MLT GlobeHematology: Hemolytic anemias & hemoglobinopathies – page 3
120 Hematology MCQs on Hemolytic anemias & hemoglobinopathies with answers and explanations.
Hydroxyurea, used in sickle cell disease and myeloproliferative neoplasms, acts mainly by inhibiting which enzyme?
Hydroxyurea blocks ribonucleotide reductase, preventing deoxyribonucleotide formation and DNA synthesis. It also raises HbF. Methotrexate inhibits dihydrofolate reductase.
Which disorder causes hemolysis chiefly outside blood vessels, in the spleen?
Spherocytes are trapped and destroyed by splenic macrophages (extravascular). PNH, ABO incompatibility and acute G6PD crises lyse cells in vessels, causing hemoglobinuria.
Which conformation of hemoglobin has the lowest oxygen affinity?
Deoxyhemoglobin takes the T form, stabilized by 2,3-BPG, with low O2 affinity. Oxygen binding shifts it to the high-affinity R form; carbon monoxide binds with very high affinity.
By what age has adult hemoglobin (HbA) largely replaced fetal hemoglobin in a healthy infant?
The γ-to-β switch begins around birth, and HbF falls to low levels by about 6 months. This is why β-globin disorders appear after a few months of age.
Which set of findings indicates intravascular hemolysis?
When red cells lyse inside vessels, free hemoglobin binds and depletes haptoglobin, then spills into urine; renal tubules store it as hemosiderin. LDH rises.
What is the chain composition of HbA2?
HbA2 (α2δ2) is normally below 3.5% of adult hemoglobin and rises in β-thalassemia trait. α2β2 is HbA, α2γ2 is HbF and ζ2ε2 is Gower-1.
In which disorder does splenectomy usually cure the anemia, although the red cell defect remains?
Spherocytes are destroyed mainly in the spleen, so removing it stops most hemolysis even though spherocytes persist. It does not correct G6PD deficiency or thalassemia.
A young adult with anemia, mild jaundice and splenomegaly has an MCHC of 37 g/dL and an affected parent. The most likely diagnosis is:
Spherocytes lose membrane and become dense, so a raised MCHC with hemolysis and dominant inheritance suggests hereditary spherocytosis. Thalassemia gives low MCV and MCH.
Unconjugated hyperbilirubinemia in β-thalassemia major is mainly caused by:
Red cell precursors and circulating cells are destroyed because of excess α chains, raising unconjugated bilirubin. Viral hepatitis and iron overload cause liver damage but are not the usual cause of jaundice.
Which is an unlikely cause of abdominal pain in β-thalassemia major?
Chronic hemolysis produces bilirubin gallstones, and the huge spleen may infarct or cause dragging pain. Vasculitis is not a feature of thalassemia.
The commonest Embden–Meyerhof pathway enzyme defect causing hereditary nonspherocytic hemolytic anemia is:
Pyruvate kinase deficiency is the most frequent glycolytic enzymopathy. G6PD deficiency is commoner overall but belongs to the hexose monophosphate shunt, not glycolysis.
A 5-year-old girl has had progressive pallor since 6 months of age and has hepatosplenomegaly. Which test is most useful for diagnosis?
Onset after 6 months, when γ chains switch to β, with pallor and organomegaly suggests β-thalassemia major, confirmed by raised HbF on electrophoresis or HPLC.
Which screening result is typical of hereditary spherocytosis?
Spherocytes have a reduced surface-to-volume ratio and lyse early in hypotonic saline. The EMA dye-binding flow test is now the preferred confirmatory test; DAT is negative.
A transfusion-dependent thalassemia patient with iron overload would be expected to show:
Transfused iron accumulates, saturating transferrin and raising ferritin. Low iron with high TIBC is iron deficiency; low iron with low TIBC is inflammation.
Mild microcytic anemia, normal ferritin, RBC count 6.1 × 10^6/µL and HbA2 of 5.2% suggest:
A raised HbA2 (above about 3.5%) with microcytosis and a high red cell count is typical of beta-thalassemia minor. Normal ferritin argues against iron deficiency, which can lower HbA2.
Spherocytes, raised MCHC, a negative DAT and increased osmotic fragility in a patient with a family history of anemia suggest:
Inherited defects of membrane proteins such as spectrin or ankyrin make cells spherical and fragile in hypotonic saline. A negative DAT separates this from warm autoimmune hemolysis, which also shows spherocytes.
The preferred test to diagnose paroxysmal nocturnal hemoglobinuria (PNH) is:
PNH cells lack GPI-anchored proteins, including the complement regulators CD55 and CD59, so complement lyses them. Flow cytometry has replaced the older Ham and sucrose lysis tests.
In hereditary spherocytosis, which membrane protein is most often affected?
Ankyrin-1 defects are the most frequent cause of hereditary spherocytosis, weakening vertical links between the lipid bilayer and the spectrin skeleton. Protein 4.1R defects mainly cause hereditary elliptocytosis, not spherocytosis.
A flow cytometry screening test for hereditary spherocytosis uses eosin-5'-maleimide (EMA). A positive result for hereditary spherocytosis is shown by:
EMA binds mainly to band 3; spherocytes have less band 3 and membrane, so their fluorescence is reduced. Loss of CD59 is a feature of PNH, not hereditary spherocytosis.
A man of African descent has an acute hemolytic episode after an infection. His G6PD activity measured during the episode is normal. The best action is to:
During hemolysis the oldest, most deficient cells are destroyed and young cells with higher G6PD activity dominate, giving a false normal result. A repeat test next day would still be affected by the reticulocytosis.