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
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- More common cause of hemolytic anemias
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- caused by alterations that render the red cell less deformable
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- principal clinical features of extravascular hemolysis
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- anemia
- splenomegaly,
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- 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.
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- Why individuals with extravascular hemolysis often benefit from splenectomy ?
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- Because much of the pathologic destruction of red cells occurs in the spleen
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- Intravascular hemolysis
- Causes
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- mechanical injury
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- 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
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- intravascular hemolysis is manifested by
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- anemia,
- hemoglobinemia,
- hemoglobinuria,
- hemosiderinuria,
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- jaundice.
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- Pathophysiology
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- 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.
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- Unlike in extravascular hemolysis, splenomegaly is not seen.
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- 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.
- Morphology
- 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
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- 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
- Hemolytic Disease due to Glucose-6-Phosphate Dehydrogenase Deficiency
- NADPH provides reducing equivalents needed for conversion of oxidized glutathione to reduced glutathione
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- reduced glutathione protects against oxidant injury by catalyzing the breakdown of compounds such as H2O2
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- It is a recessive X-linked trait
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- 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
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- viral hepatitis, pneumonia, and typhoid
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- oxidant drugs
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- antimalarials (e.g., primaquine and chloroquine),
- sulfonamides
- nitrofurantoins,
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- 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.
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- Bite cells
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- 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
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- Spherocytes are seen
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- 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.