Hematology Practice Questions

Q: Which of the following tests is used to screen a woman with a family history of thalassemia?

NESTROFT. **Explanation:** The correct answer is **NESTROFT** (Naked Eye Single Tube Red Cell Osmotic Fragility Test). **1. Why NESTROFT is correct:** In resource-limited settings and large-scale population screening (especially for Thalassemia Trait), NESTROFT is the preferred **screening test**. It is based on the principle of osmotic fragility. Thalassemic red cells are microcytic and hypochromic with a high surface-area-to-volume ratio, making them more resistant to hemolysis in hypotonic saline (0.36%) compared to normal cells. If the solution remains turbid (cannot see a black line through the tube), the test is positive, indicating a high probability of Thalassemia Trait. It is cost-effective, rapid, and has high sensitivity. **2. Why other options are incorrect:** * **Hb A2 Levels:** This is the **Gold Standard for diagnosis** of Beta-Thalassemia Trait (values >3.5%). However, it is an expensive and specialized test, making it unsuitable for initial mass screening. * **High Performance Liquid Chromatography (HPLC):** This is the **confirmatory test** used to quantify HbA2, HbF, and detect abnormal hemoglobin variants. It is the "investigation of choice" for definitive diagnosis, not primary screening. * **Peripheral Smear and Reticulocyte Count:** While a smear shows microcytic hypochromic cells and target cells, it is non-specific and cannot differentiate between Iron Deficiency Anemia (IDA) and Thalassemia. **Clinical Pearls for NEET-PG:** * **Mentzer Index:** (MCV/RBC count) 13 suggests IDA. * **Best Screening Test:** NESTROFT. * **Investigation of Choice/Confirmatory Test:** HPLC. * **Target Cells:** Characteristically seen in Thalassemia, Liver disease, and Post-splenectomy.

Q: A 70-year-old male presented with anorexia, weakness, and paresthesia. Investigations revealed a hemoglobin of 5.8 g/dL, a peripheral smear showing macrocytes and neutrophils with hypersegmented nuclei, and sluggish tendon reflexes. Endoscopy revealed atrophic gastritis. Deficiency of which of the following factors can lead to such a clinical situation?

Vitamin B12. The clinical presentation of **megaloblastic anemia** (macrocytes and hypersegmented neutrophils) combined with **neurological symptoms** (paresthesia and sluggish reflexes) is a classic hallmark of **Vitamin B12 deficiency** [1]. **Why Vitamin B12 is correct:** Vitamin B12 is essential for DNA synthesis and the maintenance of myelin in the nervous system. The patient’s **atrophic gastritis** leads to a loss of gastric parietal cells, which are responsible for secreting **Intrinsic Factor (IF)**. Without IF, Vitamin B12 cannot be absorbed in the terminal ileum (Pernicious Anemia) [1]. The lack of B12 impairs DNA synthesis, causing ineffective erythropoiesis (megaloblastic changes), and leads to the accumulation of methylmalonic acid, which causes subacute combined degeneration of the spinal cord, explaining the neurological deficits. **Why other options are incorrect:** * **Folic acid:** While folate deficiency causes identical megaloblastic changes on a peripheral smear, it **does not** cause neurological symptoms or sluggish reflexes. * **Pyridoxine (B6):** Deficiency typically leads to microcytic, hypochromic anemia (sideroblastic anemia) and peripheral neuropathy, but not macrocytosis or atrophic gastritis associations [2]. * **Riboflavin (B2):** Deficiency presents with cheilosis, glossitis, and corneal vascularization, not megaloblastic anemia. **High-Yield Clinical Pearls for NEET-PG:** * **Neurological Triad:** Loss of vibration/position sense, upper motor neuron signs (spasticity), and lower motor neuron signs (absent reflexes). * **Diagnostic Marker:** Elevated **Methylmalonic Acid (MMA)** is specific for B12 deficiency, whereas Homocysteine is elevated in both B12 and Folate deficiency. * **Schilling Test:** Historically used to determine the cause of B12 malabsorption (now largely replaced by antibody testing for IF).

Q: A patient over 70 years of age presents with generalized lymphadenopathy. The WBC count is 20,000/mm³ and the blood film shows more than 70% mature-looking lymphocytes. What is the next investigation that should be performed?

Peripheral immunophenotyping. ### Explanation **1. Why Peripheral Immunophenotyping is Correct:** The clinical presentation—an elderly patient (>70 years) with generalized lymphadenopathy and absolute lymphocytosis (mature-looking lymphocytes)—is highly suggestive of **Chronic Lymphocytic Leukemia (CLL)**. According to the International Workshop on CLL (iwCLL) guidelines, the diagnosis is established by demonstrating a persistent absolute lymphocyte count ≥5,000/µL and a characteristic immunophenotype [1]. **Peripheral blood flow cytometry (immunophenotyping)** is the "gold standard" and the most important next step to confirm the diagnosis by identifying the pathognomonic "CLL signature": CD5+, CD19+, CD20+ (weak), and CD23+ B-cells with surface immunoglobulin restriction. **2. Why Other Options are Incorrect:** * **Lymph node biopsy (A):** While it would show Small Lymphocytic Lymphoma (SLL), it is invasive and unnecessary if the diagnosis can be made via peripheral blood [2]. It is usually reserved for cases where Richter’s transformation is suspected. * **Bone marrow aspiration (C):** Bone marrow examination is **not required** for the diagnosis of CLL. It is typically performed only before starting treatment or to evaluate unexplained cytopenias. * **Peripheral blood cytogenetics (D):** While FISH (Fluorescence In Situ Hybridization) for deletions like 13q, 11q, or 17p is vital for **prognostication**, it is performed *after* the diagnosis is confirmed via immunophenotyping. **3. NEET-PG High-Yield Pearls:** * **Smudge Cells:** Characteristically seen on peripheral smears in CLL (due to fragile lymphocytes). * **Rai Staging:** Based on lymphocytosis, lymphadenopathy, organomegaly, and cytopenias (Anemia/Thrombocytopenia) [1]. * **Most common leukemia in the elderly:** CLL. * **Marker of choice:** CD5 (a T-cell marker abnormally expressed on B-cells in CLL).

Q: What is the most common cause of autosplenectomy?

Sickle cell anemia. Autosplenectomy is the progressive loss of splenic function and eventual fibrosis due to repeated episodes of splenic infarction. In SCA, deoxygenation causes hemoglobin S to polymerize, leading to the "sickling" of red blood cells [1]. These rigid, sickle-shaped cells become trapped in the narrow splenic sinusoids, causing vaso-occlusive crises. Over time, recurrent micro-infarctions lead to tissue necrosis, scarring, and shrinkage of the organ. By adulthood, the spleen in most SCA patients is reduced to a small, fibrous remnant [1]. 2. Why the other options are incorrect: * Systemic Lupus Erythematosus (SLE): While SLE can involve the spleen (e.g., "onion-skin" lesions of penicilliary arteries), it typically causes splenomegaly rather than autosplenectomy. * Pneumococcal Sepsis: This is a consequence of autosplenectomy, not a cause. Because the spleen is responsible for filtering encapsulated bacteria, patients with autosplenectomy are at high risk for Overwhelming Post-Splenectomy Infection (OPSI) caused by S. pneumoniae. * Thalassemia: Beta-thalassemia major is classically associated with massive splenomegaly due to extramedullary hematopoiesis and increased destruction of abnormal RBCs [1]. 3. NEET-PG High-Yield Pearls: * Howell-Jolly Bodies: Their presence on a peripheral blood smear is a hallmark of functional asplenia/autosplenectomy (remnants of nuclear DNA in RBCs). * Radiology: On X-ray or CT, an autosplenectomized spleen may appear as a small, shrunken, and calcified mass. * Vaccination: Patients with SCA must be vaccinated against encapsulated organisms: S. pneumoniae, H. influenzae type b, and N. meningitidis. * Age Factor: In children with SCA, the spleen is initially enlarged (splenomegaly); autosplenectomy typically completes by age 5–10 years [1].

Q: A 20-year-old female presents to the medical OPD with severe pain and redness over the dorsum of her foot. She has a past history of severe abdominal pain episodes. Peripheral smear shows anemia with the presence of poikilocytes. What is the likely diagnosis?

Sickle cell anemia. The clinical presentation is classic for **Sickle Cell Anemia (SCA)**. The "severe pain and redness over the dorsum of the foot" in a young patient describes **Hand-Foot Syndrome (Dactylitis)**, which is often the first manifestation of vaso-occlusive crises. The history of "severe abdominal pain" suggests prior mesenteric vaso-occlusive crises or splenic infarction [1]. Peripheral smear findings of anemia and **poikilocytes** (specifically sickle cells and target cells) further confirm the diagnosis [1]. **Why the other options are incorrect:** * **Hemoglobin C disease:** While it presents with target cells and mild hemolytic anemia, it rarely causes severe vaso-occlusive pain or dactylitis. * **Thalassemia minor:** Usually asymptomatic or presents with mild microcytic hypochromic anemia. It does not cause acute pain crises or dactylitis. * **G6PD deficiency:** Presents as episodic hemolysis triggered by oxidative stress (drugs, infections, fava beans) [2]. It typically manifests with jaundice and dark urine, not chronic vaso-occlusive pain. **NEET-PG High-Yield Pearls:** * **Molecular Basis:** Substitution of Glutamic acid by Valine at the 6th position of the Beta-globin chain [1]. * **Dactylitis:** The earliest sign of SCA in infants/children due to infarcts in small bones. * **Diagnosis:** **Hb Electrophoresis** is the gold standard (shows HbS); Solubility test/Sickling test are screening tools [1]. * **Radiology:** "Crew-cut" appearance on skull X-ray and "H-shaped" vertebrae (Codfish vertebrae) due to endplate infarction. * **Management:** Hydroxyurea is used to increase **HbF** levels, which inhibits sickling [1].

Q: Which of the following does not cause megaloblastic anemia?

Chloroquine. Megaloblastic anemia is characterized by impaired DNA synthesis, leading to a maturation delay between the nucleus and cytoplasm (nuclear-cytoplasmic asynchrony) [1]. This is most commonly caused by deficiencies or interference with the metabolism of Vitamin B12 and Folic acid [3]. **Why Chloroquine is the correct answer:** Chloroquine is an antimalarial and amebicidal drug. It does not interfere with DNA synthesis or folate/B12 metabolism. Therefore, it is **not** a cause of megaloblastic anemia. **Analysis of incorrect options:** * **Phenytoin:** This antiepileptic drug causes megaloblastic anemia by inhibiting the intestinal enzyme (folate conjugase), thereby reducing the absorption of dietary folates. * **Sulfasalazine:** Used in inflammatory bowel disease, it acts as a competitive inhibitor of the enzyme dihydrofolate reductase (DHFR) [2] and also impairs folate absorption. * **Alcohol:** Alcoholism is a common cause of macrocytosis. It has a direct toxic effect on the bone marrow and interferes with folate metabolism and enterohepatic circulation of folate. **High-Yield Clinical Pearls for NEET-PG:** * **Drug-induced Megaloblastic Anemia:** * **DHFR Inhibitors:** Methotrexate, Pyrimethamine, Trimethoprim [2]. * **DNA Synthesis Inhibitors:** 6-Mercaptopurine, 5-Fluorouracil, Hydroxyurea, Zidovudine (AZT). * **Absorption Interference:** Metformin, Oral Contraceptive Pills (OCPs), Phenobarbital. * **Key Finding:** The presence of **hypersegmented neutrophils** (>5 lobes) on a peripheral smear is the earliest sign of megaloblastic changes. * **Differentiation:** Unlike Vitamin B12 deficiency, Folate deficiency does **not** cause neurological symptoms (like Subacute Combined Degeneration of the spinal cord).

Q: Which of the following is seen in multiple myeloma?

Raised serum calcium. **Explanation:** **Multiple Myeloma (MM)** is a plasma cell dyscrasia characterized by the neoplastic proliferation of a single clone of plasma cells. The hallmark of bone involvement in MM is the presence of **osteolytic lesions**, which are the primary cause of **Hypercalcemia** (Option A). **Why Hypercalcemia occurs:** The neoplastic plasma cells in the bone marrow produce various cytokines, collectively known as **Osteoclast Activating Factors (OAFs)**, such as IL-1 (Osteoclast Activating Factor), IL-6, and TNF-alpha. These factors stimulate osteoclasts and inhibit osteoblasts, leading to massive bone resorption. As the bone matrix breaks down, calcium is released into the extracellular fluid, resulting in raised serum calcium levels. **Analysis of Incorrect Options:** * **Options B & C:** These are incorrect because normal or decreased calcium levels are rare in symptomatic multiple myeloma. Hypercalcemia is a defining feature of the disease, occurring in approximately 25-30% of patients at presentation. **High-Yield Clinical Pearls for NEET-PG:** * **CRAB Criteria:** Remember this mnemonic for symptomatic MM: **C**alcium elevation, **R**enal insufficiency, **A**nemia, and **B**one lesions. * **Bone Scan Paradox:** Multiple myeloma lesions are "cold" on a Technetium-99m bone scan because there is no osteoblastic activity. Plain X-rays (Skeletal Survey) showing "punched-out" lesions are the preferred initial imaging. * **Alkaline Phosphatase (ALP):** Interestingly, despite extensive bone destruction, serum ALP levels are typically **normal** in MM because there is a lack of osteoblastic (bone-forming) activity. * **M-Spike:** Found on Serum Protein Electrophoresis (SPEP), usually representing IgG (most common) or IgA.

Q: All of the following are true about Chronic Lymphocytic Leukemia, except?

T lymphocyte CLL is more common. Explanation: **Why Option D is the Correct Answer (The Exception):** Chronic Lymphocytic Leukemia (CLL) is almost exclusively a **B-cell malignancy** (over 95% of cases). The malignant cells express B-cell markers such as CD19, CD20, and CD23, along with the characteristic aberrant expression of **CD5** (a T-cell marker). True "T-cell CLL" is an outdated term; most such cases are now classified as T-cell Prolymphocytic Leukemia (T-PLL), which is rare and clinically distinct [1]. Therefore, the statement that T-lymphocyte CLL is more common is false. **Analysis of Incorrect Options:** * **Option A:** CLL is often asymptomatic in its early stages. It is frequently **diagnosed incidentally** on routine complete blood counts (CBC) performed for other reasons, showing an isolated increase in absolute lymphocyte count [1]. * **Option B:** **Leukocytosis** (specifically lymphocytosis) is the hallmark of CLL. The diagnosis requires a sustained absolute lymphocyte count of **>5,000/µL** in the peripheral blood. * **Option C:** While CLL is an indolent "chronic" disease, it can undergo a sudden transformation into an aggressive high-grade lymphoma (usually Diffuse Large B-cell Lymphoma), a phenomenon known as **Richter’s Transformation** [1]. This presents clinically like an acute, rapidly progressing malignancy. **NEET-PG High-Yield Pearls:** * **Smudge Cells:** Characteristically seen on peripheral smears due to the fragility of the neoplastic lymphocytes. * **Immunophenotype:** CD5+, CD19+, CD20+ (weak), CD23+, and surface Ig (weak). * **Staging:** Uses the **Rai** (USA) or **Binet** (Europe) systems, primarily based on lymphadenopathy, organomegaly, and cytopenias [1]. * **Hypogammaglobulinemia:** Common in late stages, leading to recurrent bacterial infections (most common cause of death) [1].

Q: What is the diagnostic test for paroxysmal nocturnal hemoglobinuria?

Analysis of GPI-linked proteins. **Explanation:** **Paroxysmal Nocturnal Hemoglobinuria (PNH)** is an acquired clonal hematopoietic stem cell disorder caused by a somatic mutation in the **PIGA gene**. This mutation leads to a deficiency of **GPI (Glycosylphosphatidylinositol) anchors**, which are necessary to attach protective proteins like **CD55** (Decay Accelerating Factor) and **CD59** (MAC Inhibitory Protein) to the cell membrane. Without these proteins, red blood cells are highly susceptible to complement-mediated lysis [1]. **Why Option D is Correct:** The gold standard for diagnosing PNH is **Flow Cytometry** to analyze the presence or absence of **GPI-linked proteins** (CD55 and CD59) on the surface of RBCs and WBCs. A more sensitive modern technique is **FLAER (Fluorescein-labeled proaerolysin)**, which binds directly to the GPI anchor itself. **Why Other Options are Incorrect:** * **A & B (Sucrose Lysis & Ham Test):** These were historical screening and confirmatory tests, respectively. They rely on the principle of acid-induced hemolysis. However, they are no longer used due to low sensitivity and specificity compared to flow cytometry. * **C (Elevated LDH):** While LDH is significantly elevated in PNH due to intravascular hemolysis, it is a non-specific marker found in many hemolytic anemias and is not diagnostic. **High-Yield Clinical Pearls for NEET-PG:** * **Triad of PNH:** Hemolytic anemia, Pancytopenia, and Formatting (most common cause of death, often in unusual sites like the Budd-Chiari syndrome). * **Urine Findings:** Hemosiderinuria is a classic finding indicating chronic intravascular hemolysis. * **Treatment:** **Eculizumab** (a monoclonal antibody against Complement C5) is the drug of choice. * **Association:** PNH is closely linked with **Aplastic Anemia** and may transform into **Acute Myeloid Leukemia (AML)**.

Question 1

Which of the following tests is used to screen a woman with a family history of thalassemia?

Accepted Answer

NESTROFT

Answer

Hb A2 Levels

Answer

High performance liquid chromatography

Answer

Peripheral smear and reticulocyte count

Question 2

A 70-year-old male presented with anorexia, weakness, and paresthesia. Investigations revealed a hemoglobin of 5.8 g/dL, a peripheral smear showing macrocytes and neutrophils with hypersegmented nuclei, and sluggish tendon reflexes. Endoscopy revealed atrophic gastritis. Deficiency of which of the following factors can lead to such a clinical situation?

Accepted Answer

Vitamin B12

Answer

Folic acid

Answer

Pyridoxine

Answer

Riboflavin

Question 3

A patient over 70 years of age presents with generalized lymphadenopathy. The WBC count is 20,000/mm³ and the blood film shows more than 70% mature-looking lymphocytes. What is the next investigation that should be performed?

Accepted Answer

Peripheral immunophenotyping

Answer

Lymph node biopsy

Answer

Bone marrow aspiration

Answer

Peripheral blood cytogenetics

Question 4

What is the most common cause of autosplenectomy?

Accepted Answer

Sickle cell anemia

Answer

Systemic Lupus Erythematosus (SLE)

Answer

Pneumococcal sepsis

Answer

Thalassemia

Question 5

A 20-year-old female presents to the medical OPD with severe pain and redness over the dorsum of her foot. She has a past history of severe abdominal pain episodes. Peripheral smear shows anemia with the presence of poikilocytes. What is the likely diagnosis?

Accepted Answer

Sickle cell anemia

Answer

Hemoglobin C disease

Answer

Thalassemia minor

Answer

G6PD deficiency

Question 6

Which of the following does not cause megaloblastic anemia?

Accepted Answer

Chloroquine

Answer

Phenytoin

Answer

Sulfasalazine

Answer

Alcohol

Question 7

A 43-year-old woman complains of constant tiredness, light-headedness, and occasional palpitations and shortness of breath. Physical examination shows pallor of the oral mucosa and glossitis. Neurologic examination reveals paresthesias, numbness, decreased vibration sensation, and loss of deep tendon reflexes. Laboratory studies include hemoglobin of 7.2 g/dL, WBC of 4,500/mL, platelets of 140,000/mL, erythrocyte folate of 220 ng/mL, serum vitamin B12 of 40 pg/mL, serum anti-intrinsic factor of 1:128, and serum anti-parietal cell antibody of 1:64. Peripheral blood shows macrocytic anemia with poikilocytosis of RBCs and hypersegmented neutrophils. Atrophic gastritis is diagnosed by gastric biopsy. What is the expected bone marrow examination finding in this patient?

Accepted Answer

Hypercellularity with megaloblastic erythroid maturation

Answer

Absent stainable bone marrow iron

Answer

Atypical megakaryocytes with fibrosis

Answer

Hypocellularity with absence of erythroid precursors

Question 8

Which of the following is seen in multiple myeloma?

Accepted Answer

Raised serum calcium

Answer

Decreased serum calcium

Answer

Normal serum calcium

Answer

None of the above

Question 9

All of the following are true about Chronic Lymphocytic Leukemia, except?

Accepted Answer

T lymphocyte CLL is more common

Answer

Diagnosed on routine blood tests

Answer

Leukocytosis is prominent

Answer

Can present as acute leukemia

Question 10

What is the diagnostic test for paroxysmal nocturnal hemoglobinuria?

Accepted Answer

Analysis of GPI-linked proteins

Answer

Sucrose lysis test

Answer

Ham test

Answer

Elevated LDH levels

Hematology — MCQs

Hematology — MCQs

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