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General Surgery: Anemia

Microcytic Anemia - Anemia of chronic disease, iron deficiency anemia 

Iron deficiency anemia
Etiology Signs and Symptoms Laboratories Treatment
  • Most common anemia in the US
  • Always consider GI bleed
  • Associated with pica and nail spooning
  • Anemia: weakness, fatigue, bruising/gum bleeding, sore tongue (unique)
  • Neuropsychiatric manifestations: peripheral neuropathy, balance probs, depression, dementia → can be irreversible if untreated
  • Glossitis: beefy red tongue

Signs: Loss of vibratory and fine touch


Decreased serum iron, ferritin, and transferrin saturation

  • Microcytic (MCV < 80) and hypochromic (↓ MCH and MCHC) anemia with low H/H
  • Low Ferritin < 15 mg/ml (best test), high TIBC
  • Target cells
Oral iron:

Ferrous sulfate (eg, as 325 mg of ferrous sulfate QD or BID) - Give between meals with juice (not milk)

Ferrous fumarate - 100-200 mg/day in 2-3 doses

Ferrous gluconate - 3-6 mg/kg/day in 3 doses

  • 6 wk to correct anemia
  • 6 mo to replete iron stores
  • Recheck blood counts every 3 mo × 1 y
  • Vitamin C—helps to absorb iron
  • Increasing reticulocyte count is an indication that iron is working
Lead poisoning is a common question on the PANCE/PANRE look for basophilic stippling and remember treatment is with EDTA.
Anemia of chronic disease
Anemia of chronic disease is a multifactorial anemia often coexistent with iron deficiency. Diagnosis generally requires the presence of chronic infection, inflammation, or cancer; microcytic or normocytic anemia; and values for serum transferrin receptor and serum ferritin that are between those typical for iron deficiency and sideroblastic anemia. Low EPO

Iron studies

  • Decreased serum iron and TIBC, transferrin saturation
  • NL to 3× increase serum ferritin

Peripheral smear: normocytic, normochromic (cancer, CKD) to microcytic hypochromic (TB, RA)

↓ serum erythropoietin levels in anemia of renal failure

ESR: increased

  • Erythropoietin 50-150 U/kg IV 3 × weekly 
  • Treat the underlying disease

Vitamin B12 and Folic acid Deficiency Anemia (Macrocytic Anemia)

CBC: MCV > 100

  • Inhibition of DNA synthesis during RBC production
  • Iron Studies
    • Normal to increased: serum iron, ferritin, and transferrin saturation
    • Normal to decreased: TIBC
    • Peripheral smear: macrocytic, megaloblastic
Vitamin B12 deficiency 
Etiology Signs and Symptoms Laboratories Treatment
  • Autoimmune destruction of gastric parietal cells → atrophic gastritis → lack of intrinsic factor production (required for absorption in small intestines)
  • Cofactor for 2 enzymatic reactions required for DNA synthesis, brain/nervous system function, formation of RBC


  • Chronic alcoholism, vegetarian, celiac and Crohn diseases, gastric bypass surgery, Parasites
  • MCC: Pernicious anemia (lack of IF)
  • Anemia: weakness, fatigue, bruising/gum bleeding, sore tongue (unique)
  • Neuropsychiatric manifestations: peripheral neuropathy, balance probs, depression, dementia → can be irreversible if untreated
  • Glossitis: beefy red tongue

Signs: Loss of vibratory and fine touch


  • B12 level: decreased, can be false (+) with folate deficiency
  • Homocysteine: increased
  • Methylmalonic acid (MMA): increased
  • Hypersegmented neutrophils
Lifelong IM B12: 1-3 ug/d (animal products, fortified cereal) for pernicious anemia

  • IV Cyanocobalamin 1 mg IM daily × 7 d, then weekly × 4 wk, then monthly for life
  • PO B12 1-2 mg PO daily for vegans and bariatric surgery
  • Years to deplete stores
Folate deficiency
Etiology Signs and Symptoms Laboratories Treatment
  • Cofactor for DNA synthesis
  • Alcoholics and malnourished have smaller stores
  • Decreased intake, increased requirement (pregnant), sickle cell anemia, thalassemia
  • Sprue, Crohn, drugs
  • looks like B12 but no neurologic symptoms
  • Neural tube defects (spina bifida)
  • Homocysteine: increased
  • Serum folic acid: low
  • RBC folic acid (more reliable show of stores): <150 (diagnostic)
  • Macro-ovalocytes and hypersegmented PMNs (pathognomonic)
  • PO folic acid 1-5 mg/d (first line)
  • Avoid ETOH and folic acid antagonists (Bactrim, phenytoin, sulfasalazine)
  • Green leafy vegetables, yeast, legumes, fruits, animal proteins
  • Prophylactic folic acid— pregnant/lactating women, contemplating pregnancy, sickle cell patient
Hemolytic Anemias: 
Glucose-6-Phosphate Dehydrogenase Deficiency, Hereditary Spherocytosis, Sickle Cell Anemia, Thalassemia
CBC: Reticulocyte count: ↑ high (Hallmark)

Symptoms of acute and chronic anemia

  • dark urine
  • back pain
  • jaundice

Iron studies

  • Increased: serum iron, ferritin, and transferrin saturation
  • Decreased TIBC
  • Check hemoglobin and hematocrit
    • Check at 12 and 18 mo, 12 y (females)
    • Hb/Hct <2× standard deviation of normal
    • Hb < 13.5 g/dL or → Hct <39% (men)
    • Hb <12 g/dL or Hct <37% (women)
  • Total (indirect) bilirubin increased, Haptoglobin decreased
    • Peripheral smear: microcytic, normochromic anemia, spherocytes Bone marrow biopsy
G6PD deficiency
Etiology Symptoms Laboratories Treatment
  • After infection or medication (oxidative stress) → Depletion of reduced glutathione = oxidation of Hgb = precipitation of Hgb → Heinz bodies) + Bite cells → RBC destruction
  • Most commonly seen in tropical geographic areas prevalent for malaria (Africa, China, and Mediterranean regions)
  • Flare triggers: Fava beans, antimalarials, sulfonamides
  • Mild jaundice
  • Mild-moderate anemia
  • Malaise, abdominal discomfort in LUQ
  • Signs: Splenomegaly
  • Peripheral smear: Bite cells, Heinz bodies
  • Avoid potentially harmful drugs, monitor infection
  • Acute—blood transfusion
Hereditary Spherocytosis
Etiology Symptoms Laboratories Treatment
  • Inherited dysfunction or deficiency in one of the erythrocyte membrane proteins (spectrin, ankyrin, band 3 protein, or protein 4.2) → spherocytic erythrocytes are sequestered and destroyed in the spleen
  • Autosomal dominant
  • Mild jaundice
  • Mild-moderate anemia
  • Malaise, abdominal discomfort in LUQ
  • Signs: Splenomegaly
CBC: anemia

  • MCV: decreased
  • Reticulocyte count, LDH, indirect bilirubin, stool urobilinogen: elevated
  • Wright-stained smear: spherocytes
  • Hgb: 4-6 g/dL (low)
  • EDW: elevated
  • Peripheral smear: spherocytes
  • Osmotic fragility: increased
  • Coombs test: negative

  • Indicated even when anemia compensated and asymptomatic
  • Delay operation until children are age 6
  • Cholecystectomy if gallstones present


  • Hypoplastic crises: follow acute viral illness → profound anemia, headache, nausea, pancytopenia, hypoactive marrow, pigmented gallstones
Sickle Cell Anemia
Etiology Symptoms Laboratories Treatment
Mutation in the β-globin gene that changes the sixth amino acid from glutamic acid to valine Acute pain

  • Few hours to 2 wks
  • RF: infection, fever, excess exercise, anxiety, an abrupt change in temperature, hypoxia, hypertonic dyes


  • Tenderness, fever, tachycardia, anxiety


  • Pulmonary hypertension, ESRD, hand-foot syndrome, priapism → permanent impotence
  • Very ↑ Retic count + Pain in African American male
  • Hemoglobin electrophoresis: Hemoglobin S
  • Blood smear: Sickled RBCs, Howell-Jolly bodies, target cells)

  • Vigorous hydration
  • Aggressive pain medication (morphine)
  • Nasal O2

Severe symptoms:

  • Hydroxyurea (mainstay), for patients 3+ crises per year or repeated ACS - Increases production of Hgb F (cannot sickle)
  • BMT

Health maintenance:

  • Regular slit lamp exams: retinopathy
  • Antibiotics for splenectomy patients undergoing dental or invasive procedures
  • Vigorous oral rehydration during or in anticipation of periods of extreme exercise, exposure to heat/cold, emotional stress, or infection
  • Pneumococcal and Hib vaccines early in life
Autoimmune Hemolytic Anemia
Etiology Symptoms Laboratories Treatment
Autoantibodies bind to the patient's own erythrocytes, leading to premature red cell destruction (hemolysis) 

Warm and cold types

  • Warm (90%) - immunoglobulin (Ig)G, that bind preferentially to the red cells at 37°C,
  • Cold (10%) < 37° C
  • anemia
  • pallor, dyspnea
  • acrocyanosis and
  • livedo reticularis
  • Mild splenomegaly is typical
+ Direct Coombs Test

  • ↑ Retic
  • ↑ LDH 
  • ↓ Haptoglobin
  • ↑ Bilirubin (indirect) 
Dependent on disease severity

  • Rituximab
  • Glucocorticoids, cyclophosphamide, cyclosporine, IVIg
Etiology Signs and Symptoms Laboratories Treatment

  • Only 2 β-globin genes on chromosome 11, but 4 α-globin genes on chromosome 16
  • Disrupts ratio between α and β chains, changing the stability of Hb → hemolysis
  • Asymptomatic
  • Mild anemia


  • Hepatosplenomegaly
  • Jaundice
Hgb electrophoresis

CBC: microcytic hypochromic anemia

Iron studies

NL to increased: serum iron, ferritin, and transferrin saturation

Normal TIBC

Peripheral smear: target cells, basophilic stippling, elliptocytes

  • Symptomatic
  • Cardiovascular instability, continued/excessive blood loss—transfuse
  • Asymptomatic:
  • PO iron repletion (200 mg per day) and B12 - only if concomitant iron deficiency anemia
  • An allogeneic bone marrow transplant
  • Folic acid 5 mg daily
  • Deferoxamine (iron chelator)
  • Splenectomy for splenomegaly
  • Poor prognostic factors: Chronic infection, liver or heart failure, die in 20-30 s


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