A mother brings her 7 year-old boy to the emergency room with a swollen left knee joint. He denies a history of trauma to the knee. He reports similar swellings in the right knee joint, right and left elbow joints. Many times he feels the bleeding before he notices the swelling. For the last few days, he has been passing very red colored urine. In the physical examination, you notice a warm, swollen, erythematous left knee joint with severe effusion. There is sensory loss over the lateral and anterior thigh. The quadriceps muscle is weak and small compared to the muscle on his right lower extremity. Patellar reflex is absent. Upon direct questioning, the mother reports that her brother suffers from a bleeding disorder, with frequent nosebleeds. Many of her relatives also have similar bleeding disorders, affecting mostly males. Laboratory tests reveal a normal bleeding time, a normal prothrombin time but a prolonged PTT. As you review the labs with the patient, he developed a severe headache, unrelenting vomiting, and slurred speech. A gross physical examination showed focal neurologic deficits. What is the most likely diagnosis in this patient?

A 52-year-old man presents to the emergency department with complaints of abdominal pain, progressive abdominal swelling, and fatigue over the past two weeks. He reports increasing difficulty breathing when lying flat and unintentional weight gain due to fluid retention. He denies fever, nausea, or significant alcohol consumption but mentions a history of intermittent headaches and dizziness. On physical examination, he is noted to have hepatomegaly, abdominal distension with shifting dullness, and mild jaundice. His blood pressure and heart rate are normal, but his oxygen saturation is slightly reduced in the supine position. Liver function tests show mild transaminase elevations and hypoalbuminemia, while abdominal ultrasound with Doppler confirms hepatic vein thrombosis, consistent with Budd-Chiari syndrome (BCS). Of the following, which is the most frequent underlying disease associated with Budd-Chiari syndrome?

Abhimelech, a 58-year-old male, comes to the clinic reporting headaches, dizziness, and pruritus, particularly after warm baths. Upon examination, he appears plethoric, with a ruddy complexion. His medical history includes hypertension, managed with medication, but no other significant conditions. Laboratory tests reveal an elevated hemoglobin level of 18.5 g/dL, hematocrit of 57%, and red blood cell count of 6.2 million per microliter, leading to a suspicion of polycythemia. Further tests confirm low erythropoietin levels, normal oxygen saturation, and the presence of the JAK2 V617F mutation, which is pathognomonic for polycythemia vera (PV). Of the following, which vitamin levels are strikingly elevated in patients with polycythemia vera?

A 58 year-old male comes to your office reporting headaches, dizziness, tinnitus, vertigo, blurred vision, and easy bruising. He feels miserable after a warm shower because his whole body itches intensely. In a dinner party last weekend, his nose bled profusely. His fingers and toes become red, painful with burning sensations and warmth. He takes low-dose aspirin for relief from the pain and redness. His past medical history is significant for deep venous thrombosis in the right lower extremity 3 months ago. He has a history of smoking one or two cigarettes a day for over 10 years. His temperature is 99 °F (37.2 °C), heart rate is 108 beats/min, blood pressure is 164/105 mm Hg, respirations are 19 breaths/min, and oxygen saturation is 99% on room air. Physical examination is remarkable for engorged retinal veins, tenderness in the epigastric region (probably due to peptic ulcer disease) and splenomegaly. Laboratory results are given below: Erythrocyte count (RBC) 7.9 million/mm³ Male: 4.3 – 5.9 million/mm³ Female: 3.5 – 5.5 million/mm³ Hematocrit 61% Male:41% – 53% Female: 36% – 46% Hemoglobin, blood 21 g/dL Male:13.5-17.5 g/dL Female 12.0 – 16.0 g/dL Hemoglobin A₁c 5.6% ≤6% Leukocyte count (WBC) 16,754 /mm³ 4500-11,000/mm³ Neutrophils, segmented 84% 54% – 62% Neutrophils, bands 12% 3% – 5% Eosinophils 7% 1% – 3% Basophils 3% 0% – 0.75% Platelet count 1,200,000 /mm³ 150,000 – 400,000/mm³ Iron 63 µg/dL Male: 65 – 175 µg/dL Female: 50 – 170 µg/dL Total iron-binding capacity 410 µg/dL 250 – 400 µg/dL Transferrin 385 mg/dL 200 – 360 mg/dL Erythropoietin (EPO) 6.8 mg/dL 2.6 – 18.5 mg/dL Vitamin B12 1750 pg/mL 160 – 950 pg/mL Carboxyhemoglobin 2.7% <2.5% Uric acid 8.9 mg/dL 3.5 - 7.2 mg/dL Bone marrow film shows hypercellular marrow with erythroid, granulocytic, and megakaryocytic hyperplasia without overt dysmorphia of cells and normal maturation sequence, normal RBC, WBC, platelet morphology. Prussian blue stain reveals absence of iron. Which of the following mutations is detectable in blood myeloid cells of this patient?

A 61 year-old male comes to your office reporting headaches, dizziness, tinnitus, vertigo, blurred vision, and easy bruising. He feels miserable after a warm shower because his whole body itches intensely. In a dinner party last weekend, his nose bled profusely.  His fingers and toes become red, painful with burning sensations and warmth. He takes low-dose aspirin for relief from the pain and redness. His past medical history is significant for deep venous thrombosis in the right lower extremity 3 months ago. He has a history of smoking one or two cigarettes a day for over 10 years.  His temperature is 99 °F (37.2 °C), heart rate is 108 beats/min, blood pressure is 164/105 mm Hg, respirations are 19 breaths/min, and oxygen saturation is 99% on room air. Physical examination is remarkable for engorged retinal veins, tenderness in the epigastric region (probably due to peptic ulcer disease) and splenomegaly. Laboratory results are given below:  Erythrocyte count (RBC) 7.9 million/mm³ Male: 4.3 – 5.9 million/mm³ Female: 3.5 – 5.5 million/mm³ Hematocrit 61%  Male:41% – 53% Female: 36% – 46% Hemoglobin, blood 21 g/dL  Male:13.5-17.5 g/dL Female 12.0 – 16.0 g/dL Hemoglobin A₁c 5.6% ≤6% Leukocyte count (WBC) 16,754 /mm³ 4500-11,000/mm³ Neutrophils, segmented 84% 54% – 62% Neutrophils, bands 12% 3% – 5% Eosinophils 7% 1% – 3% Basophils 3% 0% – 0.75% Platelet count  1,200,000 /mm³ 150,000 – 400,000/mm³ Iron 63 µg/dL Male: 65 – 175 µg/dL Female: 50 – 170 µg/dL Total iron-binding capacity 410 µg/dL 250 – 400 µg/dL Transferrin 385 mg/dL  200 – 360 mg/dL  Erythropoietin (EPO) 6.8 mg/dL  2.6 – 18.5 mg/dL  Vitamin  B12 1750 pg/mL  160 – 950 pg/mL Carboxyhemoglobin 2.7% <2.5% Uric acid  8.9 mg/dL  3.5 - 7.2 mg/dL   Bone marrow film shows hypercellular marrow with erythroid, granulocytic, and megakaryocytic hyperplasia without overt dysmorphia of cells and normal maturation sequence, normal RBC, WBC, platelet morphology. Prussian blue stain reveals absence of iron.  What is the most likely diagnosis in this patient?

A 12-year-old boy presents to the pediatric clinic with fatigue, recurrent nosebleeds, and easy bruising over the past month. His parents report he has been less active recently and noticed pale skin. There is no history of recent illness, medication use, or significant environmental exposures. His family history reveals a maternal uncle who died of bone marrow failure in his teens. You suspect aplastic anemia in this boy. As you prepare for a physical examination, you wonder about possible positive findings in this patient. Which of the following is not seen in aplastic anemia and its presence should suggest an alternative diagnosis?

A 12-year-old boy presents to the pediatric clinic with fatigue, recurrent nosebleeds, and easy bruising over the past month. His parents report he has been less active recently and noticed pale skin. There is no history of recent illness, medication use, or significant environmental exposures. His family history reveals a maternal uncle who died of bone marrow failure in his teens. On examination, the boy appears pale and has petechiae on his lower limbs but no lymphadenopathy or hepatosplenomegaly. Laboratory studies reveal pancytopenia, with low hemoglobin, platelets, and white blood cell counts. Bone marrow biopsy shows hypocellular marrow with fat replacement, consistent with aplastic anemia. Genetic testing identifies a mutation, confirming the diagnosis of a hereditary form of aplastic anemia. What is the most common hereditary cause of aplastic anemia?