Hematology Practice Questions

Q: In Beta thalassemia, what is the characteristic change in globin chain production?

Decrease in beta chain, increase in alpha chain. ### Explanation **Core Concept:** Beta thalassemia is a quantitative hemoglobinopathy caused by mutations in the *HBB* gene on chromosome 11. This results in **reduced ($\beta^+$) or absent ($\beta^0$) synthesis of beta-globin chains**. The hallmark of the disease is the **imbalance** between alpha and beta chains. Since alpha-chain production remains normal while beta-chain production is deficient, there is a **relative excess of free alpha-globin chains**. These unpaired alpha chains are unstable; they precipitate within erythroid precursors in the bone marrow and mature red cells, causing membrane damage, ineffective erythropoiesis, and extravascular hemolysis. **Analysis of Options:** * **Option B (Correct):** Accurately describes the primary defect (decreased beta) and the secondary consequence (relative increase/excess of alpha). * **Option A & D:** Incorrect because beta chain production is never increased in thalassemia; it is a disease of deficiency. * **Option C:** Incorrect because alpha chain production is not decreased in beta-thalassemia (that would be alpha-thalassemia). In fact, the co-inheritance of alpha-thalassemia with beta-thalassemia actually *improves* the condition by reducing the chain imbalance. **NEET-PG High-Yield Pearls:** * **Diagnosis:** Gold standard is **Hb Electrophoresis**, showing increased **HbA2 (>3.5%)** and increased **HbF**. * **Peripheral Smear:** Microcytic hypochromic anemia with **Target cells** and basophilic stippling. * **Mentzer Index:** (MCV/RBC count) ** 13 suggests Iron Deficiency Anemia. * **Radiology:** "Hair-on-end" appearance on skull X-ray due to compensatory extramedullary hematopoiesis. * **Complication:** Secondary hemochromatosis (iron overload) due to chronic transfusions and increased intestinal absorption.

Q: A 42-year-old man presents with chronic fatigue. His hemoglobin is 11.5 g/dL, and the blood film shows hypochromic and microcytic red blood cells. Laboratory findings include increased serum iron, normal total iron-binding capacity (TIBC), increased ferritin, and decreased HbA2. What is the most likely diagnosis for this patient presenting with hypochromic microcytic anemia?

Sideroblastic anemia. ### Explanation The correct diagnosis is **Sideroblastic Anemia**. This condition is characterized by a defect in heme synthesis (most commonly due to a deficiency in the enzyme ALA synthase or mitochondrial dysfunction), leading to iron accumulation within the mitochondria of developing erythroblasts. **Why Sideroblastic Anemia is correct:** The hallmark of sideroblastic anemia is **iron overload** despite the presence of microcytic anemia. Because heme cannot be synthesized, iron is not utilized and instead builds up in the body. This results in: * **Increased Serum Iron** and **Increased Ferritin** (reflecting high iron stores). * **Normal/Decreased TIBC** (as the body is saturated with iron). * **Hypochromic Microcytic RBCs** (due to deficient hemoglobin production). **Why other options are incorrect:** * **Iron Deficiency Anemia (IDA):** Characterized by **decreased** serum iron and ferritin, and **increased** TIBC. * **Beta-Thalassemia Trait:** Typically presents with a very low MCV but **increased HbA2** (>3.5%) and normal to high iron studies. This patient has decreased HbA2. * **Anemia of Chronic Disease (ACD):** Usually presents with **decreased** serum iron and **decreased** TIBC [1]. While ferritin is increased (as it is an acute-phase reactant), the serum iron is never elevated [1]. **Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Bone marrow examination showing **Ringed Sideroblasts** (Prussian blue stain). * **Common Causes:** Alcohol (most common), Lead poisoning, Isoniazid (B6 deficiency), and X-linked ALA synthase deficiency. * **Treatment:** Pyridoxine (Vitamin B6) is the first-line treatment for hereditary and Isoniazid-induced cases. * **Mentzer Index:** (MCV/RBC count) 13 suggests IDA. Sideroblastic anemia often mimics IDA on peripheral smear but is distinguished by iron studies.

Q: Transfusing blood after prolonged storage could lead to which of the following?

Potassium toxicity. **Explanation:** The correct answer is **Potassium toxicity**. This occurs due to the phenomenon known as the **"Storage Lesion"** of red blood cells. **Why Potassium Toxicity?** During storage, the Na+/K+-ATPase pump on the red blood cell (RBC) membrane becomes inactive due to the cold temperature (1–6°C) and depletion of ATP. Consequently, potassium leaks out of the RBCs into the plasma, while sodium enters the cells. The longer the blood is stored, the higher the extracellular potassium concentration becomes. In massive transfusions or transfusions in neonates and patients with renal failure, this can lead to life-threatening hyperkalemia. **Analysis of Incorrect Options:** * **Citrate Intoxication:** While citrate is used as an anticoagulant in blood bags, toxicity usually occurs during **massive transfusion** (rapid infusion of >10 units) where the liver cannot metabolize citrate quickly enough, leading to hypocalcemia. It is less dependent on the *duration* of storage. * **Circulatory Overload (TACO):** This is a complication related to the **volume and rate** of infusion, particularly in elderly patients or those with heart failure, rather than the age of the stored blood. * **Haemorrhagic Diathesis:** This refers to bleeding tendencies. While massive transfusion of stored blood can cause dilutional coagulopathy (due to lack of viable platelets and factors V and VIII), it is not the primary biochemical consequence of "prolonged storage" itself. **High-Yield Clinical Pearls for NEET-PG:** * **Storage Lesion Changes:** ↓ pH (lactic acid accumulation), ↓ 2,3-DPG (shifting the oxygen dissociation curve to the **left**), ↓ ATP, and ↑ Potassium. * **Shelf Life:** Whole blood/PRBCs are typically stored for **35–42 days** depending on the preservative (CPDA-1 vs. SAGM). * **Fresh Blood:** Defined as blood stored for <7 days; preferred in neonates to avoid hyperkalemia and ensure adequate 2,3-DPG levels.

Q: A 60-year-old man presented with fatigue, weight loss, and heaviness in the left hypochondrium for 6 months. The hemogram showed Hb 10 g/dL, TLC 5 lakhs/mm³, platelet count 4 lakhs/mm³, DLC: neutrophils 55%, lymphocytes 4%, monocytes 2%, basophils 6%, metamyelocytes 10%, myelocytes 18%, promyelocytes 2%, and blasts 3%. What is the most likely cytogenetic abnormality in this case?

t(9;22). ### Explanation **Diagnosis: Chronic Myeloid Leukemia (CML)** The clinical presentation of a 60-year-old male with massive splenomegaly (heaviness in the left hypochondrium) and a massive leukocytosis (TLC 5 lakhs/mm³) is classic for CML [2]. The differential leukocyte count (DLC) shows a **"myelocyte bulge"** (predominance of myelocytes and metamyelocytes) and **basophilia (6%)**, which are hallmark features of CML in the chronic phase. **1. Why t(9;22) is correct:** The cytogenetic hallmark of CML is the **Philadelphia (Ph) chromosome**, resulting from a reciprocal translocation between chromosomes 9 and 22, **t(9;22)(q34;q11)** [2]. This creates the *BCR-ABL1* fusion gene, which encodes a constitutive tyrosine kinase responsible for uncontrolled myeloid proliferation [2]. **2. Why the other options are incorrect:** * **t(1;21):** This is not a standard translocation associated with common leukemias. * **t(15;17):** This is the characteristic translocation for **Acute Promyelocytic Leukemia (APL - AML M3)**, involving the *PML-RARA* fusion [1]. Patients typically present with DIC and a high percentage of promyelocytes with Auer rods. * **Trisomy 21:** Associated with Down Syndrome, which carries an increased risk of **Acute Megakaryoblastic Leukemia (AML M7)** and Transient Myeloproliferative Disorder (TMD) in neonates. **Clinical Pearls for NEET-PG:** * **LAP Score:** Leukocyte Alkaline Phosphatase (LAP) score is characteristically **decreased** in CML (helps differentiate it from a Leukemoid reaction where it is increased). * **Basophilia:** The presence of increased basophils in a peripheral smear is a strong clue for a Myeloproliferative Neoplasm (MPN), specifically CML. * **Treatment of Choice:** Tyrosine Kinase Inhibitors (TKIs) like **Imatinib** [2]. * **Blast Crisis:** Defined as ≥20% blasts in blood or bone marrow.

Q: A 19-year-old man presents with a swollen and painful knee after an injury while playing football. He has no history of bleeding disorders. Arthrocentesis of the knee revealed hemarthrosis. Investigations show: Platelets 170,000/mL, PT normal, PTT elevated, bleeding time normal, factor VIII normal, factor IX reduced, and ristocetin cofactor assay normal. What is the most likely diagnosis for this patient's bleeding disorder?

hemophilia B. The clinical presentation of a young male with **hemarthrosis** (bleeding into joints) following minor trauma is a classic hallmark of a coagulation factor deficiency [1]. **1. Why Hemophilia B is correct:** The laboratory profile provided is the key to the diagnosis: * **Elevated PTT (aPTT):** Indicates a defect in the intrinsic pathway (Factors VIII, IX, XI, or XII). * **Normal PT and Bleeding Time:** Rules out extrinsic pathway defects and platelet/vessel wall disorders [1]. * **Factor IX reduced:** This is the definitive finding. Hemophilia B (Christmas Disease) is an X-linked recessive disorder caused by a deficiency of Factor IX [1]. **2. Why other options are incorrect:** * **von Willebrand Disease (vWD):** While it can cause an elevated aPTT (due to low Factor VIII), it typically presents with mucosal bleeding (epistaxis, menorrhagia) and an **abnormal Ristocetin Cofactor Assay**. Hemarthrosis is rare except in Type 3 vWD [2]. * **Hemophilia A:** This also presents with hemarthrosis and elevated aPTT, but it is caused by a deficiency of **Factor VIII**. The question explicitly states Factor VIII levels are normal [1]. * **Thrombotic Thrombocytopenic Purpura (TTP):** This is a microangiopathic hemolytic anemia characterized by the pentad of fever, anemia, thrombocytopenia, renal failure, and neurological symptoms. It would show a **low platelet count**, which is normal in this patient. **Clinical Pearls for NEET-PG:** * **Inheritance:** Both Hemophilia A and B are **X-linked recessive** (affecting males) [1]. * **Mixing Study:** If aPTT is prolonged, a mixing study is done. If it corrects, it indicates a factor deficiency; if not, it suggests an inhibitor. * **Treatment:** Hemophilia B is treated with recombinant Factor IX concentrate. Fresh Frozen Plasma (FFP) is used if specific concentrates are unavailable.

Q: A 26-year-old woman presents with severe menorrhagia. She reports that both her father and sister have a bleeding disorder. What is the most likely diagnosis, given an autosomal-dominant mode of inheritance for the hemostatic disorder?

von Willebrand's disease. The patient presents with **menorrhagia** (mucocutaneous bleeding) and a strong family history involving both genders (father and sister), which points toward an **Autosomal Dominant (AD)** inheritance pattern. [1] **1. Why von Willebrand’s Disease (vWD) is correct:** vWD is the most common inherited bleeding disorder. It typically presents with mucocutaneous bleeding (epistaxis, menorrhagia, gingival bleeding). [1] Most types (specifically Type 1 and Type 2A, 2B, and 2M) follow an **Autosomal Dominant** inheritance. Since it affects both males and females equally, it perfectly matches the clinical scenario. **2. Why the other options are incorrect:** * **Factor VIII (Hemophilia A) and Factor IX (Hemophilia B) deficiency:** These are **X-linked recessive** disorders. They primarily affect males, while females are typically asymptomatic carriers. They usually present with deep-seated bleeds (hemarthrosis/muscle hematomas) rather than mucosal bleeding. [1] * **Factor X deficiency:** This is a rare coagulation disorder that follows an **Autosomal Recessive** inheritance pattern, making it less likely in a multi-generational family history unless consanguinity is present. **Clinical Pearls for NEET-PG:** * **Screening Tests in vWD:** Prolonged Bleeding Time (BT) and often a prolonged Activated Partial Thromboplastin Time (aPTT) (due to low Factor VIII levels, as vWF stabilizes Factor VIII). [2] Platelet count is usually normal (except in Type 2B). * **Confirmatory Test:** Ristocetin Cofactor Assay (measures vWF activity). [2] * **Treatment of Choice:** Desmopressin (DDAVP) for Type 1; Factor VIII concentrates containing vWF for severe cases. [2] * **Inheritance Rule:** If a bleeding disorder affects both father and daughter, think AD (vWD); if it skips females and affects maternal uncles/nephews, think X-linked (Hemophilia).

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: 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].

Question 1

In Beta thalassemia, what is the characteristic change in globin chain production?

Accepted Answer

Decrease in beta chain, increase in alpha chain

Answer

Increase in beta chain, decrease in alpha chain

Answer

Decrease in beta chain, decrease in alpha chain

Answer

Increase in beta chain, increase in alpha chain

Question 2

A 42-year-old man presents with chronic fatigue. His hemoglobin is 11.5 g/dL, and the blood film shows hypochromic and microcytic red blood cells. Laboratory findings include increased serum iron, normal total iron-binding capacity (TIBC), increased ferritin, and decreased HbA2. What is the most likely diagnosis for this patient presenting with hypochromic microcytic anemia?

Accepted Answer

Sideroblastic anemia

Answer

Iron deficiency anemia

Answer

Beta-thalassemia trait

Answer

Anemia of chronic disease

Question 3

Transfusing blood after prolonged storage could lead to which of the following?

Accepted Answer

Potassium toxicity

Answer

Citrate intoxication

Answer

Circulatory overload

Answer

Haemorrhagic diathesis

Question 4

A 60-year-old man presented with fatigue, weight loss, and heaviness in the left hypochondrium for 6 months. The hemogram showed Hb 10 g/dL, TLC 5 lakhs/mm³, platelet count 4 lakhs/mm³, DLC: neutrophils 55%, lymphocytes 4%, monocytes 2%, basophils 6%, metamyelocytes 10%, myelocytes 18%, promyelocytes 2%, and blasts 3%. What is the most likely cytogenetic abnormality in this case?

Accepted Answer

t(9;22)

Answer

t(1;21)

Answer

t(15;17)

Answer

Trisomy 21

Question 5

A 19-year-old man presents with a swollen and painful knee after an injury while playing football. He has no history of bleeding disorders. Arthrocentesis of the knee revealed hemarthrosis. Investigations show: Platelets 170,000/mL, PT normal, PTT elevated, bleeding time normal, factor VIII normal, factor IX reduced, and ristocetin cofactor assay normal. What is the most likely diagnosis for this patient's bleeding disorder?

Accepted Answer

hemophilia B

Answer

von Willebrand disease

Answer

hemophilia A

Answer

thrombotic thrombocytopenic purpura (TTP)

Question 6

A 26-year-old woman presents with severe menorrhagia. She reports that both her father and sister have a bleeding disorder. What is the most likely diagnosis, given an autosomal-dominant mode of inheritance for the hemostatic disorder?

Accepted Answer

von Willebrand's disease

Answer

Factor X deficiency

Answer

Factor VIII deficiency (hemophilia A)

Answer

Factor IX deficiency (hemophilia B)

Question 7

Which of the following is the least common feature of Multiple Myeloma?

Accepted Answer

Hyperviscosity syndrome

Answer

Bone pain

Answer

Normocytic normochromic anemia

Answer

Susceptibility to bacterial infection

Question 8

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 9

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 10

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

Hematology — MCQs

Hematology — MCQs

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