Hemolytic Anemia

• • HEMOLYTIC ANEMIAS
  • physiologic destruction of senescent red cells takes place within mononuclear phagocytes

• mononuclear phagocytes are abundant in the spleen, liver, and bone marrow.
• Extravascular hemolysis
• • • More common cause of hemolytic anemias
• caused by alterations that render the red cell less deformable
• • • principal clinical features of extravascular hemolysis

• anemia
• splenomegaly,
• • • • jaundice
    • Some hemoglobin inevitably escapes from phagocytes, which leads to variable decreases in plasma haptoglobin, an α2-globulin that binds free hemoglobin and prevents its excretion in the urine.
• Why individuals with extravascular hemolysis often benefit from splenectomy ?
• • • • Because much of the pathologic destruction of red cells occurs in the spleen
  • Intravascular hemolysis
    • Causes
• mechanical injury
• • • • • cardiac valves
        • thrombotic narrowing of the microcirculation
        • repetitive physical trauma (e.g., marathon running and bongo drum beating).
      • Complement fixation
      • Toxic injury in clostridial sepsis
    • intravascular hemolysis is manifested by

• anemia,

• hemoglobinemia,

• hemoglobinuria,
• hemosiderinuria,
• • • • jaundice.
• Pathophysiology
• • • • The large amounts of free hemoglobin released from lysed red cells are promptly bound by haptoglobin, producing a complex that is rapidly cleared by mononuclear phagocytes.
      • As serum haptoglobin is depleted, free hemoglobin oxidizes to methemoglobin, which is brown in color.
      • The renal proximal tubular cells reabsorb and catabolize much of the filtered hemoglobin and methemoglobin, but some passes out in the urine, imparting a red-brown color.
      • Iron released from hemoglobin can accumulate within tubular cells, giving rise to renal hemosiderosis.
• Unlike in extravascular hemolysis, splenomegaly is not seen.
• • Morphology
    • Compensatory increases in erythropoiesis result in a prominent reticulocytosis in the peripheral blood.
    • The phagocytosis of red cells leads to hemosiderosis, which is most pronounced in the spleen, liver, and bone marrow.
    • If the anemia is severe, extramedullary hematopoiesis can appear in the liver, spleen, and lymph nodes.

• With chronic hemolysis, elevated biliary excretion of bilirubin promotes the formation of pigment gallstones (cholelithiasis).

• In all types of uncomplicated hemolytic anemias, the excess serum bilirubin is unconjugated.

• When the liver is normal, jaundice is rarely severe
• There is increased formation and fecal excretion of urobilin
• • Hemolytic Disease due to Glucose-6-Phosphate Dehydrogenase Deficiency
    • It reduce the ability of red cells to protect themselves against oxidative injuries and lead to hemolysis.
    • G6PD deficiency reduces NADP to NADPH conversion while oxidizing glucose-6-phosphate
• NADPH provides reducing equivalents needed for conversion of oxidized glutathione to reduced glutathione
• • • reduced glutathione protects against oxidant injury by catalyzing the breakdown of compounds such as H2O2
• It is a recessive X-linked trait
• • • it places males at higher risk for symptomatic disease.
    • two variants-  G6PD- and G6PD Mediterranean,
    • G6PD deficiency offers  protective effect against Plasmodium falciparum malaria.
    • older red cells are much more prone to hemolysis than younger ones.
    • common triggers of episodic hemolysis
• viral hepatitis, pneumonia, and typhoid
• • • • oxidant drugs

• antimalarials (e.g., primaquine and chloroquine),

• sulfonamides
• nitrofurantoins,
• • • • fava bean in Mediterranean variant
    • Uncommonly, G6PD deficiency presents as neonatal jaundice or a chronic low-grade hemolytic anemia in the absence of infection or known environmental triggers.
    • Oxidants cause both intravascular and extravascular hemolysis in G6PD-deficient individuals.
    • Heinz bodies
      • Exposure of G6PD-deficient red cells to high levels of oxidants causes the cross-linking of reactive sulfhydryl groups on globin chains
      • Globin chains become denatured and form membrane-bound precipitates known as Heinz bodies
      • These are seen as dark inclusions within red cells stained with crystal violet
      • Heinz bodies can damage the membrane sufficiently to cause intravascular hemolysis.
• Bite cells
• • • • As inclusion-bearing red cells pass through the splenic cords, macrophages pluck out the Heinz bodies
      • As a result of membrane damage, some of these partially devoured cells retain an abnormal shape, appearing to have a bite taken out of them
• Spherocytes are seen
• • Both bite cells and spherocytes are trapped in splenic cords and removed rapidly by phagocytes.
  • hemolysis tends to be greatest in G6PD Mediterranean variant.
  • Since only older red cells are at risk for lysis, the episode is self-limited,.
  • Since hemolytic episodes occur intermittently, features related to chronic hemolysis (e.g., splenomegaly, cholelithiasis) are absent.