Hematology Practice Questions

Q: A patient is diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). Which of the following drugs is used to reduce complement -mediated hemolysis in PNH?

Eculizumab. ***Eculizumab*** - Eculizumab is a **monoclonal antibody** that binds to **complement protein C5**, preventing the formation of the **membrane attack complex (MAC)**. - By inhibiting terminal complement activation, it effectively reduces **intravascular hemolysis**, stabilizes hemoglobin levels, and decreases the need for blood transfusions in patients with PNH. *Rituximab* - Rituximab is an **anti-CD20 monoclonal antibody** primarily used for **B-cell lymphoproliferative disorders** and certain autoimmune diseases like rheumatoid arthritis. - It has no role in the direct inhibition of the **complement cascade** required to manage the pathophysiology of PNH. *Prednisolone* - Prednisolone is a **corticosteroid** used to suppress the immune system in conditions like autoimmune hemolytic anemia (AIHA). - It is generally ineffective for the **complement-mediated lysis** seen in PNH, as the disease is driven by a defect in **CD55/CD59 expression** rather than lymphocyte-mediated mechanisms. *Hydroxyurea* - Hydroxyurea is an **antimetabolite** used to treat myeloproliferative neoplasms like **polycythemia vera** or essential thrombocythemia by reducing cell production. - It does not target the **complement pathway** and offers no therapeutic benefit in preventing the hemolysis associated with PNH.

Q: A 22-year-old male presents with anemia. Peripheral smear is given, and reticulocyte count is 6%. What is the most likely diagnosis?

Sickle cell disease. ***Sickle cell disease*** - In **Sickle cell disease**, the chronic hemolysis leads to a compensatory **reticulocytosis** (reticulocyte count > 2-3%), as the bone marrow attempts to replace destroyed red blood cells. - The peripheral smear typically reveals **sickled cells (drepanocytes)**, Howell-Jolly bodies (due to autosplenectomy), and target cells, confirming a diagnosis of hemolytic anemia. *Iron deficiency anemia* - Presents with **microcytic, hypochromic** anemia, and typically shows an **inappropriately low reticulocyte count** due to insufficient iron for erythropoiesis. - The peripheral smear classically demonstrates **pencil cells** and cigar-shaped cells, not the findings associated with hemolytic anemias. *Thalassemia trait* - Characterized by **microcytic, hypochromic** anemia with a very high red blood cell count out of proportion to the degree of anemia. - Reticulocyte counts in thalassemia trait are usually **normal or only slightly elevated**, reflecting the production of defective but not massively hemolyzed cells. *Aplastic anemia* - Defined by **pancytopenia** (affecting RBCs, WBCs, and platelets), meaning the bone marrow is failing. - The reticulocyte count is characteristically **very low (reticulocytopenia)** because the bone marrow is unable to produce new red blood cells.

Q: Factor VIII level of 50% in a patient with bleeding disorder is most suggestive of?

Von Willebrand disease. ***Von Willebrand disease*** - Type 1 Von Willebrand disease often presents with **reduced levels** of Von Willebrand factor (vWF), which serves as a carrier protein for **Factor VIII**. Because vWF protects Factor VIII from premature degradation in the plasma, mild to moderate deficiencies of vWF can lead to a secondary, proportional drop in **Factor VIII levels**. - A Factor VIII level of 50% is too high to be diagnostic of classic **Hemophilia A** (which typically presents with much lower levels, often <1%) and is more consistent with the partial deficiency seen in **vWD**, especially during stress or pregnancy where levels fluctuate. *Hemophilia A* - This is an X-linked recessive disorder characterized by a severe, primary deficiency of **Factor VIII clotting activity**; patients usually have levels significantly lower than 50% (commonly <5%). - Clinical presentation involves **deep tissue bleeding**, hemarthroses, and a prolonged **activated partial thromboplastin time (aPTT)** that does *not* correct with mixing studies, unlike vWD. *Glanzmann thrombasthenia* - This is a rare quantitative or qualitative defect of the **GPIIb/IIIa receptor** on the surface of platelets, which affects platelet aggregation. - Factor VIII levels are typically **normal** in this condition, as it is a pathology of primary hemostasis (platelet function) rather than secondary hemostasis (clotting factors). *Bernard–Soulier syndrome* - This condition is caused by a deficiency or dysfunction of the **GPIb/IX/V receptor** (von Willebrand factor receptor) on platelets, leading to impaired platelet adhesion. - Similar to Glanzmann thrombasthenia, this is a disorder of **platelet function**, and patients typically maintain **normal coagulation factor levels**, including Factor VIII.

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.

Question 1

A patient is diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). Which of the following drugs is used to reduce complement -mediated hemolysis in PNH?

Accepted Answer

Eculizumab

Answer

Rituximab

Answer

Prednisolone

Answer

Hydroxyurea

Question 2

A 22-year-old male presents with anemia. Peripheral smear is given, and reticulocyte count is 6%. What is the most likely diagnosis?

Accepted Answer

Sickle cell disease

Answer

Iron deficiency anemia

Answer

Thalassemia trait

Answer

Aplastic anemia

Question 3

Factor VIII level of 50% in a patient with bleeding disorder is most suggestive of?

Accepted Answer

Von Willebrand disease

Answer

Hemophilia A

Answer

Glanzmann thrombasthenia

Answer

Bernard–Soulier syndrome

Question 4

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 5

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 6

All of the following are seen in hypersplenism except:

Accepted Answer

Hypocellular bone marrow

Answer

Anemia

Answer

Thrombocytopenia

Answer

Splenomegaly

Question 7

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 8

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 9

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 10

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

Hematology — MCQs

Hematology — MCQs

On this page

Practice by Chapter

Want unlimited practice?