Increased destruction of red blood cells in the
peripheral blood without evidence of ineffective
erythropoiesis is known as hemolytic anemia. Such anemias
are generally classified into either inherited or acquired
Hemolysis is the premature destruction of RBCs due to
intrinsic inherited defects in the RBCs or because of
acquired intravascular abnormalities.
RBCs normally live about 120 days following bone marrow
release as reticulocytes. When the RBCs become senescent
they are removed from the peripheral blood by macrophages in
the spleen and liver.
Hemolysis may be either intravascular or extravascular.
In intravascular hemolysis RBCs lyse in the circulation
releasing hemoglobin into the plasma. Causes include
mechanical trauma, complement fixation, and other toxic
damage to the RBC. The fragmented RBCs are called
In extravascular hemolysis RBCs are phagocytized by
macrophages in the spleen and liver. Causes include RBC
membrane abnormalities such as bound immunoglobulin, or
physical abnormalities restricting RBC deformability that
prevent egress from the spleen. Extravascular hemolysis is
characterized by spherocytes.
Intravascular hemolysis releases hemoglobin which is
immediately bound by haptoglobin.
Hemoglobin-haptoglobin is cleared almost immediately from
the plasma by hepatic reticuloendothelial cells.
As intravascular hemolysis with binding to haptoglobin
generally overwhelms the rate of haptoglobin synthesis,
haptoglobin levels decrease.
After haptoglobin is saturated, excess hemoglobin is
filtered in the kidney and reabsorbed in the proximal
tubules where the iron is recovered and converted into
ferritin or hemosiderin.
Hemoglobinuria indicates severe intravascular hemolysis
overwhelming the absorptive capacity of the renal tubular
Urine hemosiderin is another indicator that intravascular
free hemoglobin is being filtered by the kidneys.
Lactic dehydrogenase (LDH) is greatly elevated in
patients with intravascular hemolysis.
Note: Haptoglobin, synthesized by the liver, is
decreased in patients with hepatocelIular disease.
In extravascular hemolysis spleen and liver macrophage Fc
receptors bind immunoglobulin attached to RBCs and then
either ingest small portions of the RBC membrane creating
spherocytes or phagocytizing the RBCs.
Amino acids from the globin chains are recycled and the
Fe removed from the heme and reused.
The heme is degraded into the tetrapyrrole, bilirubin.
Note: Because little hemoglobin escapes into the
plasma in extravascular hemolysis, haptoglobin does not
Free unconjugated bilirubin is transported to the liver
where it is conjugated to glucuronic acid.
In extravascular hemolysis plasma levels of unconjugated
bilirubin increase because the hepatocytes cannot process
the excess bilirubin.
Conjugated bilirubin is excreted into the
gastrointestinal tract where it is converted to urobilinogen
and eventually excreted in the feces as stercobilinogen.
Conjugated bilirubin levels are usually normal in
Remember unconjugated bilirubin cannot pass the
Common hereditary hemolytic anemias include the
hemoglobinopathies and abnormalities of RBC membranes and
Common acquired abnormalities include mechanical trauma,
antibody mediated damage, and other toxic or physical
Transfused normal RBCs will have a shortened survival, no
different than the short lifespan of the patient's own RBCs,
if, the abnormalities are acquired and extrinsic to the RBC.
This is the case in most hemolytic anemias
If the cause of the hemolytic anemia is intrinsic to the
red cell (a hemoglobinopathy or a membrane or enzyme
abnormality) the normal ransfused RBCs will have a normal
Normal Red Cell Membrane Review
The RBC membrane is a phospholipid bilayer with varying
amounts of membrane cholesterol. A number of transmembrane
(band 3 and several glycophorins) and membrane support
[actin; ankryn (band2.1); band4.1; spectrin] proteins are
The actin - spectrin - 4.1 complexes help maintain the
structural strength and stability of the RBC membrane. The
spectrin - ankryn - band 3 complexes stabilize the
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