Intravascular Hemolytic Anemias + Underproduction Flashcards
Paroxysmal nocturnal hemoglobinuria (PNH)
genetics
acquired defect in myeloid progenitor cells
defect: GPI anchoring protein
GPI normally anchors DAF/CD55 and MIRL
these normally prevent complement binding
GPI defect in PNH found on which cells
all blood cells: RBCs, WBC, platelets (death! due to spilling of coagulation factors) –> venous thrombosis
Why does PNH occur at night
shallow breathing –> resp acidosis
activation of complement
Tx of PNH
eculizumab
terminal complement inhibitor
CD55
ie DAF
normally inhibits complement binding to blood cells
anchored via GPI
GPI defective in PNH
Increased risk of what in PNH
AML
because mutation is in myeloid progenitor cell
increased risk of other mutations
How to diagnose PNH
look for CD55/DAF on flow
would be - in this case because GPI does not allow them to bind
Coombs test in PNH
negative
Hemosiderinuria in PNH
occurs days later
when Hb forms hemosiderin in renal tubules
then sluffs off
2 types of anemia in PNH
acute hemolytic
iron-deficient (repeat bouts)
Cause of death PNH
venous thrombosis (portal, hepatic, cerebral)
Triad of PNH
Coombs - hemolytic anemia
pancytopenia
venous thrombosis
Normal function of G6PD enzyme
reduce glutathione
glutathione normally takes care of oxidative stress in RBCs
Inheritance of G6PD deficiency
X-linked recessive
Sx of G6PD
back pain w/ insult
because Hb is nephrotoxic
