HEMOLYTIC ANEMIA

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    • 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.


    Hemolytic Anemia
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    Disclaimer: The medical information contained herein is intended for physician medical licensing exam review purposes only, and are not intended for diagnosis of any illness. If you think you may be suffering from any medical condition, you should consult your physician or seek immediate medical attention.)
    Hemolytic Anemia
    WAHA Warm Autoimmune Hemolytic Anemia AIHA
    There are two models for this: the hapten model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin and cephalosporins, will bind to certain proteins on the red cell membrane and act as haptens (small molecules that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself). Antibodies are created against the protein-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence.