Hematology Practice Questions

Q: Which of the following is a poor prognostic factor in Acute Lymphoblastic Leukemia (ALL)?

t (9;22); t (4; 11). In Acute Lymphoblastic Leukemia (ALL), prognosis is determined by age, initial white blood cell (WBC) count, and specific cytogenetic abnormalities [1]. ### **Explanation of the Correct Answer** **Option B: t(9;22) and t(4;11)** are well-established **poor prognostic factors** [1]. * **t(9;22):** Known as the Philadelphia chromosome ($Ph+$), it creates the *BCR-ABL1* fusion gene [1]. It is more common in adults and is associated with high resistance to standard chemotherapy and a high relapse rate. * **t(4;11):** Involves the *KMT2A* (MLL) gene rearrangement. It is typically seen in infant ALL and is associated with very high WBC counts and CNS involvement, signifying an aggressive disease course [1]. ### **Analysis of Incorrect Options** * **A. Hyperdiploidy:** Defined as >50 chromosomes per cell, this is a **favorable** prognostic factor. These cells are highly sensitive to methotrexate and apoptosis. * **C. 2–8 years of age:** This is the "golden age" for ALL prognosis. Patients between **1 and 10 years** have the best outcomes. Age 10 years (adolescents/adults) indicates a poorer prognosis. * **D. WBC count 50,000 in B-ALL (or >100,000 in T-ALL) is considered a high-risk feature [1]. ### **High-Yield Clinical Pearls for NEET-PG** * **Best Prognosis Cytogenetics:** t(12;21) involving *ETV6-RUNX1* (most common in children) and Hyperdiploidy. * **Worst Prognosis Cytogenetics:** t(9;22), t(4;11), and Hypodiploidy (<44 chromosomes) [1]. * **Immunophenotype:** Early pre-B cell (CD10/CALLA positive) has a better prognosis than mature B-cell or T-cell ALL. * **Minimal Residual Disease (MRD):** The most important predictor of relapse after starting treatment.

Q: A 25-year-old pregnant lady presents with leukocytosis, a platelet count less than 50,000, and fragmented red blood cells on peripheral smear. Which of the following is the least likely differential diagnosis?

Evans' syndrome. The clinical presentation describes a **Microangiopathic Hemolytic Anemia (MAHA)**, characterized by thrombocytopenia and fragmented RBCs (schistocytes) on a peripheral smear [1]. **1. Why Evans' Syndrome is the least likely (Correct Answer):** Evans' syndrome is defined as the simultaneous or sequential occurrence of **Immune Thrombocytopenic Purpura (ITP)** and **Autoimmune Hemolytic Anemia (AIHA)**. Crucially, AIHA is a warm-antibody mediated process where RBCs are destroyed by splenic macrophages, leading to **spherocytes**, not schistocytes. The absence of mechanical fragmentation (schistocytes) makes Evans' syndrome inconsistent with the peripheral smear findings provided. **2. Analysis of Incorrect Options:** * **HELLP Syndrome:** A pregnancy-specific complication (Hemolysis, Elevated Liver enzymes, Low Platelets) that is a classic cause of MAHA and schistocytes in the third trimester [1]. * **TTP:** Characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, fever, and renal failure. It is a major differential for MAHA in pregnancy [1]. * **DIC:** Often triggered by obstetric complications (e.g., abruptio placentae) [2]. It involves systemic activation of coagulation, leading to consumption of platelets and clotting factors, resulting in schistocytes on the smear [2]. **Clinical Pearls for NEET-PG:** * **Schistocytes = MAHA:** Always think of TTP, HUS, DIC, or HELLP [1]. * **Spherocytes = AIHA or Hereditary Spherocytosis:** Think of Evans' syndrome if associated with low platelets. * **TTP vs. DIC:** TTP usually has normal coagulation profiles (PT/aPTT), whereas DIC has prolonged PT/aPTT and low fibrinogen [2]. * **HELLP vs. TTP:** HELLP is typically associated with hypertension and significant transaminitis.

Q: Which of the following is the most serious late side effect of treatment of Hodgkin's disease?

Cardiac injury. The treatment of Hodgkin’s Lymphoma (HL) has a high cure rate, making the management of long-term survivorship and **late toxicities** a critical clinical focus. [1] **Cardiac injury** is considered the most serious late side effect because it is a leading cause of non-malignant morbidity and mortality in HL survivors. It typically manifests 10–20 years after treatment. The injury is multifactorial: 1. **Radiation Therapy (Mediastinal):** Causes accelerated coronary artery disease (CAD), valvular dysfunction, and pericarditis. [1] 2. **Chemotherapy (Anthracyclines like Doxorubicin):** Leads to dose-dependent, irreversible dilated cardiomyopathy and congestive heart failure. **Analysis of Incorrect Options:** * **B. Infertility:** While common (especially with alkylating agents like Procarbazine in the older MOPP regimen), it is not considered as "serious" or life-threatening as cardiac failure or secondary malignancies. Modern ABVD regimens have a much lower risk of permanent infertility. * **C. Hair Loss (Alopecia):** This is an **acute** side effect that occurs during treatment and is reversible. It is not a "late" side effect. * **D. Osteoporosis:** Can occur due to prolonged steroid use (Prednisone), but it is rarely the most life-limiting complication compared to cardiotoxicity. **NEET-PG High-Yield Pearls:** * The **most common** late cause of death in HL survivors is **Secondary Malignancies** (most commonly Breast Cancer and Lung Cancer). * If "Secondary Malignancy" is not an option, **Cardiac Injury** is the next most significant life-threatening late complication. * **Lhermitte’s sign** (electric shock sensation down the spine) is a transient late effect of neck radiation in HL patients. * Survivors require lifelong screening, including annual mammograms (starting 8-10 years post-radiation) and aggressive lipid management.

Q: To prevent excessive bleeding during surgery, a patient with hemophilia A may be given which of the following?

Factor VIII concentrate. **Explanation:** **Hemophilia A** is an X-linked recessive bleeding disorder caused by a deficiency of **Clotting Factor VIII** [1]. To achieve surgical hemostasis, the goal is to raise Factor VIII levels to 80–100% of normal. **Why Factor VIII concentrate is correct:** Factor VIII concentrate (either plasma-derived or recombinant) is the **treatment of choice** [1]. It provides a highly concentrated dose of the specific missing factor without the risk of volume overload. Recombinant products are preferred in modern practice to eliminate the risk of blood-borne viral transmission (HIV, Hepatitis B/C) [2]. **Why the other options are incorrect:** * **Whole blood:** Contains very low concentrations of clotting factors relative to volume. It is used for massive hemorrhage with shock, not targeted factor replacement. * **Fresh frozen plasma (FFP):** While FFP contains all coagulation factors, the concentration of Factor VIII is low. Achieving therapeutic levels for surgery would require massive volumes, leading to **Transfusion Associated Circulatory Overload (TACO)**. * **Factor IX concentrate:** This is the specific treatment for **Hemophilia B** (Christmas Disease). It has no role in treating Hemophilia A. **High-Yield Clinical Pearls for NEET-PG:** * **Cryoprecipitate:** Contains Factor VIII, Fibrinogen, von Willebrand Factor (vWF), and Factor XIII. It was historically used for Hemophilia A but is now a second-line treatment if concentrates are unavailable. * **Desmopressin (DDAVP):** Useful in **mild** Hemophilia A; it releases endogenous Factor VIII and vWF from endothelial Weibel-Palade bodies [2]. * **Mixing Study:** In Hemophilia, the prolonged aPTT **corrects** upon mixing with normal plasma (distinguishing it from Factor VIII inhibitors/antibodies). * **Emicizumab:** A newer bispecific monoclonal antibody that mimics Factor VIII function by bridging Factors IXa and X.

Q: Aplastic anemia can progress to all of the following except?

Pure red cell aplasia. Aplastic Anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and a hypocellular marrow. It is considered a "clonal" disorder of hematopoietic stem cells, which predisposes patients to late clonal evolution into other myeloid malignancies. **Why Pure Red Cell Aplasia (PRCA) is the correct answer:** PRCA is a condition characterized by a selective failure of erythropoiesis (only red cell precursors are absent), while white cells and platelets remain normal. It is **not** a complication or a progressive stage of Aplastic Anemia. In fact, the relationship is often the reverse: PRCA is a lineage-specific failure, whereas AA is a global stem cell failure. Progression from a global failure (AA) to a single-lineage failure (PRCA) does not occur. **Analysis of Incorrect Options:** * **Paroxysmal Nocturnal Hemoglobinuria (PNH):** There is a strong clinical link between AA and PNH. Up to 40-50% of AA patients may have a small PNH clone (PIGA mutation) at diagnosis, and many go on to develop clinical PNH. * **Myelodysplastic Syndrome (MDS) & Acute Myeloid Leukemia (AML):** These represent the "clonal evolution" of AA [1]. Approximately 10-15% of patients with AA (especially those treated with immunosuppressive therapy) may eventually develop MDS or AML, often associated with chromosomal abnormalities like Monosomy 7. **Clinical Pearls for NEET-PG:** * **Most common chromosomal abnormality** in clonal evolution of AA: **Monosomy 7**. * **Gold Standard Treatment:** Bone Marrow Transplant (for young patients with a matched sibling donor) or Immunosuppressive Therapy (ATG + Cyclosporine + Eltrombopag). * **PNH Screening:** All patients with Aplastic Anemia must be screened for PNH clones using **Flow Cytometry** (CD55/CD59 deficiency).

Q: What is the standard treatment for Central Nervous System (CNS) leukemia?

Intrathecal methotrexate. **Explanation:** The Blood-Brain Barrier (BBB) prevents most systemic chemotherapeutic agents from reaching therapeutic concentrations within the cerebrospinal fluid (CSF) [3]. Therefore, standard intravenous therapy is often ineffective for treating or preventing CNS involvement in leukemia [1]. **1. Why Intrathecal Methotrexate is Correct:** **Intrathecal (IT) Methotrexate** is the gold standard because it bypasses the BBB, delivering high concentrations of the antimetabolite directly into the subarachnoid space. It is used both as **prophylaxis** (to prevent CNS relapse in ALL) and as **treatment** for active CNS leukemia [1]. It is often used alone or as part of "triple intrathecal therapy" (Methotrexate + Cytarabine + Hydrocortisone). **2. Why the other options are incorrect:** * **Vincristine and Prednisolone (Option B):** While these are backbone drugs for induction therapy in Acute Lymphoblastic Leukemia (ALL) [1], they are administered systemically and do not achieve sufficient CNS penetration to treat active CNS disease. * **Intrathecal Vincristine (Option C):** **CRITICAL CONTRAINDICATION.** Vincristine is highly neurotoxic if given intrathecally. Accidental IT administration leads to progressive ascending paralysis and is almost **universally fatal**. It must only be given intravenously. * **Intravenous Prednisolone (Option D):** While glucocorticoids (like Dexamethasone) have some CNS penetration [2], they are insufficient as monotherapy for CNS leukemia. **Clinical Pearls for NEET-PG:** * **Prophylaxis:** CNS prophylaxis is mandatory in all patients with ALL because the CNS acts as a "pharmacological sanctuary." * **Triple IT Therapy:** Consists of Methotrexate, Cytarabine (Ara-C), and Hydrocortisone. * **Fatal Error:** Always remember: *"Vincristine is for the Vein only."* * **Alternative:** Cranial irradiation is an alternative but is less preferred in children due to long-term neurocognitive sequelae.

Q: A 23-year-old female presented with jaundice and pallor for 2 months. Her peripheral blood smear shows the presence of spherocytes. What is the most relevant investigation to arrive at a diagnosis?

Coombs test. **Explanation:** The presence of **spherocytes** on a peripheral blood smear in a patient with jaundice and pallor indicates extravascular hemolysis [1]. The two primary differential diagnoses for spherocytosis are **Hereditary Spherocytosis (HS)** and **Autoimmune Hemolytic Anemia (AIHA)** [1]. 1. **Why Coombs Test is the correct answer:** The most critical step in evaluating spherocytosis is to differentiate between an inherited membrane defect (HS) and an acquired immune-mediated process (AIHA). The **Direct Antiglobulin Test (Coombs test)** is the first-line investigation [1]. A positive result confirms AIHA, while a negative result points toward HS. Given the patient's age and presentation, ruling out an immune cause is the clinical priority [1]. 2. **Why other options are incorrect:** * **Osmotic Fragility Test:** While this test is classically associated with HS (showing increased fragility), it is **not specific**. Spherocytes in AIHA will also show increased osmotic fragility. Furthermore, it has been largely replaced by the Eosin-5-maleimide (EMA) binding test. * **Tests for PNH:** PNH typically presents with intravascular hemolysis and cytopenias [1]; the characteristic finding is "schistocytes" or normal morphology, not spherocytes. * **Reticulocyte Count:** This helps confirm that hemolysis is occurring (showing marrow response) but does not provide a specific diagnosis for the cause of spherocytosis. **Clinical Pearls for NEET-PG:** * **Spherocytes** lack central pallor because they have the lowest surface-area-to-volume ratio. * **MCHC** (Mean Corpuscular Hemoglobin Concentration) is typically **increased** (>36 g/dL) in spherocytosis [1]. * If the Coombs test is negative, the most sensitive modern test for Hereditary Spherocytosis is the **EMA Binding Test** (Flow cytometry).

Q: What is the most common site of thrombosis in paroxysmal nocturnal hemoglobinuria?

Intra-abdominal veins. **Explanation:** **Paroxysmal Nocturnal Hemoglobinuria (PNH)** is an acquired clonal hematopoietic stem cell disorder characterized by a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins (like CD55 and CD59) due to a mutation in the **PIGA gene**. This deficiency leads to uncontrolled complement-mediated hemolysis and a profound prothrombotic state. **Why Intra-abdominal veins are correct:** Thrombosis is the leading cause of mortality in PNH (accounting for ~40% of deaths). Unlike the general population, where deep vein thrombosis (DVT) of the legs is most common, PNH has a unique predilection for **atypical sites**. The **intra-abdominal veins** (specifically the **hepatic vein**, leading to Budd-Chiari syndrome) are the most common sites of thrombosis. Other frequent sites include the portal, splenic, and mesenteric veins, as well as cerebral dural sinuses. **Why other options are incorrect:** * **A & D (Femoral and Saphenous veins):** While DVT can occur in PNH, these are the "typical" sites for thrombosis in the general population (e.g., post-surgery or immobilization). They are not the *most characteristic* or most common sites specific to the PNH disease process. * **B (Median cubital vein):** This is a superficial vein of the upper limb, usually associated with phlebitis due to IV cannulation, not the systemic hypercoagulable state of PNH. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Flow cytometry (shows absence of CD55/CD59). * **Classic Triad:** Hemolytic anemia, Pancytopenia, and Venous thrombosis. * **Treatment of Choice:** Eculizumab (a monoclonal antibody against C5 complement). * **Screening:** Always screen for PNH in patients presenting with unexplained Budd-Chiari syndrome or mesenteric ischemia.

Question 1

Which of the following is a poor prognostic factor in Acute Lymphoblastic Leukemia (ALL)?

Accepted Answer

t (9;22); t (4; 11)

Answer

Hyperdiploidy

Answer

2-8 years of age

Answer

WBC count < 50,000

Question 2

A 25-year-old female presented with mild pallor and moderate hepatosplenomegaly. Her hemoglobin was 92 g/L and fetal hemoglobin level was 65%. She has not received any blood transfusions to date. She is most likely to be suffering from:

Accepted Answer

Thalassemia intermedia

Answer

Thalassemia major

Answer

Hereditary persistent fetal hemoglobin, homozygous state

Answer

Hemoglobin D, homozygous state

Question 3

A 25-year-old pregnant lady presents with leukocytosis, a platelet count less than 50,000, and fragmented red blood cells on peripheral smear. Which of the following is the least likely differential diagnosis?

Accepted Answer

Evans' syndrome

Answer

Disseminated Intravascular Coagulation (DIC)

Answer

Thrombotic Thrombocytopenic Purpura (TTP)

Answer

HELLP syndrome

Question 4

Which of the following is the most serious late side effect of treatment of Hodgkin's disease?

Accepted Answer

Cardiac injury

Answer

Infertility

Answer

Hair loss

Answer

Osteoporosis

Question 5

To prevent excessive bleeding during surgery, a patient with hemophilia A may be given which of the following?

Accepted Answer

Factor VIII concentrate

Answer

Whole blood

Answer

Fresh frozen plasma

Answer

Factor IX concentrate

Question 6

Aplastic anemia can progress to all of the following except?

Accepted Answer

Pure red cell aplasia

Answer

Acute myeloid leukemia (AML)

Answer

Myelodysplastic syndrome

Answer

Paroxysmal nocturnal hemoglobinuria (PNH)

Question 7

What is the standard treatment for Central Nervous System (CNS) leukemia?

Accepted Answer

Intrathecal methotrexate

Answer

Vincristine and prednisolone

Answer

Intrathecal vincristine

Answer

Intravenous prednisolone

Question 8

A 23-year-old female presented with jaundice and pallor for 2 months. Her peripheral blood smear shows the presence of spherocytes. What is the most relevant investigation to arrive at a diagnosis?

Accepted Answer

Coombs test

Answer

Tests for paroxysmal nocturnal hemoglobinuria (PNH)

Answer

Osmotic fragility test

Answer

Reticulocyte count

Question 9

What is the most common site of thrombosis in paroxysmal nocturnal hemoglobinuria?

Accepted Answer

Intra-abdominal veins

Answer

Femoral vein

Answer

Median cubital vein

Answer

Saphenous vein

Question 10

A 67-year-old man presents with 5 months of increasing weakness, fatigue, and weight loss. He has experienced decreasing vision in both eyes, headaches, and dizziness. His hands are sensitive to cold. Physical examination reveals generalized lymphadenopathy and hepatosplenomegaly. Laboratory studies show a serum protein level of 15.5 g/dL and an albumin concentration of 3.2 g/dL. A bone marrow biopsy shows infiltration by numerous small plasmacytoid lymphoid cells with Russell bodies in the cytoplasm. Which of the following additional laboratory findings is most likely to be reported for this patient?

Accepted Answer

Monoclonal IgM spike in serum

Answer

Bence Jones proteinuria

Answer

Hypercalcemia

Answer

Karyotype with t(14;18) translocation

Hematology — MCQs

Hematology — MCQs

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