Hemolytic Anemia.ppt - HEMOLYTIC ANEMIAS HEMOLYTIC ANEMIA...

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HEMOLYTIC ANEMIAS
HEMOLYTIC ANEMIA Anemia of increased destruction Normochromic, normochromic anemia Shortened RBC survival Reticulocytosis - Response to increased RBC destruction Increased indirect bilirubin Increased LDH
HEMOLYTIC ANEMIA Testing Absent haptoglobin Hemoglobinuria Hemoglobinemia
HEMOLYTIC ANEMIA Causes INTRACORPUSCULAR HEMOLYSIS Membrane Abnormalities Metabolic Abnormalities Hemoglobinopathies EXTRACORPUSCULAR HEMOLYSIS Nonimmune Immune
HEMOLYTIC ANEMIA Membrane Defects Microskeletal defects Hereditary spherocytosis Membrane permeability defects Hereditary stomatocytosis Increased sensitivity to complement Paroxysmal nocturnal hemoglobinuria
RED CELL CYTOSKELETON
HEREDITARY SPHEROCYTOSIS Defective or absent spectrin molecule Leads to loss of RBC membrane, leading to spherocytosis Decreased deformability of cell Increased osmotic fragility Extravascular hemolysis in spleen
SPLENIC ARCHITECTURE
HEREDITARY SPHEROCYTOSIS Osmotic Fragility 0 20 40 60 80 100 0.3 0.4 0.5 0.6 NaCl (% of normal saline) % Hemolysis Normal HS
Paroxysmal Nocturnal Hemoglobinuria Clonal cell disorder Ongoing Intra- & Extravascular hemolysis; classically at night Testing Acid hemolysis (Ham test) Sucrose hemolysis CD-59 negative (Product of PIG-A gene) Acquired deficit of GPI-Associated proteins (including Decay Activating Factor)
GPI BRIDGE
Paroxysmal Nocturnal Hemoglobinuria GPI Proteins GPI links a series of proteins to outer leaf of cell membrane via phosphatidyl inositol bridge, with membrane anchor via diacylglycerol bridge PIG-A gene, on X-chromosome, codes for synthesis of this bridge; multiple defects known to cause lack of this bridge Absence of decay accelerating factor leads to failure to inactivate complement & thereby to increased cell lysis
HEMOLYTIC ANEMIA Membrane abnormalities - Enzymopathies Deficiencies in Hexose Monophosphate Shunt Glucose 6-Phosphate Dehydrogenase Deficiency Deficiencies in the EM Pathway Pyruvate Kinase Deficiency
G6PD DEFICIENCY Function of G6PD G6PD GSSG 2 GSH NADPH NADP 2 H 2 O H 2 O 2 6-PG G6P Hgb Sulf-Hgb Heinz bodies Hemolysis Infections Drugs
Glucose 6-Phosphate Dehydrogenase Functions Regenerates NADPH, allowing

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