Snapshot A 22-year-old Vietnamese woman presents for a routine gyn exam. Her menstrual cycle is normal, and there is no evidence of other bleeding. Guaiac is negative. Her hemoglobin is at 11 (12-16), RBC is 5.8 (3.5-5.5), and an MCV of 70 (80-100) with a normal RDW of 10. WBC and platelets are normal. Hemoglobin electrophoresis shows an increase in the amount of Hgb A2, and Hgb F. Introduction Autosomal recessive disease caused by decreased production of hemoglobin may involve mutations in α (α-thalassemia) or β (β-thalassemia) globin gene There are 4 α genes (2 on each chromosome) and 2 β genes that make up three forms of Hgb Hgb A subunits: α,α,β,β 96-98% of adult hemoglobin Hgb A2 subunits: α,α,δ,δ present in trace amounts in adults. Hgb F subunits: α,α,γ,γ declines in the first year of life cannot bind 2,3 DPG so has a left-shifted curve α-thalassemia types 1 gene deletion is asymptomatic 2 gene deletion is associated with a mild anemia with RBC hyperplasia called α-thalassemia trait seen in Asians and Africans Asians more commonly have a deletion of two α genes on 1 chromosome (cis deletion) Africans more commonly have a deletion of 1 α gene from each chromosome (trans deletion) 3 gene deletion is associated with severe anemia 4 gene deletion is not compatible with life will cause hydrops fetalis β-thalassemia types 1 gene involvement called β-thalassemia minor chain may be truncated (β+) or deleted (β0) β/β+ is the most benign form may be caused by mutation in Kozak consensus sequence 2 gene involvement called β-thalassemia major β0/β0 is the most severe form α,α,α,α hemoglobin present Presentation Symptoms α-thalassemia mild anemia in 2 gene deletion severe anemia in 3 gene deletion symptoms being at birth β-thalassemia minor form largely asymptomatic intermedia form hypochromic, microcytic anemia major form severe anemia symptoms begin after several months of life due to initial presence of HbF chipmunk facies secondary to extramedullary hematopoiesis in the skull Physical exam β-thalassemia major form hepatosplenomegaly due to chronic hemolysis, additionally exacerbated by extramedullary hematopoiesis in these organs Evaluation Peripheral smear 3 gene deletion α-thalassemia target, hypochromic, microcytic cells, with Heinz bodies from HbH β-thalassemia minor target, hypochromic, microcytic cells β-thalassemia major nucleated RBCs target, hypochromic, microcytic cells Hemoglobin gel-electrophoresis α-thalassemia trait normal 3 gene deletion α-thalassemia HbH (β,β,β,β) 4 gene deletion α-thalassemia Hb Barts (γ,γ,γ,γ) β-thalassemia minor ↑ HbA2, HbF ↓ HbA β-thalassemia major ↑ HbA2, HbF no HbA Imaging β-thalassemia major hair-on-end/crew cut appearance of the skull secondary to extramedullary hematopoiesis in the skull Treatment β-thalassemia major frequent transfusions required can cause iron overload and hemochromatosis Prognosis, Prevention, and Complications β-thalassemia major ↑ risk of B19-mediated aplastic crises Thalassemia trait protects against malaria
QUESTIONS 1 of 7 1 2 3 4 5 6 7 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 . = + (M1.HE.48) A 23-year-old Sicilian male presents to his primary care physician complaining of lethargy, joint pain, and urinary frequency. Vitals signs include T 98.7 F, HR 96 bpm, BP 135/71 mm/Hg, RR 18 breaths/minute, O2 99%. Laboratory findings include: random glucose 326 mg/dL, Hemoglobin 7.1, and elevated reticulocyte count and transferrin saturation. The patient is not surprised that his "blood level is low" and suggests that he might need another transfusion. An echocardiogram demonstrates restrictive cardiomyopathy. The disorder with which this patient presents can be characterized by which of the following? Review Topic QID: 106320 1 Absence of the hemoglobin alpha-chain 5% (6/123) 2 Absence of the hemoglobin beta-chain 65% (80/123) 3 Presence of the fetal hemoglobin 5% (6/123) 4 Mutation resulting in increased iron absorption 19% (23/123) 5 Mutations resulting in copper accumulation 5% (6/123) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.20) The Kozak sequence for the Beta-globin gene has a known mutation which decreases, though does not abolish, translation of the Beta-globin mRNA, leading to a phenotype of thalassemia intermedia. What would the blood smear be expected to show in a patient positive for this mutation? Review Topic QID: 100085 1 Macrocytic red blood cells 3% (6/188) 2 Hyperchromic red blood cells 4% (7/188) 3 Microcytic red blood cells 77% (145/188) 4 Bite cells 7% (13/188) 5 Ringed sideroblasts 8% (15/188) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.HE.131) A 7-year-old male is brought to his pediatrician for an annual physical. Routine blood work demonstrates hematocrit of 35% and a mean corpuscular volume of 72 fL. Red cell distribution width (RDW) is within normal limits. His peripheral blood smear is shown in Figure A. Electrophoresis demonstrates slightly diminished HbA1, elevated HbA2 and and normal HbF. Of the following, which is the most appropriate next step in management? Review Topic QID: 104771 FIGURES: A 1 Splenectomy 7% (11/156) 2 Folic acid supplementation 3% (5/156) 3 Blood transfusion 21% (32/156) 4 No treatment is necessary 56% (87/156) 5 Iron supplementation 12% (18/156) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.HE.47) A 28-year-old male is found to have 93% HbA, 2% HbF, and 5% HbA2 on hemoglobin electrophoresis. Which of the following is the most likely diagnosis? Review Topic QID: 101357 1 Sickle cell trait 7% (12/163) 2 Alpha thalassemia major with Hb Bart's 9% (15/163) 3 Beta-thalassemia minor 64% (104/163) 4 Beta-thalassemia major 14% (23/163) 5 Diabetes mellitus 2% (4/163) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3