The basic pathophysiology of HS is that spectrin, ankyrin, or band 3 defects weaken the _____ and destabilize the ______.
cytoskeleton; lipid bilayer
______ are more susceptible in vitro to osmotic stress, the basis for a common test for the disorder.
Spherocytes
What happens when the cold antibodies and RBC move centrally to areas of higher temperature?
the Ab dissociates b/c of low affinity and complement destroys the RBC (intravascular hemolysis)
The basic pathophysiology of HS is that ____, _____, or _____ weaken the cytoskeleton and destabilize the lipid bilayer.
spectrin; ankyrin; band 3 defects
By definition, autoimmune hemolytic anemia should have a _____.
positive DAT
What does the AIHA smear look like?
spherocytes, teardrop cells, bite cells
The tetramer form of _____ is unstable and dissociates into αβ dimers which may immediately bind to haptoglobin.
hemoglobin
What are 2 complications of HS?
1) aplastic crisis 2) bilirubin stones
What is the treatment for G6PD?
none- just avoid oxidant drugs and foods; treat anemia as needed
How is G6PD inherited?
X-linked recessive
Cold antibodies bound to the RBC activate ______ through the C5-C9 attack complex, which creates holes in the plasma membrane.
complement
In ______, phosphoenolpyruvate cannot be converted to pyruvate, so ATP is decreased, 2,3-DPG is increased, membrane plasticity is reduced, and the spleen destroys the RBCs
pyruvate kinase (PK) deficiency
How do you prevent sepsis in pts with a splenectomy?
immunizations against the flu and pneumonia; prophylactic antibiotics
What is the method of inheritance of HS?
75% auto dominant; 25% recessive
Defects in the RBC _____ and associated ____ pathways may present with hemolytic anemia.
glycolytic; enzyme
The tetramer form of hemoglobin is unstable and dissociates into αβ dimers which may immediately bind to _____.
haptoglobin
What does G6PD protect against?
oxidant stress
The unconjugated bilirubin fraction will be _____ in hemolytic anemia.
elevated
By definition, _____ should have a positive DAT.
autoimmune hemolytic anemia
What morphologic features of RBCs are seen in G6PD?
bite cells, microspherocytes
Defects in the RBC glycolytic and associated enzyme pathways may present with ______.
hemolytic anemia
At what temperature is maximal effect of warm hemolytic anemia seen?
37 deg C
Why is splenectomy contraindicated in children under 5?
it is important for development of the adaptive humoral response and is the origin of IgM agglutinins, especially for encapsulated organisms
_____ is characterized by the acute or chronic onset of anemia, pallor, jaundice, and dark urine.
Autoimmune hemolytic anemia (AIHA)
Autoimmune hemolytic anemia (AIHA) is characterized by the acute or chronic onset of ____, ____, ____, and _____.
anemia; pallor; jaundice; dark urine
How will the metheme or methemalbumin appear in the CBC in hemolytic anemia?
increased
G6PD is associated with selective resistance to _____.
plasmodium vivax/malaria
What is the most common glycolytic enzyme defect affecting RBCs?
pyruvate kinase (PK) deficiency
What is the rate of sepsis in splenectomy pts as compared to the general population?
200x
What 2 enzymes may be elevated in hemolytic anemia after being spilled by RBCs?
SGOT and LDH
What tests should be run to check for IgG and/or complement on the RBCs?
antiglobulin or Coombs tests
How are RBCs bound by warm antibodies destroyed?
antibody-mediated phagocytosis via the splenic macs (extravascular hemolysis)
The hemoglobin/haptoglobin complex is removed from circulation by the ____.
liver
Cold antibodies bound to the RBC activate complement through the ______, which creates holes in the plasma membrane.
C5-C9 attack complex
What kind of antibodies are seen in warm hemolytic anemia?
IgG
What cells in the spleen remove the fragile RBCs?
macs
Red cells undergoing _____ release hemoglobin into the circulation.
intravascular hemolysis
What are the 2 kinds of autoimmune hemolytic anemia?
cold and warm
The tetramer form of hemoglobin is unstable and dissociates into ____ which may immediately bind to haptoglobin.
αβ dimers
Red cells undergoing intravascular hemolysis release _____ into the circulation.
hemoglobin
The symptoms of HS can be variable, so what is the hallmark of the disorder?
loss of PM and formation of the microspherocyte
With _____, the red cell is ingested by macrophages of the reticuloendothelial (RE) system.
extravascular hemolysis
Hereditary spherocytosis (HS) is a familial disorder characterized by ____, _____, _____, and _____.
anemia, intermittent jaundice, splenomegaly, responsiveness to splenectomy
____ is associated with selective resistance to plasmodium vivax/malaria.
G6PD
What happens in pyruvate kinase (PK) deficiency?
phosphoenolpyruvate cannot be converted to pyruvate, so ATP is decreased, 2,3-DPG is increased, membrane plasticity is reduced, and the spleen destroys the RBCs
What are the treatments for HS?
supportive care, transfusions, splenectomy
What are milder syndromes assoc. with defects in the RBC cytoskeleton?
1) hereditary elliptocytosis 2) stomatocytosis 3) acanthocytosis 4) echinocytosis
The _____ is removed from circulation by the liver.
hemoglobin/haptoglobin complex
What is aplastic crisis?
when a viral infection causes severe anemia bc of suppressed erythropoiesis coupled to short RBC lifespan
Spherocytes are more susceptible in vitro to ____, the basis for a common test for the disorder.
osmotic stress
With extravascular hemolysis, the RBC is ingested by _____ of the reticuloendothelial (RE) system.
macrophages
Loss of membrane and formation of the spherocyte leads to decreased _____ and ______.
deformability; entrapment in the spleen
What intracellular disorders can result in shortened RBC lifespans?
defects in the plasma membrane/cytoskeleton, enzyme disorders, and hemoglobinopathies
How will the serum haptoglobin levels appear on the CBC in hemolytic anemia?
decreased
What kind of antibodies are seen in cold hemolytic anemia?
IgG and IgM
Hemoglobin in the plasma or urine indicates _____.
intravascular hemolysis
What happens in G6PD deficient RBCs?
they are unable to restore reduced glutathione, which deforms the membrane
On the CBC, what bilirubin test will be elevated in hemolytic anemia?
the unconjugated bilirubin fraction
At what temperature is maximal effect of cold hemolytic anemia seen?
4 deg C
With extravascular hemolysis, the red cell is ingested by macrophages of the _____.
reticuloendothelial (RE) system
What cell morphology will be seen in PKD?
nothing specific
What is the most common infection seen in pts post splenectomy?
S. pneumoniae
How are RBCs bound by cold antibodies destroyed?
intravascular hemolysis
Why are bilirubin stones common in HS?
large amounts of bilirubin circulates
_____ bound to the RBC activate complement through the C5-C9 attack complex, which creates holes in the plasma membrane.
Cold antibodies
_____ is a familial disorder characterized by anemia, intermittent jaundice, splenomegaly, and responsiveness to splenectomy.
Hereditary spherocytosis (HS)
What are the 2 mechanisms of RBC destruction?
1) intravascular 2) extravascular