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 parameter is primarily used to diagnose macrocytosis in a complete blood count (CBC)?

• A. Hematocrit
• B. Mean Corpuscular Hemoglobin Concentration (MCHC)
• C. Mean Corpuscular Volume (MCV) (Correct Answer)
• D. None of the options

Hematology Explanation: ***Mean Corpuscular Volume (MCV)*** - **MCV** measures the **average volume of red blood cells**, making it the primary indicator for classifying them as microcytic, normocytic, or macrocytic. - An **elevated MCV** (typically above 100 fL) indicates **macrocytosis**, meaning the red blood cells are larger than normal. *Mean Corpuscular Hemoglobin Concentration (MCHC)* - **MCHC** reflects the **average concentration of hemoglobin** in red blood cells, primarily used to classify cells as normochromic or hypochromic. - It does **not directly measure cell size** and therefore is not used to diagnose macrocytosis. *Hematocrit* - **Hematocrit** measures the **percentage of red blood cells** in a given volume of blood. - While it indicates the overall red cell mass, it **does not provide information about the average size** of individual red blood cells. *None of the options* - As **MCV** is explicitly listed and is the correct parameter for diagnosing macrocytosis, this option is incorrect. - The other parameters listed are important for other aspects of red blood cell analysis but not for classifying cell size.

Hematology Indian Medical PG Question 3: A 69-year-old woman, with poor dietary habits and alcoholism, is found to have a macrocytic anemia with hyper segmented neutrophils. Which of the following is the most appropriate diagnostic test?

• A. serum folate levels
• B. bone marrow
• C. RBC folate levels (Correct Answer)
• D. Schilling test

Hematology Explanation: RBC folate levels - **RBC folate levels** reflect **tissue folate stores** and are less susceptible to daily dietary fluctuations than serum folate. - This test is considered a more reliable indicator for diagnosing **chronic folate deficiency**, which is consistent with poor dietary habits and alcoholism. *serum folate levels* - **Serum folate levels** are easily influenced by recent dietary intake, making them less indicative of long-term folate stores [1]. - A normal serum folate level can be seen in patients with **tissue folate deficiency** if they have recently ingested folate-rich foods [1]. *bone marrow* - A **bone marrow biopsy** might show megaloblastic changes, but it is an invasive procedure and is usually reserved for cases where the diagnosis remains unclear after less invasive tests [2]. - While it can confirm **megaloblastic anemia**, it does not specifically differentiate between **folate** and **B12 deficiencies** as the primary diagnostic tool. *Schilling test* - The **Schilling test** is used to diagnose **vitamin B12 malabsorption** (pernicious anemia or other causes), not folate deficiency. - This patient's clinical picture points more towards a **folate deficiency** given the poor dietary habits and alcoholism, although B12 deficiency can also cause macrocytic anemia [3].

Hematology Indian Medical PG Question 4: Radiotherapy has the most significant therapeutic role in:

• A. Monoclonal gammopathy
• B. Tuberculosis
• C. Sarcomas (Correct Answer)
• D. Sarcoidosis

Hematology Explanation: ***Sarcomas*** - **Radiotherapy** plays a crucial therapeutic role in **sarcomas**, though typically as **adjuvant therapy** combined with surgical resection - Used for **local control** in soft tissue sarcomas, particularly when wide margins cannot be achieved - **Primary radiotherapy** is the treatment of choice for certain radiation-sensitive sarcomas like **Ewing's sarcoma** and in cases of **inoperable tumors** - Essential for reducing **local recurrence rates** in high-grade soft tissue sarcomas - Among the options listed, sarcomas have the **strongest and most established indication** for radiotherapy *Monoclonal gammopathy* - Generally **observation only** for MGUS (Monoclonal Gammopathy of Undetermined Significance) - Radiotherapy used only for **solitary plasmacytoma**, which is a specific localized manifestation - Multiple myeloma (if it progresses) is treated with **chemotherapy** and targeted agents, not radiotherapy as primary treatment *Tuberculosis* - An **infectious disease** caused by *Mycobacterium tuberculosis* - Treated exclusively with **anti-tubercular drug regimens** (RIPE: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) - Radiotherapy has **no role** in treating infections *Sarcoidosis* - A **systemic inflammatory condition** with non-caseating granulomas - Primary treatment is **corticosteroids** for symptomatic cases - Immunosuppressants used for refractory cases - Radiotherapy has **no role** in inflammatory/granulomatous diseases

Hematology Indian Medical PG Question 5: International prognostic index for lymphomas includes the following prognostic factors, EXCEPT:

• A. LDH
• B. Number of extralymphatic sites involved
• C. Hemoglobin and albumin (Correct Answer)
• D. Stage of disease

Hematology Explanation: ***Hemoglobin and albumin*** - While hemoglobin and albumin can be indicators of overall health and nutritional status, they are **not part of the standard International Prognostic Index (IPI)** for lymphomas. - The IPI specifically focuses on factors directly related to tumor burden and patient vitality, not general systemic markers like these. *LDH* - **Lactate dehydrogenase (LDH)** is a crucial component of the IPI, reflecting tumor burden and aggressiveness [1]. - Elevated LDH levels indicate a higher risk and are associated with a poorer prognosis [1]. *Number of extralymphatic sites involved* - The **number of extralymphatic sites involved** is a key prognostic factor in the IPI. - Involvement of more than one extralymphatic site indicates more widespread disease and a worse prognosis. *Stage of disease* - The **stage of disease**, as defined by the Ann Arbor staging system, is an essential element of the IPI [1]. - Advanced stages (III or IV) are associated with a poorer prognosis compared to early stages [1].

Hematology Indian Medical PG Question 6: What are the key characteristics of Evans syndrome?

• A. Autoimmune hemolytic anemia and immune thrombocytopenia (Correct Answer)
• B. Low lymphocyte and red blood cell counts
• C. High platelet and lymphocyte counts
• D. A reduction in all blood cell types

Hematology Explanation: ***Autoimmune hemolytic anemia and immune thrombocytopenia*** - **Evans syndrome** is defined by the simultaneous or sequential occurrence of **autoimmune hemolytic anemia (AIHA)** and **immune thrombocytopenia (ITP)** [1], [2]. - Both conditions involve the immune system mistakenly attacking and destroying **red blood cells** and **platelets**, respectively [1], [2]. *Low lymphocyte and red blood cell counts* - While **red blood cell counts** are low in Evans syndrome due to AIHA, **lymphocyte counts** are not a defining characteristic; they can vary. - This option does not fully capture the dual autoimmune destruction of red blood cells and platelets specific to Evans syndrome. *High platelet and lymphocyte counts* - **Platelet counts** are **low** in Evans syndrome due to ITP, not high. - **Lymphocyte counts** are not characteristically high; a high count might suggest other conditions like leukemias or lymphomas. *A reduction in all blood cell types* - A reduction in all (red blood cells, white blood cells, and platelets) is known as **pancytopenia**, which is not the defining feature of Evans syndrome. - Evans syndrome specifically involves the destruction of **red blood cells** and **platelets**, but not necessarily all white blood cell types.

Hematology Indian Medical PG Question 7: Most radio-resistant phase in the cell cycle:

• A. G2
• B. Late S (Correct Answer)
• C. Early S
• D. G1

Hematology Explanation: ***Late S*** - The **late S phase** is the **most radio-resistant phase** of the cell cycle due to high levels of DNA repair enzymes and mechanisms active during this period. - During late S phase, chromatin is **tightly packed** and DNA synthesis is accompanied by robust **homologous recombination repair** capacity, making cells less vulnerable to radiation-induced damage. - This is a well-established principle in radiobiology, with cells in late S showing **2-3 times more resistance** compared to G2/M phases. *Early S* - While S phase overall is relatively radio-resistant, **early S is less resistant than late S** because repair mechanisms are not yet fully upregulated. - DNA replication has just begun, and the cell has moderate levels of repair enzymes compared to late S phase. *G1* - Cells in G1 phase have **moderate radio-sensitivity**, more sensitive than S phase but less sensitive than G2/M phases. - While cells have time for repair in G1, they lack the enhanced repair enzyme levels present during S phase. - G1 cells are in an **active metabolic state** preparing for DNA synthesis. *G2* - G2 phase is one of the **most radio-sensitive phases** along with mitosis (M phase). - Cells have **duplicated DNA** (4n content) and are preparing for division, making them highly vulnerable to radiation damage. - Any unrepaired DNA damage will be transmitted to both daughter cells during the upcoming mitosis.

Hematology Indian Medical PG Question 8: Arrange the following according to good outcome a - zone of stasis b - zone of coagulation c - zone of hyperemia

• A. a > b > c
• B. a > c > b
• C. c > a > b (Correct Answer)
• D. a = c > b

Hematology Explanation: **Context:** This question refers to Jackson's burn wound model, which describes three concentric zones in a burn injury. ***c > a > b*** (Correct Answer) - The **zone of hyperemia (c)** has the **best prognosis** for recovery because tissue damage is minimal, involving primarily vasodilation and increased blood flow. This zone typically recovers completely within 7-10 days. - The **zone of stasis (a)** has an **intermediate prognosis**; tissue here is potentially salvageable but at risk of progression to necrosis within 24-48 hours if not properly managed (adequate fluid resuscitation, prevention of infection, avoiding vasoconstrictors). - The **zone of coagulation (b)** has the **worst prognosis**, as cellular damage is irreversible with immediate coagulative necrosis. This tissue will eventually slough off and requires debridement. *a > b > c* - Incorrectly suggests the **zone of stasis** has better outcome than **zone of hyperemia**, which contradicts the pathophysiology of burn injuries. - The **zone of coagulation** cannot have better outcome than **zone of hyperemia** as it represents dead tissue. *a > c > b* - Incorrectly places **zone of stasis** as having the best outcome when it has only intermediate prognosis. - The **zone of hyperemia** should be first as it has the highest probability of complete recovery without intervention. *a = c > b* - Incorrectly equates the prognosis of **zone of stasis** and **zone of hyperemia**, despite clear differences in severity and reversibility of tissue damage. - The **zone of hyperemia** has unequivocally better prognosis than the **zone of stasis**.

Hematology Indian Medical PG Question 9: ALL L3 morphology is a malignancy arising from which cell lineage –

• A. Mature B cell (Correct Answer)
• B. Mixed B cell & T cell
• C. Immature T cell
• D. Precursor B cell

Hematology Explanation: ***Mature B cell*** - ALL L3, also known as **Burkitt-type ALL**, arises from a **mature B-cell lineage**. [1] - This is characterized by specific immunophenotypic markers (e.g., strong expression of **surface immunoglobulin** and **CD20**) and frequent chromosomal translocations involving the **MYC oncogene**, typically t(8;14). [1] *Mixed B cell & T cell* - This refers to **mixed phenotype acute leukemia (MPAL)**, which exhibits features of both B-cell and T-cell lineages. - MPAL is distinct from ALL L3, which is definitively B-cell in origin based on morphology and immunophenotype. *Immature T cell* - Malignancies arising from immature T cells are classified as **T-cell ALL**, which have a different morphology (L1 or L2) and distinct immunophenotype (e.g., expression of **cytoplasmic CD3**, CD1a, CD2, CD5, CD7). [1] - T-cell ALL is characterized by **T-cell receptor gene rearrangements** and typically presents with a mediastinal mass, unlike ALL L3. [1] *Precursor B cell* - Most cases of ALL (ALL L1 and L2) arise from **precursor B cells**, also known as B-lymphoblastic leukemia. [2] - These are characterized by lack of surface immunoglobulin expression and generally express **CD10, CD19, CD22**, and **TdT**, contrasting with the mature B-cell immunophenotype of ALL L3. [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, p. 606. [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. 596-598.

Hematology Indian Medical PG Question 10: Which of the following statements about cold agglutinin disease is false?

• A. Rituximab is not effective as a therapeutic measure as it can not control hemolysis effectively (Correct Answer)
• B. The antibody is usually IgM with an anti-I specificity
• C. Blood transfusion is not very effective because donor red cells are I-positive and will be rapidly removed
• D. Hemolysis is more prominent the more the body is exposed to the cold

Hematology Explanation: ***Rituximab is not effective as a therapeutic measure as it can not control hemolysis effectively*** - This statement is **false**. **Rituximab** is a **monoclonal antibody** targeting CD20 on B-lymphocytes, and it is an **effective treatment** for cold agglutinin disease, especially in chronic cases [1]. - By depleting the B-cells responsible for producing the cold agglutinins (autoantibodies), rituximab can significantly **reduce hemolysis** and improve patient outcomes [1]. *The antibody is usually IgM with an anti-I specificity* - This statement is **true**. Cold agglutinins are typically **IgM autoantibodies** that react optimally at temperatures below 37°C [1]. - They most commonly target the **I antigen** on the surface of red blood cells, leading to agglutination and hemolysis when exposed to cold temperatures [1]. *Blood transfusion is not very effective because donor red cells are I-positive and will be rapidly removed* - This statement is **true**. Most individuals, including blood donors, have **I-positive red blood cells**. - Therefore, transfused red blood cells will also carry the I antigen and be susceptible to destruction by the patient's cold agglutinins, making transfusions less effective and potentially risky. *Hemolysis is more prominent the more the body is exposed to the cold* - This statement is **true**. The defining characteristic of cold agglutinin disease is the **temperature-dependent activity** of the autoantibodies [1]. - Exposure to **colder temperatures** increases the binding of IgM antibodies to red blood cells, leading to more extensive agglutination, complement activation, and subsequent hemolysis [1].

Hematology Flashcard 1 of 10

Question: NPM1 and CEBPA mutation is associated with a _____ prognosis in patients with acute myeloid leukemia (AML).

Answer: good

Hematology Flashcard 2 of 10

Question: Aplastic anemia may be caused by _____ anemia, which occurs due to a dsDNA repair defect, resulting in bone marrow failure

Answer: Fanconi

Hematology Flashcard 3 of 10

Question: _____ syndrome is simultaneous or sequential direct Coombs-positive autoimmune hemolytic anemia in conjunction with immune-mediated thrombocytopenia

Answer: Evans

Hematology Flashcard 4 of 10

Question: The pentad of classical symptoms seen in _____ may be remembered using the mnemonic FAT RN: F: Fever (1/5 patients)A*: Anemia (Microangiopathic Hemolytic Anemia)T*: ThrombocytopeniaR: Renal symptoms (1/2 of patients)-More common in HUSN: Neurologic symptoms (2/3 of patients)-More common in TTP

Answer: thrombotic thrombocytopenic purpura (TTP)

Hematology Flashcard 5 of 10

Question: What AML subtype is associated with sweet syndrome?_____

Answer: AML M5

Hematology Flashcard 6 of 10

Question: Tumor lysis syndrome is most common with treatment of _____ and acute lymphoblastic leukemia

Answer: lymphoma

Hematology Flashcard 7 of 10

Question: The given instrument is a _____ needle used for bone marrow biopsy.

Answer: Klima

Hematology Flashcard 8 of 10

Question: The given image shows leukemia cutis seen in AML M_____ and M_____

Answer: 4

Hematology Flashcard 9 of 10

Question: _____ classically presents with intense itching, especially after a hot shower

Answer: Polycythemia vera

Hematology Flashcard 10 of 10

Question: Vitamin B9 (folate) deficiency most commonly occurs due to _____, alcoholism, or drugs (e.g. phenytoin, sulfonamides, methotrexate)

Answer: pregnancy