Hemoglobinopathies — MCQs

10 questions

Which of the following is the most sensitive and specific test during antenatal check-up for a pregnant lady with family history of Thalassemia?

What should you do next for a 35-year-old man who is positive for HBsAg and HBeAg, discovered incidentally during blood donation screening, with normal SGOT and SGPT laboratory values?

Which of the following statements about sickle cell anemia is false?

A 59-year-old male came with Hb 18.0 gm/dl on three occasions. The resident doctor wants to exclude Polycythemia Vera. Which of the following is the most relevant investigation :

Which of the following statements about sickle cell disease is true?

Diagnosis of beta thalassemia is established by what?

34 week primigravida punjabi khatri comes with history of consanguineous marriage, with history of repeated blood transfusion to her sibling since 8 months of age. The first diagnostic test is -

Which of the following is the recommended treatment for iron poisoning in a 4-year-old child?

A 10-month-old child with coarse facies is referred for developmental delay. On examination, hepatosplenomegaly was noted. WBC N-acetylglucosamine-1-phosphotransferase activity was absent. The X-ray is shown below. What is the diagnosis?

Q10Medium

A 5-year-old boy presents with petechial bleeding and bruising on his torso and limbs. He has no other signs or symptoms and does not appear ill. His mother reports a gastrointestinal infection several weeks prior to the onset of petechiae and bruising. Complete blood count reveals thrombocytopenia (<20 x 10^9/L), with other parameters within the expected range for his age. Prothrombin time, partial thromboplastin time, and metabolic panels are all within the reference range. What is the expected outcome of this blood disorder?

Hemoglobinopathies Indian Medical PG Practice Questions and MCQs

Question 1: Which of the following is the most sensitive and specific test during antenatal check-up for a pregnant lady with family history of Thalassemia?

A. P. smear and reticulocyte count
B. Hemoglobin electrophoresis
C. High performance liquid chromatography (Correct Answer)
D. NESTROFT

Explanation: ***High performance liquid chromatography*** - **HPLC** is considered the most sensitive and specific test for diagnosing thalassemia and other hemoglobinopathies due to its ability to accurately quantify different hemoglobin fractions. - It provides a detailed **hemoglobin profile**, allowing for precise identification of abnormal hemoglobins and accurate assessment of thalassemia carrier status. *P. smear and reticulocyte count* - A **peripheral smear** can show microcytic, hypochromic red blood cells, which are characteristic of thalassemia, but this finding is not specific. - A **reticulocyte count** can indicate increased red blood cell production, but it is a general indicator of hemolysis or bone marrow activity and not specific for thalassemia. *Hemoglobin electrophoresis* - **Hemoglobin electrophoresis** separates different hemoglobin types based on their electrical charge, which is useful for identifying hemoglobinopathies. - While it can detect abnormal hemoglobins, its resolution and quantitative accuracy are generally lower than that of HPLC, making it less sensitive for detecting subtle variations or quantifying small amounts of abnormal hemoglobin. *NESTROFT* - **NESTROFT** (Naked eye single tube red cell osmotic fragility test) is a screening test used to detect beta-thalassemia carriers by assessing red cell osmotic fragility. - It is a good, inexpensive screening tool but lacks the sensitivity and specificity of definitive diagnostic tests like HPLC, and positive results require confirmation with other methods.

Question 2: What should you do next for a 35-year-old man who is positive for HBsAg and HBeAg, discovered incidentally during blood donation screening, with normal SGOT and SGPT laboratory values?

A. HBV-DNA estimation (Correct Answer)
B. Observation
C. Liver biopsy
D. Interferon therapy

Explanation: ***HBV-DNA estimation*** - The presence of **HBsAg** and **HBeAg** indicates **active viral replication**, necessitating quantification of HBV-DNA to assess viral load [1]. - Normal SGOT and SGPT suggest compensated liver function, but **viral load** is crucial for staging the disease and guiding future management [1]. *Observation* - While liver enzymes are normal, the presence of **HBsAg** and **HBeAg** indicates active hepatitis B infection, which warrants further investigation, not just observation [1]. - Undiagnosed and untreated chronic hepatitis B can lead to serious complications such as **cirrhosis** and **hepatocellular carcinoma** [1]. *Liver biopsy* - **Liver biopsy** is an invasive procedure typically reserved for cases where histological assessment is required to confirm **fibrosis** or **inflammation severity**, or when there's discordance between viral markers and clinical presentation. - It's not the initial step for a patient with normal transaminases and clear serological markers of active infection; **HBV-DNA estimation** is generally performed first [1]. *Interferon therapy* - **Interferon therapy** is a treatment for chronic hepatitis B, but initiating treatment requires a comprehensive assessment including **HBV-DNA levels**, in addition to liver enzyme levels and evaluation of liver damage [2]. - It would be premature to consider treatment without a **viral load** measurement and a full workup to determine the phase of infection and the need for therapy [2].

Question 3: Which of the following statements about sickle cell anemia is false?

A. Sickle cells are present in sickle cell anemia.
B. Target cells are commonly seen in sickle cell anemia.
C. Ringed sideroblasts are associated with sickle cell anemia. (Correct Answer)
D. Howell Jolly bodies can be found in sickle cell anemia.

Explanation: ***Ringed sideroblast*** - **Ringed sideroblasts** are not typically associated with sickle cell anemia; they are indicative of disorders like **sideroblastic anemia**. - In sickle cell anemia, the primary findings include **hemolysis** and ineffective erythropoiesis, not ringed sideroblasts [3]. *Howell jolly bodies* - These bodies are remnants of nuclear material and can be found in individuals with **spleen dysfunction**, which can occur in sickle cell anemia [1]. - They are actually a common finding due to **hyposplenism** or **asplenia** in patients with sickle cell disease [2]. *Sickle cells* - The presence of **sickle-shaped red blood cells** is a hallmark of sickle cell anemia, caused by the mutation in the **beta-globin chain** [3]. - These sickle cells are responsible for the characteristic complications of the disease, such as **vaso-occlusive crises** [1][3]. *Target cells* - Target cells, or **codocytes**, are often seen in disorders like **thalassemia** and liver disease, and can also be present in sickle cell anemia. - They are formed due to an increase in the **surface area to volume ratio** of red blood cells, often secondary to **membrane abnormalities** seen in sickle cell changes [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 644-646. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 570-571. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599.

Question 4: A 59-year-old male came with Hb 18.0 gm/dl on three occasions. The resident doctor wants to exclude Polycythemia Vera. Which of the following is the most relevant investigation :

A. Hematocrit (Correct Answer)
B. Reticulocyte count
C. JAK2 V617F mutation testing
D. Serum erythropoietin (EPO) levels

Explanation: **Hematocrit** - The **hematocrit** measures the percentage of red blood cells in the blood and is directly reflective of the **red cell mass**, which is crucially elevated in polycythemia vera [1]. - A persistently high hemoglobin level of 18.0 gm/dL warrants further evaluation of the red cell mass, and **hematocrit** is the most direct and initial step to confirm true erythrocytosis before pursuing more specific tests [1]. *Reticulocyte count* - **Reticulocyte count** measures the number of immature red blood cells and primarily assesses the bone marrow's response to anemia, not polycythemia. - In polycythemia vera, the erythropoiesis is unregulated and uncontrolled, but a high reticulocyte count is not a primary diagnostic criterion. *JAK2 V617F mutation testing* - This is a highly specific test for **Polycythemia Vera**, as the **JAK2 V617F mutation** is present in about 95% of patients with the condition [1]. - While essential for definitive diagnosis, it should be performed after demonstrating an unexplained persistent increase in **red cell mass** or hemoglobin/hematocrit, as suggested by the initial blood tests [1]. *Serum erythropoietin (EPO) levels* - **Serum EPO levels** are typically suppressed or low in **Polycythemia Vera** due to the constitutive activation of the JAK2 pathway, which makes erythropoiesis independent of EPO. - While an important diagnostic marker, it is usually assessed after confirming an elevated red cell mass and before more specific genetic testing.

Question 5: Which of the following statements about sickle cell disease is true?

A. Sickling is completely reversible with oxygenation, making it clinically insignificant.
B. Sickling leads to a significant increase in overall MCHC levels in the blood.
C. Fetal hemoglobin inhibits sickling. (Correct Answer)
D. Sickling occurs exclusively in the homozygous state and never in the heterozygous state.

Explanation: ***Sickling is reversible with oxygenation*** - When oxygen tension is restored, hemoglobin S can re-hydrate and revert to its normal shape, reducing sickling. - This reversible process is essential for managing episodes of vaso-occlusive crisis in sickle cell disease. *Fetal hemoglobin facilitates Sickling* - Fetal hemoglobin (HbF) actually inhibits sickling by stabilizing the erythrocyte shape and reducing the proportion of hemoglobin S [1]. - Individuals with higher levels of HbF experience fewer sickling-related complications [1]. *Sickling occurs both in heterozygous and homozygous state* - Sickling primarily occurs in the homozygous state (HbSS); heterozygotes (HbAS) usually do not experience significant sickling effects [1]. - Heterozygous individuals may have a selective advantage against malaria, but they are not prone to sickle cell crises. *Sickling Leads to decreased MCHC* - Sickling does not directly lead to decreased mean corpuscular hemoglobin concentration (MCHC); MCHC is typically normal in sickle cell patients. - In fact, sickle cell disease often results in hemolysis and can lead to increased MCHC in some cases.

Question 6: Diagnosis of beta thalassemia is established by what?

A. Hb electrophoresis (Correct Answer)
B. NESTROFT screening test
C. Hemoglobin A1c test
D. Presence of target cells in blood smear

Explanation: Hb electrophoresis - Hemoglobin electrophoresis directly measures the relative proportions of different hemoglobin types (HbA, HbA2, HbF), which is crucial for identifying the characteristic reduction in HbA and elevation of HbA2 and HbF in beta thalassemia. [1] - This method provides a definitive diagnostic profile by separating hemoglobin based on their electrical charge and size, allowing for quantification of abnormal hemoglobin variants. [1] *NESTROFT screening test* - The NESTROFT (Naked Eye Single Tube Red cell Osmotic Fragility Test) is a screening tool used to identify individuals with thalassemia traits and is not a definitive diagnostic test. - While useful for mass screening due to its simplicity and cost-effectiveness, it requires confirmation with more specific tests like hemoglobin electrophoresis. [1] *Hemoglobin A1c test* - The Hemoglobin A1c (HbA1c) test is primarily used to monitor long-term blood glucose control in individuals with diabetes. [2] - It measures the percentage of hemoglobin glycated over a period of 2-3 months and has no direct diagnostic utility for thalassemia. [2] *Presence of target cells in blood smear* - The presence of target cells in a blood smear is a non-specific finding that can be observed in various conditions, including iron deficiency anemia, liver disease, and other hemoglobinopathies, in addition to thalassemia. - While suggestive of a thalassemic disorder, it is not a conclusive diagnostic criterion and requires further investigation with specific diagnostic tests.

Question 7: 34 week primigravida punjabi khatri comes with history of consanguineous marriage, with history of repeated blood transfusion to her sibling since 8 months of age. The first diagnostic test is -

A. HPLC
B. Bone marrow
C. Blood smear
D. Hb electrophoresis (Correct Answer)

Explanation: ***Hb electrophoresis*** - The patient's history of **consanguineous marriage**, a sibling requiring **repeated blood transfusions** since 8 months of age, and Punjabi Khatri ethnicity strongly suggest a **hemoglobinopathy**, likely **beta-thalassemia major or intermedia**. - **Hemoglobin electrophoresis** is the traditional gold standard for definitive diagnosis of various hemoglobin variants and thalassemia types, identifying and characterizing abnormal hemoglobin patterns (e.g., elevated HbF, HbA2). - It remains a primary diagnostic test for hemoglobinopathies, particularly useful for pattern recognition of various thalassemia syndromes. *HPLC* - **High-performance liquid chromatography (HPLC)** is an equally valid and increasingly preferred method for diagnosing hemoglobinopathies, offering automated, precise quantification of hemoglobin fractions (HbA, HbA2, HbF). - In modern practice, HPLC is often used as a first-line screening tool due to its accuracy, reproducibility, and ability to provide quantitative data crucial for thalassemia diagnosis. - Both HPLC and Hb electrophoresis are acceptable diagnostic approaches; the choice between them depends on laboratory availability and practice patterns. For this 2013 exam, Hb electrophoresis was considered the traditional first diagnostic test. *Blood smear* - A **peripheral blood smear** would show morphological changes like **microcytic hypochromic red blood cells**, **target cells**, **anisopoikilocytosis**, and **nucleated RBCs**, which are suggestive of thalassemia. - These findings are indicative but non-specific and require confirmatory tests like hemoglobin electrophoresis or HPLC to identify the specific hemoglobin disorder and establish a definitive diagnosis. *Bone marrow* - A **bone marrow** examination would show **erythroid hyperplasia** due to increased ineffective erythropoiesis in thalassemia but is an invasive procedure and not the initial diagnostic test for hemoglobinopathies. - It provides details about cellularity and maturation but does not directly identify hemoglobin abnormalities, making it unsuitable as the first diagnostic step in suspected hemoglobinopathies.

Question 8: Which of the following is the recommended treatment for iron poisoning in a 4-year-old child?

A. Blood transfusion
B. Stomach lavage
C. Observation and supportive care
D. Deferoxamine IV at a dose of 15 mg/kg/hour (Correct Answer)

Explanation: ***Deferoxamine IV at a dose of 15 mg/kg/hour*** - **Deferoxamine** is a chelating agent specifically used to bind free iron, forming a complex that can be excreted renally. - An intravenous infusion at 15 mg/kg/hour is the recommended dose for severe iron poisoning, particularly when serum iron levels are high or symptoms indicate significant toxicity. *Stomach lavage* - **Stomach lavage** is generally not recommended for iron poisoning due to the risk of pushing iron tablets further into the intestine, potential for perforation, and limited efficacy in removing large, unabsorbed iron tablets. - Iron tablets are often **large** and **poorly soluble**, making lavage ineffective for complete removal. *Blood transfusion* - **Blood transfusion** is not a primary treatment for iron poisoning because iron toxicity is due to free iron in the body, not a deficiency that would be corrected by transfused blood. - It would only be considered in cases of severe anemia or significant blood loss, which are not direct treatments for iron overload. *Observation and supportive care* - While supportive care is crucial in managing complications of iron poisoning, **observation alone is insufficient** for moderate to severe cases of iron poisoning. - Significant iron overdose requires active intervention to prevent systemic toxicity, organ damage, and potentially fatal outcomes.

Question 9: A 10-month-old child with coarse facies is referred for developmental delay. On examination, hepatosplenomegaly was noted. WBC N-acetylglucosamine-1-phosphotransferase activity was absent. The X-ray is shown below. What is the diagnosis?

A. I cell disease (Correct Answer)
B. MPS type II
C. Proteus syndrome
D. Larsen syndrome

Explanation: ***I cell disease*** - **I-cell disease** (Mucolipidosis II) is characterized by **coarse facial features**, developmental delay, hepatosplenomegaly, and **skeletal abnormalities** (dysostosis multiplex) seen on X-ray, which are consistent with the image. - The absence of **N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase)** activity leads to misrouting of lysosomal enzymes, resulting in accumulation of mucolipids within cells. *MPS type II* - **MPS type II** (Hunter syndrome) also presents with coarse facies, developmental delay, and hepatosplenomegaly, and can show skeletal abnormalities. - However, the enzymatic defect is in **iduronate sulfatase**, not GlcNAc-1-phosphotransferase, and the clinical course tends to be slightly milder than I-cell disease, particularly in early infancy. *Proteus syndrome* - **Proteus syndrome** is characterized by **overgrowth of tissues**, asymmetric growth, and various tumors, not by the specific metabolic defect or typical pattern of skeletal changes described. - It does not involve absent GlcNAc-1-phosphotransferase activity. *Larsen syndrome* - **Larsen syndrome** primarily involves **skeletal abnormalities**, such as joint dislocations (especially knees, hips, and elbows), flattened facial appearance, and clubfoot. - It does not feature the same metabolic defect (absent GlcNAc-1-phosphotransferase activity) or the prominent coarse facial features and hepatosplenomegaly seen in the patient.

Question 10: A 5-year-old boy presents with petechial bleeding and bruising on his torso and limbs. He has no other signs or symptoms and does not appear ill. His mother reports a gastrointestinal infection several weeks prior to the onset of petechiae and bruising. Complete blood count reveals thrombocytopenia (<20 x 10^9/L), with other parameters within the expected range for his age. Prothrombin time, partial thromboplastin time, and metabolic panels are all within the reference range. What is the expected outcome of this blood disorder?

A. Complete resolution is expected. (Correct Answer)
B. Survival rate is up to 70% depending on risk stratification.
C. Lifelong disease dependent on factor VIII substitution.
D. Lifelong disease dependent on factor IX substitution.

Explanation: ### Explanation The clinical presentation describes a classic case of **Immune Thrombocytopenic Purpura (ITP)**, the most common cause of isolated thrombocytopenia in children. **1. Why Option A is Correct:** In children, ITP typically follows a viral infection (respiratory or gastrointestinal) after a 1–4 week latent period. It is characterized by the sudden onset of petechiae and bruising in an otherwise healthy-appearing child. The hallmark is **isolated thrombocytopenia** (Platelets <100 x 10⁹/L) with normal PT, PTT, and hemoglobin. The prognosis is excellent; approximately **70–80% of children achieve complete spontaneous resolution** within 6 months, regardless of therapy. **2. Why the Other Options are Incorrect:** * **Option B:** This refers to the survival rates of pediatric malignancies like Acute Lymphoblastic Leukemia (ALL). While ALL presents with bruising, it typically involves "sick" symptoms (fever, bone pain), hepatosplenomegaly, and abnormalities in other cell lines (anemia/leukocytosis). * **Options C & D:** These describe **Hemophilia A (Factor VIII)** and **Hemophilia B (Factor IX)**. Hemophilias are coagulation factor deficiencies that present with deep tissue bleeds (hemarthrosis/hematomas) and a **prolonged aPTT**, rather than petechiae and isolated thrombocytopenia. **3. NEET-PG High-Yield Pearls:** * **Pathophysiology:** Anti-platelet antibodies (IgG) directed against GP IIb/IIIa or GP Ib/IX. * **Bone Marrow:** Not routinely required but would show **increased megakaryocytes** (compensatory). * **Management:** Observation is preferred if bleeding is minimal (dry purpura). If treatment is needed (wet purpura/active bleeding), **IVIG** or **Corticosteroids** are first-line. * **Chronic ITP:** Defined as thrombocytopenia persisting >12 months (occurs in ~20% of cases).

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