Hematology — MCQs

A 17-year-old boy presents with petechiae, sternal tenderness on examination, and a retrosternal mass on X-ray. Bone marrow biopsy shows hypercellularity with more than 20% lymphoblasts. Peripheral smear reveals very low TLC and the presence of lymphoblasts. Which of the following is NOT true about the condition the patient is suffering from?

Q16Medium

A patient on bilonatumomab for refractory B cell ALL is now resistant to the drug. Which drug should be used next?

Q17Easy

Which of the following is NOT used in the treatment of hairy cell leukemia?

Q18Easy

All of the following are seen in hypersplenism except:

Q19Easy

Which statement regarding megaloblastic anemia is true?

Q20Easy

Which of the following investigations is NOT required in the initial evaluation of a patient with chronic myeloid leukemia?

Hematology Indian Medical PG Practice Questions and MCQs

Question 11: Which of the following is NOT present in Sideroblastic anaemia?

A. Microcytic anaemia
B. Decreased transferrin saturation (Correct Answer)
C. Sideroblast cells in blood smear film
D. Ineffective erythropoiesis

Explanation: In Sideroblastic Anemia (SA), the core defect is the **inability to incorporate iron into the protoporphyrin ring** to form heme, despite adequate iron stores. ### Why "Decreased Transferrin Saturation" is the Correct Answer In SA, iron is not utilized for heme synthesis. This leads to an "iron overload" state. Consequently, **Serum Iron increases**, **Ferritin increases**, and **Total Iron Binding Capacity (TIBC) decreases**. This results in an **Increased Transferrin Saturation** (often >50%). Therefore, decreased saturation is not a feature of SA; it is characteristic of Iron Deficiency Anemia. ### Explanation of Other Options * **Microcytic Anemia:** Since heme synthesis is impaired, hemoglobin production drops, leading to microcytic, hypochromic RBCs. A "dimorphic" blood picture (both normocytic and microcytic cells) is a classic hallmark. * **Sideroblast cells (Ringed Sideroblasts):** These are the pathognomonic finding. Iron accumulates in the mitochondria surrounding the nucleus of erythroid precursors, visible with **Prussian Blue stain**. Note: While primarily seen in the bone marrow, they are the defining pathological feature of the disease process. * **Ineffective Erythropoiesis:** The iron-laden mitochondria are damaged by free radicals, leading to the premature death of RBC precursors within the bone marrow before they can be released into circulation. ### NEET-PG High-Yield Pearls * **Most common hereditary cause:** X-linked deficiency of **ALAS-2 enzyme**. * **Most common acquired cause:** Alcoholism (reversible) and Lead poisoning. * **Drug-induced:** Isoniazid (antagonizes Vitamin B6/Pyridoxine, a cofactor for ALAS). * **Treatment:** Trial of **Pyridoxine (B6)** is the first-line management for many patients.

Question 12: Secondary polycythemia may be seen in which of the following conditions?

A. Cor pulmonale (Correct Answer)
B. Congestive cardiac failure
C. Acyanotic congenital heart disease
D. All of the above

Explanation: **Explanation:** The core physiological mechanism behind **secondary polycythemia** is an increase in Erythropoietin (EPO) production, usually triggered by **chronic tissue hypoxia** [1]. **1. Why Cor Pulmonale is Correct:** Cor pulmonale refers to right-sided heart failure resulting from chronic lung disease (e.g., COPD, interstitial lung disease). These underlying pulmonary conditions cause **chronic arterial hypoxemia**. In response to low oxygen tension, the kidneys increase the production of Erythropoietin, which stimulates the bone marrow to produce more red blood cells (erythrocytosis) to improve oxygen-carrying capacity. **2. Why the other options are incorrect:** * **Congestive Cardiac Failure (CCF):** While CCF involves poor systemic perfusion, it does not typically cause significant arterial hypoxemia unless there is associated pulmonary edema. Even then, the hypoxia is usually acute or subacute, which does not lead to the sustained EPO elevation required for secondary polycythemia [2]. * **Acyanotic Congenital Heart Disease (CHD):** In acyanotic conditions (like small ASD or VSD), there is a left-to-right shunt. Since oxygenated blood is recirculated to the lungs, systemic arterial oxygen saturation remains normal. Therefore, there is no hypoxic stimulus for EPO production. In contrast, **Cyanotic CHD** (right-to-left shunt) is a classic cause of secondary polycythemia. **High-Yield Clinical Pearls for NEET-PG:** * **Primary vs. Secondary:** Polycythemia Vera (Primary) is characterized by **low EPO** levels and the **JAK2 mutation**. Secondary polycythemia is characterized by **elevated EPO** levels. * **Gaisbock Syndrome:** Also known as "Relative Polycythemia," where RBC mass is normal but plasma volume is decreased (seen in stressed, hypertensive, obese males). * **Other causes of Secondary Polycythemia:** High altitude, Smoking (Carboxyhemoglobin), and EPO-secreting tumors (Renal Cell Carcinoma, Hepatocellular Carcinoma, Hemangioblastoma) [1].

Question 13: A 32-year-old asymptomatic female, not requiring blood transfusion, presents with Hb 13.0 gm/dl. Her HbF levels are 95% and HbA2 levels are 1.5%. Which of the following is the most likely diagnosis?

A. Hereditary persistence of fetal hemoglobin (Correct Answer)
B. Beta homozygous thalassemia
C. Thalassemia intermedia
D. Beta heterozygous thalassemia

Explanation: The key to this question lies in the **asymptomatic presentation** and the **normal hemoglobin level (13.0 gm/dl)** despite a massive elevation in HbF (95%). **1. Why Hereditary Persistence of Fetal Hemoglobin (HPFH) is correct:** HPFH is a benign genetic condition where the "gamma-to-beta globin switch" fails to occur after birth. Unlike thalassemia, there is no imbalance between alpha and non-alpha chains; instead, gamma-chain production compensates perfectly for the lack of beta-chains. Because HbF (α2γ2) functions effectively as an oxygen carrier, patients remain **asymptomatic** with **normal red cell indices** and no anemia. In the pancellular form of HPFH, HbF can reach 100%. **2. Why the other options are incorrect:** * **Beta Homozygous Thalassemia (Thalassemia Major):** Presents in infancy with severe anemia (Hb <7 gm/dl), hepatosplenomegaly, and transfusion dependency. While HbF is high (70-90%), the patient would never be asymptomatic with a normal Hb of 13.0 gm/dl. * **Thalassemia Intermedia:** These patients have moderate anemia (Hb 7-10 gm/dl) and clinical symptoms like bony changes or splenomegaly. They do not maintain a normal Hb of 13.0 gm/dl. * **Beta Heterozygous Thalassemia (Thalassemia Trait):** Characterized by a mild anemia and a hallmark **elevation of HbA2 (>3.5%)**. HbF is usually normal or only slightly elevated (1-5%). **Clinical Pearls for NEET-PG:** * **HPFH vs. Thalassemia:** The defining difference is the **absence of ineffective erythropoiesis** in HPFH. * **HbA2 levels:** Normal is <3.5%. Elevated HbA2 is the most reliable diagnostic marker for **Beta-Thalassemia Trait**. * **Kleihauer-Betke test:** In pancellular HPFH, HbF is distributed uniformly across all RBCs, whereas in Thalassemia, it is distributed heterogeneously (F-cells).

Question 14: What is the most common inherited cause of aplastic anemia?

A. Idiopathic
B. Fanconi anemia (Correct Answer)
C. Shwachman-Diamond syndrome
D. Down syndrome

Explanation: **Explanation:** **Fanconi Anemia (FA)** is the most common inherited cause of aplastic anemia. It is an autosomal recessive (rarely X-linked) DNA repair disorder caused by mutations in the FANC genes. This leads to hypersensitivity to DNA cross-linking agents, resulting in progressive bone marrow failure, typically manifesting in the first decade of life (median age 7–8 years). **Analysis of Options:** * **Fanconi Anemia (Correct):** It accounts for the majority of inherited bone marrow failure syndromes. It is characterized by the triad of pancytopenia, physical anomalies (e.g., absent/hypoplastic thumbs, short stature, café-au-lait spots), and a high risk of malignancies (AML and squamous cell carcinomas). * **Idiopathic (Incorrect):** While idiopathic (immune-mediated) is the most common cause of **acquired** aplastic anemia overall, the question specifically asks for the **inherited** cause. * **Shwachman-Diamond Syndrome (Incorrect):** This is the second most common inherited cause of pancreatic insufficiency (after Cystic Fibrosis) and can cause bone marrow failure, but it is less common than Fanconi Anemia. * **Down Syndrome (Incorrect):** While associated with an increased risk of transient myeloproliferative disorder and leukemia (AMKL), it is not a primary cause of aplastic anemia. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Test:** Chromosomal breakage analysis using **Diepoxybutane (DEB)** or **Mitomycin C**. * **Physical Clue:** Look for "radial ray defects" (absent thumb or radius) in clinical vignettes. * **Treatment:** Hematopoietic stem cell transplant (HSCT) is the definitive treatment for hematologic complications. * **Mnemonic:** "Fanconi" starts with **F** – think **F**irst (most common), **F**ragile DNA, and **F**ingers (thumb anomalies).

Question 15: A 17-year-old boy presents with petechiae, sternal tenderness on examination, and a retrosternal mass on X-ray. Bone marrow biopsy shows hypercellularity with more than 20% lymphoblasts. Peripheral smear reveals very low TLC and the presence of lymphoblasts. Which of the following is NOT true about the condition the patient is suffering from?

A. It has a good prognosis (Correct Answer)
B. Notch gene mutation may be present
C. An immature T-cell phenotype (TdT/CD34/CD7 positive) may be seen
D. Thymic involvement is common

Explanation: The patient presents with classic features of **T-cell Acute Lymphoblastic Leukemia (T-ALL)**. Key diagnostic clues include the adolescent age (17 years), **sternal tenderness** (bone marrow expansion), a **retrosternal mass** (mediastinal/thymic enlargement), and >20% lymphoblasts in the marrow. The diagnosis is confirmed by morphological examination of the marrow, immunophenotyping of cell surface markers, and identifying specific molecular changes [1]. ### 1. Why Option A is the Correct Answer (The "NOT True" statement) While pediatric B-cell ALL generally has a high cure rate, **T-ALL is traditionally associated with a poorer prognosis** compared to B-ALL [2]. It often presents with high-risk features such as a high white blood cell count (though this patient has low TLC, which can occur), bulky lymphadenopathy, and a higher risk of Central Nervous System (CNS) involvement and early relapse. For adults, high white counts over 100 × 10⁹/L are established as poor prognostic factors [2]. Therefore, stating it has a "good prognosis" is incorrect in the comparative context of ALL subtypes. ### 2. Analysis of Other Options * **Option B (Notch gene mutation):** Mutations in the **NOTCH1 gene** are found in over 50-60% of T-ALL cases. This is a high-yield molecular marker for this condition. * **Option C (Immature T-cell phenotype):** T-ALL blasts typically express immature markers like **TdT** (terminal deoxynucleotidyl transferase), **CD34**, and pan-T-cell markers like **CD7** and cytoplasmic **CD3** [1]. These cells are derived from the lymphoid stem cell lineage [1]. * **Option D (Thymic involvement):** T-ALL frequently presents as a **mediastinal (thymic) mass**, leading to symptoms like superior vena cava syndrome or respiratory distress. ### Clinical Pearls for NEET-PG * **Age Distribution:** B-ALL peaks at ~3 years; T-ALL peaks in adolescence. * **Presentation:** T-ALL = **T**eenagers, **T**hymic mass, **T**errible prognosis (relative to B-ALL) [2]. * **Cytochemistry:** Lymphoblasts are **MPO negative** and often **PAS positive** (block-like pattern). * **TdT:** A specialized DNA polymerase used as a marker for both B and T lymphoblasts (absent in mature lymphocytes and myeloid cells).

Question 16: A patient on bilonatumomab for refractory B cell ALL is now resistant to the drug. Which drug should be used next?

A. Vorinostat
B. Brentuximab
C. Pembrolizumab (Correct Answer)
D. Tisagenlecleucel

Explanation: The correct answer is **Pembrolizumab**. **Mechanism and Rationale:** Blinatumomab is a Bispecific T-cell Engager (BiTE) that bridges CD19+ B-cells and CD3+ T-cells, leading to T-cell-mediated cytotoxicity. Resistance to blinatumomab often occurs due to **T-cell exhaustion**, mediated by the upregulation of the **PD-1/PD-L1 pathway**. When T-cells become "exhausted," they lose their effector function despite being in proximity to the tumor. **Pembrolizumab**, a PD-1 inhibitor, can reverse this exhaustion and restore the efficacy of T-cells, making it the preferred salvage therapy in blinatumomab-resistant refractory B-ALL. **Analysis of Incorrect Options:** * **Vorinostat (A):** An HDAC inhibitor used primarily in Cutaneous T-cell Lymphoma (CTCL); it has no established role in overcoming blinatumomab resistance in B-ALL. * **Brentuximab (B):** An anti-CD30 antibody-drug conjugate used in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. B-ALL cells do not typically express CD30. * **Tisagenlecleucel (D):** This is a CAR-T cell therapy. While used in refractory B-ALL, it targets CD19 [1]. If resistance is due to CD19-negative escape (a common mechanism), CAR-T may fail. In the specific context of reversing T-cell exhaustion post-blinatumomab, checkpoint inhibitors are the targeted pharmacological choice. **Clinical Pearls for NEET-PG:** * **Blinatumomab Side Effects:** Watch for **Cytokine Release Syndrome (CRS)** and neurotoxicity (ICANS). * **High-Yield Association:** PD-1 expression on T-cells is a primary biomarker for blinatumomab resistance. * **Pembrolizumab:** Also used in MSI-high tumors and metastatic melanoma.

Question 17: Which of the following is NOT used in the treatment of hairy cell leukemia?

A. Steroid (Correct Answer)
B. Pentostatin
C. Splenectomy
D. Alpha-interferon

Explanation: **Explanation:** Hairy Cell Leukemia (HCL) is a rare B-cell lymphoproliferative disorder characterized by pancytopenia, splenomegaly, and "hairy" cytoplasmic projections. The primary goal of treatment is to manage cytopenias and reduce tumor burden. **Why Steroids are NOT used:** **Steroids (Option A)** have no therapeutic role in HCL. Unlike other lymphoid malignancies (like CLL or Lymphoma), HCL does not respond to corticosteroids. In fact, steroids are generally **contraindicated** because they significantly increase the risk of life-threatening infections in patients who are already profoundly neutropenic and monocytopenic. **Analysis of Incorrect Options:** * **Pentostatin (Option B):** Along with **Cladribine**, this is a Purine Nucleoside Analog (PNA). PNAs are the current **standard of care** and first-line treatment for HCL, offering high complete remission rates. * **Splenectomy (Option C):** Historically the treatment of choice, it is now reserved for refractory cases, massive painful splenomegaly, or during pregnancy when chemotherapy is contraindicated. It effectively improves blood counts but does not treat the underlying bone marrow disease. * **Alpha-interferon (Option D):** This was the first effective medical therapy for HCL. While largely replaced by PNAs, it is still used in patients who cannot tolerate chemotherapy or those with severe cytopenias. **High-Yield Clinical Pearls for NEET-PG:** * **Marker of choice:** CD103 (most specific), CD11c, CD25, and Annexin A1. * **Genetic Mutation:** **BRAF V600E** mutation is present in almost all cases. * **Diagnostic Hallmark:** "Dry tap" on bone marrow aspiration due to increased reticulin fibrosis; TRAP (Tartrate-Resistant Acid Phosphatase) positive staining. * **Classic Presentation:** Massive splenomegaly without lymphadenopathy.

Question 18: All of the following are seen in hypersplenism except:

A. Anemia
B. Thrombocytopenia
C. Splenomegaly
D. Hypocellular bone marrow (Correct Answer)

Explanation: ### Explanation **Hypersplenism** is a clinical syndrome characterized by an overactive spleen that prematurely removes or sequesters circulating blood cells. To diagnose hypersplenism, the **Dameshek’s Criteria** must be met, which includes: 1. Splenomegaly. 2. Cytopenia (Anemia, Leukopenia, and/or Thrombocytopenia). 3. **Hypercellular or Normal bone marrow** (a compensatory response). 4. Correction of cytopenia following splenectomy. #### Why "Hypocellular bone marrow" is the correct answer: In hypersplenism, the peripheral destruction or pooling of cells triggers a feedback mechanism to the bone marrow. The marrow responds by increasing production (**compensatory hyperplasia**) to replace the lost cells. Therefore, the bone marrow is typically **hypercellular**. A hypocellular marrow would suggest a primary bone marrow failure (like Aplastic Anemia) rather than a splenic sequestration issue. #### Analysis of Incorrect Options: * **A & B (Anemia & Thrombocytopenia):** These are hallmark features of hypersplenism [1]. The spleen normally stores about 30% of the body's platelets; in massive splenomegaly, this can increase to 90%, leading to peripheral thrombocytopenia [1]. Similarly, increased red cell destruction leads to anemia. * **C (Splenomegaly):** This is a mandatory component of the syndrome. While not all enlarged spleens cause hypersplenism, hypersplenism (by definition) requires an enlarged or overactive spleen. #### NEET-PG High-Yield Pearls: * **Most common cause of hypersplenism in India:** Cirrhosis leading to Portal Hypertension (Congestive Splenomegaly). * **Splenic Sequestration:** Platelets are the most commonly affected cell line, followed by leucocytes and then erythrocytes [1]. * **Pitted RBCs:** The presence of Howell-Jolly bodies or Pitted RBCs on a peripheral smear indicates **hyposplenism** (asplenia), the functional opposite of this condition.

Question 19: Which statement regarding megaloblastic anemia is true?

A. Megaloblastic precursors are present in the bone marrow.
B. Mean corpuscular volume is increased.
C. Serum lactate dehydrogenase (LDH) is increased.
D. All of the above. (Correct Answer)

Explanation: Megaloblastic anemia is a macrocytic anemia characterized by impaired DNA synthesis, most commonly due to Vitamin B12 or Folate deficiency [1]. This leads to a hallmark finding called **nuclear-cytoplasmic asynchrony**, where the nucleus matures slower than the cytoplasm. **Explanation of Options:** * **Option A:** In the bone marrow, erythroid precursors appear larger than normal (**megaloblasts**) with immature, lacy chromatin despite hemoglobinization of the cytoplasm. This is the definitive morphological feature of the disease. * **Option B:** Due to the impaired cell division, the red blood cells that do enter circulation are larger than normal. This results in an **increased Mean Corpuscular Volume (MCV)**, typically >100 fL. * **Option C:** Megaloblastic anemia is characterized by **ineffective erythropoiesis**. Many megaloblasts are fragile and undergo intramedullary hemolysis (destruction within the bone marrow) before they can mature. This releases massive amounts of intracellular **Lactate Dehydrogenase (LDH)** into the serum, often reaching levels much higher than those seen in other hemolytic anemias. **Clinical Pearls for NEET-PG:** 1. **Peripheral Smear:** Look for **hypersegmented neutrophils** (5% of neutrophils with ≥5 lobes or one with ≥6 lobes); this is often the earliest sign. 2. **Pancytopenia:** Severe megaloblastic anemia can present with low WBC and platelet counts, mimicking leukemia or aplastic anemia. 3. **Neurological Symptoms:** Subacute Combined Degeneration (SCD) of the spinal cord is specific to **Vitamin B12 deficiency**, not folate deficiency. 4. **Biochemical Markers:** Homocysteine is elevated in both B12 and Folate deficiency, but **Methylmalonic Acid (MMA)** is elevated *only* in B12 deficiency [2].

Question 20: Which of the following investigations is NOT required in the initial evaluation of a patient with chronic myeloid leukemia?

A. Peripheral smear
B. Test for Philadelphia chromosome
C. Bone marrow testing
D. HLA typing (Correct Answer)

Explanation: **Explanation:** The initial evaluation of Chronic Myeloid Leukemia (CML) focuses on confirming the diagnosis, determining the disease phase (Chronic, Accelerated, or Blast crisis), and identifying the molecular driver. **Why HLA typing is the correct answer:** HLA typing is used to match donors for an Allogeneic Hematopoietic Stem Cell Transplant (HSCT). While HSCT was once a primary treatment, the advent of **Tyrosine Kinase Inhibitors (TKIs)** like Imatinib has made medical management the first-line standard of care [1]. HLA typing is **not required initially** unless the patient presents in an advanced phase (Blast Crisis) or fails to respond to TKI therapy, making them a candidate for transplant. **Why the other options are incorrect:** * **Peripheral Smear:** Essential to demonstrate the characteristic "myelocyte bulge," leukocytosis with a full spectrum of myeloid cells, and to calculate the percentage of blasts for staging. * **Test for Philadelphia Chromosome:** This is the **gold standard** for diagnosis [1]. It identifies the $t(9;22)$ translocation or the $BCR-ABL1$ fusion gene via Cytogenetics (Karyotyping) or FISH. * **Bone Marrow Testing:** Mandatory at baseline to assess cellularity, morphology, and specifically to determine the blast count and presence of basophilia, which are critical for Sokal or Hasford risk scoring [1]. **Clinical Pearls for NEET-PG:** * **Hallmark:** Presence of the Philadelphia chromosome $t(9;22)$ leading to the $BCR-ABL1$ fusion gene. * **LAP Score:** Leukocyte Alkaline Phosphatase (LAP) score is characteristically **decreased** in CML (useful to differentiate from a Leukemoid reaction where it is increased). * **Drug of Choice:** Imatinib (a BCR-ABL Tyrosine Kinase Inhibitor) [1]. * **Most common physical finding:** Splenomegaly (often massive).

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Anemia Evaluation and Management

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Hemoglobinopathies

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Thalassemias

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Platelet Disorders

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Coagulation Disorders

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Thrombotic Disorders

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Leukemias

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Lymphomas

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Multiple Myeloma and Plasma Cell Disorders

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Myeloproliferative Neoplasms

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Transfusion Medicine

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Hematopoietic Stem Cell Transplantation

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Hematology — MCQs

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