Hematology

Hematology Indian Medical PG Question 1: Which of the following is the most common myeloproliferative disorder?

• A. Essential Thrombocythemia (Correct Answer)
• B. Polycythemia rubra vera
• C. CML
• D. Myelofibrosis

Hematology Explanation: ***Essential Thrombocythemia*** - **Essential thrombocythemia (ET)** is the **most common myeloproliferative neoplasm**, with an incidence of approximately 1.5-2.4 per 100,000 per year. - It is characterized by **persistent thrombocytosis** (platelet count >450,000/μL) and megakaryocytic proliferation [1]. - Commonly associated with **JAK2 V617F mutation** (~55-60%), **CALR mutations** (~25-30%), and **MPL mutations** (~3-5%) [2]. *Polycythemia rubra vera* - **Polycythemia vera (PV)** is the **second most common** classic MPN, with an incidence of approximately 0.8-2.3 per 100,000 per year. - Characterized by increased red blood cell mass, often with leukocytosis and thrombocytosis [1]. - Strongly associated with **JAK2 V617F mutation** (present in >95% of cases) [2][3]. *CML* - **Chronic myeloid leukemia (CML)** has similar incidence to PV (approximately 1-2 per 100,000 per year). - Defined by the presence of the **Philadelphia chromosome (BCR-ABL1 fusion gene)** [2]. - Treated distinctly with tyrosine kinase inhibitors (TKIs). *Myelofibrosis* - **Primary myelofibrosis (PMF)** is the **least common** of the classic MPNs, with an incidence of approximately 0.3-1.5 per 100,000 per year. - Characterized by bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly [3]. - Associated with **JAK2, CALR, or MPL mutations** [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 627-628. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 624. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615.

Hematology Indian Medical PG Question 2: Which is the cell of origin of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma?

• A. Mature B cells
• B. Progenitor T cells
• C. Mature T cells
• D. Naïve B cells (Correct Answer)

Hematology Explanation: ***Naïve B cells*** - Chronic Lymphocytic Leukaemia (CLL) and Small Lymphocytic Lymphoma (SLL) originate from **CD5-positive B lymphocytes** arrested in a mature but **naïve differentiation stage** [1]. - These cells express both **B-cell markers (CD19, CD20, CD23)** and a T-cell marker (CD5), which is characteristic of the clone [4]. *Mature B cells* - While CLL/SLL are derived from B cells, they are specifically from **naïve, not fully mature, B cells**. - **Other B-cell lymphomas** like follicular lymphoma or mantle cell lymphoma originate from distinct stages of mature B-cell differentiation [2]. *Progenitor T cells* - **Progenitor T cells** are the cells of origin for **T-cell acute lymphoblastic leukaemia (T-ALL)**, not CLL/SLL [3]. - T-ALL involves immature T lymphocytes and presents with different clinical and immunophenotypic features [3]. *Mature T cells* - **Mature T cells** can give rise to various **peripheral T-cell lymphomas**, like peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) or cutaneous T-cell lymphoma (Mycosis Fungoides). - These are distinct from CLL/SLL, which is a B-cell neoplasm [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 596-598. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 610-612. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 598-599. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 598.

Hematology Indian Medical PG Question 3: What is the typical bone marrow finding in myelofibrosis?

• A. Megaloblastic cells
• B. Microcytic cells
• C. Thrombocytosis
• D. Dry tap (hypocellular) (Correct Answer)

Hematology Explanation: ***Dry tap (hypocellular)*** - In myelofibrosis, the bone marrow is often **hypocellular** due to fibrosis [1][2], leading to a **dry tap** during aspiration. - The presence of **reticulin** and collagen deposition replaces normal hematopoietic cells [2], resulting in ineffective hematopoiesis. *Thrombocytosis* - Myelofibrosis typically leads to **thrombocytopenia**, not thrombocytosis, due to ineffective megakaryopoiesis and splenic sequestration. - Though elevated platelets can occur, they are generally a **secondary response** to the disease and not a hallmark finding. *Megaloblastic cells* - Megaloblastic changes are associated with **vitamin B12** or **folate deficiencies**, which do not occur in myelofibrosis. - In myelofibrosis, the predominant issue is **marrow fibrosis** [1][2], which does not lead to megaloblastosis. *Microcytic cells* - Microcytic cells are commonly linked to **iron deficiency anemia**, not myelofibrosis. - Myelofibrosis typically results in **variable red cell morphology** [1], but microcytic anemia is not a primary characteristic. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 628-629. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 615-616.

Hematology Indian Medical PG Question 4: Which of the following are neonatal complications of maternal diabetes during pregnancy? I. Hyperbilirubinemia II. Hypocalcemia III. Cardiomyopathy IV. Hypoglycemia Select the correct answer using the code given below :

• A. I, II and III
• B. I, II and IV (Correct Answer)
• C. II, III and IV
• D. I, III and IV

Hematology Explanation: ***I, II and IV*** - This correctly identifies the three **most common and clinically significant neonatal complications** of maternal diabetes: **hyperbilirubinemia**, **hypocalcemia**, and **hypoglycemia**. - **Hypoglycemia** is the **most frequent complication** (25-50% of infants), occurring due to fetal hyperinsulinemia that persists after birth when maternal glucose supply is cut off. - **Hypocalcemia** occurs in 20-50% of cases due to impaired parathyroid hormone response, hypomagnesemia, and altered calcium-phosphorus metabolism. - **Hyperbilirubinemia** results from polycythemia (due to chronic intrauterine hypoxia), increased RBC breakdown, and impaired hepatic conjugation. *I, II and III* - While this includes **hyperbilirubinemia**, **hypocalcemia**, and **cardiomyopathy**, it inappropriately excludes **hypoglycemia**, which is the **most common and most critical** neonatal complication requiring immediate monitoring and management. - Omitting hypoglycemia makes this option medically incorrect as a primary answer. *II, III and IV* - This option excludes **hyperbilirubinemia**, which is a very common finding (occurs in up to 25% of infants of diabetic mothers) due to increased erythropoiesis and RBC destruction. - Fetal hyperinsulinemia drives increased oxygen consumption, leading to relative hypoxia and compensatory polycythemia. *I, III and IV* - This option misses **hypocalcemia**, which is one of the **classic metabolic complications** seen in 20-50% of infants of diabetic mothers. - Hypocalcemia typically presents in the first 24-72 hours of life and is exacerbated by concurrent **magnesium deficiency**, which impairs PTH secretion and action. **Note:** All four listed complications (I, II, III, and IV) are recognized complications of maternal diabetes. Hypertrophic cardiomyopathy occurs in 10-20% of cases but is generally less common than the metabolic triad of hypoglycemia, hypocalcemia, and hyperbilirubinemia, which require routine screening in all infants of diabetic mothers.

Hematology Indian Medical PG Question 5: A newborn presents with the clinical features shown in the image below. What is the most likely diagnosis?

• A. Trisomy 21
• B. Trisomy 18 (Correct Answer)
• C. Trisomy 13
• D. Trisomy 12

Hematology Explanation: ***18 trisomy*** - The image shows a newborn with an **omphalocele (abdominal wall defect)** and characteristic **clenched hands with overlapping fingers**, which are common features of Trisomy 18 (Edwards syndrome). - Other typical features include **low-set ears**, **micrognathia**, **rocker-bottom feet**, and severe developmental delay, contributing to a poor prognosis. *21 trisomy* - Trisomy 21 (Down syndrome) typically presents with **upslanting palpebral fissures**, an **epicanthal fold**, a **single palmar crease**, and **intellectual disability**, which are not the prominent features seen here. - While congenital heart defects can be present in both, the specific hand posture and omphalocele are more indicative of Trisomy 18. *13 trisomy* - Trisomy 13 (Patau syndrome) is characterized by severe malformations, including **cleft lip and palate**, **polydactyly**, **cutis aplasia**, and **microphthalmia**, which are distinct from the features in the image. - **Holoprosencephaly** is also common in Trisomy 13, which is not suggested by the visual findings. *12 trisomy* - Trisomy 12 is **not a recognized viable chromosomal aneuploidy** in humans that leads to a distinct syndrome such as those related to chromosomes 13, 18, or 21. - Genetic disorders involving chromosome 12 are typically mosaic or involve partial aneuploidies.

Hematology Indian Medical PG Question 6: A 10-month-old child with coarse facies is referred for developmental delay. On examination, hepatosplenomegaly was noted. WBC N-acetylglucosamine-1-phosphotransferase activity was absent. The X-ray is shown below. What is the diagnosis?

• A. I cell disease (Correct Answer)
• B. MPS type II
• C. Proteus syndrome
• D. Larsen syndrome

Hematology Explanation: ***I cell disease*** - **I-cell disease** (Mucolipidosis II) is characterized by **coarse facial features**, developmental delay, hepatosplenomegaly, and **skeletal abnormalities** (dysostosis multiplex) seen on X-ray, which are consistent with the image. - The absence of **N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase)** activity leads to misrouting of lysosomal enzymes, resulting in accumulation of mucolipids within cells. *MPS type II* - **MPS type II** (Hunter syndrome) also presents with coarse facies, developmental delay, and hepatosplenomegaly, and can show skeletal abnormalities. - However, the enzymatic defect is in **iduronate sulfatase**, not GlcNAc-1-phosphotransferase, and the clinical course tends to be slightly milder than I-cell disease, particularly in early infancy. *Proteus syndrome* - **Proteus syndrome** is characterized by **overgrowth of tissues**, asymmetric growth, and various tumors, not by the specific metabolic defect or typical pattern of skeletal changes described. - It does not involve absent GlcNAc-1-phosphotransferase activity. *Larsen syndrome* - **Larsen syndrome** primarily involves **skeletal abnormalities**, such as joint dislocations (especially knees, hips, and elbows), flattened facial appearance, and clubfoot. - It does not feature the same metabolic defect (absent GlcNAc-1-phosphotransferase activity) or the prominent coarse facial features and hepatosplenomegaly seen in the patient.

Hematology Indian Medical PG Question 7: A 5 year old child presented with periorbital swelling and oliguria. Nephrotic syndrome is suspected. Which of the following is the commonest type of nephrotic syndrome in this child?

• A. Focal segmental glomerulosclerosis (FSGS)
• B. Chronic glomerulonephritis
• C. Minimal change disease (Correct Answer)
• D. Congenital nephrotic syndrome

Hematology Explanation: ***Minimal change disease*** - This is the **most common cause of nephrotic syndrome** in children, accounting for approximately 80% of cases. - It presents with sudden onset of **periorbital edema**, **generalized edema**, and often **oliguria** due to severe proteinuria. *Focal segmental glomerulosclerosis (FSGS)* - While a significant cause of nephrotic syndrome in children, it ranks second to minimal change disease in frequency. - FSGS tends to have a **poorer response to steroids** and a higher risk of progression to **end-stage renal disease**. *Chronic glomerulonephritis* - This is a broad category of glomerular diseases, typically having a **more insidious onset** and often associated with hematuria and hypertension, which are not mentioned in this acute presentation. - It usually presents with features that suggest **nephritic syndrome** (e.g., hematuria, hypertension) rather than primarily nephrotic syndrome features. *Congenital nephrotic syndrome* - This is a **rare genetic condition** that presents within the first 3 months of life, which is much earlier than the 5-year-old age of this patient. - It is characterized by severe proteinuria from birth and is typically part of inherited syndromes.

Hematology Indian Medical PG Question 8: A 5-year-old boy presents with petechial bleeding and bruising on his torso and limbs. He has no other signs or symptoms and does not appear ill. His mother reports a gastrointestinal infection several weeks prior to the onset of petechiae and bruising. Complete blood count reveals thrombocytopenia (<20 x 10^9/L), with other parameters within the expected range for his age. Prothrombin time, partial thromboplastin time, and metabolic panels are all within the reference range. What is the expected outcome of this blood disorder?

• A. Complete resolution is expected. (Correct Answer)
• B. Survival rate is up to 70% depending on risk stratification.
• C. Lifelong disease dependent on factor VIII substitution.
• D. Lifelong disease dependent on factor IX substitution.

Hematology Explanation: ### Explanation The clinical presentation describes a classic case of **Immune Thrombocytopenic Purpura (ITP)**, the most common cause of isolated thrombocytopenia in children. **1. Why Option A is Correct:** In children, ITP typically follows a viral infection (respiratory or gastrointestinal) after a 1–4 week latent period. It is characterized by the sudden onset of petechiae and bruising in an otherwise healthy-appearing child. The hallmark is **isolated thrombocytopenia** (Platelets <100 x 10⁹/L) with normal PT, PTT, and hemoglobin. The prognosis is excellent; approximately **70–80% of children achieve complete spontaneous resolution** within 6 months, regardless of therapy. **2. Why the Other Options are Incorrect:** * **Option B:** This refers to the survival rates of pediatric malignancies like Acute Lymphoblastic Leukemia (ALL). While ALL presents with bruising, it typically involves "sick" symptoms (fever, bone pain), hepatosplenomegaly, and abnormalities in other cell lines (anemia/leukocytosis). * **Options C & D:** These describe **Hemophilia A (Factor VIII)** and **Hemophilia B (Factor IX)**. Hemophilias are coagulation factor deficiencies that present with deep tissue bleeds (hemarthrosis/hematomas) and a **prolonged aPTT**, rather than petechiae and isolated thrombocytopenia. **3. NEET-PG High-Yield Pearls:** * **Pathophysiology:** Anti-platelet antibodies (IgG) directed against GP IIb/IIIa or GP Ib/IX. * **Bone Marrow:** Not routinely required but would show **increased megakaryocytes** (compensatory). * **Management:** Observation is preferred if bleeding is minimal (dry purpura). If treatment is needed (wet purpura/active bleeding), **IVIG** or **Corticosteroids** are first-line. * **Chronic ITP:** Defined as thrombocytopenia persisting >12 months (occurs in ~20% of cases).

Hematology Indian Medical PG Question 9: A 21-year-old male presents with anemia and mild hepatosplenomegaly. His hemoglobin is 5 gm/dL, and he has a history of a single blood transfusion to date. What is the most probable diagnosis?

• A. Thalassemia major
• B. Thalassemia minor
• C. Thalassemia intermedia
• D. Autoimmune hemolytic anemia (Correct Answer)

Hematology Explanation: ### Explanation **Correct Option: D. Autoimmune Hemolytic Anemia (AIHA)** The key to this question lies in the **age of presentation** and the **transfusion history**. 1. **Age:** A 21-year-old presenting with severe anemia (Hb 5 gm/dL) for the first time suggests an acquired or late-onset condition rather than a severe congenital hemoglobinopathy. 2. **Transfusion History:** The patient has received only **one transfusion** in 21 years despite a very low hemoglobin. This "transfusion-sparing" clinical course rules out Thalassemia Major. 3. **Clinical Features:** Hepatosplenomegaly is common in AIHA due to extramedullary hematopoiesis and splenic sequestration of antibody-coated RBCs. --- ### Why the other options are incorrect: * **A. Thalassemia Major:** This typically presents in **infancy (6–9 months)** as fetal hemoglobin (HbF) levels drop. Without regular monthly transfusions, these patients do not survive to age 21 with a hemoglobin of 5 gm/dL. * **B. Thalassemia Minor:** This is usually an asymptomatic carrier state. While mild anemia may be present, the hemoglobin rarely drops to 5 gm/dL, and hepatosplenomegaly is typically absent. * **C. Thalassemia Intermedia:** While these patients present later than Thalassemia Major and are "transfusion-independent," they usually maintain a hemoglobin between 7–10 gm/dL. A drop to 5 gm/dL at age 21 without a prior history of regular transfusions is more characteristic of an acute hemolytic process like AIHA. --- ### NEET-PG High-Yield Pearls: * **Thalassemia Major:** "Transfusion-dependent"; presents with "Chipmunk facies" and "Hair-on-end" appearance on X-ray. * **AIHA Diagnosis:** The gold standard investigation is the **Direct Coombs Test (Direct Antiglobulin Test)**. * **Clinical Clue:** If a young adult presents with sudden severe anemia and splenomegaly, always consider AIHA or a late-presenting Hereditary Spherocytosis.

Hematology Indian Medical PG Question 10: What is the recommended treatment for Kostmann's syndrome?

• A. Anti-thymocyte globulin plus cyclosporin
• B. Anti-thymocyte globulin plus cyclosporin plus GM-CSF
• C. G-CSF (Correct Answer)
• D. GM-CSF

Hematology Explanation: **Explanation:** **Kostmann’s Syndrome** (Severe Congenital Neutropenia) is an autosomal recessive disorder characterized by a maturation arrest of neutrophil precursors in the bone marrow at the **promyelocyte/myelocyte stage**. This leads to absolute neutrophil counts (ANC) frequently below 200/mm³, predisposing infants to life-threatening pyogenic infections. **Why G-CSF is the Correct Answer:** The primary goal of treatment is to increase the production and maturation of neutrophils. **Granulocyte Colony-Stimulating Factor (G-CSF)** is the gold-standard treatment. It effectively increases the ANC in over 90% of patients, significantly reducing the frequency of infections and improving survival. While Hematopoietic Stem Cell Transplant (HSCT) is the definitive cure, G-CSF is the first-line medical management. **Why Other Options are Incorrect:** * **Options A & B:** Anti-thymocyte globulin (ATG) and Cyclosporin are immunosuppressive therapies used for **Aplastic Anemia**, where the pathology is T-cell mediated destruction of stem cells. Kostmann’s is a genetic maturation defect, not an autoimmune process. * **Option D:** **GM-CSF** (Granulocyte-Macrophage CSF) is less effective than G-CSF and is associated with more systemic side effects (like fever and bone pain) without providing a superior neutrophil response in these patients. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** Most common mutation in Severe Congenital Neutropenia is **ELANE** (autosomal dominant), but the classic **Kostmann’s** specifically refers to the **HAX1** mutation (autosomal recessive). * **Bone Marrow Finding:** Characterized by "maturation arrest" at the promyelocyte stage. * **Malignancy Risk:** Patients have a significantly increased risk of developing **Acute Myeloid Leukemia (AML)** or Myelodysplastic Syndrome (MDS), even with G-CSF treatment. * **Definitive Treatment:** For patients refractory to G-CSF or those developing MDS/AML, **Stem Cell Transplant** is the only curative option.

Hematology Flashcard 1 of 9

Question: Both acute lymphoblastic and acute myeloid leukemia in children are associated with _____ anemia.

Answer: fanconi

Hematology Flashcard 2 of 9

Question: Kostmann syndrome can evolve into _____ leukemia

Answer: acute myeloid

Hematology Flashcard 3 of 9

Question: _____ leukemia is associated with Down syndrome; usually arises before the age of 5

Answer: Acute megakaryoblastic

Hematology Flashcard 4 of 9

Question: -thalassemia _____ is characterized by expansion of hematopoiesis into facial bones, leading to "chipmunk facies"

Answer: major

Hematology Flashcard 5 of 9

Question: On serum analysis, patients with Systemic Juvenile Idiopathic Arthritis will frequently present with:- _____ RBCs- increased WBCs- increased TBCs

Answer: decreased

Hematology Flashcard 6 of 9

Question: _____ syndrome is a syndrome of thrombocytopenia and consumptive coagulopathy in a patient of hemangioma

Answer: Kasabach-Merritt

Hematology Flashcard 7 of 9

Question: Kids with sickle cell disease should undergo _____ starting at age of 2 yrs to reduce the incidence of overt stroke

Answer: transcranial doppler ultrasound

Hematology Flashcard 8 of 9

Question: _____ is a common presenting sign of sickle cell anemia in infants (age group)

Answer: Dactylitis

Hematology Flashcard 9 of 9

Question: _____ leukemia is associated with Down syndrome; usually arises after the age of 5 years

Answer: Acute lymphoblastic