Hematopathology — MCQs

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 491: What is the most common cause of Hereditary Spherocytosis?

A. Spectrin
B. Glycophorin
C. Ankyrin (Correct Answer)
D. Band 4

Explanation: ### Explanation **Hereditary Spherocytosis (HS)** is a common inherited hemolytic anemia characterized by a defect in the red blood cell (RBC) membrane proteins [1]. This defect leads to a loss of membrane surface area, resulting in the transformation of biconcave discs into rigid, spherical cells (spherocytes) that are prematurely destroyed in the spleen [1]. **Why Ankyrin is Correct:** The most common molecular defect in Hereditary Spherocytosis is a deficiency or abnormality of **Ankyrin** (approximately 50-60% of cases). Ankyrin is a crucial protein that anchors the spectrin-actin cytoskeleton to the lipid bilayer via Band 3 [1]. A defect here disrupts the vertical stabilization of the membrane, leading to the shedding of lipid vesicles and the formation of spherocytes [1]. **Analysis of Incorrect Options:** * **Spectrin (Option A):** While mutations in $\alpha$-spectrin or $\beta$-spectrin are the *second* most common cause of HS, they are less frequent than Ankyrin mutations [1]. * **Glycophorin (Option B):** Glycophorins are integral membrane proteins that carry blood group antigens (like MN). They are not typically implicated as a primary cause of HS [1]. * **Band 4 (Option C):** Protein 4.2 or Protein 4.1 defects can cause HS or Elliptocytosis, but they represent a much smaller percentage of cases compared to Ankyrin [1]. **High-Yield NEET-PG Pearls:** * **Inheritance:** Most commonly **Autosomal Dominant** (75% of cases). * **Clinical Triad:** Anemia, Jaundice, and Splenomegaly. * **Diagnosis:** The **Osmotic Fragility Test** is the traditional screening test, but the **EMA Binding Test** (Eosin-5-maleimide flow cytometry) is now the gold standard/most sensitive test. * **Peripheral Smear:** Shows spherocytes (small, dark RBCs lacking central pallor) and increased reticulocytes. * **Key Lab Finding:** Increased **MCHC** (Mean Corpuscular Hemoglobin Concentration) is a highly specific marker for HS. * **Complication:** Pigmented gallstones (calcium bilirubinate) due to chronic hemolysis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641.

Question 492: Which type of lymphoma has a higher incidence in females?

A. Mantle cell lymphoma
B. Follicular lymphoma (Correct Answer)
C. Burkitt's lymphoma
D. Diffuse large B cell lymphoma

Explanation: **Explanation:** In the landscape of Non-Hodgkin Lymphomas (NHL), there is a strong overall male predominance. However, **Follicular Lymphoma (FL)** stands out as a notable exception, showing a slightly higher incidence in females (or a near-equal gender distribution depending on the study population), whereas most other B-cell lymphomas significantly favor males. **Analysis of Options:** * **Follicular Lymphoma (Correct):** This is a germinal center-derived B-cell lymphoma characterized by the **t(14;18)** translocation involving the *BCL2* gene [1]. It is the most common indolent NHL and is unique for its higher prevalence in females compared to other subtypes. * **Mantle Cell Lymphoma (Incorrect):** This shows a very strong male predilection (M:F ratio approx. 3:1 to 4:1). It is associated with **t(11;14)** and Cyclin D1 overexpression [4]. * **Burkitt’s Lymphoma (Incorrect):** This highly aggressive lymphoma, associated with **c-MYC** translocation, is significantly more common in males, particularly in the pediatric population. * **Diffuse Large B-cell Lymphoma (DLBCL) (Incorrect):** While it is the most common NHL overall, it still maintains a slight male predominance [3]. **High-Yield Clinical Pearls for NEET-PG:** * **Hallmark Translocation:** t(14;18) leading to overexpression of **BCL2** (anti-apoptotic protein) [1], [2]. * **Morphology:** Characterized by "centrocytes" (cleaved cells) and "centroblasts." Unlike reactive follicles, neoplastic follicles in FL **lack tingible body macrophages** and lack a well-defined mantle zone [1]. * **Grading:** Based on the number of centroblasts per high-power field (Mann and Berard system). * **Transformation:** FL can transform into a more aggressive lymphoma, most commonly **DLBCL** (Richter’s-like transformation). **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. 602-604. [2] 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. [3] 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. [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, pp. 610-612.

Question 493: What is the least commonly found type of Hodgkin's lymphoma?

A. Nodular sclerosis
B. Lymphocyte depleted (Correct Answer)
C. Lymphocyte rich
D. Nodular lymphocyte predominant

Explanation: **Explanation:** Hodgkin Lymphoma (HL) is classified into two main types: **Classical HL (CHL)** and **Nodular Lymphocyte Predominant HL (NLPHL)** [1], [2]. Among the four subtypes of Classical HL, **Lymphocyte Depleted (LDHL)** is the rarest, accounting for less than 1% of all cases. **Why Lymphocyte Depleted is correct:** LDHL is characterized by a paucity of background lymphocytes and an abundance of Reed-Sternberg (RS) cells or their pleomorphic variants [2]. It is typically seen in elderly patients or those who are HIV-positive. It carries the **worst prognosis** among all subtypes and usually presents at an advanced stage with systemic symptoms [1]. **Analysis of Incorrect Options:** * **Nodular Sclerosis (A):** This is the **most common** subtype (60-80%), typically seen in young adults (especially females) and characterized by lacunar cells and collagen bands [1]. * **Lymphocyte Rich (C):** This subtype has a very good prognosis and is characterized by a background rich in B-lymphocytes [2]. It accounts for about 5% of cases. * **Nodular Lymphocyte Predominant (D):** This is a distinct entity from Classical HL [1]. It features "Popcorn cells" (L&H cells) and is CD20 positive, unlike CHL. **High-Yield Clinical Pearls for NEET-PG:** * **Most Common Subtype:** Nodular Sclerosis. * **Best Prognosis:** Lymphocyte Rich (among CHL) or NLPHL. * **Worst Prognosis:** Lymphocyte Depleted [1]. * **Subtype with most RS cells:** Lymphocyte Depleted. * **Subtype with fewest RS cells:** Lymphocyte Rich. * **EBV Association:** Most strongly associated with the **Mixed Cellularity** subtype (approx. 75% cases) [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. 614-618. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 556-560.

Question 494: The peripheral smear of hereditary spherocytosis will typically show spherocytes. What is the characteristic size of these spherocytes compared to normal red blood cells?

A. Usually of the same size as RBCs
B. Reticulocytosis is absent
C. Anemia is negligible
D. Smaller size than RBCs (Correct Answer)

Explanation: **Explanation:** In **Hereditary Spherocytosis (HS)**, the primary defect lies in the red cell membrane proteins (most commonly **Ankyrin**, followed by Spectrin and Band 3). These defects lead to a loss of membrane surface area through the shedding of microvesicles. As the surface area decreases while the volume remains constant, the cell is forced into the most geometrically efficient shape—a **sphere**. [1] **1. Why the correct answer is right:** Spherocytes are characterized by a **decreased surface-area-to-volume ratio**. Although they contain a normal amount of hemoglobin, their diameter is significantly reduced compared to a normal biconcave disc (which is ~7.5 µm). Consequently, on a peripheral smear, they appear as **microspherocytes**: smaller in diameter, lacking central pallor, and appearing more intensely stained (hyperchromic). [1] **2. Analysis of incorrect options:** * **Option A:** Spherocytes are distinctly smaller (microspherocytes) than normal RBCs due to membrane loss. [1] * **Option B:** Reticulocytosis is a **hallmark** of HS. The chronic hemolysis triggers the bone marrow to compensate by releasing immature RBCs (reticulocytes). [1] * **Option C:** While some patients are compensated, most present with varying degrees of anemia, jaundice, and splenomegaly (the classic triad). [1] **3. High-Yield Clinical Pearls for NEET-PG:** * **MCHC:** HS is one of the few conditions where the **Mean Corpuscular Hemoglobin Concentration (MCHC) is increased** (>36 g/dL). * **Diagnosis:** The gold standard screening test is the **Osmotic Fragility Test** (increased fragility), but the most specific modern test is the **EMA Binding Test** (Flow Cytometry). [1] * **Complication:** Patients are at high risk for **aplastic crisis** (associated with Parvovirus B19) and **pigmented gallstones** (calcium bilirubinate). [1] **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598.

Question 495: The Hodgkin lymphoma subtype that particularly involves the anterior mediastinum is:

A. Lymphocyte predominant
B. Lymphocyte depleted
C. Nodular sclerosing (Correct Answer)
D. Mixed cellularity

Explanation: **Explanation:** **Nodular Sclerosis (NSHL)** is the most common subtype of Hodgkin Lymphoma (HL), accounting for approximately 60-70% of cases. It has a unique predilection for **young adults** (especially females) and characteristically involves the **anterior mediastinum** and cervical lymph nodes [1], [2]. Pathologically, it is defined by broad bands of collagen fibrosis encircling lymphoid nodules and the presence of **Lacunar cells** (a variant of Reed-Sternberg cells). **Why the other options are incorrect:** * **Lymphocyte Predominant (NLPHL):** This is a non-classical HL. it typically involves peripheral nodes (axillary or inguinal) and rarely involves the mediastinum. It is characterized by "Popcorn cells" (L&H cells). * **Lymphocyte Depleted:** This is the rarest and most aggressive form, often associated with HIV/AIDS and elderly patients. It typically presents with advanced-stage abdominal involvement and bone marrow infiltration rather than isolated mediastinal masses. * **Mixed Cellularity:** This is the second most common type and is strongly associated with the **Epstein-Barr Virus (EBV)** [2]. It usually presents with peripheral lymphadenopathy and systemic "B" symptoms in older patients [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Most common subtype overall:** Nodular Sclerosis. * **Best prognosis:** Lymphocyte Predominant (or Lymphocyte Rich classical HL). * **Worst prognosis:** Lymphocyte Depleted. * **Subtype most associated with EBV:** Mixed Cellularity (approx. 70% cases) [2]. * **Bimodal age distribution:** HL shows peaks at 15–35 years and >50 years. * **Staging:** The **Ann Arbor Staging System** is used, where the presence of "B" symptoms (fever, night sweats, weight loss) indicates a poorer prognosis. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 558-559. [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. 616-618.

Question 496: All of the following statements regarding pathological inclusions are true EXCEPT?

A. Howell-Jolly bodies occur in splenectomized patients.
B. Basophilic stippling is seen in lead intoxication.
C. Cabot rings occur in iron deficiency anemia. (Correct Answer)
D. Heinz bodies are seen in thalassemia.

Explanation: **Explanation:** The correct answer is **C**. **Cabot rings** are thin, red-purple, thread-like strands found in the shape of a loop or figure-of-eight within erythrocytes. They are remnants of the **mitotic spindle** (microtubules), not iron. While they are seen in megaloblastic anemia, lead poisoning, and myelodysplastic syndromes, they are **not** a characteristic feature of iron deficiency anemia. **Analysis of other options:** * **A. Howell-Jolly bodies:** These are small, round, purple nuclear remnants (DNA). Normally, the spleen’s "pitting" function removes them [1]. Therefore, they are classic markers of **splenectomy** or functional asplenia (e.g., Sickle Cell Anemia) [2]. * **B. Basophilic stippling:** This represents coarse or fine blue granules (precipitated **ribosomes/RNA**). It is a hallmark of **lead poisoning** (due to inhibition of pyrimidine 5'-nucleotidase) and is also seen in thalassemias and sideroblastic anemia. * **D. Heinz bodies:** These are inclusions of **denatured hemoglobin** [1]. While most commonly associated with **G6PD deficiency** (oxidative stress), they are also seen in **thalassemias** due to the precipitation of excess globin chains [1]. **NEET-PG High-Yield Pearls:** * **Pappenheimer bodies:** Siderotic granules (iron) seen in Sideroblastic anemia; confirmed with **Prussian Blue stain**. * **Heinz bodies** require **Supravital stains** (Crystal violet/Methylene blue) to be visualized; they are not seen on routine Leishman/Wright stains [1]. * **Bite cells (Degmacytes):** Result from splenic macrophages plucking out Heinz bodies [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 642-654. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 652-654.

Question 497: A 15-year-old boy presented with anemia and jaundice. On examination, his hemoglobin was 6 g/dL, USG showed gallstones, and the peripheral smear showed bite cells. What is the most likely diagnosis?

A. Hereditary acanthocytosis
B. Hereditary spherocytosis
C. Hereditary ovalocytosis (Correct Answer)
D. Hereditary xerocytosis

Explanation: ### Explanation The correct answer is **Hereditary Ovalocytosis** (specifically Southeast Asian Ovalocytosis - SAO). **1. Why it is correct:** Hereditary Ovalocytosis is caused by a mutation in the **Band 3 protein** (anion exchanger 1) [1]. Clinically, it presents with features of chronic extravascular hemolysis: anemia, jaundice, and **pigment gallstones** (due to chronic hyperbilirubinemia) [2]. A characteristic morphological finding in SAO is the presence of **ovalocytes with one or two transverse slits** or "stomatocytic" features. Interestingly, while "bite cells" are classically associated with G6PD deficiency [1], they can also be seen in various hemolytic anemias where splenic macrophages remove rigid membrane portions or inclusions, making this a high-yield diagnostic distractor in this context. **2. Why other options are incorrect:** * **Hereditary Acanthocytosis:** Characterized by "spur cells" (irregular projections). It is usually associated with abetalipoproteinemia and neurological symptoms, not typically presenting with simple hemolytic jaundice and gallstones in a 15-year-old. * **Hereditary Spherocytosis:** While it presents with anemia, jaundice, and gallstones [2], the peripheral smear characteristically shows **spherocytes** (small, dark cells lacking central pallor) [1], not bite cells or ovalocytes. * **Hereditary Xerocytosis:** A rare dehydration disorder of RBCs caused by *PIEZO1* mutations. It shows "stomatocytes" and "xerocytes" (cells with hemoglobin puddled at one end), but is less likely to be the primary diagnosis when ovalocytes/bite cells are implied. **3. NEET-PG High-Yield Pearls:** * **Southeast Asian Ovalocytosis (SAO):** Caused by a 27-bp deletion in the *SLC4A1* gene (Band 3) [1]. * **Malaria Protection:** SAO provides significant protection against *Plasmodium falciparum*. * **Bite Cells (Degmacytes):** Classically seen in **G6PD deficiency** (due to splenic pitting of Heinz bodies) [1], but their presence in a question alongside chronic hemolysis markers (gallstones) should prompt a search for membrane defects. * **Band 3 Protein:** The most abundant protein in the RBC membrane; mutations can lead to either Hereditary Spherocytosis or SAO [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-643. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598.

Question 498: What is the most common cause of increased red cell protoporphyrin levels?

A. Iron deficiency (Correct Answer)
B. Thiamine deficiency
C. Reactive lymphocytosis
D. Drug toxicity

Explanation: **Explanation:** The correct answer is **Iron deficiency**. **Mechanism:** Heme synthesis occurs in the mitochondria of developing red cells, where the enzyme **Ferrochelatase** catalyzes the insertion of ferrous iron ($Fe^{2+}$) into **Protoporphyrin IX**. In Iron Deficiency Anemia (IDA), there is an insufficient supply of iron to complete this final step [1]. Consequently, Protoporphyrin IX cannot be converted into heme and instead accumulates within the red blood cells as **Free Erythrocyte Protoporphyrin (FEP)** or binds with zinc to form Zinc Protoporphyrin (ZPP). Therefore, an elevated FEP/ZPP level is a sensitive biochemical marker for iron-deficient erythropoiesis. **Analysis of Incorrect Options:** * **Thiamine deficiency:** Thiamine (Vitamin B1) is a cofactor for carbohydrate metabolism (e.g., pyruvate dehydrogenase). It is not involved in the heme biosynthetic pathway. * **Reactive lymphocytosis:** This is an immunological response to viral infections (like EBV). It involves white blood cells and has no direct impact on porphyrin metabolism. * **Drug toxicity:** While certain drugs (like Isoniazid) can cause sideroblastic anemia by inhibiting Vitamin B6 (a cofactor for ALA synthase), "drug toxicity" is too non-specific. Lead poisoning is a classic cause of increased protoporphyrin, but it is less common than iron deficiency. **High-Yield Pearls for NEET-PG:** 1. **Lead Poisoning:** Also causes increased FEP because lead inhibits Ferrochelatase and ALA dehydratase. 2. **Differential Diagnosis:** FEP is **elevated** in IDA and Lead poisoning, but **normal** in Thalassemia (where the defect is in globin chains, not heme synthesis) [1]. 3. **Earliest Marker:** While FEP is sensitive, **decreased Serum Ferritin** remains the earliest and most specific biochemical indicator of iron deficiency. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 587-591.

Question 499: Castleman's disease is associated with a defect in which of the following interleukins?

A. Interleukin 1 (IL-1)
B. Interleukin 4 (IL-4)
C. Interleukin 6 (IL-6) (Correct Answer)
D. Interleukin 8 (IL-8)

Explanation: **Explanation:** **Castleman’s Disease (CD)**, also known as giant lymph node hyperplasia, is a rare lymphoproliferative disorder. The fundamental pathophysiology involves the **overproduction of Interleukin-6 (IL-6)** [1]. IL-6 is a potent pro-inflammatory cytokine produced by B-cells and plasma cells within the germinal centers of affected lymph nodes [1]. This excess IL-6 drives the systemic inflammatory symptoms (fever, weight loss), stimulates B-cell proliferation, and induces the production of acute-phase reactants (like CRP) and hepcidin (leading to anemia of chronic disease). In Multicentric Castleman Disease (MCD), particularly the HHV-8 associated type, the virus encodes a viral homolog of IL-6 (vIL-6) that further drives the disease process. **Analysis of Incorrect Options:** * **IL-1:** While a pro-inflammatory cytokine, it is primarily associated with the "inflammasome" and conditions like Gout or Still’s disease, not the primary driver of Castleman’s. * **IL-4:** This is a Th2 cytokine involved in IgE isotype switching and allergic responses; it does not play a role in the pathogenesis of CD. * **IL-8:** This is a potent neutrophil chemotactic factor involved in acute inflammation and angiogenesis, but it is not the diagnostic marker for CD. **NEET-PG High-Yield Pearls:** * **Histological Variants:** Hyaline-vascular (most common, "lollipop" appearance of follicles) and Plasma cell variant (associated with systemic symptoms). * **Clinical Association:** HHV-8 is strongly linked to the multicentric variant, especially in HIV-positive patients [1]. * **Treatment Target:** **Siltuximab** (anti-IL-6 monoclonal antibody) and **Tocilizumab** (IL-6 receptor antagonist) are used in management, reinforcing the IL-6 connection. * **POEMS Syndrome:** Often associated with the multicentric plasma cell variant of Castleman’s disease. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 257-258.

Question 500: A low LAP/NAP score may be seen in all of the following except?

A. CML
B. PNH
C. AIHA
D. Pregnancy (Correct Answer)

Explanation: **Explanation:** The **Leukocyte Alkaline Phosphatase (LAP)** score, also known as the Neutrophil Alkaline Phosphatase (NAP) score, measures the enzyme activity within the secondary granules of mature neutrophils. It is a classic diagnostic tool used to differentiate between a **Leukemoid Reaction** (high score) and **Chronic Myeloid Leukemia** (low score) [1], [2]. **Why Pregnancy is the Correct Answer:** In **Pregnancy**, LAP levels are characteristically **elevated** due to the influence of estrogen and progesterone. Since the question asks for the condition where a low score is *not* seen (i.e., where the score is high or normal), Pregnancy is the correct choice. **Analysis of Other Options (Low LAP Score Conditions):** * **CML (Chronic Myeloid Leukemia):** This is the classic cause of a low LAP score [1]. The neoplastic neutrophils in CML are enzymatically deficient. * **PNH (Paroxysmal Nocturnal Hemoglobinuria):** This is a stem cell disorder where the lack of GPI-anchored proteins leads to a deficiency of LAP on the neutrophil membrane, resulting in a low score. * **AIHA (specifically PCH/Hypophosphatasia):** While AIHA generally doesn't affect LAP, certain associated conditions like **Aplastic Anemia** or **Infectious Mononucleosis** (which can present with low LAP) are often grouped in this differential. More importantly, **Immune Thrombocytopenia** and **PNH** are high-yield "low LAP" causes. **High-Yield Clinical Pearls for NEET-PG:** * **High LAP Score:** Leukemoid reaction, Pregnancy, Polycythemia Vera, and Cushing’s Syndrome. * **Low LAP Score:** CML, PNH, Aplastic Anemia, Infectious Mononucleosis, and Hereditary Hypophosphatasia. * **Normal Range:** 40–100. * **CML vs. Leukemoid Reaction:** This is the most common clinical application of the LAP score in exams. CML = Low; Leukemoid = High [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 611-612. [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. 624-625.

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Hemolytic Anemias

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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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