Hemolytic Anemias: Intracorpuscular Defects
Terms
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Types of Hemolysis
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- Extravascular vs. intravascular sites
- extracorpuscular vs. intracorpuscular defects
- hereditary vs acquired disorders
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Hemolysis: Clinical features
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- decreased RBC
- accelerated Hgb breakdown
- increased bilirubin
- decreased haptoglobin
- hemosiderin in kidney tubules
- increased urobilinogen in urine and feces
- hemoglobin in urine
- Bone marrow response to Hemolysis
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- erythroid hyperplasia
- skeletal deformities
- results in following peripheral blood:
- NRBC
- increased reticulocytes
- howell-jolly bodies
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Intracorpuscular Defects: Defective RBC membrane
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- Hereditary spherocytosis
- Hereditary elliptocytosis
- Hereditary stomatocytosis
- Hereditary xerocytosis (cremated cells)
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Hereditary spherocytosis- Etiology and Clinical features
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- spectrin and ankrin deficiency
- conditioning of RBCs by spleen
- age of presentation varies
- jaundice
- anemia
- enlarged spleen
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Hereditary spherocytosis: Lab findings
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- hyperbilirubinemia
- haptoglobin variably reduced
- no classic signs of intravascular hemolysis
- increased reticulocytes
- avg Hgb is 12-13 g/dL
- MCV and MCH vary
- MCHC is usually increased above 36%
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Hereditary Spherocytosis- Peripheral blood
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- Spherocytes
- may have A&P before splenectomy
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Hereditary Spherocytosis: Lab tests
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- osmotic fragility
- autohemolysis test
- sterile incubation of RBCs in own plasma for 48 hrs
- ATP and GLC needed to keep "leaky" Na+ out of cell (pump)
- cells are fragile in GLC depletion
- 10-50% frag
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Hereditary Spherocytosis- Treatment
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- Splenectomy
- deferred until after6 yrs in children to due infection with Strep pneumoniae
- Splenectomy
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Hereditary elliptocytosis- Etiology and clincial features
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- spectrin and/or protein deficiency or dysfunction
- membrane is weakened in stress
- most cases are asymptomatic
- few have traditional symptoms of severe hemolytic anemia (HA)
- Hereditary elliptocytosis: Lab findings
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- most cases of HE have a mild, compensated HA with minimal hemolysis
- slight reticulocytosis
- decreased haptoglobin levels
- normal RBC indices
- many cases show no evidence of a hemolytic process
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Hereditary Elliptocytosis: Lab tests
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- osmotic fragility and autohemolysis tests are usually normal in mild cases
- RBC membrane studies
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Hereditary Elliptocytosis: Treatment
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- no treatment necessary
- more severe cases may require splenectomy
- no treatment necessary
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Hereditary Stomatocytosis and hereditary Xerocytosis- Etiology
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- Permeable memb permits cation "leaks" into and out of RBC
- sodium leaks into cell and potassium leaks out of cell
- net loss of sodium is higher
- water enters the cell with sodium and RBCs swell
- Hereditary Stomatocytosis and Hereditary Xerocytosis - Clinical features and Treatment
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- most cases have no severe hemolytic symptoms
- Hereditary Stomatocytosis treatment:
- patients with hemolysis respond well to splenectomy
- Hereditary Xerocytosis treatment:
- patients do not ben
- Hereditary Xerocytosis- Etiology
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- Permeable memb permits cation "leaks" into and out of RBC
- net loss of potassium is higher
- water exits the cell with sodium and RBCs become dehydrated
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Hereditary Stomatocytosis: Lab findings
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- increased MCV
- decreased MCHC
- macrocytosis
- stomatocytes (bowl-like)
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Hereditary xerocytosis: Lab findings
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- target cells
- small echinocytes
- increased MCV
- increased MCHC
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Intracorpuscular Defects: Enzyme Abnormalities
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- G-6-PD deficiency
- Pyruvate kinase deficiency
- methemoglobin reductase deficiency
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G-6-PD Deficiency- Etiology
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- Enzyme failure to catalyze reactions to reduce glutathione in RBC
- Glutathione is necessary to protect HGb from oxidative denaturation
- oxidation results in ppt of irreversilby denatured Hgb (Heinz bodies)
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G-6-PD Deficiency -Clinical features
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- many are asymptomatic
- 2-3 days after offending drug adminstration
- back pain
- hemoglobinuria
- jaundice
- others present with more severe hemolytic symptoms
- G-6-PD Deficiency- lab findings
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- 2-3 days after offending drug adminstration
- decreased RBC
- decreased Hgb
- normocytic, normochromic anemia
- severe hemolytic reactions
- decreased Hgb and Hct
- hemoglobinuria (brown to black):
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G-6-PD Deficiency- lab tests
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- Heinz body staining (screen)
- G-6-PD assay to determine true deficiency
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Pyruvate Kinase Deficiency- Etiology
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- deficiency causes decreased ATP production in Embden-Meyerhof pathway
- leads to cell water loss and shrinkage
- distortion of cell shape
- increased memb rigidity
- Abnormal cell types are destroyed by spleen and
- Pyruvate Kinase Deficiency- Clinical features
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- severe cases are jaundiced at birth
- lesssevere diagnosed at childhood or young adult
- Pyruvate Kinase Deficiency- lab findings
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- Less severe cases
- normocytic, normochromic anemia
- varying reticulocytosis
- more severe cases
- decreased hgb and hct
- polychromasia, NRBC
- A&P
- increased bilirubin
- decrease
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Pyruvate Kinase Deficiency- Lab tests and treatment
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- pyruvate kinase enzyme assay
- possible transfusions
- sme may benefit from splenectomy
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Methemoglobin Reductase Deficiency- Etiology
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- deficiency causes increased levels of methemoglobin
- not an effective carrier of oxygen
- may not be a problem unless exposed to drug
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Methemoglobin Reductase Deficiency- Clinical features, lab findings, treatment
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- cyanosis
- lab findings: mild compensatory polycythemia
- treatment: remove offending drug