Hematology Practice Questions

Q: Reticulocytosis is NOT a feature of which of the following conditions?

Anemia in chronic renal failure. ### Explanation The **Reticulocyte Count** is a direct indicator of the bone marrow's erythropoietic activity. To have reticulocytosis (an increase in young RBCs), two conditions must be met: a functional bone marrow and adequate levels of **Erythropoietin (EPO)**. [1] **Why Option D is Correct:** In **Chronic Renal Failure (CRF)**, the primary cause of anemia is the **deficiency of Erythropoietin**, which is produced by the peritubular interstitial cells of the kidney. [1] Without EPO, the bone marrow is not stimulated to produce RBCs despite the anemia. Therefore, CRF is characterized by a **low reticulocyte count** (hypoproliferative anemia). **Why Other Options are Incorrect:** * **Paroxysmal Nocturnal Hemoglobinuria (PNH) & Hereditary Spherocytosis:** Both are hemolytic anemias. In hemolysis, the bone marrow is healthy and responds to the low hemoglobin by increasing RBC production, leading to significant **reticulocytosis**. * **Following Acute Bleeding:** After a sudden loss of blood, the body compensates by releasing EPO to stimulate the marrow. [1] Within 3–5 days, the reticulocyte count rises as the marrow attempts to replace the lost volume. ### High-Yield Clinical Pearls for NEET-PG * **Corrected Reticulocyte Count (CRC):** In anemia, always use CRC to assess marrow response. $CRC = \text{Observed Retic \%} \times (\text{Patient's Hct} / \text{Normal Hct})$. * **Reticulocyte Production Index (RPI):** An **RPI > 2%** indicates an adequate marrow response (hemolysis/hemorrhage), while **RPI < 2%** indicates an inadequate response (nutritional deficiencies or marrow failure). * **Anemia in CRF:** Usually Normocytic Normochromic. Treatment involves recombinant human erythropoietin (target Hb: 10–12 g/dL). * **Other causes of low reticulocyte count:** Aplastic anemia, Iron/B12/Folate deficiency, and Bone marrow suppression (chemotherapy). [1]

Q: Which of the following is a characteristic feature of multiple myeloma?

Monoclonal proliferation of B cells. **Explanation:** **Multiple Myeloma (MM)** is a hematologic malignancy characterized by the **monoclonal proliferation of plasma cells** in the bone marrow [1]. While plasma cells are the immediate effector cells, they are the terminal stage of B-cell differentiation. The underlying pathophysiology involves a malignant transformation of a B-cell clone that matures into plasma cells, which then overproduce a specific monoclonal (M) protein. **Analysis of Options:** * **Option A (Correct):** MM is fundamentally a disease of monoclonal B-cell lineage. The neoplastic process begins with a "hit" in the B-cell development stage (often during isotype switching in the germinal center), leading to the clonal expansion of cells that eventually secrete monoclonal immunoglobulins. * **Option B & C (Incorrect):** In MM, the malignant cells are **plasma cells**, not mature B cells [1]. These plasma cells are typically confined to the bone marrow (Option B) and are rarely seen in peripheral blood (Option C) unless the disease progresses to the aggressive "Plasma Cell Leukemia" stage. * **Option D (Incorrect):** While plasma cells *do* secrete immunoglobulins, this is a **normal physiological function** of all plasma cells. The characteristic feature of MM is the secretion of **monoclonal** immunoglobulins (paraproteins) by a malignant clone, not just general secretion [1]. **High-Yield NEET-PG Pearls:** * **CRAB Criteria:** Diagnosis requires end-organ damage: **C**alcium (hypercalcemia), **R**enal insufficiency, **A**nemia, and **B**one lesions (lytic) [1]. * **Diagnosis:** Bone marrow biopsy showing **>10% clonal plasma cells** [1]. * **Peripheral Smear:** Characterized by **Rouleaux formation** due to high protein levels. * **Urinalysis:** Bence-Jones proteins (free light chains) are detected via heat precipitation or electrophoresis, not by standard dipstick.

Q: Bone marrow transplantation is not indicated in which of the following conditions?

Congenital spherocytosis. **Explanation:** Bone marrow transplantation (BMT), specifically Hematopoietic Stem Cell Transplantation (HSCT), is indicated for conditions where the primary defect lies within the bone marrow stem cells or where high-dose chemotherapy has obliterated the marrow. **Why Congenital Spherocytosis is the correct answer:** Congenital Spherocytosis is a hereditary hemolytic anemia caused by defects in red blood cell (RBC) membrane proteins (e.g., ankyrin, spectrin) [1]. While the defect is genetic, the clinical problem is the premature destruction of these spherical RBCs by the **spleen**. The bone marrow itself is functional and hyperplastic. Therefore, the definitive treatment is **Splenectomy**, not BMT [1]. BMT is an invasive procedure with high morbidity and is unnecessary for a condition manageable by removing the site of hemolysis. **Analysis of Incorrect Options:** * **Aplastic Anemia:** This is a primary bone marrow failure syndrome. HSCT is the treatment of choice, especially in young patients with a matched sibling donor, to replace the non-functional marrow. * **Thalassemia:** This is a hemoglobinopathy resulting from a genetic defect in globin chain synthesis within the erythroid precursors. HSCT is the only curative treatment available to replace the defective erythropoietic system. * **AML in First Remission:** High-risk Acute Myeloid Leukemia (AML) often requires HSCT during the first complete remission (CR1) to prevent relapse by providing a "graft-versus-leukemia" effect and replacing the malignant clone. **Clinical Pearls for NEET-PG:** * **Treatment of Choice (TOC) for Congenital Spherocytosis:** Splenectomy (usually deferred until after age 5 to reduce sepsis risk) [1]. * **Most common protein defect in Spherocytosis:** Ankyrin [1]. * **BMT Indication:** Always consider BMT for "Stem Cell" or "Marrow" failures; consider Splenectomy for "Peripheral Destruction" (like Spherocytosis or ITP).

Q: In multiple myeloma, which of the following is typically NOT seen?

Anion gap raised. In Multiple Myeloma (MM), the characteristic finding is a **low anion gap**, not a raised one. This occurs because the M-proteins (monoclonal immunoglobulins) are cationic (positively charged) at physiological pH. To maintain electroneutrality, there is an increase in chloride and bicarbonate (unmeasured anions), which mathematically reduces the calculated anion gap [AG = Na - (Cl + HCO3)]. **Explanation of Options:** * **A. Anion gap raised (Correct Answer):** As explained, MM typically presents with a **decreased anion gap**. A raised anion gap is usually seen in conditions like ketoacidosis, lactic acidosis, or renal failure (though MM causes renal failure, the cationic effect of paraproteins often predominates). * **B. Lytic bone lesion:** This is a hallmark of MM [1]. Myeloma cells secrete RANKL and inhibit osteoprotegerin, leading to osteoclast activation and "punched-out" lytic lesions, most commonly in the skull and spine [1]. * **C. Polyarticular pain:** Bone pain is the most common presenting symptom in MM [1]. It often involves the back and ribs and can mimic polyarticular involvement due to multiple pathological fractures or bone destruction. * **D. M spike with polyneuropathy:** An M-spike (monoclonal gammopathy) is the diagnostic signature on protein electrophoresis [1]. Polyneuropathy can occur in MM due to amyloidosis (AL type) or as part of **POEMS syndrome** (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). **High-Yield Clinical Pearls for NEET-PG:** * **CRAB Criteria:** **C**alcium (High), **R**enal insufficiency, **A**nemia, **B**one lesions [1]. * **Diagnosis:** Bone marrow plasma cells **≥10%** or biopsy-proven plasmacytoma [1]. * **Peripheral Smear:** **Rouleaux formation** (due to increased ESR/fibrinogen). * **Urine:** Bence-Jones proteins (detected by sulfosalicylic acid test, not by standard dipstick).

Q: Suggested criteria for the clinical diagnosis of Polycythemia vera (PV) include all except?

Low aerial oxygen saturation. **Explanation:** Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by the autonomous production of red blood cells, independent of erythropoietin (EPO) levels. **Why "Low arterial oxygen saturation" is the correct answer:** In PV, the increase in red cell mass is **primary**, meaning it is caused by a mutation (usually JAK2 V617F) in the bone marrow, not as a response to hypoxia [1]. Therefore, arterial oxygen saturation ($SaO_2$) is typically **normal** ($\geq 92\%$). Conversely, a low $SaO_2$ suggests **Secondary Polycythemia**, where the body increases RBC production as a compensatory mechanism for chronic hypoxia [1]. **Analysis of other options:** * **Elevated red cell mass:** This is the hallmark of PV. It leads to hyperviscosity and is a classic diagnostic criterion (though modern WHO criteria focus more on hemoglobin/hematocrit levels) [1]. * **Increased counts of cells of all lineages:** PV is a "panmyelosis." While erythrocytosis is dominant, most patients also exhibit leukocytosis (increased WBCs) and thrombocytosis (increased platelets). * **Splenomegaly:** Found in approximately 70% of patients at diagnosis, splenomegaly is a classic clinical finding due to the sequestration of excess cells and extramedullary hematopoiesis [1]. **NEET-PG High-Yield Pearls:** * **WHO Major Criteria (2016/2022):** 1. Hemoglobin >16.5 g/dL (men) / >16.0 g/dL (women); 2. Bone marrow biopsy showing hypercellularity/panmyelosis; 3. Presence of **JAK2 V617F** or JAK2 exon 12 mutation [1]. * **Minor Criterion:** Subnormal (low) serum erythropoietin level. * **Clinical Sign:** **Aquagenic pruritus** (itching after a warm bath) is highly specific for PV [1]. * **Treatment of choice:** Phlebotomy and low-dose Aspirin; Hydroxyurea for high-risk patients.

Q: Which of the following conditions is LEAST likely to be pre-leukemic?

Paroxysmal cold hemoglobinuria. The term "pre-leukemic" refers to hematological disorders that have a significant risk of transforming into Acute Myeloid Leukemia (AML). The correct answer is **Paroxysmal Cold Hemoglobinuria (PCH)** because it is a purely immune-mediated hemolytic process, not a stem cell disorder. **1. Why Paroxysmal Cold Hemoglobinuria (PCH) is the correct answer:** PCH is a rare form of autoimmune hemolytic anemia caused by the **Donath-Landsteiner antibody** (an IgG autoantibody against the P antigen). It involves the destruction of mature red blood cells via complement activation. Since it does not involve a clonal mutation in hematopoietic stem cells or bone marrow failure, it carries **no risk** of leukemic transformation. **2. Why the other options are "Pre-leukemic":** * **Paroxysmal Nocturnal Hemoglobinuria (PNH):** This is a clonal stem cell disorder (PIGA gene mutation). While primarily hemolytic, it is closely linked to bone marrow failure syndromes and can progress to AML in approximately 2-5% of cases. * **Aplastic Anemia:** Chronic aplastic anemia involves intense selective pressure on the bone marrow. Over time, clonal evolution can occur, leading to MDS or AML (transformation rate ~5-10%). * **Myelodysplastic Syndrome (MDS):** This is the classic "pre-leukemic" state. It is characterized by cytopenias and dysplastic changes; it carries the highest risk of transformation to AML (up to 30%). **Clinical Pearls for NEET-PG:** * **PCH:** Associated with syphilis (historically) and viral infections in children. Diagnosis: **Donath-Landsteiner Test.** * **PNH:** Triad of Hemolysis, Pancytopenia, and Thrombosis (Budd-Chiari). Diagnosis: **Flow cytometry** (CD55/CD59 deficiency). * **Rule of Thumb:** Any condition involving **clonal hematopoiesis** or **bone marrow failure** has pre-leukemic potential; purely peripheral destructive processes (like PCH) do not.

Q: Which of the following does NOT cause sideroblastic anemia?

Mercury poisoning. **Explanation:** Sideroblastic anemia is characterized by the presence of **ringed sideroblasts** in the bone marrow, which are erythroblasts with iron-laden mitochondria encircling the nucleus. This occurs due to a failure to incorporate iron into protoporphyrin to form heme. **Why Mercury Poisoning is the Correct Answer:** While several heavy metals interfere with heme synthesis [1], **Lead poisoning** is the classic cause of sideroblastic anemia. **Mercury poisoning**, conversely, typically presents with neurological symptoms (tremors, erethism), renal failure, or acrodynia [2], but it does **not** characteristically cause sideroblastic anemia. **Analysis of Incorrect Options:** * **Isoniazid (INH):** This is a classic cause. INH is a Vitamin B6 (Pyridoxine) antagonist. Since Pyridoxine is a required cofactor for **ALAS (delta-aminolevulinic acid synthase)**, the rate-limiting enzyme in heme synthesis [1], its deficiency leads to sideroblastic changes. * **Chloramphenicol:** This antibiotic inhibits mitochondrial protein synthesis, interfering with the mitochondrial enzymes necessary for heme production. * **Myelodysplastic Syndrome (MDS):** Specifically, the subtype **RARS (Refractory Anemia with Ringed Sideroblasts)** is a common primary/acquired cause of sideroblastic anemia in the elderly due to mitochondrial DNA mutations. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Bone marrow examination with **Prussian Blue stain** showing $\geq 5$ siderotic granules covering $\geq 1/3$ of the nuclear circumference. * **Reversible Causes:** Alcohol (most common), Lead, INH, and Copper deficiency. * **Treatment:** For INH-induced cases, administer **Pyridoxine (B6)**. * **Blood Smear:** Look for **dimorphic anemia** (two populations of RBCs: microcytic and normocytic) and **Pappenheimer bodies**.

Question 1

Reticulocytosis is NOT a feature of which of the following conditions?

Accepted Answer

Anemia in chronic renal failure

Answer

Paroxysmal nocturnal hemoglobinuria

Answer

Following acute bleeding

Answer

Hereditary spherocytosis

Question 2

A 27-year-old woman presents with epistaxis, rash on her feet, and fevers. She appears unwell, pale, jaundiced, and has multiple petechiae on her feet. Physical examination reveals clear lungs, normal heart sounds, and a soft abdomen with no palpable spleen or liver. Laboratory investigations show: Bilirubin 2 mg/dL (predominantly indirect), normal AST, ALT, and ALP. Hemoglobin is 8.7 g/dL, platelets are 24,000/mL, PT/PTT are normal, and bleeding time is elevated. A peripheral blood smear reveals anemia, thrombocytopenia, and red blood cell fragments. What is the most likely diagnosis for this patient presenting with a bleeding disorder?

Accepted Answer

Thrombotic thrombocytopenic purpura (TTP)

Answer

von Willebrand disease

Answer

Hemophilia A

Answer

Hemophilia B

Question 3

Which of the following is a characteristic feature of multiple myeloma?

Accepted Answer

Monoclonal proliferation of B cells

Answer

Presence of B cells in bone marrow

Answer

Presence of B cells in peripheral blood

Answer

Plasma cells secreting immunoglobulin

Question 4

A 63-year-old man has noticed a lump in his neck for 2 months. Examination reveals a group of three discrete nontender right posterior cervical lymph nodes, and a mass of enlarged right axillary lymph nodes. Chest and abdominal CT scans show mediastinal lymphadenopathy and hepatosplenomegaly. Microscopic examination of a cervical lymph node biopsy reveals abundant large CD15+ and CD30+ binucleate cells with prominent acidophilic nucleoli, scattered within a sparse lymphocytic infiltrate. What is molecular analysis of this lesion most likely to reveal?

Accepted Answer

Clonal Epstein-Barr virus (EBV) integration in the large cells

Answer

BCL6 gene rearrangements in the large cells

Answer

Deletions of 5q in all the cells

Answer

Helicobacter pylori infection in all the cells

Question 5

Bone marrow transplantation is not indicated in which of the following conditions?

Accepted Answer

Congenital spherocytosis

Answer

Aplastic anaemia

Answer

Thalassemia

Answer

Acute myeloid leukaemia in first remission

Question 6

In multiple myeloma, which of the following is typically NOT seen?

Accepted Answer

Anion gap raised

Answer

Lytic bone lesion

Answer

Polyarticular pain

Answer

M spike present with polyneuropathy

Question 7

Suggested criteria for the clinical diagnosis of Polycythemia vera (PV) include all except?

Accepted Answer

Low aerial oxygen saturation

Answer

Elevated red cell mass

Answer

Increased counts of cells of all lineages

Answer

Splenomegaly

Question 8

Which of the following blood diseases has a racial predilection?

Accepted Answer

Thalassemia

Answer

Purpura

Answer

Hemophilia

Answer

Polycythemia

Question 9

Which of the following conditions is LEAST likely to be pre-leukemic?

Accepted Answer

Paroxysmal cold hemoglobinuria

Answer

Paroxysmal nocturnal hemoglobinuria

Answer

Aplastic anemia

Answer

Myelodysplastic syndrome

Question 10

Which of the following does NOT cause sideroblastic anemia?

Accepted Answer

Mercury poisoning

Answer

Isoniazid (INH)

Answer

Chloramphenicol

Answer

Myelodysplastic syndrome

Hematology — MCQs

Hematology — MCQs

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