-thalassemia)

A 3-year-old girl lives in an older house that is being renovated, and her parents have seen her chewing paint flakes. Results: Hb 9.8 g/dL [98 g/L] (reference for age 11.5-13.5 g/dL), RBC 4.20 × 10^6/µL [4.20 × 10^12/L], MCV 71 fL (reference for age 75-87 fL), RDW 15.1%, reticulocytes 1.4%, ferritin 42 ng/mL [42 µg/L] (reference 12-150 ng/mL) and zinc protoporphyrin 210 µmol/mol heme (reference < 40). The blood film shows many red cells with coarse basophilic stippling. Her WBC and platelet counts are normal. Which test should be done next?

Pyrimidine 5'-nucleotidase assay

A 31-year-old man with beta-thalassemia intermedia has never needed a transfusion. He takes no iron or vitamin supplements and drinks little alcohol. Results: Hb 8.4 g/dL [84 g/L], MCV 63 fL, nucleated red cells 6/100 WBC, reticulocytes 4.0%, Hb F 28%, Hb A2 4.8%, ferritin 1,280 ng/mL [1,280 µg/L] (reference 30-400 ng/mL), transferrin saturation 81% (reference 20-50%) and a normal CRP. HFE genotyping finds no C282Y or H63D variant, and his serum hepcidin is low. What is the main cause of his iron overload?

Erythroid drive suppressing hepcidin

Unrecognized hereditary hemochromatosis

Hepatic inflammation raising ferritin

Iron released from hemolyzed red cells

A 30-year-old woman of Greek descent has MCV 61 fL, RBC 5.1 x 10^6/µL [5.1 x 10^12/L], ferritin 5 ng/mL [5 µg/L] (reference 15-150) and Hb A2 3.2% (reference 2.0-3.3%). Her brother has beta-thalassemia trait. The best next step is:

Repeat Hb A2 after iron stores are replete

Report beta-thalassemia trait as excluded

Order alpha-globin gene deletion testing

Request a bone marrow iron stain

Microcytic anemias: iron deficiency, thalassemia, sideroblastic, chronic inflammation

30 ASCP MLS practice questions on Microcytic anemias: iron deficiency, thalassemia, sideroblastic, chronic inflammation, part of Hematology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 27-year-old woman of Chinese descent has been told she has had mild anemia since childhood. Three days after starting nitrofurantoin for a urinary infection, she becomes jaundiced. Results: Hb 7.2 g/dL [72 g/L] (usually about 9.5 g/dL [95 g/L]), RBC 4.80 × 10^6/µL [4.80 × 10^12/L], MCV 60 fL, reticulocytes 9%, ferritin 110 ng/mL [110 µg/L] (reference 15-150 ng/mL) and DAT negative. After incubation with brilliant cresyl blue, many red cells show fine, evenly spaced inclusions. HPLC shows a very early-eluting (fast) peak of 11%, Hb A2 1.4% (reference 2.0-3.3%) and Hb F 0.8%. Which disorder best explains all of these findings?
1. AG6PD deficiency
2. BUnstable hemoglobin variant
3. CBeta-thalassemia intermedia
4. DHb H disease (alpha-thalassemia)
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Answer: D · Hb H disease (alpha-thalassemia)
A lifelong microcytic anemia with a normal ferritin, a low Hb A2, a fast HPLC peak and fine 'golf ball' inclusions after brilliant cresyl blue incubation is the picture of Hb H disease. Loss or failure of three of the four alpha genes leaves excess beta chains, which form Hb H tetramers. Hb H is unstable and precipitates under oxidant stress, so drugs such as nitrofurantoin and infections can cause acute hemolytic episodes on top of the chronic anemia. G6PD deficiency also causes oxidant hemolysis, but it does not explain lifelong microcytosis, a low Hb A2 or a fast Hb H peak. An unstable variant forms a few large Heinz bodies, and beta-thalassemia intermedia raises Hb A2 and Hb F.
- A: G6PD deficiency causes oxidant hemolysis but not lifelong microcytosis, a low Hb A2 or a fast Hb H peak.
- B: Unstable variants form a few large Heinz bodies, not many fine inclusions with a fast HPLC peak.
- C: Beta-thalassemia raises Hb A2 and usually Hb F; here Hb A2 is low.
Question 2 · Hard
A 3-year-old girl lives in an older house that is being renovated, and her parents have seen her chewing paint flakes. Results: Hb 9.8 g/dL [98 g/L] (reference for age 11.5-13.5 g/dL), RBC 4.20 × 10^6/µL [4.20 × 10^12/L], MCV 71 fL (reference for age 75-87 fL), RDW 15.1%, reticulocytes 1.4%, ferritin 42 ng/mL [42 µg/L] (reference 12-150 ng/mL) and zinc protoporphyrin 210 µmol/mol heme (reference < 40). The blood film shows many red cells with coarse basophilic stippling. Her WBC and platelet counts are normal. Which test should be done next?
1. APyrimidine 5'-nucleotidase assay
2. BVenous whole-blood lead level
3. CHb A2 and Hb F quantitation
4. DBone marrow iron stain
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Answer: B · Venous whole-blood lead level
Paint chewing in an older home, coarse basophilic stippling and a very high zinc protoporphyrin with a normal ferritin point to lead poisoning. Lead inhibits delta-aminolevulinic acid dehydratase and ferrochelatase, so zinc instead of iron enters protoporphyrin, and it inhibits pyrimidine 5'-nucleotidase, so RNA remnants form the stippling. A venous whole-blood lead level confirms the diagnosis and guides treatment; a raised fingerstick result should be confirmed on a venous sample. The Mentzer index of 16.9 (71 ÷ 4.20) and the normal ferritin argue against thalassemia trait and iron deficiency. A marrow examination is invasive and not needed when the cause is this clear.
- A: Inherited P5'N deficiency causes hemolysis; lead, which inhibits the same enzyme, must be excluded first.
- C: A Mentzer index of 16.9 and the exposure history do not suggest thalassemia trait.
- D: A marrow iron stain is invasive and would not identify the toxin.
Question 3 · Hard
A 31-year-old man with beta-thalassemia intermedia has never needed a transfusion. He takes no iron or vitamin supplements and drinks little alcohol. Results: Hb 8.4 g/dL [84 g/L], MCV 63 fL, nucleated red cells 6/100 WBC, reticulocytes 4.0%, Hb F 28%, Hb A2 4.8%, ferritin 1,280 ng/mL [1,280 µg/L] (reference 30-400 ng/mL), transferrin saturation 81% (reference 20-50%) and a normal CRP. HFE genotyping finds no C282Y or H63D variant, and his serum hepcidin is low. What is the main cause of his iron overload?
1. AUnrecognized hereditary hemochromatosis
2. BHepatic inflammation raising ferritin
3. CIron released from hemolyzed red cells
4. DErythroid drive suppressing hepcidin
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Answer: D · Erythroid drive suppressing hepcidin
In thalassemia intermedia the marrow is greatly expanded, but many erythroblasts die before they are released (ineffective erythropoiesis). The expanded erythroblast mass secretes erythroferrone, which suppresses hepcidin in the liver, so ferroportin stays active and the gut absorbs far more iron than the body needs, even without transfusion. The high transferrin saturation with a low hepcidin, a normal CRP and no HFE variant fits this mechanism. Iron from red cells destroyed in the marrow or spleen is recycled by macrophages and does not add to total body iron. Non-transfused patients can therefore become iron overloaded and need regular ferritin monitoring and sometimes chelation.
- A: No HFE variant is found, and hepcidin suppression by erythroid drive explains the picture.
- B: CRP is normal, and inflammation raises hepcidin and lowers transferrin saturation, the opposite of this.
- C: Iron from destroyed red cells is recycled within the body and does not raise total body iron.
Question 4 · Hard
A 34-year-old man was given oral iron for microcytosis. After 3 months, MCV is unchanged at 63 fL, RBC 6.2 x 10^6/µL [6.2 x 10^12/L], RDW 13.0% and ferritin 140 ng/mL [140 µg/L] (reference 30-400). The most appropriate next step is:
1. ABone marrow iron stain
2. BSwitch to intravenous iron
3. CTest vitamin B12 and folate
4. DHb A2 and Hb F quantitation
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Answer: D · Hb A2 and Hb F quantitation
The indices fit thalassemia trait: a high RBC count, a normal RDW and a Mentzer index of 10.2 (63 ÷ 6.2). Ferritin is now normal, yet the MCV has not moved, so iron deficiency was not the cause of the microcytosis. Hb A2 and Hb F quantitation by HPLC or capillary electrophoresis is the next step, and a raised Hb A2 would confirm beta-thalassemia trait. Continuing iron in a carrier with normal stores brings no benefit and can cause harm.
- A: Ferritin already shows adequate stores, so a marrow stain adds little.
- B: Stores are now replete, so more iron by any route will not help.
- C: B12 or folate deficiency causes macrocytosis, not a low MCV.
Question 5 · Hard
A 30-year-old woman of Greek descent has MCV 61 fL, RBC 5.1 x 10^6/µL [5.1 x 10^12/L], ferritin 5 ng/mL [5 µg/L] (reference 15-150) and Hb A2 3.2% (reference 2.0-3.3%). Her brother has beta-thalassemia trait. The best next step is:
1. AReport beta-thalassemia trait as excluded
2. BOrder alpha-globin gene deletion testing
3. CRepeat Hb A2 after iron stores are replete
4. DRequest a bone marrow iron stain
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Answer: C · Repeat Hb A2 after iron stores are replete
Iron deficiency reduces Hb A2 synthesis, so a normal Hb A2 does not exclude beta-thalassemia trait in an iron-deficient patient. Her very low ferritin confirms iron deficiency, while the family history and a Mentzer index of 12.0 (61 ÷ 5.1) raise the chance of coexisting thalassemia trait. Hb A2 should be measured again once iron stores are replete. If it is still normal, alpha-thalassemia testing can then be considered.
- A: Iron deficiency can push Hb A2 down into the normal range, so trait is not excluded.
- B: Alpha-thalassemia testing comes later, after iron repletion and a repeat Hb A2.
- D: Ferritin already shows iron deficiency; a marrow stain adds nothing.
Question 6 · Medium
In anemia of chronic inflammation, hepcidin lowers serum iron mainly by:
1. ABlocking transferrin synthesis in the liver
2. BIncreasing iron loss in the urine
3. CDegrading ferroportin, blocking iron export
4. DInhibiting ferrochelatase in erythroblasts
Answer and explanation in LearnFree account
Question 7 · Easy
In a ring sideroblast, the iron granules seen with Prussian blue stain lie in:
1. AGranules scattered in the cytoplasm
2. BThe nucleus of the erythroblast
3. CMitochondria that encircle the nucleus
4. DNearby bone marrow macrophages
Answer and explanation in LearnFree account
Question 8 · Hard
Given Hb 11.1 g/dL [111 g/L], RBC 5.70 x 10^6/µL [5.70 x 10^12/L] and MCV 62 fL, what is the Mentzer index, and what does it suggest?
1. A10.9, favoring iron deficiency
2. B10.9, favoring thalassemia trait
3. C0.09, favoring thalassemia trait
4. D5.6, favoring thalassemia trait
Answer and explanation in LearnFree account
Question 9 · Easy
Hb A2, which rises in beta-thalassemia trait, is made of two alpha chains and two:
1. AGamma chains
2. BEpsilon chains
3. CDelta chains
4. DBeta chains
Answer and explanation in LearnFree account
Question 10 · Medium
Why does zinc protoporphyrin rise in red cells during iron-deficient erythropoiesis?
1. AFerrochelatase inserts zinc when iron is lacking
2. BALA dehydratase is inhibited by iron lack
3. CFerrochelatase is lost from iron-poor erythroblasts
4. DZinc absorption rises as iron absorption falls
Answer and explanation in LearnFree account
Question 11 · Easy
The most common hereditary sideroblastic anemia is X-linked. Its gene codes for which heme synthesis enzyme?
1. AUroporphyrinogen decarboxylase
2. BALA dehydratase
3. CALA synthase (ALAS2)
4. DFerrochelatase
Answer and explanation in LearnFree account
Question 12 · Hard
A woman with active rheumatoid arthritis has Hb 9.8 g/dL [98 g/L], MCV 74 fL, ferritin 70 ng/mL [70 µg/L] (reference 15-150), a raised CRP and a soluble transferrin receptor above its reference range. The best interpretation is:
1. AAnemia of chronic kidney disease
2. BAnemia of inflammation alone
3. CFolate deficiency from methotrexate
4. DIron deficiency plus anemia of inflammation
Answer and explanation in LearnFree account
Question 13 · Easy
Pagophagia, a compulsive craving to chew ice, is most closely linked with:
1. AVitamin B12 deficiency
2. BIron deficiency
3. CAnemia of chronic inflammation
4. DFolate deficiency
Answer and explanation in LearnFree account
Question 14 · Hard
Given these results: Hb 11.8 g/dL [118 g/L], MCV 68 fL, normal ferritin, Hb A2 2.6% (reference 2.0-3.3%), Hb F 12%, and Hb F spread unevenly among the red cells (heterocellular). What is the most likely diagnosis?
1. ABeta-thalassemia trait
2. BAlpha-thalassemia trait
3. CHereditary persistence of fetal Hb
4. DDelta-beta thalassemia trait
Answer and explanation in LearnFree account
Question 15 · Medium
In a patient with microcytic anemia, which other finding most favors iron deficiency over thalassemia trait?
1. AAn RBC count of 6.2 x 10^6/µL [6.2 x 10^12/L]
2. BMany target cells on the film
3. CBasophilic stippling
4. DAn RDW of 19.0%
Answer and explanation in LearnFree account
Question 16 · Hard
Given these results: Hb 13.6 g/dL [136 g/L], MCV 84 fL, ferritin 7 ng/mL [7 µg/L] (reference 15-150), transferrin saturation 9% (reference 20-50%) and raised zinc protoporphyrin. Which stage of iron deficiency do they show?
1. AEstablished iron deficiency anemia
2. BFunctional iron deficiency
3. CStorage iron depletion only
4. DIron-deficient erythropoiesis without anemia
Answer and explanation in LearnFree account
Question 17 · Hard
A woman from Cambodia has Hb 12.1 g/dL [121 g/L] and MCV 72 fL. Cation-exchange HPLC reports 28% hemoglobin in the Hb A2 window, with the rest Hb A. The most likely diagnosis is:
1. AAlpha-thalassemia trait
2. BHemoglobin E trait
3. CBeta-thalassemia trait
4. DHemoglobin C trait
Answer and explanation in LearnFree account
Question 18 · Medium
Beta-thalassemia major is usually silent at birth and appears at about 6 to 12 months of age. Why?
1. AAlpha-chain synthesis starts after birth
2. BMaternal Hb A is cleared from the baby
3. CMaternal iron stores run out
4. DGamma-chain production declines after birth
Answer and explanation in LearnFree account
Question 19 · Hard
Both partners in a couple from Thailand carry the cis two-gene alpha-thalassemia deletion (--/αα). What is the chance, in each pregnancy, of a fetus with Hb Bart's hydrops fetalis?
1. A50%
2. B0%
3. C75%
4. D25%
Answer and explanation in LearnFree account
Question 20 · Hard
A man on isoniazid, rifampin, pyrazinamide and ethambutol for tuberculosis develops anemia with a dimorphic film and Pappenheimer bodies. Ferritin is raised and the marrow shows ring sideroblasts. He takes no vitamin supplements. The most likely cause is:
1. AEthambutol
2. BIsoniazid
3. CPyrazinamide
4. DRifampin
Answer and explanation in LearnFree account
Question 21 · Medium
A blood film shows two red cell populations, one normocytic and one microcytic and hypochromic, with Pappenheimer bodies. Serum iron and ferritin are raised. The most likely diagnosis is:
1. AAnemia of chronic inflammation
2. BIron deficiency anemia
3. CSideroblastic anemia
4. DBeta-thalassemia trait
Answer and explanation in LearnFree account
Question 22 · Medium
Soluble transferrin receptor (sTfR) helps separate iron deficiency from anemia of chronic inflammation because sTfR:
1. AIs an acute-phase reactant that rises like ferritin
2. BRises in iron deficiency, not with inflammation
3. CReflects storage iron in marrow macrophages
4. DFalls in iron deficiency, rises with inflammation
Answer and explanation in LearnFree account
Question 23 · Medium
A 64-year-old man has newly found iron deficiency anemia. He eats a normal diet and takes no drugs. The cause that must be looked for first is:
1. AIncreased iron requirement
2. BGastrointestinal blood loss
3. CPoor dietary iron intake
4. DHemosiderinuria from hemolysis
Answer and explanation in LearnFree account
Question 24 · Medium
Which iron profile is typical of anemia of chronic inflammation?
1. AHigh iron, low TIBC, high ferritin
2. BNormal iron, normal TIBC, low ferritin
3. CLow iron, high TIBC, low ferritin
4. DLow iron, low TIBC, normal or high ferritin
Answer and explanation in LearnFree account
Question 25 · Medium
An adult has Hb 11.6 g/dL [116 g/L], MCV 69 fL, a normal ferritin, Hb A2 2.4% (reference 2.0-3.3%) and normal Hb F. Which test would confirm the most likely cause?
1. AAlpha-globin gene deletion analysis by PCR
2. BBone marrow Prussian blue stain
3. CHemoglobin solubility test
4. DRepeat Hb A2 after a trial of oral iron
Answer and explanation in LearnFree account

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Microcytic anemias: iron deficiency, thalassemia, sideroblastic, chronic inflammation

A 34-year-old man was given oral iron for microcytosis. After 3 months, MCV is unchanged at 63 fL, RBC 6.2 x 10^6/µL [6.2 x 10^12/L], RDW 13.0% and ferritin 140 ng/mL [140 µg/L] (reference 30-400). The most appropriate next step is:

A 30-year-old woman of Greek descent has MCV 61 fL, RBC 5.1 x 10^6/µL [5.1 x 10^12/L], ferritin 5 ng/mL [5 µg/L] (reference 15-150) and Hb A2 3.2% (reference 2.0-3.3%). Her brother has beta-thalassemia trait. The best next step is:

In anemia of chronic inflammation, hepcidin lowers serum iron mainly by:

In a ring sideroblast, the iron granules seen with Prussian blue stain lie in:

Given Hb 11.1 g/dL [111 g/L], RBC 5.70 x 10^6/µL [5.70 x 10^12/L] and MCV 62 fL, what is the Mentzer index, and what does it suggest?

Hb A2, which rises in beta-thalassemia trait, is made of two alpha chains and two:

Why does zinc protoporphyrin rise in red cells during iron-deficient erythropoiesis?

The most common hereditary sideroblastic anemia is X-linked. Its gene codes for which heme synthesis enzyme?

A woman with active rheumatoid arthritis has Hb 9.8 g/dL [98 g/L], MCV 74 fL, ferritin 70 ng/mL [70 µg/L] (reference 15-150), a raised CRP and a soluble transferrin receptor above its reference range. The best interpretation is:

Pagophagia, a compulsive craving to chew ice, is most closely linked with:

Given these results: Hb 11.8 g/dL [118 g/L], MCV 68 fL, normal ferritin, Hb A2 2.6% (reference 2.0-3.3%), Hb F 12%, and Hb F spread unevenly among the red cells (heterocellular). What is the most likely diagnosis?

In a patient with microcytic anemia, which other finding most favors iron deficiency over thalassemia trait?

Given these results: Hb 13.6 g/dL [136 g/L], MCV 84 fL, ferritin 7 ng/mL [7 µg/L] (reference 15-150), transferrin saturation 9% (reference 20-50%) and raised zinc protoporphyrin. Which stage of iron deficiency do they show?

A woman from Cambodia has Hb 12.1 g/dL [121 g/L] and MCV 72 fL. Cation-exchange HPLC reports 28% hemoglobin in the Hb A2 window, with the rest Hb A. The most likely diagnosis is:

Beta-thalassemia major is usually silent at birth and appears at about 6 to 12 months of age. Why?

Both partners in a couple from Thailand carry the cis two-gene alpha-thalassemia deletion (--/αα). What is the chance, in each pregnancy, of a fetus with Hb Bart's hydrops fetalis?

A man on isoniazid, rifampin, pyrazinamide and ethambutol for tuberculosis develops anemia with a dimorphic film and Pappenheimer bodies. Ferritin is raised and the marrow shows ring sideroblasts. He takes no vitamin supplements. The most likely cause is:

A blood film shows two red cell populations, one normocytic and one microcytic and hypochromic, with Pappenheimer bodies. Serum iron and ferritin are raised. The most likely diagnosis is:

Soluble transferrin receptor (sTfR) helps separate iron deficiency from anemia of chronic inflammation because sTfR:

A 64-year-old man has newly found iron deficiency anemia. He eats a normal diet and takes no drugs. The cause that must be looked for first is:

Which iron profile is typical of anemia of chronic inflammation?

An adult has Hb 11.6 g/dL [116 g/L], MCV 69 fL, a normal ferritin, Hb A2 2.4% (reference 2.0-3.3%) and normal Hb F. Which test would confirm the most likely cause?