Updated: 1/24/2017

Anemia of Chronic Disease

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Snapshot
  • A 40-year-old woman with rheumatoid arthritis has felt tired and weak for several months. She attributed this to her autoimmune disease. However, in the past week, she has begun feeling very short of breath even walking to the grocery store; something she was able to do easily before. Her husband also noticed that she has been very pale. On physical exam, she has conjunctival pallor but an otherwise baseline physical exam. Laboratory results reveal anemia, decreased serum iron, increased ferritin, and decreased TIBC.
Introduction

 
  • Anemia of chronic disease resulting from decreased red blood cell production is a
    • normochromic, normocytic anemia
  • Pathogenesis
    • iron is stored in macrophages or bound with ferritin
    • hepcidin is an acute-phase reactant that is increased in states of inflammation
      • inflammation causes release of hepcidin by the liver
      • ↑ hepcidin during inflammation
        • binds ferroportin on intestinal mucosa
          • inhibits iron absorption from diet
          • prevents release of iron bound by ferritin from macrophages
        • causes anemia
  • Associated conditions
    • chronic inflammatory condition
    • chronic infection
    • longstanding malignancy
  • Prognosis
    • varied based on underlying inflammatory condition
Presentation
  • Symptoms of anemia
    • generalized weakness
    • fatigue
    • headache
    • shortness of breath
  • Physical exam
    • pallor
    • tachycardia
Evaluation
  • Labs
    • ↑ ferritin
    • ↓ serum iron
    • ↓ TIBC, transferrin saturation, and MCV
  • Peripheral blood smears
    • normochromic RBCs
    • may be normocytic or microcytic
    • basophilic stippling
      • can be seen in alcohol abuse, lead poisoning, thalassemias, and hereditary pyrimidine 5'-nucleotidase deficiency
Differential Diagnosis
  • Anemia of renal disease
  • Iron deficiency anemia
  • Aplastic anemia
Treatment
  • Treat underlying disease
  • If underlying disease is unknown or treatment of underlying disease does not improve symptomatic anemia
    • measure EPO
      • if low, administer EPO or erythropoiesis-stimulating agents (ESAs)
        • make sure iron stores (ferritin) are sufficient
        • if insufficient, patients may be resistant to EPO
Complications
  • Severe anemia
 

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Questions (2)
Lab Values
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/L
Female: 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/mL
Female: 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/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative 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/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 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/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 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/min
Female: 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 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 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
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(M1.HE.201) A 37-year-old woman presents to her primary care physician with a 6-month history of fatigue. She denies any recent history of fevers, chills or headaches. She does not smoke or drink alcohol. A CBC demonstrates a microcytic anemia. Iron studies are ordered and demonstrate the following:
Serum iron: 40 µg/dL (normal 50–170 µg/dL);
TIBC: 230 µg/dL (normal 250–370 µg/dL);
Transferrin saturation: 10% (normal 15–50%);
Serum ferritin: 180 µg/L (normal 15-150 µg/L);
Which of the following is a likely cause of this patient's iron studies findings? Review Topic

QID: 106247
1

Lead poisoning

20%

(3/15)

2

Dysfunctional uterine bleeding

7%

(1/15)

3

Splenic sequestration of RBCs

13%

(2/15)

4

Rheumatoid arthritis

53%

(8/15)

5

RBC enzyme deficiency

7%

(1/15)

M1

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