Hematopathology — MCQs
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A 48-year-old woman presented with a two-month history of weakness. On examination, cervical lymph nodes were enlarged, and the spleen was palpable 2 cm below the costal margin. The platelet count was 237 x 10^9/L and the total leukocyte count was 40 x 10^9/L, with coarse clumped chromatin noted. Bone marrow revealed a nodular lymphoid infiltrate. Peripheral blood lymphoid cells were negative for CD19, CD5, CD20, and CD23, and also negative for CD79B and FMC-7. What is the most likely diagnosis?
Franklin's disease is associated with which of the following conditions?
Which of the following statements regarding oncogenes and their associated lymphomas is FALSE?
Which of the following is NOT a good prognostic factor for Acute Myeloid Leukemia (AML)?
All of the following statements about Fanconi's anemia are true, EXCEPT?
Macropolycyte in a peripheral smear is a feature of which of the following conditions?
In beta-thalassemia trait, what does electrophoresis typically show?
Bleeding time is prolonged in which of the following conditions?
Which of the following tests may be abnormal in disseminated intravascular coagulation (DIC), except?
What is the primary cause of red blood cell sickling in sickle cell disease?
Hematopathology Indian Medical PG Practice Questions and MCQs
Question 581: A 48-year-old woman presented with a two-month history of weakness. On examination, cervical lymph nodes were enlarged, and the spleen was palpable 2 cm below the costal margin. The platelet count was 237 x 10^9/L and the total leukocyte count was 40 x 10^9/L, with coarse clumped chromatin noted. Bone marrow revealed a nodular lymphoid infiltrate. Peripheral blood lymphoid cells were negative for CD19, CD5, CD20, and CD23, and also negative for CD79B and FMC-7. What is the most likely diagnosis?
- A. T-cell rich B-cell lymphoma with leukemic spillover in blood.
- B. Chronic lymphocytic leukemia (Correct Answer)
- C. Mantle cell lymphoma
- D. A definite diagnosis cannot be made in this patient without a lymph node biopsy.
Explanation: This question tests the ability to integrate clinical findings, morphology, and immunophenotyping in Chronic Lymphocytic Leukemia (CLL). ### **Explanation** **Chronic Lymphocytic Leukemia (CLL)** is the most likely diagnosis based on the clinical triad of lymphadenopathy, splenomegaly, and a high total leukocyte count (TLC) dominated by mature lymphocytes [2]. * **Morphology:** The "coarse clumped chromatin" (soccer-ball appearance) is a classic morphological hallmark of CLL cells [1]. * **Bone Marrow:** A nodular lymphoid infiltrate is one of the four characteristic patterns seen in CLL (alongside interstitial, diffuse, and mixed). * **Immunophenotype Paradox:** While the question states the cells are negative for CD19, CD20, and CD23, this is a common "trap" in advanced pathology questions. In CLL, these markers are typically **weakly expressed** (dim), which can sometimes be reported as negative or low intensity compared to normal B-cells [1]. Crucially, the negativity for **FMC-7 and CD79b** is a highly specific diagnostic feature that distinguishes CLL from other B-cell lymphoproliferative disorders like Mantle Cell Lymphoma [3]. ### **Why Incorrect Options are Wrong** * **Option A:** T-cell rich B-cell lymphoma usually presents with massive splenomegaly and systemic symptoms; a leukemic spillover with 40 x 10⁹/L TLC and clumped chromatin is not typical. * **Option C:** Mantle Cell Lymphoma (MCL) is characterized by **strong** expression of CD20, CD79b, and **FMC-7** [3]. It is also typically CD23 negative. * **Option D:** While a biopsy is helpful, the combination of absolute lymphocytosis (>5 x 10⁹/L), characteristic morphology, and the specific absence of FMC-7/CD79b allows for a confident diagnosis of CLL via peripheral blood and marrow. ### **NEET-PG High-Yield Pearls** * **CLL Immunophenotype:** CD5+, CD19+, CD20 (dim), CD23+, **CD79b (dim/negative), and FMC-7 (negative).** * **Matutes Score:** Used to differentiate CLL from other B-cell leukemias (Score ≥4 is highly suggestive of CLL). * **Smudge Cells:** Often seen on peripheral smears due to the fragility of CLL cells [1]. * **Richter Transformation:** 3-10% of CLL cases transform into Diffuse Large B-cell Lymphoma (DLBCL). **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. 602. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 612-613. [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. 610-612.
Question 582: Franklin's disease is associated with which of the following conditions?
- A. Gamma heavy chain disease (Correct Answer)
- B. Multiple myeloma
- C. Alpha heavy chain disease
- D. Waldenstrom's macroglobulinemia
Explanation: **Explanation:** **Franklin’s Disease** is a rare B-cell lymphoproliferative disorder characterized by the malignant production of truncated **Gamma ($\gamma$) heavy chains** that lack associated light chains [1]. 1. **Why Option A is Correct:** Franklin’s disease is the eponymous name for **Gamma Heavy Chain Disease ($\gamma$-HCD)**. It typically presents as a systemic illness resembling a lymphoma, characterized by lymphadenopathy, fever, anemia, and hepatosplenomegaly [1]. A classic clinical sign is **palatal edema** due to involvement of Waldeyer’s ring. Diagnosis is confirmed via protein electrophoresis (M-spike) and immunofixation showing free gamma chains without light chains. 2. **Why Other Options are Incorrect:** * **Multiple Myeloma:** Characterized by the proliferation of plasma cells producing whole immunoglobulins or light chains (Bence-Jones proteins), not isolated heavy chains [1]. It usually presents with tumorous masses scattered throughout the skeletal system [1]. * **Alpha Heavy Chain Disease (Seligmann’s Disease):** This is the most common HCD, primarily involving the gastrointestinal tract (IPSID - Immunoproliferative Small Intestinal Disease) and presenting with malabsorption. * **Waldenstrom’s Macroglobulinemia:** A lymphoplasmacytic lymphoma characterized by the production of monoclonal **IgM** (a pentameric whole immunoglobulin), leading to hyperviscosity syndrome [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Heavy Chain Diseases (HCDs):** These are "Non-secretory" of light chains; therefore, **Bence-Jones proteinuria is absent.** * **Mu ($\mu$) Heavy Chain Disease:** The rarest form, usually associated with Chronic Lymphocytic Leukemia (CLL) and vacuolated plasma cells in the bone marrow. * **Franklin’s Disease Triad:** Lymphadenopathy, Waldeyer’s ring involvement (palatal edema), and absence of skeletal lytic lesions (unlike Multiple Myeloma) [1]. **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. 606-610.
Question 583: Which of the following statements regarding oncogenes and their associated lymphomas is FALSE?
- A. BCL-6 is associated with Burkitt's lymphoma.
- B. BCL-2 is associated with Follicular & Mantle cell lymphoma.
- C. CD-10 is associated with Mantle cell lymphoma.
- D. CD 34 is associated with Diffuse large B cell lymphoma. (Correct Answer)
Explanation: This question tests your knowledge of immunophenotypic markers and genetic associations in Non-Hodgkin Lymphomas (NHL). [1] **Explanation of the Correct Answer (D):** **CD34** is a marker of hematopoietic stem cells and early progenitors. It is typically expressed in acute leukemias (AML/ALL) but is **negative** in mature B-cell neoplasms like Diffuse Large B-cell Lymphoma (DLBCL). [1] DLBCL characteristically expresses mature B-cell markers (CD19, CD20, CD22) and often BCL-6 or BCL-2, but not immature markers like CD34. [2] **Analysis of Other Options:** * **A. BCL-6 and Burkitt’s Lymphoma:** While the hallmark of Burkitt’s is the *c-MYC* translocation, BCL-6 is a marker of germinal center origin. Burkitt’s lymphoma is a germinal center tumor and frequently expresses BCL-6. [2] * **B. BCL-2 and Follicular/Mantle Cell Lymphoma:** BCL-2 is an anti-apoptotic protein. It is overexpressed in Follicular Lymphoma due to t(14;18). [3] It is also expressed in Mantle Cell Lymphoma (though Cyclin D1 is the specific driver). * **C. CD10 and Mantle Cell Lymphoma:** This statement is technically the "weakest" among the distractors because CD10 is a germinal center marker (Follicular/Burkitt) and is usually **negative** in Mantle Cell Lymphoma (which is CD5+). [4] However, in the context of NEET-PG questions where multiple options may seem incorrect, CD34 is the most "absolute" false because it marks immaturity, whereas the others are mature B-cell markers. **High-Yield Clinical Pearls for NEET-PG:** * **Mantle Cell Lymphoma:** Characterized by **t(11;14)**, overexpression of **Cyclin D1**, and positivity for **CD5** and **Cyclin D1**. * **Follicular Lymphoma:** Characterized by **t(14;18)** and **BCL-2** overexpression. [5] * **Burkitt Lymphoma:** Characterized by **t(8;14)**, **c-MYC** activation, and a "Starry Sky" appearance. * **CD34 & TdT:** Always think of **Acute** Lymphoblastic Leukemia/Lymphoma (blasts) rather than mature lymphomas. [1] **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] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 563-564. [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. 602-604. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 562-563. [5] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 561-562.
Question 584: Which of the following is NOT a good prognostic factor for Acute Myeloid Leukemia (AML)?
- A. Age less than 2 years
- B. Acute promyelocytic leukemia (APL)
- C. Acute megakaryoblastic leukemia (AMkL) (Correct Answer)
- D. Associated with Down syndrome
Explanation: ### Explanation In Acute Myeloid Leukemia (AML), prognosis is determined by cytogenetic abnormalities, age, and underlying clinical conditions [1]. **1. Why Acute Megakaryoblastic Leukemia (AMkL - M7) is the Correct Answer:** AMkL (FAB classification M7) is generally associated with a **poor prognosis**, especially when it occurs in adults or non-Down syndrome children. It often presents with extensive bone marrow fibrosis (myelofibrosis) and is frequently associated with high-risk cytogenetic abnormalities like t(1;22) or complex karyotypes, making it resistant to standard chemotherapy compared to other subtypes. **2. Analysis of Incorrect Options (Good Prognostic Factors):** * **Age < 2 years:** In the pediatric population, very young age (infants/toddlers) often correlates with specific subtypes like Down syndrome-associated AML, which responds exceptionally well to low-dose cytarabine. * **Acute Promyelocytic Leukemia (APL - M3):** This is considered the **best prognostic subtype** of AML [1]. The use of All-trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO) targets the underlying t(15;17) translocation, leading to extremely high cure rates (>90%) [3]. * **Associated with Down Syndrome:** Children with Down syndrome who develop AML (usually the M7 subtype) have a significantly **better prognosis** than non-Down syndrome children with the same subtype. They exhibit increased sensitivity to chemotherapeutic agents like Cytarabine due to GATA1 mutations. **High-Yield Clinical Pearls for NEET-PG:** * **Best Prognosis:** t(15;17) [APL], t(8;21), and inv(16) [1]. * **Poor Prognosis:** Monosomy 5 or 7, 11q23 rearrangements (MLL gene) [1], and AML secondary to prior chemotherapy or MDS [2]. * **Down Syndrome Link:** Children with Down syndrome are at a 10-20 fold increased risk of leukemia; they typically develop **TMD (Transient Myeloproliferative Disorder)** in the neonatal period and **AMkL** before age 5. **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. 620. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 607-608. [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. 620-621.
Question 585: All of the following statements about Fanconi's anemia are true, EXCEPT?
- A. Autosomal dominant inheritance (Correct Answer)
- B. Hypocellular Bone Marrow
- C. Congenital Anomalies
- D. Usually normocytic / macrocytic cell morphology
Explanation: ### Explanation **Fanconi’s Anemia (FA)** is the most common form of inherited aplastic anemia [1]. The correct answer is **Option A** because Fanconi’s anemia is primarily an **Autosomal Recessive** disorder (though rare X-linked and autosomal dominant subtypes exist, the classic inheritance pattern tested in exams is recessive). It is caused by mutations in the FANC gene family, leading to defects in DNA repair (specifically inter-strand cross-link repair). **Analysis of Options:** * **Option A (Incorrect Statement):** As stated, the inheritance is typically **Autosomal Recessive**. This defect leads to chromosomal instability, which is diagnostic when cells are exposed to DNA-crosslinking agents like Mitomycin C or Diepoxybutane. * **Option B (True):** FA leads to progressive bone marrow failure. The marrow becomes **hypocellular**, with hematopoietic stem cells being replaced by fat cells, resulting in pancytopenia [2]. * **Option C (True):** Approximately 70% of patients have **congenital anomalies**, most characteristically **thumb and radius defects**, short stature, microcephaly, and "café-au-lait" spots. * **Option D (True):** The anemia in FA is typically **macrocytic** (elevated MCV) or normocytic [2]. Macrocytosis is often the earliest hematologic sign, preceding the drop in hemoglobin. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Test:** Chromosomal breakage analysis (using Mitomycin C). * **Cancer Risk:** Patients have a significantly high risk of developing **AML** (Acute Myeloid Leukemia) and squamous cell carcinomas (head, neck, and anogenital). * **Physical Exam Triad:** Short stature + Thumb/Radial defects + Skin hyperpigmentation (Café-au-lait spots). * **Treatment:** Bone marrow transplant is the definitive treatment for hematologic complications. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 595-596. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 662-663.
Question 586: Macropolycyte in a peripheral smear is a feature of which of the following conditions?
- A. Hereditary spherocytosis
- B. Iron deficiency anemia
- C. Sickle cell anemia
- D. Megaloblastic anemia (Correct Answer)
Explanation: **Explanation:** **Megaloblastic anemia** is the correct answer. The hallmark of this condition is **impaired DNA synthesis** [2] (most commonly due to Vitamin B12 or Folate deficiency), which leads to "nuclear-cytoplasmic asynchrony." While the cytoplasm matures normally, the nucleus remains immature and large [1]. This results in the formation of **Macropolycytes**, which are abnormally large neutrophils (usually >12μm) that are typically **hypersegmented** (containing 6 or more nuclear lobes) [1], [2]. These are among the earliest peripheral blood findings in megaloblastic anemia. **Analysis of Incorrect Options:** * **A. Hereditary Spherocytosis:** Characterized by spherical, small, dense red cells (spherocytes) due to membrane protein defects (e.g., Ankyrin). It does not involve neutrophil morphology. * **B. Iron Deficiency Anemia:** A microcytic hypochromic anemia. The peripheral smear typically shows small RBCs with increased central pallor and occasionally "pencil cells," but not macropolycytes. * **C. Sickle Cell Anemia:** Characterized by sickle-shaped RBCs (drepanocytes) and Howell-Jolly bodies due to hemoglobin polymerization (HbS). Neutrophil morphology remains largely unaffected. **High-Yield Clinical Pearls for NEET-PG:** * **Definition of Hypersegmentation:** Presence of even a single neutrophil with $\geq$ 6 lobes, or $>5\%$ of neutrophils with 5 lobes. * **Earliest Sign:** Hypersegmented neutrophils often appear in the peripheral smear *before* the onset of macrocytic anemia. * **Pancytopenia:** Severe megaloblastic anemia can present with low counts across all cell lines (RBCs, WBCs, and Platelets) due to ineffective hematopoiesis [1]. * **MCV:** Typically elevated (>100 fL). **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 593-594. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 654-655.
Question 587: In beta-thalassemia trait, what does electrophoresis typically show?
- A. Increased HbF and normal HbA2
- B. Normal HbF and normal HbA2
- C. Normal HbF and increased HbA2 (Correct Answer)
- D. Decreased HbF and normal HbA2
Explanation: **Explanation:** **1. Why the Correct Answer is Right:** Beta-thalassemia trait (Beta-thalassemia minor) is caused by a heterozygous mutation in one of the two beta-globin genes ($\beta/\beta^+$ or $\beta/\beta^0$). This results in a mild reduction in $\beta$-chain synthesis. To compensate for the lack of $\beta$-chains, there is a relative increase in the synthesis of alternative globin chains. Specifically, the excess $\alpha$-chains bind with $\delta$-chains to form **HbA2 ($\alpha_2\delta_2$)**. * **Diagnostic Hallmark:** An **HbA2 level >3.5%** (typically 4–8%) is the most reliable diagnostic finding on electrophoresis for Beta-thalassemia trait. * **HbF ($\alpha_2\gamma_2$):** While HbF can be slightly elevated in some cases, it is **typically normal** or only minimally increased (1–5%) in the trait form. **2. Why the Incorrect Options are Wrong:** * **Option A & D:** HbF is usually normal in the trait. Significant increases in HbF (>10–90%) are characteristic of **Beta-thalassemia Major**, not the trait [1]. Decreased HbF is not a feature of thalassemias. * **Option B:** Normal HbA2 levels (usually 1.5–3.5%) would rule out Beta-thalassemia trait. If a patient has microcytic anemia with normal HbA2, one must consider Iron Deficiency Anemia (IDA) or $\alpha$-thalassemia [1]. **3. NEET-PG High-Yield Pearls:** * **Mentzer Index:** (MCV/RBC count) <13 suggests Thalassemia; >13 suggests Iron Deficiency Anemia. * **Peripheral Smear:** Shows microcytic hypochromic cells with **Target cells** and basophilic stippling. * **Confounding Factor:** Co-existing **Iron Deficiency** can normalize HbA2 levels in a Thalassemia patient, potentially masking the diagnosis. Always replenish iron before confirming the trait via electrophoresis. * **HbA1:** In Beta-thalassemia trait, HbA1 is slightly decreased but remains the major hemoglobin fraction. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 600-601.
Question 588: Bleeding time is prolonged in which of the following conditions?
- A. Von Willebrand's disease (Correct Answer)
- B. Christmas disease
- C. Hemophilia
- D. Polycythemia
Explanation: **Explanation:** **Bleeding Time (BT)** is a clinical test that measures the **primary hemostatic response**, which depends on two factors: adequate platelet numbers and functional platelet-vessel wall interaction [4]. 1. **Why Von Willebrand’s Disease (vWD) is correct:** vWD is the most common inherited bleeding disorder. Von Willebrand Factor (vWF) is essential for **platelet adhesion** to the subendothelial collagen (via GpIb receptors) [3]. In vWD, the deficiency or dysfunction of vWF impairs this initial platelet plug formation, leading to a **prolonged Bleeding Time**. Additionally, because vWF stabilizes Factor VIII, the aPTT may also be prolonged [2]. 2. **Why the other options are incorrect:** * **Christmas Disease (Hemophilia B) & Hemophilia A:** These are disorders of **secondary hemostasis** (clotting cascade). They involve deficiencies of Factor IX and Factor VIII, respectively. Since platelet function and vessel integrity are normal, the **Bleeding Time is normal**, but the aPTT is prolonged. * **Polycythemia:** This is characterized by an increased red cell mass. While it can lead to thrombotic or hemorrhagic complications due to hyperviscosity or acquired platelet dysfunction in some myeloproliferative forms, it is not a classic cause of prolonged BT in the context of standard competitive exams. **High-Yield Clinical Pearls for NEET-PG:** * **BT vs. CT:** Bleeding Time = Platelet function; Clotting Time = Coagulation factors. * **Bernard-Soulier Syndrome:** Prolonged BT with giant platelets (Deficiency of GpIb) [1]. * **Glanzmann Thrombasthenia:** Prolonged BT (Deficiency of GpIIb/IIIa) [1]. * **Aspirin:** The most common pharmacological cause of prolonged BT (irreversible inhibition of COX-1). * **vWD Triad:** ↑ BT, ↑ aPTT (sometimes), and normal Platelet Count. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 669-670. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 619-620.
Question 589: Which of the following tests may be abnormal in disseminated intravascular coagulation (DIC), except?
- A. Prothrombin time (PT)
- B. Activated partial thromboplastin time (APTT)
- C. D-dimer
- D. Clot solubility (Correct Answer)
Explanation: **Explanation:** Disseminated Intravascular Coagulation (DIC) is a complex consumptive coagulopathy characterized by systemic activation of the coagulation cascade, leading to the formation of microthrombi and subsequent depletion of clotting factors and platelets [1]. **Why Clot Solubility is the Correct Answer:** The **Clot Solubility Test** (using 5M urea or monochloroacetic acid) is a specific screening test for **Factor XIII deficiency**. In DIC, while many clotting factors are consumed, the primary pathology involves the consumption of fibrinogen and factors II, V, and VIII [1]. Factor XIII deficiency is not a hallmark of DIC diagnosis; therefore, the clot solubility test remains normal. **Analysis of Incorrect Options:** * **Prothrombin Time (PT) & APTT:** These are **prolonged** in DIC due to the systemic consumption of coagulation factors (Factor V, VIII, X, and Prothrombin) and the interference of Fibrin Degradation Products (FDPs) with fibrin polymerization [1]. * **D-dimer:** This is the **most sensitive** marker for DIC. It indicates that not only has a clot formed (thrombin activation), but it is also being broken down (plasmin activation) [2]. Elevated D-dimer levels confirm reactive fibrinolysis. **High-Yield Clinical Pearls for NEET-PG:** * **Peripheral Smear:** Look for **Schistocytes** (fragmented RBCs), indicating microangiopathic hemolytic anemia (MAHA) [1]. * **Platelet Count:** Characteristically **decreased** (Thrombocytopenia) [1]. * **Fibrinogen:** One of the few markers that **decreases** (acute phase reactant, but consumption overrides production in DIC) [1]. * **Best Screening Test:** Platelet count + PT + D-dimer. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 625-626. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 151-152.
Question 590: What is the primary cause of red blood cell sickling in sickle cell disease?
- A. Decreased hemoglobin solubility (Correct Answer)
- B. Decreased hemoglobin stability
- C. Altered hemoglobin function
- D. Altered oxygen binding capacity of hemoglobin
Explanation: **Explanation:** The primary pathophysiology of sickle cell disease (SCD) involves a point mutation in the $\beta$-globin gene, where **valine** replaces **glutamic acid** at the 6th position [1]. This substitution creates a hydrophobic patch on the surface of the hemoglobin molecule. **Why Option A is Correct:** The hallmark of Sickle Hemoglobin (HbS) is its **decreased solubility** in the deoxygenated state [1]. When oxygen levels drop, HbS molecules undergo conformational changes that allow them to polymerize into long, stiff, needle-like fibers [2]. These polymers distort the red blood cell into the characteristic "sickle" shape, leading to vaso-occlusion and hemolysis [1], [2]. **Why Other Options are Incorrect:** * **B. Decreased hemoglobin stability:** This typically refers to **unstable hemoglobins** (e.g., Hb Köln), which precipitate to form Heinz bodies. While HbS is less stable than HbA, the primary driver of sickling is polymerization due to insolubility, not spontaneous denaturation. * **C. Altered hemoglobin function:** While HbS function is technically altered, this is a broad, non-specific term. The specific mechanism required for the "sickling" morphology is the physical change in solubility. * **D. Altered oxygen binding capacity:** Although the oxygen dissociation curve is shifted to the right in SCD (facilitating oxygen release), this is a physiological consequence rather than the primary cause of the physical sickling process. **NEET-PG High-Yield Pearls:** * **Mutation:** Missense mutation (GAG $\rightarrow$ GTG) on Chromosome 11. * **Factors promoting sickling:** Hypoxia, acidosis, dehydration (increased MCHC), and increased 2,3-BPG [2]. * **Protective factor:** **HbF (Fetal Hemoglobin)** inhibits polymerization; hence, Hydroxyurea is used in treatment to increase HbF levels. * **Metabisulfite test:** Used to induce sickling in vitro for screening. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 643-644, 652-654.
Practice by Chapter
Anemias: Classification and Approach
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Hemolytic Anemias
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Myeloproliferative Neoplasms
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Myelodysplastic Syndromes
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Acute Leukemias
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Chronic Leukemias
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Lymphomas and Lymphoid Neoplasms
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Plasma Cell Disorders
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Bleeding Disorders
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Thrombotic Disorders
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