Hemolytic Anemia | Anatomy2Medicine
Hemolytic Anemia Causes

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.