Hematopathology — MCQs

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 1091: Marked bleeding is seen in which of the following conditions?

A. VMA disease
B. Haemophilia A
C. Haemophilia B
D. All of the above (Correct Answer)

Explanation: ### Explanation The correct answer is **D. All of the above**. The underlying medical concept here is the impairment of the **coagulation cascade**, specifically the intrinsic pathway, which leads to a failure in forming a stable fibrin clot. This results in a severe bleeding diathesis characterized by deep tissue hemorrhages, hemarthrosis (bleeding into joints), and prolonged bleeding after minor trauma [1], [3]. * **Haemophilia A:** This is an X-linked recessive disorder caused by a deficiency of **Factor VIII** [2], [3]. It is the most common hereditary disease associated with life-threatening bleeding [3]. The clinical picture involves recurrent spontaneous haemarthrosis and soft tissue haemorrhage [1]. * **Haemophilia B (Christmas Disease):** This is an X-linked recessive disorder caused by a deficiency of **Factor IX** [3]. Clinically, it is indistinguishable from Haemophilia A and also presents with marked bleeding tendencies [3]. * **VMA Disease (Von Willebrand Disease):** While often presenting with mucosal bleeding (epistaxis, menorrhagia), severe forms (especially Type 3) or cases with significantly low levels of **von Willebrand Factor (vWF)** lead to a secondary deficiency of Factor VIII (since vWF stabilizes Factor VIII) [3]. This results in a clinical picture of marked bleeding similar to hemophilia. #### **High-Yield Clinical Pearls for NEET-PG:** * **Lab Findings:** In all three conditions, the **Activated Partial Thromboplastin Time (aPTT)** is prolonged, while the Prothrombin Time (PT) and Platelet count are typically normal. * **Bleeding Time (BT):** BT is **prolonged in vWD** (due to platelet adhesion defect) but **normal in Haemophilia A and B**. * **Mixing Studies:** If aPTT corrects with normal plasma, it indicates a factor deficiency; if it doesn't, it suggests an inhibitor. * **Treatment:** Recombinant Factor VIII for Haemophilia A; Factor IX concentrate for Haemophilia B; Desmopressin (DDAVP) or vWF concentrate for vWD. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 623-624. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 670-671. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 622-623.

Question 1092: Which of the following is NOT typically seen in sickle cell disease?

A. Gamma Gandy bodies
B. Moderate to massive splenomegaly (Correct Answer)
C. Fish mouth vertebra
D. Decreased ESR

Explanation: In Sickle Cell Disease (SCD), the hallmark pathological process involving the spleen is **autosplenectomy**, not splenomegaly [1]. ### Why "Moderate to massive splenomegaly" is the correct answer: In the early years of life, children with SCD may exhibit splenomegaly due to red cell sequestration [3]. However, repeated episodes of microvascular occlusion and splenic infarction (due to sickling in the hypoxic, acidic environment of the splenic cords) lead to progressive fibrosis and shrinkage [2]. By adulthood, the spleen becomes a small, shrunken, siderofibrotic remnant [2][3]. This process is called **autosplenectomy**. Massive splenomegaly is characteristic of conditions like Myelofibrosis or Chronic Myeloid Leukemia, but not adult SCD. ### Explanation of other options: * **Gamma Gandy bodies:** These are small, brown-yellow siderofibrotic nodules containing calcium and hemosiderin deposits. They are frequently found in the spleens of SCD patients due to organized focal hemorrhages. * **Fish mouth vertebra:** Chronic compensatory erythroid hyperplasia causes expansion of the bone marrow [3]. This leads to thinning of the cortical bone and biconcave indentation of the vertebral bodies (codfish vertebrae), a classic radiological finding in SCD. * **Decreased ESR:** Sickled cells are unable to form "rouleaux" (stacks of RBCs) due to their abnormal shape. Since rouleaux formation is necessary to increase the sedimentation rate, the **ESR is characteristically low** in SCD. ### High-Yield Clinical Pearls for NEET-PG: * **Howell-Jolly Bodies:** Their presence on a peripheral smear is a functional indicator of autosplenectomy [3]. * **Salmonella Osteomyelitis:** SCD patients have a unique predisposition to *Salmonella* bone infections. * **Hand-Foot Syndrome:** Dactylitis (painful swelling of hands/feet) is often the first clinical manifestation of SCD in infants [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. 631-632. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 645-646. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 644-645.

Question 1093: Chloroma is a manifestation of which hematologic malignancy?

A. Acute Myeloid Leukemia (AML) (Correct Answer)
B. Chronic Lymphocytic Leukemia (CLL)
C. Acute Lymphoblastic Leukemia (ALL)
D. Non-Hodgkin's Lymphoma

Explanation: **Explanation:** **Chloroma**, also known as **Granulocytic Sarcoma** or Myeloid Sarcoma, is an extramedullary solid tumor mass composed of primitive myeloid cells (leukemic blasts). It is a classic manifestation of **Acute Myeloid Leukemia (AML)** [1]. 1. **Why AML is Correct:** The term "Chloroma" is derived from the Greek word *chloros* (green), referring to the greenish hue the tumor often exhibits. This color is due to the high concentration of **Myeloperoxidase (MPO)**, an enzyme found in myeloid cells. It most commonly involves the bone, periosteum, soft tissues, and lymph nodes. It can occur concurrently with AML, as a relapse, or occasionally as a precursor to systemic marrow involvement [1]. 2. **Why Other Options are Incorrect:** * **CLL & ALL:** These are lymphoid malignancies. Lymphoid cells lack Myeloperoxidase; therefore, they do not produce the characteristic green pigment or form granulocytic sarcomas. * **Non-Hodgkin’s Lymphoma:** While NHL presents as solid masses (lymphadenopathy or extranodal masses), these are composed of mature or immature lymphocytes, not myeloid precursors. **High-Yield Clinical Pearls for NEET-PG:** * **Most Common Association:** Chloromas are most frequently associated with **AML-M2** (with t(8;21)) and **AML-M4/M5** subtypes [1]. * **Common Site:** In children, the **orbit** is a classic site of involvement, leading to proptosis. * **Histochemistry:** The tumor cells will stain positive for **MPO**, Sudan Black B, and CD34. * **Prognostic Significance:** The presence of a chloroma in a patient with AML generally signifies a poor prognosis or advanced disease stage. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 607-611.

Question 1094: Which disease is characterized by insidious onset and an absolute increase in the number of circulating RBCs and in total blood volume?

A. Leukopenia
B. Osler's disease (Correct Answer)
C. Mediterranean disease
D. Aplastic anaemia

Explanation: **Explanation:** The question describes the classic presentation of **Polycythemia Vera (PV)**, also known as **Osler’s disease** (or Vaquez-Osler disease). **1. Why Osler’s Disease is Correct:** Osler’s disease is a chronic myeloproliferative neoplasm characterized by the autonomous overproduction of erythroid progenitors [1]. This leads to an **absolute increase in red blood cell (RBC) mass**, independent of erythropoietin levels [1]. The clinical hallmark is an insidious onset of symptoms related to hyperviscosity and increased **total blood volume**, such as headaches, dizziness, and plethora [1], [2]. **2. Why the Other Options are Incorrect:** * **Leukopenia (A):** This refers to a decrease in the total white blood cell count, which is the opposite of the proliferative process described. * **Mediterranean Disease (C):** This is an eponym for **Thalassemia major**. While it involves the hematopoietic system, it is characterized by microcytic anemia (decreased RBC parameters) and ineffective erythropoiesis, not an absolute increase in RBCs. * **Aplastic Anemia (D):** This is a state of bone marrow failure resulting in pancytopenia (reduction in RBCs, WBCs, and platelets). **3. NEET-PG High-Yield Pearls:** * **Genetic Marker:** Over 95% of PV cases are associated with the **JAK2 V617F mutation** (located on exon 14) [2]. * **Clinical Sign:** **Aquagenic pruritus** (itching after a warm bath) is a highly specific symptom. * **Complications:** Patients are at high risk for both arterial/venous thrombosis (e.g., Budd-Chiari syndrome) and transformation into myelofibrosis or Acute Myeloid Leukemia (AML) [2]. * **Lab Findings:** Characterized by low serum Erythropoietin (EPO) levels and hypercellular bone marrow with "panmyelosis" [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 663-664. [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. 626-627.

Question 1095: Basophilic stippling is seen in poisoning with what substance?

A. Lead (Correct Answer)
B. Arsenic
C. Copper
D. Phosphorous

Explanation: **Explanation:** **Basophilic stippling** (punctate basophilia) refers to the presence of numerous small, blue-purple granules within the cytoplasm of red blood cells on a peripheral smear. These granules represent **precipitates of ribosomes and polyribosomes.** **1. Why Lead is the Correct Answer:** In **Lead Poisoning (Plumbism)**, lead inhibits the enzyme **5'-nucleotidase**. This enzyme is responsible for the degradation of ribosomal RNA in maturing erythrocytes. When inhibited, undegraded RNA aggregates and precipitates, appearing as basophilic stippling [1]. Additionally, lead inhibits ferrochelatase and ALA dehydratase, leading to sideroblastic anemia and microcytic hypochromic morphology [2]. **2. Why Other Options are Incorrect:** * **Arsenic:** Poisoning typically presents with Mees' lines (nails), garlic breath, and increased risk of skin/lung cancer, but not classic basophilic stippling. * **Copper:** Deficiency (not poisoning) can cause sideroblastic anemia; toxicity usually leads to Wilson’s disease or acute Coombs-negative hemolytic anemia. * **Phosphorous:** Poisoning (e.g., yellow phosphorus) primarily causes acute liver failure (fulminant hepatitis) and "phossy jaw," not specific RBC inclusions. **3. High-Yield Clinical Pearls for NEET-PG:** * **Differential Diagnosis of Basophilic Stippling:** Remember the mnemonic **"TAAL"**: **T**halassemia, **A**rsenic (rarely), **A**nemia of chronic disease, and **L**ead poisoning. It is also seen in **Sideroblastic anemia** [2]. * **Coarse vs. Fine Stippling:** Coarse stippling is highly suggestive of Lead poisoning or Thalassemia; fine stippling is seen in various nutritional anemias [1]. * **Burton’s Line:** A bluish-grey line on the gums is a classic clinical sign of lead poisoning. * **Erythrocyte Protoporphyrin:** Levels are elevated in lead poisoning due to the inhibition of ferrochelatase. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-420. [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. 133-134.

Question 1096: In multiple myeloma, which anatomical location is most commonly involved?

A. Bone marrow (Correct Answer)
B. Cortex of bone
C. Metaphyses
D. Epiphyses

Explanation: **Explanation:** **Multiple Myeloma (MM)** is a plasma cell neoplasm characterized by the multifocal proliferation of malignant plasma cells [1]. The correct answer is **Bone Marrow** because MM is fundamentally a disease of the hematopoietic compartment. These neoplastic plasma cells originate and reside primarily within the bone marrow, where they depend on the marrow microenvironment (specifically IL-6) for growth and survival [1]. **Analysis of Options:** * **Bone Marrow (Correct):** The primary pathology involves the replacement of normal marrow by sheets of malignant plasma cells [1]. This leads to the classic "punched-out" lytic lesions seen on imaging, as the plasma cells stimulate osteoclasts via the RANK/RANKL pathway, causing bone resorption from the inside out [2]. * **Cortex of Bone:** While MM eventually causes thinning and destruction of the cortex, the disease does not *originate* there. Cortical involvement is a secondary consequence of marrow expansion and osteoclast activation. * **Metaphyses/Epiphyses:** These terms refer to specific longitudinal segments of long bones. While MM can affect these areas, it is not restricted to them. MM preferentially involves the **axial skeleton** (skull, spine, ribs, pelvis) because these sites contain the highest concentration of active red bone marrow in adults [1]. **NEET-PG High-Yield Pearls:** * **Diagnostic Triad:** Marrow plasmacytosis (>10%), lytic bone lesions, and M-protein in serum/urine [1]. * **CRAB Criteria:** Calcium elevation, Renal insufficiency, Anemia, and Bone lesions [2]. * **Morphology:** Look for **Flame cells** (IgA myeloma) and **Mott cells** (containing Russell bodies). * **Radiology:** Skeletal survey is preferred over bone scans (bone scans are often negative because there is no osteoblastic activity) [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 616-618. [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. 606-608.

Question 1097: In hemolytic anemias, what happens to the urobilinogen level in the blood?

A. Increase (Correct Answer)
B. Be absent
C. Decrease
D. Mildly decrease

Explanation: ### Explanation **Correct Answer: A. Increase** In hemolytic anemia, there is an accelerated destruction of red blood cells (RBCs), leading to an overproduction of **unconjugated bilirubin** [2]. This bilirubin is transported to the liver, conjugated, and excreted into the bile [1]. Once in the intestine, bacterial flora convert conjugated bilirubin into **urobilinogen** [1]. While most urobilinogen is excreted in feces (as stercobilin), a significant portion is reabsorbed into the portal circulation (**enterohepatic circulation**) [1]. Because the liver is overwhelmed by the massive load of bilirubin produced during hemolysis, it cannot re-process all the reabsorbed urobilinogen. Consequently, levels of urobilinogen **increase in the blood** and subsequently spill over into the urine (**urobilinogenuria**). **Why Incorrect Options are Wrong:** * **B. Be absent:** Urobilinogen is absent only in **complete obstructive jaundice**, where bile cannot reach the intestine for bacterial conversion. * **C & D. Decrease/Mildly decrease:** These occur in conditions where bilirubin production is low or its entry into the intestine is blocked. In hemolysis, the pathway is hyperactive, making a decrease physiologically impossible. **NEET-PG High-Yield Pearls:** 1. **Urine Findings in Hemolysis:** Increased urobilinogen but **absent bilirubin** (acholuric jaundice), because unconjugated bilirubin is water-insoluble and cannot pass the glomerular filter [2]. 2. **Haptoglobin:** The most sensitive marker for intravascular hemolysis is **decreased** serum haptoglobin [2]. 3. **Reticulocyte Count:** Always **elevated** in hemolytic anemia as the bone marrow attempts to compensate for RBC loss [2]. 4. **LDH:** Serum Lactate Dehydrogenase is typically **increased** due to release from ruptured RBCs. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 858-860. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 639-640.

Question 1098: Hereditary spherocytosis is due to deficiency of which protein?

A. Ankyrin (Correct Answer)
B. Actin
C. Selectin
D. Integrin

Explanation: **Explanation:** **Hereditary Spherocytosis (HS)** is an autosomal dominant disorder characterized by a defect in the red blood cell (RBC) membrane proteins [1]. These proteins are responsible for anchoring the lipid bilayer to the underlying cytoskeleton. 1. **Why Ankyrin is correct:** The most common molecular defect in HS is a deficiency of **Ankyrin** (approx. 50-60% of cases), followed by Band 3, Spectrin, and Protein 4.2 [1]. Ankyrin normally bridges Spectrin to the transmembrane protein Band 3 [1]. Its deficiency leads to a loss of membrane surface area, forcing the cell to assume the most thermodynamically stable shape—a **sphere** [1]. These spherocytes are rigid and undergo premature destruction in the splenic sinusoids (extravascular hemolysis) [1]. 2. **Why other options are incorrect:** * **Actin:** While actin is part of the RBC cytoskeleton, primary mutations in actin are not a classic cause of HS. * **Selectins & Integrins:** These are **cell adhesion molecules**. Selectins (E, L, and P) mediate the initial "rolling" of leukocytes, while Integrins mediate "firm adhesion" during the inflammatory response. They are not structural components of the RBC membrane. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Anemia, Splenomegaly, and Jaundice. * **Diagnosis:** The gold standard is the **Eosin-5-maleimide (EMA) binding test** (Flow cytometry). The Osmotic Fragility Test is also used (increased fragility). * **Peripheral Smear:** Spherocytes (small, dark RBCs lacking central pallor) and increased **MCHC** (>36 g/dL). * **Complication:** Risk of aplastic crisis associated with **Parvovirus B19** infection and pigment gallstones (cholelithiasis). * **Treatment:** Splenectomy is the definitive treatment for symptomatic cases (post-splenectomy, **Howell-Jolly bodies** appear on smear). **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 1099: Wrinkled paper appearance of macrophage in bone marrow aspirate is characteristic of which condition?

A. Niemann-Pick disease
B. Gaucher disease (Correct Answer)
C. Hemophagocytic lymphohistiocytosis
D. Langerhans cell histiocytosis

Explanation: **Explanation** **Gaucher disease** is the correct answer because it is characterized by the accumulation of glucocerebroside within macrophages due to a deficiency of the enzyme **glucocerebrosidase** (β-glucosidase). These lipid-laden macrophages are known as **Gaucher cells**. Under light microscopy, the cytoplasm of these cells has a classic **"wrinkled paper"** or **"crumpled silk"** appearance [1]. This unique morphology is caused by the intralysosomal accumulation of tubular bimolecular leaflets of glucocerebroside [1]. **Analysis of Incorrect Options:** * **A. Niemann-Pick disease:** This condition involves a deficiency of sphingomyelinase. The characteristic cells are **"foamy macrophages"** (vacuolated cytoplasm) rather than wrinkled ones [2]. * **C. Hemophagocytic lymphohistiocytosis (HLH):** This is characterized by activated macrophages engulfing erythrocytes, leukocytes, and platelets (**hemophagocytosis**), not lipid accumulation. * **D. Langerhans cell histiocytosis:** This features Birbeck granules (tennis-racket shaped) on electron microscopy and cells with grooved, **"coffee-bean"** nuclei, not wrinkled cytoplasm. **High-Yield Clinical Pearls for NEET-PG:** * **Gaucher Disease** is the most common lysosomal storage disorder. * **Biomarker:** Serum **ACE levels** and **TRAP** (Tartrate-resistant acid phosphatase) are often elevated. * **Clinical Triad:** Hepatosplenomegaly, bone involvement (Erlenmeyer flask deformity of the femur), and pancytopenia [1]. * **Pseudo-Gaucher cells:** These can be seen in conditions with high cell turnover, such as **Chronic Myeloid Leukemia (CML)** and Multiple Myeloma. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 162-163. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 161-162.

Question 1100: In the investigation of a patient with suspected essential thrombocythaemia, in which of the following genes may you find abnormalities?

A. BCL-2
B. BCR
C. c-MYC
D. CAL-R (Correct Answer)

Explanation: **Explanation:** Essential Thrombocythaemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by the autonomous overproduction of platelets [1]. The pathogenesis involves mutations that lead to constitutive activation of the **JAK-STAT signaling pathway**, driving megakaryopoiesis [1]. **1. Why CAL-R is correct:** Approximately 90% of ET cases are driven by one of three "driver mutations": * **JAK2 (V617F):** Present in ~50-60% of cases [1]. * **CALR (Calreticulin):** Found in ~25-30% of cases (specifically in those who are JAK2 negative) [1]. * **MPL:** Found in ~3-5% of cases [1]. **CALR** mutations (typically insertions or deletions in Exon 9) result in a mutant protein that activates the thrombopoietin receptor (MPL), leading to uncontrolled platelet production [1]. **2. Why the other options are incorrect:** * **BCL-2:** An anti-apoptotic protein associated with **Follicular Lymphoma** due to the t(14;18) translocation. * **BCR:** Part of the **BCR-ABL1** fusion gene (Philadelphia chromosome) seen in **Chronic Myeloid Leukemia (CML)** [1]. ET is specifically defined by the *absence* of the BCR-ABL1 rearrangement. * **c-MYC:** A proto-oncogene associated with **Burkitt Lymphoma** due to the t(8;14) translocation. **Clinical Pearls for NEET-PG:** * **Triple Negative ET:** Refers to the ~10% of patients who lack JAK2, CALR, and MPL mutations. * **Morphology:** Bone marrow shows increased numbers of enlarged, mature megakaryocytes with "staghorn" or deeply lobulated nuclei [1]. * **Clinical Feature:** Erythromelalgia (burning pain and erythema of hands/feet) is a classic symptom due to microvascular occlusion. * **Prognosis:** CALR-mutated ET generally has a lower risk of thrombosis compared to JAK2-mutated ET. **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.

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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