Hematology Practice Questions

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

Pembrolizumab. 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.

Q: All of the following are seen in hypersplenism except:

Hypocellular bone marrow. ### 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.

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

HLA typing. **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).

Q: What is the earliest hematological response to iron supplementation in iron deficiency anemia?

Increase in reticulocyte count. **Explanation:** The correct answer is **B. Increase in reticulocyte count.** **Why it is correct:** When iron is administered to a patient with iron deficiency anemia (IDA), the bone marrow—which was previously "starved" of iron—rapidly utilizes the new supply to produce new red blood cells. The earliest measurable hematological response is an increase in the **reticulocyte count** (immature RBCs). This typically begins within **3 to 5 days** and peaks around **7 to 10 days** after starting therapy. This "reticulocyte response" serves as a clinical indicator that the patient is responding to treatment. **Why the other options are incorrect:** * **A. Increase in serum ferritin:** Ferritin reflects the body's iron stores. It is the **last** parameter to normalize because the body prioritizes hemoglobin synthesis over storage. It usually takes 3 to 6 months of therapy to replenish stores. * **C. Increase in TIBC:** In IDA, TIBC is high. Successful treatment leads to a **decrease** in TIBC as iron saturation improves, not an increase. * **D. Increase in hemoglobin:** While hemoglobin begins to rise shortly after the reticulocyte peak, a significant increase (usually ~1-2 g/dL) is typically seen after **2 to 3 weeks**, and it takes about 2 months to reach normal levels. [1] **High-Yield Clinical Pearls for NEET-PG:** * **Subjective Improvement:** The very first sign of recovery is often the patient's **subjective feeling of well-being** (increased appetite/energy), occurring within 24–48 hours. * **Sequence of Recovery:** Reticulocytosis (Days 3–7) → Rise in Hb (Weeks 2–3) → Normalization of Hb (Month 2) → Replenishment of Stores/Ferritin (Months 3–6). * **Failure to respond:** If the reticulocyte count does not rise, consider poor compliance, malabsorption (e.g., Celiac disease), or ongoing occult blood loss. [1]

Q: All of the following are true about beta-thalassemia trait, except?

Patient requires blood transfusion. **Explanation:** **Beta-thalassemia trait (Beta-thalassemia minor)** is a heterozygous state where there is a mutation in only one of the two beta-globin genes [1]. This condition is typically **asymptomatic** or presents with mild anemia that does not require clinical intervention. 1. **Why Option D is the correct answer:** Patients with beta-thalassemia trait have sufficient hemoglobin production from the single functional beta gene to maintain near-normal levels. Unlike Thalassemia Major (Cooley’s anemia), which is transfusion-dependent, the trait is a **benign carrier state**. Transfusions are not required and, if given unnecessarily, could lead to iatrogenic iron overload. 2. **Analysis of Incorrect Options:** * **Option A (Microcytic hypochromic picture):** This is a classic finding. Due to reduced beta-chain synthesis, RBCs are smaller (Low MCV) and pale (Low MCH). A key differentiator from iron deficiency is a high RBC count despite low Hb (Mentzer Index 3.5% (normal is 13**, it suggests Iron Deficiency Anemia. * **Target Cells:** Commonly seen on the peripheral blood smear. * **NEVER** treat thalassemia trait with iron unless co-existing iron deficiency is proven; it can lead to lead to secondary hemochromatosis.

Q: A young patient is hospitalized with petechiae of the oral mucous membrane, marginal gingival hemorrhage, and a platelet count of 45,000/cc. The bleeding time (BT) and clot retraction time are increased, while RBC and TLC are normal. What condition is the patient likely suffering from?

Thrombocytopenic purpura. The clinical presentation of petechiae and mucosal bleeding (gingival hemorrhage) points toward a **primary hemostatic defect** [1]. The laboratory findings of a low platelet count (**45,000/cc**; normal: 1.5–4.5 lakh/cc) and a prolonged **Bleeding Time (BT)** are classic hallmarks of **Thrombocytopenic Purpura** [2]. In this condition, the reduction in platelet numbers impairs the formation of the primary platelet plug. Furthermore, **Clot Retraction Time** is increased because clot retraction is a platelet-dependent process (mediated by the protein thrombosthenin). Normal RBC and TLC counts help rule out generalized bone marrow failure or malignancy. [3] **Analysis of Incorrect Options:** * **Infectious Mononucleosis:** While it can occasionally cause mild thrombocytopenia, it typically presents with a triad of fever, pharyngitis, and lymphadenopathy, with characteristic atypical lymphocytes on a blood smear (increased TLC). * **Leukemia:** Although leukemia causes thrombocytopenia, it is almost always accompanied by significant abnormalities in the **RBC count** (anemia) and **TLC** (either marked leukocytosis with blasts or leukopenia), which are normal in this patient. [3] * **Hemophilia:** This is a secondary hemostatic defect (clotting factor deficiency). It presents with deep tissue hematomas or hemarthrosis [1]. The **Bleeding Time and platelet count are normal** in hemophilia; only the aPTT is prolonged. **NEET-PG High-Yield Pearls:** * **BT vs. CT:** Bleeding Time (BT) assesses platelet function/number; Clotting Time (CT) assesses the coagulation cascade. * **Clot Retraction:** Directly proportional to the platelet count and inversely proportional to the red cell mass. * **Dry vs. Wet Purpura:** Mucosal bleeding (as seen here) is termed "wet purpura" and indicates a higher risk of life-threatening intracranial hemorrhage compared to "dry purpura" (skin only). [3]

Q: A 23-year-old man with hemophilia is recently wheelchair bound. Which of the following best accounts for this development?

Hemarthrosis. Explanation: 1. Why Hemarthrosis is Correct: Hemophilia (Factor VIII or IX deficiency) is characterized by a bleeding diathesis, primarily affecting deep tissues. Hemarthrosis (bleeding into joint spaces) is the most common clinical manifestation, occurring in up to 80% of patients. Recurrent bleeding into the same joint (target joint) leads to Chronic Hemophilic Arthropathy [1]. This involves synovial hypertrophy, cartilage destruction, and joint fibrosis, eventually causing permanent deformity and loss of mobility [1]. In a young patient, this progression is the leading cause of becoming wheelchair-bound. The knee is the most commonly affected joint, followed by the elbow and ankle [1]. 2. Why Incorrect Options are Wrong: * Hematemesis (B) and Hematochezia (D): While gastrointestinal bleeding can occur in hemophilia, it usually presents as an acute emergency rather than a chronic condition leading to long-term physical disability or immobilization. * Hematocephalus (C): Intracranial hemorrhage is the most common cause of death in hemophiliacs, but it typically presents with acute neurological deficits or sudden mortality rather than progressive orthopedic impairment leading to wheelchair use. 3. Clinical Pearls for NEET-PG: * Most common joint involved: Knee joint [1]. * Earliest sign on X-ray: Soft tissue swelling. * Late X-ray findings: Subchondral cysts, narrowing of joint space, and "squared-off" patella (Jordan's sign). * Management: Acute bleeds require immediate factor replacement (aim for 40-50% levels). Prophylactic factor replacement is the gold standard to prevent arthropathy. * Note: Avoid NSAIDs (except COX-2 inhibitors) and intramuscular injections in these patients.

Question 1

A patient presents with fatigue. Hemogram analysis reveals low hemoglobin and high Mean Corpuscular Volume (MCV). What is the next appropriate investigation?

Accepted Answer

Reticulocyte count

Answer

Vitamin B12 and folate levels

Answer

Bone marrow examination

Answer

Serum iron studies

Question 2

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

Accepted Answer

Pembrolizumab

Answer

Vorinostat

Answer

Brentuximab

Answer

Tisagenlecleucel

Question 3

All of the following are seen in hypersplenism except:

Accepted Answer

Hypocellular bone marrow

Answer

Anemia

Answer

Thrombocytopenia

Answer

Splenomegaly

Question 4

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

Accepted Answer

HLA typing

Answer

Peripheral smear

Answer

Test for Philadelphia chromosome

Answer

Bone marrow testing

Question 5

What is the earliest hematological response to iron supplementation in iron deficiency anemia?

Accepted Answer

Increase in reticulocyte count

Answer

Increase in serum ferritin

Answer

Increase in total iron-binding capacity

Answer

Increase in hemoglobin

Question 6

Spontaneous muscle bleeding is typically seen in which of the following conditions?

Accepted Answer

Hemophilia

Answer

Afibrinogenemia

Answer

Von Willebrand's disease

Answer

Scott's syndrome

Question 7

All of the following are true about beta-thalassemia trait, except?

Accepted Answer

Patient requires blood transfusion

Answer

Microcytic hypochromic picture

Answer

Increased HbA2

Answer

Increased HbF

Question 8

A young patient is hospitalized with petechiae of the oral mucous membrane, marginal gingival hemorrhage, and a platelet count of 45,000/cc. The bleeding time (BT) and clot retraction time are increased, while RBC and TLC are normal. What condition is the patient likely suffering from?

Accepted Answer

Thrombocytopenic purpura

Answer

Infectious mononucleosis

Answer

Leukemia

Answer

Hemophilia

Question 9

A 23-year-old man with hemophilia is recently wheelchair bound. Which of the following best accounts for this development?

Accepted Answer

Hemarthrosis

Answer

Hematemesis

Answer

Hematocephalus

Answer

Hematochezia

Question 10

A 60-year-old industrial worker presents with shortness of breath for the past week. Blood withdrawn shows a thick brownish-red color. What is the most likely diagnosis?

Accepted Answer

Methemoglobinemia

Answer

Sickle cell anemia

Answer

Hemolytic anemia

Answer

G6PD deficiency

Hematology — MCQs

Hematology — MCQs

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