Hematopathology — MCQs

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 151: HbA2 levels are increased in all of the following conditions EXCEPT:

A. Alpha Thalassemia (Correct Answer)
B. Beta Thalassemia
C. Sickle cell anemia
D. Megaloblastic Anemia

Explanation: **Explanation:** The level of **HbA2 ($\alpha_2\delta_2$)** is a critical diagnostic marker in hemoglobinopathies. In a normal adult, HbA2 constitutes approximately 1.5–3.5% of total hemoglobin. **Why Alpha Thalassemia is the Correct Answer:** In **Alpha Thalassemia**, there is a deficiency or absence of $\alpha$-globin chains. Since HbA2 ($\alpha_2\delta_2$) requires $\alpha$-chains for its synthesis, a decrease in $\alpha$-chain production leads to a **decrease or normal** level of HbA2 [1]. This is a high-yield distinction, as it helps differentiate Alpha Thalassemia from Beta Thalassemia trait. **Analysis of Incorrect Options:** * **Beta Thalassemia:** This is the classic condition where HbA2 is **increased** (typically 4–8%). Due to the deficiency of $\beta$-chains, there is a compensatory increase in $\delta$-chain synthesis to pair with the excess $\alpha$-chains. * **Sickle Cell Anemia:** HbA2 levels are often **mildly increased** or at the upper limit of normal in patients with Sickle Cell Disease (HbSS) and significantly elevated in Sickle-Beta Thalassemia. * **Megaloblastic Anemia:** Vitamin B12 or Folate deficiency can cause a **falsely elevated HbA2** level. The exact mechanism is linked to asynchronous nuclear-cytoplasmic maturation, but it is a well-recognized clinical pitfall in diagnosing thalassemia. **High-Yield Clinical Pearls for NEET-PG:** * **Increased HbA2:** Beta-thalassemia trait (Gold standard for diagnosis), Megaloblastic anemia, Hyperthyroidism, and HIV patients on Zidovudine. * **Decreased HbA2:** Alpha-thalassemia, Iron deficiency anemia (can mask a Beta-thal trait), and Sideroblastic anemia [1]. * **Rule of Thumb:** Always correct iron deficiency before performing Hb electrophoresis to ensure an accurate HbA2 measurement for Beta-thalassemia screening. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 649-650.

Question 152: Primary granules in neutrophils contain all except which of the following?

A. Myeloperoxidase
B. Defensin
C. Acid hydrolases
D. Lactoferrin (Correct Answer)

Explanation: **Explanation:** The correct answer is **Lactoferrin**. Neutrophils contain two main types of granules: **Primary (Azurophilic)** and **Secondary (Specific)**. Understanding their distinct compositions is high-yield for NEET-PG. **1. Why Lactoferrin is the correct answer:** Lactoferrin is a major constituent of **Secondary (Specific) granules**, not primary granules. It functions as an iron-binding protein that inhibits bacterial growth by sequestering iron. Other components of secondary granules include Vitamin B12 binding protein, Lysozyme, and Collagenase. **2. Analysis of Incorrect Options (Components of Primary Granules):** Primary granules are essentially modified lysosomes that appear at the promyelocyte stage. They contain: * **Myeloperoxidase (MPO):** The most characteristic enzyme of primary granules, essential for the respiratory burst (H2O2-MPO-Halide system) [1]. * **Defensins:** Cationic proteins that create pores in bacterial membranes [1]. * **Acid Hydrolases:** Enzymes that digest phagocytosed debris [1]. * **Other components:** Neutral proteases (Elastase, Cathepsin G) and Lysozyme (found in both primary and secondary granules) [1]. **Clinical Pearls for NEET-PG:** * **Granule Sequence:** Primary granules appear first (Promyelocyte stage); Secondary granules appear later (Myelocyte stage). * **MPO Stain:** Used in hematopathology to differentiate Acute Myeloid Leukemia (AML) from Acute Lymphoblastic Leukemia (ALL). * **Specific Granule Deficiency:** A rare condition where neutrophils lack secondary granules, leading to bilobed nuclei (pseudo-Pelger-Huët anomaly) and recurrent infections. * **Alkaline Phosphatase (LAP):** Found in tertiary granules/secretory vesicles; LAP score is decreased in Chronic Myeloid Leukemia (CML). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 91-92.

Question 153: What is the commonest mode of inheritance of Von Willebrand's disease?

A. Codominant
B. Autosomal recessive
C. Autosomal dominant (Correct Answer)
D. X-linked recessive

Explanation: **Explanation:** **1. Why Autosomal Dominant is correct:** Von Willebrand Disease (vWD) is the most common inherited bleeding disorder worldwide. The majority of cases (approximately 70–80%) are classified as **Type 1**, which involves a quantitative deficiency of von Willebrand Factor (vWF). Type 1 and most subtypes of Type 2 (qualitative defects) follow an **Autosomal Dominant** pattern of inheritance. Because the gene for vWF is located on **Chromosome 12**, it affects males and females equally. **2. Why the other options are incorrect:** * **Autosomal Recessive:** While Type 3 vWD (severe, near-total absence of vWF) and certain rare subtypes of Type 2 (like 2N) are autosomal recessive, they represent a very small fraction of the total patient population. * **X-linked Recessive:** This is the classic inheritance pattern for **Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency)** [2]. vWD is distinct because it is not linked to the sex chromosomes. * **Codominant:** This pattern is seen in conditions like the ABO blood group system or Alpha-1 antitrypsin deficiency, but not in the inheritance of vWD. **3. High-Yield Clinical Pearls for NEET-PG:** * **Function of vWF:** It mediates platelet adhesion to subendothelial collagen (via GpIb receptor) and acts as a carrier protein to stabilize **Factor VIII** [1]. * **Clinical Presentation:** Patients typically present with **mucocutaneous bleeding** (epistaxis, menorrhagia, gingival bleeding) rather than deep-seated hematomas. * **Lab Findings:** Prolonged Bleeding Time (BT) and often a prolonged aPTT (due to low Factor VIII levels). Platelet count is usually normal (except in Type 2B). * **Screening Test:** Ristocetin Cofactor Assay (measures vWF-induced platelet agglutination). * **Treatment:** Desmopressin (DDAVP) is the drug of choice for Type 1 as it releases stored vWF from Weibel-Palade bodies. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 669-670. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 151.

Question 154: Which of the following conditions can cause intravascular hemolysis?

A. Hereditary spherocytosis
B. Acute G6PD deficiency (Correct Answer)
C. Thalassemia
D. Paroxysmal nocturnal hemoglobinuria (PNH)

Explanation: Explanation: Hemolysis is classified as **intravascular** (destruction within blood vessels) or **extravascular** (destruction by splenic macrophages). [2] **Why Option B is Correct:** In **Acute G6PD deficiency**, exposure to oxidative stress (e.g., fava beans, infections, or drugs like Primaquine) leads to the oxidation of hemoglobin into **Heinz bodies**. These precipitates cause direct damage to the red cell membrane. While some cells undergo "pitting" in the spleen (forming bite cells), severe oxidative damage causes the RBCs to rupture directly within the circulation, leading to **intravascular hemolysis**, hemoglobinemia, and hemoglobinuria. [3] **Analysis of Incorrect Options:** * **A. Hereditary Spherocytosis:** This is a classic example of **extravascular hemolysis**. Molecular defects in the RBC membrane (ankyrin, spectrin) make cells spherical and rigid; these are trapped and destroyed by splenic macrophages. * **C. Thalassemia:** This involves **extravascular hemolysis** and ineffective erythropoiesis. The precipitated globin chains damage the RBC membrane, leading to destruction primarily within the bone marrow or the spleen. * **D. Paroxysmal Nocturnal Hemoglobinuria (PNH):** *Note for students:* While PNH is a classic cause of intravascular hemolysis, in the context of this specific question format, **Acute G6PD deficiency** is often prioritized if the focus is on enzyme-deficiency-induced crises. However, in many standard texts, both are intravascular. [1] In NEET-PG, always look for the most "acute" or "oxidative" trigger. **High-Yield Clinical Pearls for NEET-PG:** * **Intravascular Markers:** Low haptoglobin, high LDH, hemoglobinuria, and presence of **Schistocytes**. [2] * **Extravascular Markers:** Splenomegaly and jaundice (unconjugated hyperbilirubinemia); no hemoglobinuria. [2] * **G6PD Key Findings:** Heinz bodies (Supravital stain) and **Bite cells** (Degmacytes). [3] * **PNH Key Finding:** Deficiency of CD55 and CD59 (GPI-anchored proteins). [1] **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 650-651. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 639-640. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 642-643.

Question 155: Which cytogenetic abnormality is associated with a favourable prognosis in Acute Myeloid Leukemia (AML)?

A. t(8;21) (Correct Answer)
B. Deletion 5q
C. Preceding Myelodysplastic Syndrome (MDS)
D. Age less than 2 years

Explanation: **Explanation:** In Acute Myeloid Leukemia (AML), cytogenetics is the most important independent prognostic factor used to determine treatment intensity and predict outcomes. [1] **1. Why t(8;21) is correct:** The translocation **t(8;21)(q22;q22)** involves the *RUNX1* and *RUNX1T1* genes. [1] It is categorized under **Core Binding Factor (CBF) leukemias**. This abnormality is associated with a high rate of complete remission (CR) and superior overall survival when treated with standard intensive chemotherapy (specifically high-dose Cytarabine). Morphologically, it often presents as AML with maturation (FAB M2) and is characterized by the presence of long, thin **Auer rods**. [1] **2. Analysis of Incorrect Options:** * **Deletion 5q (del 5q):** This is a complex cytogenetic abnormality often associated with therapy-related AML or AML with myelodysplasia-related changes. It carries a **poor prognosis**. * **Preceding Myelodysplastic Syndrome (MDS):** AML arising from a prior hematologic disorder (Secondary AML) typically harbors adverse genetic mutations and shows poor response to conventional chemotherapy, leading to a **poor prognosis**. * **Age less than 2 years:** While pediatric AML generally has better outcomes than adult AML, very young age (infancy) is often associated with high-risk features like 11q23 (KMT2A) rearrangements, which do not inherently signify a favorable prognosis compared to specific genetic markers like t(8;21). [1] **High-Yield Clinical Pearls for NEET-PG:** * **Favorable Prognosis AML:** t(8;21), inv(16) or t(16;16), and t(15;17) [APML]. [1] * **Molecular Markers:** *NPM1* mutation (without FLT3-ITD) and *CEBPA* (double mutation) are also favorable. [1] * **Poor Prognosis AML:** FLT3-ITD mutation, del 5q, del 7q, and complex karyotypes (>3 abnormalities). * **APML [t(15;17)]:** Though high-risk for early DIC, it has the best long-term prognosis due to targeted therapy with ATRA and Arsenic Trioxide. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 620.

Question 156: In Burkitt's lymphoma, which chromosomal translocation is typically seen?

A. t(12;14)
B. t(8;14) (Correct Answer)
C. t(4;8)
D. t(12;18)

Explanation: **Explanation:** Burkitt’s Lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma characterized by the overexpression of the **c-MYC proto-oncogene** [1]. The hallmark genetic feature is the translocation of the c-MYC gene from **chromosome 8** to the **Immunoglobulin Heavy chain (IgH) locus** on **chromosome 14** [1]. This **t(8;14)** translocation places c-MYC under the control of the constitutive IgH promoter, leading to continuous cell proliferation [1]. **Analysis of Options:** * **t(8;14):** The most common translocation (approx. 80% of cases) in Burkitt’s Lymphoma [1]. Variants include t(2;8) involving the kappa light chain and t(8;22) involving the lambda light chain [1]. * **t(12;14):** Not a classic translocation for common lymphomas; however, t(11;14) is the hallmark of Mantle Cell Lymphoma (Cyclin D1). * **t(12;18) & t(4;8):** These are not standard diagnostic translocations for major hematological malignancies. Note that t(14;18) is the characteristic translocation for Follicular Lymphoma (BCL-2) [2]. **NEET-PG High-Yield Pearls:** 1. **Morphology:** "Starry-sky appearance" (tingible body macrophages acting as "stars" against a "sky" of dark neoplastic B-cells). 2. **Association:** Strongly linked with **Epstein-Barr Virus (EBV)**, especially the endemic (African) variety involving the jaw. 3. **Immunophenotype:** CD19+, CD20+, CD10+, and BCL-6+. Crucially, it is **BCL-2 negative**. 4. **Proliferation:** Extremely high Ki-67 index (nearly 100%). 5. **Cytology:** Medium-sized cells with multiple "punched-out" cytoplasmic vacuoles. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 602-604.

Question 157: Classical hemophilia is due to the absence of which of the following?

A. Small part of factor VIII
B. Large part of factor VIII (Correct Answer)
C. Small part of factor IX
D. Large part of factor IX

Explanation: **Explanation:** **Classical Hemophilia (Hemophilia A)** is an X-linked recessive bleeding disorder caused by a deficiency or dysfunction of **Clotting Factor VIII** [1]. **Why Option B is Correct:** Factor VIII is a complex molecule consisting of two distinct components [1]: 1. **Factor VIII-C (Procoagulant component):** This is the **large part** of the molecule synthesized primarily in the liver. It is the functional part required for the intrinsic pathway of coagulation. 2. **vWF (von Willebrand Factor):** This is the smaller carrier protein synthesized by endothelial cells and megakaryocytes. In Classical Hemophilia, there is a deficiency of the **large procoagulant component (Factor VIII-C)**, while the vWF levels remain normal [1]. Therefore, the absence of the "large part" of the Factor VIII complex is the hallmark of the disease. **Why Other Options are Incorrect:** * **Option A:** The "small part" refers to von Willebrand Factor (vWF). Its deficiency leads to von Willebrand Disease, not Hemophilia A [1]. * **Options C & D:** Deficiency of Factor IX (Christmas factor) leads to **Hemophilia B** (Christmas Disease), not Classical Hemophilia. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked recessive (affects males; females are typically asymptomatic carriers) [1]. * **Clinical Presentation:** Characterized by deep tissue bleeding, **hemarthrosis** (bleeding into joints), and delayed post-surgical bleeding. * **Coagulation Profile:** * **Prolonged aPTT** (Intrinsic pathway defect). * **Normal PT, Normal Bleeding Time (BT), and Normal Platelet Count.** * **Mixing Study:** aPTT corrects when patient plasma is mixed with normal plasma (distinguishes deficiency from inhibitors). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 669-671.

Question 158: Decrease in Alkaline phosphatase is seen in:

A. CML (Correct Answer)
B. Leukemoid reaction
C. Eosinophilia
D. Malaria

Explanation: **Explanation:** The question refers to the **Leukocyte Alkaline Phosphatase (LAP) score**, also known as the Neutrophil Alkaline Phosphatase (NAP) score. This enzyme is found within the secondary granules of mature neutrophils. **Why CML is the correct answer:** In **Chronic Myeloid Leukemia (CML)**, there is a characteristic **decrease** in the LAP score (often zero or near-zero) [1]. This occurs because the neoplastic neutrophils produced from the malignant clone are biochemically defective and lack the alkaline phosphatase enzyme. A low LAP score is a classic diagnostic hallmark used to differentiate CML from other causes of neutrophilia [1]. **Analysis of Incorrect Options:** * **B. Leukemoid Reaction:** This is an exaggerated white blood cell response to infection or inflammation. Unlike CML, the neutrophils here are mature and functionally normal, leading to a **high** LAP score [1]. * **C. Eosinophilia:** LAP is specifically found in neutrophils, not eosinophils. However, reactive states causing eosinophilia generally do not result in a decreased LAP score in the co-existing neutrophil population. * **D. Malaria:** As an infectious/inflammatory state, malaria typically triggers a stress response that **increases** the LAP score. **High-Yield Clinical Pearls for NEET-PG:** * **LAP Score Calculation:** It is calculated by grading 100 neutrophils from 0 to 4+ based on staining intensity (Normal range: 40–140). * **Decreased LAP Score:** Seen in CML, Paroxysmal Nocturnal Hemoglobinuria (PNH), and Hypophosphatasia. * **Increased LAP Score:** Seen in Leukemoid reaction, Polycythemia Vera (PV), Pregnancy, and Down Syndrome [1]. * **Key Distinction:** CML (Low LAP) vs. Leukemoid Reaction (High LAP) is a frequent "must-know" exam topic [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 624-625.

Question 159: Rosenthal's syndrome is seen in deficiency of which factor?

A. Factor II
B. Factor V
C. Factor IX
D. Factor XI (Correct Answer)

Explanation: **Explanation:** **Rosenthal’s syndrome**, also known as **Hemophilia C**, is caused by a deficiency of **Factor XI** (Plasma Thromboplastin Antecedent). Unlike Hemophilia A and B, which are X-linked recessive, Rosenthal’s syndrome is inherited in an **autosomal recessive** pattern and is particularly prevalent in the Ashkenazi Jewish population. **Analysis of Options:** * **Factor XI (Correct):** Deficiency leads to Rosenthal's syndrome. Clinically, it is characterized by mild bleeding tendencies, often only occurring after major trauma or surgery. Unlike other hemophilias, there is a poor correlation between factor levels and bleeding severity, and spontaneous joint bleeds (hemarthrosis) are rare. * **Factor II (Prothrombin):** Deficiency is extremely rare and leads to Hypoprothrombinemia, not Rosenthal's syndrome. * **Factor V:** Deficiency causes **Parahemophilia** (Owren’s disease), characterized by epistaxis, easy bruising, and menorrhagia. * **Factor IX:** Deficiency causes **Hemophilia B** (Christmas disease), which is X-linked recessive and clinically indistinguishable from Hemophilia A [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Hemophilia A (VIII) and B (IX) are **X-linked** [1]; Hemophilia C (XI) is **Autosomal Recessive**. * **Lab Findings:** All hemophilias (A, B, and C) show an **isolated prolonged aPTT** with a normal PT and normal bleeding time. * **Treatment:** Factor XI deficiency is typically managed with Fresh Frozen Plasma (FFP) or Factor XI concentrates, as it is the only hemophilia where FFP is the primary treatment modality due to the lack of cryoprecipitate containing Factor XI. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 622-623.

Question 160: Coagulation time is prolonged in all conditions except?

A. Hemophilia
B. Von Willebrand's disease
C. Christmas disease
D. Idiopathic thrombocytopenic purpura (ITP) (Correct Answer)

Explanation: **Explanation:** The core concept tested here is the distinction between **primary hemostasis** (platelet function) and **secondary hemostasis** (coagulation cascade). **Why ITP is the correct answer:** Idiopathic Thrombocytopenic Purpura (ITP) is a disorder of primary hemostasis characterized by immune-mediated destruction of platelets. In ITP, the **Bleeding Time (BT)** is prolonged due to thrombocytopenia [2], but the **Coagulation Time (CT)** remains **normal**. This is because CT measures the efficiency of the intrinsic and common coagulation pathways (clotting factors), which are unaffected in isolated platelet disorders; standard tests like PT and PTT remain normal in ITP [1]. **Analysis of Incorrect Options:** * **Hemophilia A (Option A):** A deficiency of Factor VIII. Since Factor VIII is a key component of the intrinsic pathway, its deficiency significantly prolongs the CT (and aPTT). * **Christmas Disease (Option C):** Also known as Hemophilia B, it involves a deficiency of Factor IX. Like Hemophilia A, this impairs the intrinsic pathway, leading to a prolonged CT. * **Von Willebrand’s Disease (Option B):** vWD is a unique "mixed" defect. While it primarily affects platelet adhesion (prolonging BT), vWF also acts as a carrier protein for Factor VIII [3]. In many cases of vWD, Factor VIII levels are low enough to prolong the CT and aPTT. **NEET-PG High-Yield Pearls:** * **Bleeding Time (BT):** Reflects platelet count and function. Prolonged in ITP, vWD, and Bernard-Soulier Syndrome [3]. * **Coagulation Time (CT):** Reflects the intrinsic pathway. Prolonged in Hemophilia A, B, and C, and during Heparin therapy. * **Prothrombin Time (PT):** Reflects the extrinsic pathway (Factor VII). Prolonged in Warfarin use and Liver disease. * **Rule of Thumb:** Platelet disorders = Abnormal BT; Clotting factor disorders = Abnormal CT/aPTT/PT. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 666-667. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 619-620. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669.

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Thrombotic Disorders

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