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.

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

Hematology — MCQs

Hematology — MCQs

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