Snapshot A 59-year-old woman presents to her primary care physician with overwhelming fatigue, headaches, and some blurry vision. She is worried that old age is finally catching up. While she is happy about losing 10 lbs over the past month, she is also confused since she has not changed her diet or exercise routine. On further questioning, she reveals that she is extremely itchy after a hot bath or shower. She is otherwise healthy. A blood smear shows RBC precursors. Introduction Myeloproliferative neoplasm characterized by increased production of RBCs leads to highly viscous blood Epidemiology presentation in those aged 60-70 Pathogenesis mutations in JAK2 (Janus kinase) V617F mutation constitutively active Janus kinase → unregulated myeloproliferation erythrocytosis → ↑ blood viscosity leukocytosis thrombocytosis Associated conditions risk of progression to myelofibrosis or leukemia Budd-Chiari syndrome caused by occlusion of IVC or hepatic veins leading to congestive liver disease Prognosis 1.6x higher mortality than general population Presentation Symptoms headaches visual disturbance bleeding caused by engorged vessels constitutional symptoms fatigue night sweats weight loss fever malaise pruritus caused by histamine release from increased basophils often triggered by hot shower or bath Physical exam erythromelalgia (rare but classic) caused by thrombosis characterized by painful burning sensation with increased temperatures in digits and episodic blood clots in extremities hepatosplenomegaly bruising ischemic digits large retinal veins on funduscopy Evaluation Labs complete blood count with smear will show ↑ hemoglobin > 16 g/dL (females) or > 16.5 g/dL (males) ↑ hct > 48% (F) or > 49% (M) JAK2 mutation in peripheral blood ↓ serum EPO ↑ RBC despite low EPO if EPO is high, consider ectopic EPO production (e.g., in renal cell carcinoma) ↓ MCV SaO2 normal Bone marrow biopsy shows hypercellularity and prominent proliferation of all cell lines commonly see precursor cells used to confirm diagnosis used as a baseline for assessing disease progression Differential Diagnosis Secondary polycythemia Tumor-driven polycythemia Other myeloproliferative neoplasm Treatment Reduce risk of thrombosis low-dose aspirin phlebotomy indicated for a hematocrit < 45% Myelosuppression hydroxyurea Gout prophylaxis allopurinol Complications Thrombosis leading cause of morbidity and mortality Peptic ulcers increased histamine release from basophils Gout increased uric acid from high number of cell turnover Progression to myelofibrosis CML AML
QUESTIONS 1 of 3 1 2 3 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.ON.4798) A 66-year-old male with a history of diabetes and knee osteoarthritis presents to his primary care provider in July complaining of headaches and blurry vision. He reports a 6-month history of occasional dull diffuse headaches and blurry vision. He notes that the episodes have increased in severity since the weather got warmer and that he occasionally feels extremely itchy when he spends time outdoors. The patient lives in southern Arizona. Moreover, he has felt chronically fatigued and has lost 10 pounds without dieting or changing his appetite. He currently takes metformin and his most recent hemoglobin A1c was 6.5%. Physical examination reveals multiple bruises on the bilateral upper and lower extremities and hepatosplenomegaly. Fundoscopic examination demonstrates enlarged retinal veins. Multiple laboratory tests are pending. At steady state, which of the following sets of findings is most likely in this patient? Review Topic QID: 109194 1 Increased plasma volume, increased RBC mass, decreased EPO, normal SaO2 43% (36/83) 2 Normal plasma volume, increased RBC mass, increased EPO, normal SaO2 19% (16/83) 3 Decreased plasma volume, normal RBC mass, normal EPO, normal SaO2 12% (10/83) 4 Normal plasma volume, increased RBC mass, increased EPO, decreased SaO2 18% (15/83) 5 Increased plasma volume, decreased RBC mass, decreased EPO, normal SaO2 4% (3/83) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.ON.75) A 56-year-old man presents to his primary care physician endorsing fatigue, episodic pruritus, and headaches. These symptoms have been occurring for the last 1-2 months but have gotten progressively worse over time. His wife has noticed a new "ruddy" color to his skin that has developed during this period. He is otherwise healthy, with no medical problems. On examination, the patient appears fatigued and plethoric. A complete blood cell count reveals a hematocrit of 59% with no other abnormalities. A peripheral blood smear is shown in Figure A. Mutation in which of the following genes is responsible for the patient's condition? Review Topic QID: 106754 FIGURES: A 1 BCR-ABL 9% (9/99) 2 RET 6% (6/99) 3 p53 8% (8/99) 4 JAK2 74% (73/99) 5 FLT3 1% (1/99) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4
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