Anemias (Hemolytic, Microcytic, Macrocytic, Hemoglobinopathies) MCQs

Pathology · 140 free questions with answers & explanations.

1. A 20-year-old man has recurrent hemolytic crises triggered by infections and oxidant drugs. Peripheral smear shows Heinz bodies on supravital staining. Enzyme assay confirms the diagnosis. Which step in the hexose monophosphate shunt is directly impaired in this condition?
2. A 30-year-old Nigerian woman is found to have HbSC disease. Compared to homozygous HbSS sickle cell disease, HbSC disease typically shows:
3. A 45-year-old alcoholic presents with macrocytic anemia and hypersegmented neutrophils. Bone marrow biopsy shows megaloblastic changes. Serum methylmalonic acid (MMA) and homocysteine levels are both elevated. The most likely nutritional deficiency is:
4. In hereditary spherocytosis, the most common molecular defect responsible for loss of membrane stability involves which protein?
5. A 25-year-old woman develops episodic hemolytic anemia triggered by fava beans and infections. G6PD deficiency is suspected. The enzyme is most critical in which pathway that protects erythrocytes from oxidative damage?
6. On peripheral smear of a patient with hereditary spherocytosis, the spherocytes lack central pallor and have increased MCHC. The underlying molecular defect most commonly involves which cytoskeletal protein?
7. Beta-thalassemia major patients require regular transfusions starting in infancy because the predominant hemoglobin in adult life (HbA = α2β2) cannot be synthesized. Splenomegaly in these patients is primarily attributable to:
8. Cold agglutinin disease is characterized by IgM autoantibodies that agglutinate red cells optimally at 4°C. These antibodies most commonly have specificity against which antigen?
9. A 24-year-old African-American man develops sudden jaundice, hemoglobinuria, and anemia three days after starting trimethoprim-sulfamethoxazole for a UTI. His hemogram shows Heinz bodies on crystal violet stain and 'bite cells' on peripheral smear. Enzyme assay confirms G6PD deficiency. Which form of G6PD enzyme is most common in affected African Americans?
10. A 3-year-old child presents with pallor, jaundice, and splenomegaly. CBC shows MCV 62 fL, MCHC elevated at 38 g/dL, and osmotic fragility increased. EMA (eosin-5-maleimide) binding test is reduced to 68% of normal. Which protein deficiency most likely underlies this condition?
11. A 30-year-old woman from West Africa has sickle cell trait (HbAS). She is incidentally found to have hematuria. Which complication of sickle cell trait explains this finding?
12. A 22-year-old Southeast Asian man has thalassemia intermedia. Hemoglobin electrophoresis shows HbE 65%, HbF 30%, HbA 0%, HbA2 5%. Which genetic compound heterozygosity best explains this phenotype?
13. A patient with chronic hemolytic anemia develops an acute aplastic crisis with sudden drop in Hb from 9 to 4 g/dL, reticulocyte count drops to near zero. The most likely cause is:
14. Pyruvate kinase (PK) deficiency causes hemolytic anemia. Unlike hereditary spherocytosis, the red cells in PK deficiency are NOT spherocytic; instead they may be echinocytic. The mechanism of hemolysis in PK deficiency is:
15. In β-thalassemia major, organ damage in untransfused patients results from iron overload. However, even in transfusion-dependent patients, iron overload occurs. Which mechanism explains iron overload despite low dietary iron in transfused thalassemia patients?
16. A patient with hereditary spherocytosis undergoes splenectomy. Post-operatively, peripheral smear shows Howell-Jolly bodies and target cells appear along with persistent spherocytes. The Howell-Jolly bodies represent:
17. A newborn is found to have hemoglobin Bart (γ4 tetramers) constituting 80% of total hemoglobin on HPLC. This hemoglobin pattern in a hydrops fetalis case indicates deletion of how many alpha-globin genes?
18. In sickle cell disease, the vasoocclusion in small vessels during crisis is initiated primarily by which molecular mechanism?
19. A 30-year-old woman of African descent has chronic hemolytic anemia with splenomegaly. Her peripheral smear shows spherocytes and osmotic fragility is increased. Eosin-5-maleimide (EMA) binding test is markedly reduced. The most likely protein deficient is:
20. In sickle cell disease, the primary trigger for vaso-occlusion at the molecular level involves:
21. A neonate presents with severe hemolytic anemia, hydrops fetalis, and a peripheral blood smear showing numerous nucleated red cells but very few normal erythrocytes. Hemoglobin electrophoresis shows almost exclusively Hb Barts (γ4). The genetic basis is:
22. Ham's test (acidified serum lysis test) is classically positive in paroxysmal nocturnal hemoglobinuria (PNH). The underlying molecular defect causing erythrocyte sensitivity to complement is:
23. A 25-year-old woman with hereditary spherocytosis undergoes splenectomy. Her reticulocyte count normalizes and Hb improves, but she now develops thrombocytosis (platelets 900,000/μL) and Howell-Jolly bodies on peripheral smear. What is the mechanism of Howell-Jolly body formation?
24. A 3-year-old boy presents with severe hemolytic anemia, hepatosplenomegaly, and bone marrow expansion causing frontal bossing ('hair-on-end' skull X-ray). Hemoglobin electrophoresis shows predominantly HbF with HbA2 in the normal range. The diagnosis is β-thalassemia major. The primary cause of ineffective erythropoiesis in this condition is:
25. In autoimmune hemolytic anemia (AIHA), cold agglutinin disease is associated with IgM antibodies that fix complement optimally at 4°C. The characteristic RBC morphology seen on peripheral blood smear in cold AIHA is:
26. A 35-year-old man of African descent develops acute intravascular hemolysis following primaquine therapy. His G6PD enzyme assay performed during the acute hemolytic episode appears near-normal. The most likely explanation for this near-normal result is:
27. A 25-year-old Nigerian man with sickle cell disease (HbSS) develops acute chest syndrome. The pathogenesis of in situ pulmonary microvascular occlusion in this context involves which key adhesion event?
28. A 28-year-old South-Asian woman has mild hemolytic anemia with elliptocytes, osmotic fragility slightly elevated, and a spectrin dimer self-association defect on gel electrophoresis. The molecular basis of hereditary elliptocytosis in most cases involves:
29. A 30-year-old man is found to have HbH disease (three alpha-globin gene deletions, genotype --/-α). Peripheral smear shows hypochromic microcytic cells with HbH inclusion bodies after brilliant cresyl blue staining. What is the clinical severity compared to the two major forms of alpha-thalassemia?
30. A patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) has a PIGA somatic mutation. This leads to hemolysis because:
31. A 25-year-old male of African descent presents with chronic hemolytic anemia, spherocytes on peripheral smear, and negative Coombs test. His father has the same condition. Red cell osmotic fragility is increased. Eosin-5-maleimide (EMA) binding test shows reduced fluorescence. The most likely deficient protein is:
32. A newborn is diagnosed with hemolytic disease of the fetus and newborn (HDFN) caused by anti-Kell alloantibodies. Unlike anti-D, anti-Kell causes more severe fetal anemia by a mechanism beyond hemolysis alone. What additional mechanism explains the disproportionate severity?
33. A patient with sickle cell disease starts hydroxyurea therapy. After 3 months, HbF rises from 4% to 22%. The mechanism by which hydroxyurea increases HbF involves inhibition of which enzyme, and which transcription factor does this ultimately reactivate?
34. A 30-year-old woman has hemolytic anemia with episodic dark urine after infections. Flow cytometry of red cells shows absence of CD55 and CD59. The underlying defect is a somatic mutation in which gene?
35. A 28-year-old patient with sickle cell disease develops sudden severe aplastic crisis with Hb dropping to 4 g/dL and reticulocyte count near zero. The most likely causative agent and mechanism is:
36. Beta-thalassemia major results in ineffective erythropoiesis. The primary mechanism of anemia in beta-thalassemia is:
37. In paroxysmal nocturnal hemoglobinuria (PNH), the absence of GPI-anchored proteins is due to somatic mutation in which gene in hematopoietic stem cells?
38. A 30-year-old African American man develops acute intravascular hemolysis with hemoglobinuria after taking primaquine for malaria prophylaxis. Peripheral smear shows bite cells and Heinz bodies. His G6PD enzyme activity is markedly reduced. G6PD A– is the most common variant in sub-Saharan Africa. Why are older red cells preferentially destroyed while reticulocytes and young RBCs survive during an oxidative challenge?
39. A 4-year-old girl of Mediterranean origin presents with severe anemia (Hb 4.5 g/dL), hepatosplenomegaly, and facial bone deformities. HPLC reveals HbF 95%, HbA2 3.5%, and HbA absent. Her parents have mild microcytic anemia. Which of the following best explains the pathophysiology of extramedullary hematopoiesis causing hepatosplenomegaly in this condition?
40. A patient with paroxysmal nocturnal hemoglobinuria (PNH) is at highest risk for which serious complication, and what is the molecular basis linking the GPI-anchor deficiency to this complication?
41. A patient with chronic haemolytic anaemia develops severe aplastic crisis with a sudden drop in haemoglobin to 4 g/dL. Reticulocyte count is 0.2%. The most likely responsible pathogen is:
42. In hereditary spherocytosis (HS) due to ankyrin-1 mutation, the molecular defect leads to spherocyte formation through which primary mechanism?
43. A newborn of Mediterranean descent has haemoglobin electrophoresis showing only HbF and HbH (beta4 tetramers) with no HbA. The most likely genotype is:
44. A neonate develops severe hemolytic anemia within 24 hours of birth. Peripheral smear shows hypochromia, microcytosis, target cells and nucleated red blood cells. Hemoglobin electrophoresis shows predominantly Hb Barts (gamma4 tetramers). Which molecular defect underlies this condition?
45. A 35-year-old man of African descent develops recurrent hemolytic crises precipitated by antimalarials and fava beans. G6PD assay performed during crisis shows near-normal enzyme activity. What is the explanation for this diagnostic pitfall?
46. A 28-year-old woman presents with hemolytic anemia, thrombosis and recurrent pregnancy loss. Flow cytometry on peripheral blood erythrocytes shows markedly decreased CD59 and CD55 expression on a major clone. Which mechanism is responsible for the complement sensitivity in this condition?
47. Peripheral smear of a patient with hereditary spherocytosis (HS) is examined. Flow cytometry using eosin-5-maleimide (EMA) binding shows reduced fluorescence. Which membrane protein deficiency most commonly underlies HS in Northern European populations?
48. A 35-year-old woman of Mediterranean descent has hemolytic anemia, splenomegaly, and HbH inclusions on brilliant cresyl blue staining. Hemoglobin electrophoresis shows no HbA, elevated HbH (β4), and trace HbBart (γ4). Genetic testing would most likely show:
49. In Diamond-Blackfan anemia (DBA), which molecular mechanism underlies the selective failure of erythropoiesis?
50. A patient with sickle cell disease develops acute severe back pain, fever, and a rapidly falling hemoglobin from 9 g/dL to 4 g/dL over 24 hours. Reticulocyte count is 0.2%. LDH is minimally elevated. What is the most likely diagnosis?
51. A 25-year-old African man presents with episodic hemolytic anemia precipitated by antimalarials. His G6PD level drawn during an acute episode is normal. The most appropriate next diagnostic step is:
52. A newborn with Hb Bart's hydrops fetalis (gamma4 tetramers) has which underlying genotype and the most clinically critical consequence?
53. A 40-year-old woman with paroxysmal nocturnal hemoglobinuria (PNH) develops sudden-onset severe abdominal pain. The pathophysiologic mechanism of thrombosis in PNH directly involves:
54. A 28-year-old woman with Diamond-Blackfan anemia (DBA) is found to have a heterozygous pathogenic variant in RPS19. She develops a macrocytic anemia with pure red cell aplasia, elevated MCV, and elevated erythrocyte adenosine deaminase (eADA). The molecular mechanism linking ribosomal protein haploinsufficiency to erythroid failure is:
55. A patient with sickle cell disease develops sudden-onset severe anemia, reticulocytopenia, and absent erythroid precursors in the bone marrow during a febrile illness. Parvovirus B19 serology is positive. What is the pathophysiology of this aplastic crisis?
56. A 25-year-old woman of Mediterranean origin has HbH disease (three alpha-globin gene deletions). Peripheral smear shows hypochromic microcytic red cells with Heinz bodies after brilliant cresyl blue staining (HbH inclusions). What is the molecular basis of HbH formation?
57. A patient presents with episodic hemolytic crises precipitated by infections and oxidant drugs. G6PD deficiency is suspected. Enzyme assay performed during a hemolytic crisis shows near-normal G6PD activity. What explains this finding?
58. A newborn of Southeast Asian parents presents with hydrops fetalis, severe anemia (Hb 3 g/dL), and Hb Barts on HPLC. Both parents have alpha-thalassemia trait. What is the genotype of the affected neonate?
59. A 30-year-old woman presents with hemolytic anemia, thrombocytopenia, and renal failure following a diarrheal illness caused by Shiga toxin-producing E. coli. The peripheral smear shows schistocytes and reduced platelets, but clotting studies are normal. What is the pathomechanism by which Shiga toxin causes glomerular injury?
60. Hydrops fetalis in alpha-thalassemia results from hemoglobin Bart's (γ4 tetramers). What is the molecular consequence of having all four alpha-globin genes deleted, and why does hemoglobin Bart's cause tissue hypoxia despite apparently 'carrying' oxygen?
61. A patient with hemolytic anemia is found to have a negative direct Coombs test but positive osmotic fragility and spherocytes on the smear. Ektacytometry shows a biphasic pattern with reduced deformability at low osmolality. Which protein deficiency is most likely responsible?
62. A patient develops intravascular hemolysis triggered by fava bean ingestion. Peripheral smear shows bite cells and Heinz bodies on crystal violet stain. The molecular basis of erythrocyte vulnerability is:
63. Sickle cell trait (HbAS genotype) confers resistance to severe falciparum malaria. The mechanism involves:
64. In hereditary spherocytosis due to ankyrin deficiency, the primary structural consequence is:
65. A 25-year-old woman of Mediterranean descent presents with hemolytic anemia after taking primaquine. Blood film shows Heinz bodies and bite cells. G6PD enzyme assay is normal. What is the BEST explanation for the normal assay result?
66. A newborn is found to have hydrops fetalis and hemoglobin Barts (γ4 tetramers) on electrophoresis. What is the underlying genetic defect?
67. A 35-year-old man with sickle cell disease is admitted with acute chest syndrome. Which pathological mechanism is MOST responsible for the vaso-occlusion in sickle cell disease?
68. Peripheral blood smear shows target cells, basophilic stippling, and nucleated red blood cells. Hemoglobin electrophoresis reveals HbF 90%, HbA2 4%, no HbA. What is the diagnosis?
69. In paroxysmal nocturnal hemoglobinuria (PNH), the molecular defect is a somatic mutation in PIG-A gene, leading to absence of GPI-anchored complement regulatory proteins. Which two proteins, when absent, make red cells vulnerable to complement-mediated lysis?
70. A 25-year-old woman of Mediterranean origin has a splenomegaly, mild chronic haemolytic anaemia, and peripheral smear showing target cells and basophilic stippling. Haemoglobin electrophoresis shows HbA2 6.5% (normal <3.5%) and HbF 3%. The diagnosis is beta-thalassaemia trait (minor). The elevated HbA2 is due to increased synthesis of which globin chain?
71. In autoimmune haemolytic anaemia (AIHA) due to cold agglutinin disease, the IgM antibodies cause haemolysis primarily through which mechanism?
72. A 28-year-old African-American woman develops acute intravascular hemolysis with hemoglobinuria 2 days after starting primaquine for malaria prophylaxis. The peripheral smear shows 'bite cells' and Heinz bodies on crystal violet stain. The enzyme deficient in this condition is located in which metabolic pathway?
73. In hereditary spherocytosis, the MOST common protein defect causing the disease in Northern European populations is:
74. A 3-year-old child from Southeast Asia presents with severe anemia, hepatosplenomegaly, and skull X-ray showing 'hair-on-end' appearance. Hemoglobin electrophoresis shows predominant HbF with absent HbA. This is consistent with which condition?
75. Which of the following correctly explains why sickle cell trait (HbAS) confers protection against falciparum malaria?
76. A 25-year-old woman of Mediterranean descent has mild haemolytic anaemia triggered by fava bean ingestion. Blood film shows Heinz bodies and bite cells. The enzyme deficient in this condition protects red cells from oxidative damage by maintaining:
77. A newborn presents with severe hydrops fetalis, hepatosplenomegaly, and pallor. Haemoglobin electrophoresis shows only HbH (β4 tetramers) and a trace of Hb Barts (γ4). No HbA, HbA2, or HbF is detected. Which alpha-thalassaemia genotype does this represent?
78. A 40-year-old man on haemodialysis for CKD has Hb 8.5 g/dL with normocytic normochromic red cells, normal iron stores, and low reticulocyte count. The primary pathophysiological mechanism of anaemia of chronic kidney disease is:
79. A neonate with Hb Bart's hydrops fetalis has four defective alpha-globin genes. Which hemoglobin tetramers form Hb Bart's, and what is its oxygen affinity?
80. In sickle cell disease, the primary molecular defect is a point mutation substituting glutamate with valine at position 6 of the beta-globin chain. Which biochemical consequence directly drives sickling?
81. A patient with paroxysmal nocturnal hemoglobinuria (PNH) lacks GPI-anchored complement regulatory proteins. The absence of which two proteins specifically protects normal red cells from complement-mediated lysis?
82. In hereditary spherocytosis caused by spectrin deficiency, why is the osmotic fragility increased?
83. A 25-year-old man of West African origin develops acute intravascular hemolysis after starting primaquine for malaria prophylaxis. The underlying enzyme deficiency leads to hemolysis by which mechanism?
84. In beta-thalassemia major, the primary mechanism of anemia is:
85. Which of the following laboratory findings best distinguishes intravascular hemolysis from extravascular hemolysis?
86. A 25-year-old man of West African origin develops acute intravascular hemolysis after starting primaquine. The underlying enzyme deficiency causes hemolysis by which mechanism?
87. In beta-thalassemia major, the primary mechanism producing severe anemia is:
88. Which laboratory finding best distinguishes intravascular from extravascular hemolysis?
89. A 25-year-old West African man develops acute hemolysis after taking primaquine. Peripheral smear shows bite cells and Heinz bodies on crystal violet stain. The enzyme deficiency responsible causes hemolysis because:
90. A newborn has severe hemolytic anemia requiring exchange transfusion. Hemoglobin electrophoresis shows predominantly Hb Barts (γ4). This pattern is diagnostic of:
91. A 30-year-old woman with known sickle cell disease presents with sudden onset severe back pain and priapism. Her crisis is best explained by the pathophysiological mechanism of:
92. A 55-year-old with macrocytic anemia, a smooth tongue, and absent ankle jerks has serum B12 of 85 pg/mL (normal >200). Peripheral smear shows hypersegmented neutrophils. Anti-intrinsic factor antibodies are positive. The intrinsic factor in pernicious anemia is normally secreted by:
93. A 40-year-old woman with autoimmune hemolytic anemia has a positive direct Coombs test. The direct Coombs test detects:
94. A 35-year-old woman with autoimmune hypothyroidism develops warm autoimmune hemolytic anemia (WAIHA). The Fc receptor on splenic macrophages responsible for extravascular hemolysis recognizes IgG bound to which part of the RBC-antibody complex?
95. A 2-year-old child from a Mediterranean family has severe anemia with a hemoglobin of 4 g/dL, massive hepatosplenomegaly, and skeletal deformities. Peripheral smear shows target cells and nucleated RBCs. The finding on Hb electrophoresis that confirms beta-thalassemia major is:
96. A newborn presents with severe hemolytic anemia, pallor, and splenomegaly. Peripheral smear shows hypochromic microcytic red cells, target cells, and nucleated RBCs. Hemoglobin electrophoresis reveals HbF 90%, HbA2 3%, and no HbA. This pattern is consistent with:
97. Paroxysmal nocturnal hemoglobinuria (PNH) occurs due to a somatic mutation in which gene, and what is the direct consequence of this mutation?
98. A 30-year-old woman of West African descent develops acute hemolytic anemia after starting dapsone for dermatitis herpetiformis. Heinz body preparation is positive. Which RBC enzyme deficiency is responsible?
99. A patient with G6PD deficiency develops acute hemolytic anemia after eating fava beans. Peripheral smear shows 'bite cells' and Heinz bodies. The fundamental mechanism of RBC destruction is:
100. In beta-thalassemia major, ineffective erythropoiesis leads to massive extramedullary hematopoiesis. The characteristic 'hair-on-end' appearance on skull X-ray is due to:
101. In sickle cell disease, the repeated sickling-unsickling cycle primarily leads to irreversible RBC membrane damage via which mechanism?
102. A patient with hereditary spherocytosis shows osmotic fragility, spherocytes on smear, and negative direct Coombs test. The primary molecular defect in the most common form is deficiency of:
103. A 25-year-old woman of African descent has chronic hemolytic anemia. Blood smear shows target cells, irreversibly sickled cells, and Howell-Jolly bodies. The Howell-Jolly bodies indicate:
104. In beta-thalassemia major, ineffective erythropoiesis leads to all of the following EXCEPT:
105. A 40-year-old man has episodes of dark-colored urine in the morning and is found to have hemolytic anemia with thrombocytopenia. Flow cytometry shows absence of CD55 and CD59 on RBCs. Which mechanism leads to hemolysis in this condition?
106. Diamond-Blackfan anemia differs from Fanconi anemia in that Diamond-Blackfan anemia is characterized by:
107. A 25-year-old African-American man develops acute hemolytic anemia with Heinz bodies after taking primaquine. The enzymatic defect causes hemolysis because:
108. A 30-year-old Mediterranean woman has chronic hemolytic anemia, splenomegaly, target cells, HbA2 6.5%, and HbF 45% on electrophoresis. The molecular defect is:
109. Microangiopathic hemolytic anemia with schistocytes, thrombocytopenia, and NORMAL PT and aPTT is MOST characteristic of:
110. A 50-year-old man has megaloblastic anemia and subacute combined degeneration of the spinal cord. Anti-intrinsic factor antibodies are positive. The gastric lesion underlying this condition is:
111. A 25-year-old African American woman develops sudden onset jaundice, hemoglobinuria, and anemia after taking primaquine for malaria prophylaxis. Peripheral smear shows Heinz bodies and bite cells. Which enzyme deficiency accounts for this presentation?
112. A newborn is found to have severe hemolytic anemia requiring transfusion. Hemoglobin electrophoresis shows only HbF and HbH (β4 tetramers). Which genotype most likely accounts for this presentation?
113. A 30-year-old woman with sickle cell disease presents with acute chest syndrome. The pathophysiology of sickling under hypoxia involves primarily which molecular event?
114. A 30-year-old African man develops intravascular hemolysis and hemoglobinuria after taking primaquine. His RBCs show Heinz bodies on crystal violet staining. The enzyme deficiency responsible acts at which step of the hexose monophosphate (HMP) shunt?
115. In beta-thalassemia major, the principal mechanism of anemia is:
116. A neonate born to a mother with sickle cell trait and a father with hemoglobin C disease will most likely have which hemoglobin genotype?
117. A 20-year-old woman of Mediterranean origin has chronic hemolytic anemia, splenomegaly, and indirect hyperbilirubinemia. Peripheral blood shows target cells, basophilic stippling, and nucleated RBCs. Hb electrophoresis: HbA 0%, HbF 95%, HbA2 5%. The molecular defect most likely involves:
118. Paroxysmal nocturnal hemoglobinuria (PNH) results from a somatic mutation in which gene, causing deficiency of which anchoring protein?
119. A newborn is found to have hemolytic jaundice. Peripheral blood smear shows microspherocytes. The direct Coombs (DAT) test is positive. The mother's blood group is O Rh-positive, and the baby's is A Rh-positive. The most likely cause is:
120. A patient has cold agglutinin hemolytic anemia. The antibody class responsible and the complement pathway primarily activated are:
121. A 3-year-old child with sickle cell disease (HbSS) has acute chest syndrome. The pathophysiological mechanism underlying acute chest syndrome is:
122. In hereditary spherocytosis due to ankyrin deficiency, spherocytes form because the lipid bilayer is destabilised from the inner cytoskeletal network. The spherocytes are then sequestered and destroyed in a specific anatomical compartment of the spleen. Which compartment is responsible?
123. A 28-year-old Ghanaian man presents with haemolytic crisis after taking primaquine. G6PD enzyme deficiency leads to haemolysis by which mechanism?
124. Sickle cell trait (HbAS) confers partial protection against severe falciparum malaria because sickling occurs in parasitised cells. Which haemoglobin switch accounts for the observation that sickle cell disease (HbSS) does not manifest clinically at birth but becomes apparent at 4–6 months of age?
125. A patient with hereditary spherocytosis undergoes splenectomy. Postoperatively, the spherocytes on peripheral smear persist, but the hemoglobin normalizes. The most likely explanation is:
126. A neonate develops severe hemolytic anemia. Peripheral smear shows nucleated RBCs and polychromasia. The direct Coombs (DAT) test is strongly positive. The most likely mechanism is:
127. Hemoglobin S polymerizes under deoxygenated conditions because of which molecular change compared to normal hemoglobin A?
128. Beta-thalassemia major leads to extramedullary hematopoiesis primarily in the liver, spleen and skull (hair-on-end appearance). The immediate driver of extramedullary hematopoiesis is:
129. A 32-year-old man presents with episodic hemolytic anemia, dark morning urine, and thrombosis. Flow cytometry shows a deficiency of CD55 and CD59 on red blood cells. The somatic mutation responsible for this disorder occurs in which gene?
130. In glucose-6-phosphate dehydrogenase (G6PD) deficiency, which of the following molecular events is the proximate cause of erythrocyte hemolysis during oxidant stress?
131. A newborn is found to have hemoglobin Bart's (γ4 tetramers) on neonatal hemoglobin electrophoresis. Which of the following best explains why hemoglobin Bart's causes severe fetal anemia?
132. A 28-year-old woman with sickle cell disease is found to have a concurrent alpha thalassemia trait (two alpha gene deletions). Which clinical outcome would you expect compared to a patient with sickle cell disease alone?
133. In paroxysmal nocturnal hemoglobinuria (PNH), hemolysis occurs due to lack of GPI-anchored complement regulatory proteins. Which complement component, when unregulated, is the final effector of PNH hemolysis?
134. Hemoglobin E (HbE) results from a substitution at codon 26 of the beta-globin gene (Glu→Lys). At the molecular level, this mutation is significant because it:
135. A 10-year-old child from a Mediterranean family has hemoglobin of 6.5 g/dL, splenomegaly, facial bossing, and hemoglobin electrophoresis showing HbA absent, HbF 92%, HbA2 8%. What is the pathophysiology of facial bossing in this condition?
136. In hereditary spherocytosis (HS), the primary molecular defect most commonly affects which red cell membrane protein pair?
137. In hereditary spherocytosis (HS), the red cell membrane defect most commonly involves mutations in which protein?
138. G6PD deficiency is an X-linked disorder most common in individuals from malaria-endemic regions. Oxidative haemolysis is triggered by oxidative stress and visualised on peripheral smear as cells with displaced haemoglobin (Heinz bodies). The standard stain for detecting Heinz bodies is:
139. Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutation in the PIGA gene, causing deficiency of GPI-anchored proteins CD55 and CD59. Which complement pathway is primarily uncontrolled, leading to intravascular hemolysis?
140. A patient with thalassemia intermedia (beta-thalassemia with moderate hemoglobin) develops progressive splenomegaly, leg ulcers, and gallstones, but does not require regular transfusions. The gallstones in this patient are primarily composed of: