At premarital screening in Abu Dhabi, a 25-year-old woman is found to carry beta-thalassemia trait (Hb A2 5.6%, MCV 64 fL, normal ferritin). Her fiancé lives abroad and has sent only a CBC from a local clinic: hemoglobin 147 g/L (14.7 g/dL), RBC 6.45 × 10^12/L, MCV 67 fL, MCH 22.8 pg and RDW 13.0% (reference 11.5-14.5%). No ferritin or hemoglobin studies were done. The laboratory uses a Mentzer index cut-off of 13. Based on his Mentzer index and the other results, what should the laboratory advise the couple?

Measure his Hb A2 before counselling them

Reassure them that his results exclude a carrier state

Plan prenatal diagnosis for every pregnancy

Treat him for iron deficiency, then repeat the CBC

A couple attends premarital screening. The woman has beta-thalassemia trait (Hb A2 5.1%, MCV 65 fL, normal ferritin). The man, aged 28, is well and takes no medicines: hemoglobin 151 g/L (15.1 g/dL), RBC 5.6 × 10^12/L, MCV 81 fL (reference 80-100), MCH 27.0 pg (reference 27-32) and ferritin 96 µg/L (reference 30-400), with normal serum B12 and thyroid function. HPLC: Hb A2 5.3% (laboratory cut-off for beta-thalassemia trait 3.5%), Hb F 0.9%, no variant peak; sickle solubility negative. A second sample gives the same result. How should his result be interpreted?

Beta-thalassemia carrier; the couple is at risk

Not a carrier, because his MCV and MCH are normal

Hb A2 raised by vitamin B12 deficiency

Four adults all have MCV 66-74 fL (Hb A2 reference 2.0-3.3%; ferritin reference 15-150 µg/L; RBC in x 10^12/L). Which result set best fits beta-thalassemia trait?

RBC 6.1, ferritin 90 µg/L, Hb A2 5.2%

RBC 5.8, ferritin 85 µg/L, Hb A2 2.4%

RBC 4.3, ferritin 400 µg/L, Hb A2 2.6%

RBC 4.1, ferritin 6 µg/L, Hb A2 2.1%

Thalassemias and premarital screening

27 DOH Abu Dhabi (HAAD) lab licensing practice questions on Thalassemias and premarital screening, 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
At premarital screening in Abu Dhabi, a 25-year-old woman is found to carry beta-thalassemia trait (Hb A2 5.6%, MCV 64 fL, normal ferritin). Her fiancé lives abroad and has sent only a CBC from a local clinic: hemoglobin 147 g/L (14.7 g/dL), RBC 6.45 × 10^12/L, MCV 67 fL, MCH 22.8 pg and RDW 13.0% (reference 11.5-14.5%). No ferritin or hemoglobin studies were done. The laboratory uses a Mentzer index cut-off of 13. Based on his Mentzer index and the other results, what should the laboratory advise the couple?
1. AMeasure his Hb A2 before counselling them
2. BReassure them that his results exclude a carrier state
3. CPlan prenatal diagnosis for every pregnancy
4. DTreat him for iron deficiency, then repeat the CBC
Show answerHide answer
Answer: A · Measure his Hb A2 before counselling them
His Mentzer index is MCV ÷ RBC = 67 ÷ 6.45 = 10.4, below 13, and with a high RBC count, low MCH and normal RDW it favors thalassemia trait over iron deficiency. Because his fiancée carries beta-thalassemia, the key question is whether he does too: if both are beta carriers, each pregnancy has a 1 in 4 chance of beta-thalassemia major. The next step is Hb A2 measurement by HPLC or capillary electrophoresis, with a ferritin and a variant screen. A raised Hb A2 would confirm beta-thalassemia trait, while a normal Hb A2 with normal ferritin would point to alpha-thalassemia trait, which does not combine with her trait to cause thalassemia major. The index is only a screening aid, and prenatal diagnosis is offered once both partners are shown to be carriers.
- B: An index below 13 suggests, rather than excludes, thalassemia trait.
- C: Prenatal diagnosis is offered only after both partners are confirmed as carriers.
- D: An index of 10.4 with a high RBC count and normal RDW points away from iron deficiency.
Question 2 · Hard
A couple attends premarital screening. The woman has beta-thalassemia trait (Hb A2 5.1%, MCV 65 fL, normal ferritin). The man, aged 28, is well and takes no medicines: hemoglobin 151 g/L (15.1 g/dL), RBC 5.6 × 10^12/L, MCV 81 fL (reference 80-100), MCH 27.0 pg (reference 27-32) and ferritin 96 µg/L (reference 30-400), with normal serum B12 and thyroid function. HPLC: Hb A2 5.3% (laboratory cut-off for beta-thalassemia trait 3.5%), Hb F 0.9%, no variant peak; sickle solubility negative. A second sample gives the same result. How should his result be interpreted?
1. ADelta-beta thalassemia trait
2. BNot a carrier, because his MCV and MCH are normal
3. CHb A2 raised by vitamin B12 deficiency
4. DBeta-thalassemia carrier; the couple is at risk
Show answerHide answer
Answer: D · Beta-thalassemia carrier; the couple is at risk
A Hb A2 of 5.3%, confirmed on a second sample with normal ferritin, identifies beta-thalassemia trait whatever the red cell indices. Near-normal MCV and MCH in a beta carrier are usually explained by co-inherited alpha-thalassemia, which is very common in the Gulf: fewer alpha chains balance the reduced beta chains, so the cells fill better, while Hb A2 stays raised. B12 deficiency can raise Hb A2 slightly, but his B12 is normal, and delta-beta thalassemia trait gives a normal or low Hb A2 with a raised Hb F. Because both partners carry beta-thalassemia, each pregnancy has a 1 in 4 chance of beta-thalassemia major, so they need genetic counselling. This is why premarital programs measure Hb A2 in everyone rather than only in people with low indices.
- A: Delta-beta thalassemia trait has a normal or low Hb A2 and a raised Hb F.
- B: Hb A2 decides beta-carrier status; co-inherited alpha-thalassemia can make the indices near normal.
- C: His B12 is normal, and B12 deficiency raises Hb A2 only slightly.
Question 3 · Hard
At premarital screening, a 26-year-old man whose family comes from the eastern Mediterranean has hemoglobin 132 g/L (13.2 g/dL), RBC 5.9 × 10^12/L, MCV 69 fL, MCH 22.4 pg and ferritin 88 µg/L (reference 30-400). The sickle solubility test is negative. Cation-exchange HPLC: Hb A 81.9%, a peak in the Hb A2 window of 12.6% (laboratory cut-off for beta-thalassemia trait 3.5%), Hb F 5.1% (reference below 1%), and no other peak. A repeat sample gives the same pattern. His fiancée carries beta-thalassemia trait. The most likely interpretation of his result is:
1. AHb Lepore trait
2. BBeta-thalassemia trait
3. CHb E trait
4. DDelta-beta thalassemia trait
Show answerHide answer
Answer: A · Hb Lepore trait
A value of 12.6% in the Hb A2 window is too high for beta-thalassemia trait, in which Hb A2 rarely exceeds about 7-8%, so a variant eluting with Hb A2 should be suspected. Hb Lepore is a delta-beta fusion globin made at a low rate; it forms about 5-15% of the hemoglobin in carriers and elutes in or close to the Hb A2 window on many HPLC systems. Carriers have microcytosis and a mildly raised Hb F, as here. Hb E trait gives about 25-30% in the same window, and delta-beta thalassemia trait has a normal or low Hb A2. The variant should be confirmed by a second method or DNA analysis, because Hb Lepore inherited with his fiancée's beta-thalassemia gene can cause thalassemia major or intermedia, so the couple is at risk.
- B: Beta-thalassemia trait rarely gives more than about 7-8% Hb A2.
- C: Hb E trait gives about 25-30% in the Hb A2 window.
- D: Delta-beta thalassemia trait has a normal or low Hb A2.
Question 4 · Hard
The pedigree shows a family's HPLC results; II-1 has transfusion-dependent beta-thalassemia major, and all tested adults have a normal ferritin. II-2 is well, has not been tested, and plans to marry II-3. Before she is tested, what is the risk that their first child will have beta-thalassemia major?
Figure: MedExams
1. A1 in 4
2. B1 in 12
3. C1 in 8
4. D1 in 6
Show answerHide answer
Answer: D · 1 in 6
Both parents have a raised Hb A2 with normal iron stores, so both carry beta-thalassemia, as their affected son confirms. Their children can be normal, carriers or affected in a 1:2:1 ratio; II-2 is well, so she is one of the three unaffected outcomes and her chance of being a carrier is 2/3. II-3 carries the trait (Hb A2 5.6%), and two carriers have a 1 in 4 chance of an affected child. The risk is 2/3 × 1/4 = 1/6, and testing II-2 (CBC, HPLC and ferritin) will change it to either 1 in 4 or almost nil.
- A: 1 in 4 assumes II-2 is certainly a carrier.
- B: 1 in 12 takes her carrier chance as 1/3.
- C: 1 in 8 takes her carrier chance as 1/2, ignoring that she is unaffected.
Question 5 · Hard
Four adults all have MCV 66-74 fL (Hb A2 reference 2.0-3.3%; ferritin reference 15-150 µg/L; RBC in x 10^12/L). Which result set best fits beta-thalassemia trait?
1. ARBC 5.8, ferritin 85 µg/L, Hb A2 2.4%
2. BRBC 4.3, ferritin 400 µg/L, Hb A2 2.6%
3. CRBC 6.1, ferritin 90 µg/L, Hb A2 5.2%
4. DRBC 4.1, ferritin 6 µg/L, Hb A2 2.1%
Show answerHide answer
Answer: C · RBC 6.1, ferritin 90 µg/L, Hb A2 5.2%
Beta-thalassemia trait gives microcytosis with a normal or high RBC count, normal iron stores and an Hb A2 above the reference range, typically 4-6%. A low ferritin with a low RBC count and a low-normal Hb A2 is iron deficiency. A high RBC count with normal ferritin and normal Hb A2 suggests alpha-thalassemia trait, which needs DNA testing. A high ferritin with a low RBC count fits anemia of inflammation.
- A: A normal Hb A2 with normal ferritin suggests alpha-thalassemia trait.
- B: A high ferritin with a low RBC count suggests anemia of inflammation.
- D: A low ferritin with a low RBC count is iron deficiency.
Question 6 · Easy
Unlike most beta-thalassemia, most alpha-thalassemia is caused by:
1. APoint mutations in promoters or splice sites
2. BDeletions of whole alpha-globin genes
3. CUnstable alpha-chain structural variants
4. DFusion of the delta- and beta-globin genes
Answer and explanation in LearnFree account
Question 7 · Medium
A premarital screen shows that both partners carry beta-thalassemia trait. In each pregnancy, the chance of a child who inherits both thalassemia genes is:
1. A50%
2. B100%
3. C75%
4. D25%
Answer and explanation in LearnFree account
Question 8 · Medium
Why does routine HPLC usually look normal in an adult with two-gene alpha-thalassemia trait?
1. AThe missing alpha chains are replaced by embryonic zeta chains
2. BEvery adult hemoglobin has alpha chains, so the ratios stay normal
3. CAlpha-thalassemia raises Hb A2 only after the age of 40
4. DIron deficiency is always present and masks the change
Answer and explanation in LearnFree account
Question 9 · Hard
A man with beta-thalassemia trait plans to marry. His partner has not been tested; in her community about 1 in 10 people carry beta-thalassemia. Before she is tested, the risk that their first child has beta-thalassemia major is:
1. A1 in 20
2. B1 in 40
3. C1 in 10
4. D1 in 4
Answer and explanation in LearnFree account
Question 10 · Hard
A 26-year-old woman at premarital screening has Hb 118 g/L (11.8 g/dL), MCV 69 fL, RBC 5.7 x 10^12/L, ferritin 70 µg/L (reference 15-150) and Hb A2 2.4% (reference 2.0-3.3%), with no abnormal HPLC peaks. Which test is best to confirm the most likely diagnosis?
1. ASerum soluble transferrin receptor
2. BBeta-globin gene sequencing
3. CRepeat HPLC after three months of oral iron
4. DGap-PCR for common alpha-globin deletions
Answer and explanation in LearnFree account
Question 11 · Medium
Why should a premarital program not rely on the Mentzer index alone to decide who carries beta-thalassemia?
1. AIt needs a manual red cell count to be valid
2. BIts values overlap, so some carriers are misclassified
3. CIt is valid only in children under 12 years
4. DIt detects alpha but not beta-thalassemia
Answer and explanation in LearnFree account
Question 12 · Hard
A 4-year-old Emirati child has Hb 88 g/L (8.8 g/dL), MCV 58 fL, many Hb H inclusions on brilliant cresyl blue and an Hb H peak on HPLC. Gap-PCR for the common alpha-globin deletions is negative. What is the best next step?
1. ASequence the alpha-globin genes for point mutations
2. BSequence the beta-globin genes for mutations
3. CReport the Hb H peak as a storage artefact
4. DRepeat gap-PCR on a fresh sample in 3 months
Answer and explanation in LearnFree account
Question 13 · Medium
Cord blood from a newborn contains about 25% Hb Bart's. How many alpha-globin genes has the baby most likely lost?
1. AThree genes lost (Hb H disease)
2. BOne gene lost (silent carrier)
3. CTwo genes lost (alpha-thalassemia trait)
4. DFour genes lost (Hb Bart's hydrops)
Answer and explanation in LearnFree account
Question 14 · Medium
In beta-thalassemia major, most red cell precursors die in the marrow before release. The main cause is:
1. ALack of iron for heme synthesis
2. BFormation of Hb Bart's tetramers
3. CPrecipitation of unpaired alpha chains
4. DAutoantibodies against erythroblasts
Answer and explanation in LearnFree account
Question 15 · Easy
Which HPLC finding is the hallmark of typical beta-thalassemia trait?
1. AHb F above about 20%
2. BA fast-eluting Hb H peak
3. CHb A2 below about 2.0%
4. DHb A2 above about 3.5%
Answer and explanation in LearnFree account
Question 16 · Hard
A referral report lists Hb 112 g/L (11.2 g/dL), Hct 0.36 L/L and MCV 60 fL, but no RBC count. What is the Mentzer index?
1. A5.4
2. B10.0
3. C1.7
4. D100
Answer and explanation in LearnFree account
Question 17 · Medium
What is the main reason a beta-thalassemia carrier has an increased proportion of Hb A2?
1. AFewer beta chains leave more alpha chains to pair with delta
2. BGamma chains are converted into delta chains after birth
3. CThe delta-globin gene is duplicated on the affected chromosome
4. DIron deficiency in carriers increases delta-chain synthesis
Answer and explanation in LearnFree account
Question 18 · Medium
Alpha-thalassemia is very common in the Arabian Gulf, yet Hb Bart's hydrops fetalis is rare there. What is the main reason?
1. AMost carriers lack one gene per chromosome (-α), not two (--)
2. BMost affected fetuses are treated by intrauterine transfusion
3. CHigh Hb F in Arab populations prevents fetal hydrops
4. DAlpha-thalassemia in the Gulf is mainly caused by Hb E
Answer and explanation in LearnFree account
Question 19 · Medium
A 1-year-old from a consanguineous family has Hb 58 g/L (5.8 g/dL), MCV 62 fL, many target cells and nucleated red cells, and a large spleen. He has never been transfused. HPLC: Hb F 96%, Hb A2 4%, no Hb A. The most likely diagnosis is:
1. AHb H disease
2. BHomozygous beta-zero thalassemia
3. CHomozygous HPFH
4. DBeta-thalassemia trait
Answer and explanation in LearnFree account
Question 20 · Hard
At premarital screening the man has MCV 64 fL, normal ferritin and Hb A2 5.4%. The woman has MCV 71 fL, normal ferritin, Hb A2 2.5% and no variant peak. For this couple, the risk of a child with beta-thalassemia major is:
1. A50%, as his Hb A2 is markedly raised
2. B12.5%, as her alpha trait halves the risk
3. C25%, as both appear to be thalassemia carriers
4. DVery low, as only he carries a beta-thalassemia gene
Answer and explanation in LearnFree account
Question 21 · Easy
Hb Bart's, found in newborns with alpha-thalassemia, is a tetramer of:
1. ATwo alpha and two gamma chains
2. BFour beta chains
3. CFour gamma chains
4. DTwo alpha and two delta chains
Answer and explanation in LearnFree account
Question 22 · Hard
Two children are homozygous for the same severe beta-thalassemia mutation. The one who also has two-gene alpha-thalassemia (-α/-α) is much less anemic. Why?
1. AIron absorption is lower, so less iron overload occurs
2. BFewer free alpha chains precipitate in the erythroblasts
3. CThe child makes Hb Bart's, which delivers oxygen well
4. DAlpha-thalassemia increases the production of beta chains
Answer and explanation in LearnFree account
Question 23 · Medium
After incubating blood with brilliant cresyl blue, many red cells show fine, evenly spread blue inclusions, like a golf ball. This finding is most typical of:
1. AHb H disease
2. BHereditary spherocytosis
3. CG6PD deficiency
4. DLead poisoning
Answer and explanation in LearnFree account
Question 24 · Hard
At premarital screening, a 24-year-old man has Hb 128 g/L (12.8 g/dL), RBC 6.2 x 10^12/L and MCV 66 fL. Using a cut-off of 13, his Mentzer index and its interpretation are:
1. A5.2, favoring thalassemia trait
2. B10.6, favoring iron deficiency
3. C0.09, favoring thalassemia trait
4. D10.6, favoring thalassemia trait
Answer and explanation in LearnFree account
Question 25 · Hard
DNA testing shows that a woman has the two-gene cis deletion (--/αα) and her partner is a silent carrier (-α/αα). What is the chance of Hb H disease in each pregnancy?
1. A25%
2. B12.5%
3. C50%
4. D0%
Answer and explanation in LearnFree account

2 more Thalassemias and premarital screening questions

Answer them one by one, keep your score and see your weak topics in Learn. Signed-out visitors try 25 per exam; sign in with Google to see them all.

Study Hematology

Thalassemias and premarital screening

Four adults all have MCV 66-74 fL (Hb A2 reference 2.0-3.3%; ferritin reference 15-150 µg/L; RBC in x 10^12/L). Which result set best fits beta-thalassemia trait?

Unlike most beta-thalassemia, most alpha-thalassemia is caused by:

A premarital screen shows that both partners carry beta-thalassemia trait. In each pregnancy, the chance of a child who inherits both thalassemia genes is:

Why does routine HPLC usually look normal in an adult with two-gene alpha-thalassemia trait?

A man with beta-thalassemia trait plans to marry. His partner has not been tested; in her community about 1 in 10 people carry beta-thalassemia. Before she is tested, the risk that their first child has beta-thalassemia major is:

A 26-year-old woman at premarital screening has Hb 118 g/L (11.8 g/dL), MCV 69 fL, RBC 5.7 x 10^12/L, ferritin 70 µg/L (reference 15-150) and Hb A2 2.4% (reference 2.0-3.3%), with no abnormal HPLC peaks. Which test is best to confirm the most likely diagnosis?

Why should a premarital program not rely on the Mentzer index alone to decide who carries beta-thalassemia?

A 4-year-old Emirati child has Hb 88 g/L (8.8 g/dL), MCV 58 fL, many Hb H inclusions on brilliant cresyl blue and an Hb H peak on HPLC. Gap-PCR for the common alpha-globin deletions is negative. What is the best next step?

Cord blood from a newborn contains about 25% Hb Bart's. How many alpha-globin genes has the baby most likely lost?

In beta-thalassemia major, most red cell precursors die in the marrow before release. The main cause is:

Which HPLC finding is the hallmark of typical beta-thalassemia trait?

A referral report lists Hb 112 g/L (11.2 g/dL), Hct 0.36 L/L and MCV 60 fL, but no RBC count. What is the Mentzer index?

What is the main reason a beta-thalassemia carrier has an increased proportion of Hb A2?

Alpha-thalassemia is very common in the Arabian Gulf, yet Hb Bart's hydrops fetalis is rare there. What is the main reason?

A 1-year-old from a consanguineous family has Hb 58 g/L (5.8 g/dL), MCV 62 fL, many target cells and nucleated red cells, and a large spleen. He has never been transfused. HPLC: Hb F 96%, Hb A2 4%, no Hb A. The most likely diagnosis is:

At premarital screening the man has MCV 64 fL, normal ferritin and Hb A2 5.4%. The woman has MCV 71 fL, normal ferritin, Hb A2 2.5% and no variant peak. For this couple, the risk of a child with beta-thalassemia major is:

Hb Bart's, found in newborns with alpha-thalassemia, is a tetramer of:

Two children are homozygous for the same severe beta-thalassemia mutation. The one who also has two-gene alpha-thalassemia (-α/-α) is much less anemic. Why?

After incubating blood with brilliant cresyl blue, many red cells show fine, evenly spread blue inclusions, like a golf ball. This finding is most typical of:

At premarital screening, a 24-year-old man has Hb 128 g/L (12.8 g/dL), RBC 6.2 x 10^12/L and MCV 66 fL. Using a cut-off of 13, his Mentzer index and its interpretation are:

DNA testing shows that a woman has the two-gene cis deletion (--/αα) and her partner is a silent carrier (-α/αα). What is the chance of Hb H disease in each pregnancy?