Ch 17.2 Paroxysmal Nocturnal Hemoglobinuria –
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Terms in this set (85)
Define Paroxysmal nocturnal A rare, clonal HSC disorder that manifests with a
hemoglobinuria chronic intravascular hemolytic anemia from
uncontrolled complement activation, a propensity for
thrombosis, and bone marrow failure.
Triad:
1) Chronic intravascular hemolysis
2) Thrombosis
3) Pancytopenia
Mechanism of hemolysis in PNH? The hemolysis is largely mediated by the alternative
pathway of complement.
Clinical manifestations in PNH are the CD55 and CD59
result of the lack of what 2 specific
cell surface proteins CD55: Decay Accelerating Factor (DAF)
C59: Protectin or MIRL (Membrane Inhibitor of
Reactive Lysis aka MAC inhibitory protein)
Lack of CD55 and CD59, on PNH cells PIGA gene in HSCs, which results in
are the result of a somatic mutation in failure to synthesize the glycosylphosphatidylinositol
the what gene (GPI)
anchor
PIGA = Phosphatidyl Inositol Glycan A (class A)
,Hemolysis in PNH is _______________ Complement (for both spaces)
mediated and is a direct result of the
mutated PNH cells acquiring a
deficiency of _____________ regulatory
proteins.
In PNH, what is the consequence of The first step in biosynthesis of the GPI anchor
the defect of the enzyme encoded by protein (AP) cannot be completed normally (Figure
the mutant PIGA gene 17-4B), and all GPI-anchored proteins are absent on
the surface of progeny cells of all hematopoietic
lineages derived from the
affected stem cell with increased susceptibility to
hemolysis (Figures 17-4C and D)
What is the role of GPI-anchored They attenuate complement activation on the surface
proteins (CD55 and CD59) of erythrocytes.
What is the difference between PNH Depending on the type of mutation in the PIGA gene,
type I, II and II cells various degrees of CD55 and CD59 deficiency can
occur.
Patients with PNH may have in their circulation an
admixture of normal complement-resistant red blood
cells (so-called PNH I cells), as well as mildly (PNH
II) or markedly (PNH III) abnormal complement-
sensitive cells.
What contributes to the variability in The type of mutation in the PIGA gene
intravascular hemolysis seen in PNH
patients. Different types of mutation result in various degrees
of CD55 and CD59 deficiency
Thus, PNH cells may be normal complement-
resistant red blood cells (so-called PNH I cells), as
well as mildly (PNH II) or markedly (PNH III)
abnormal complement-sensitive cells.
The difference in the proportion of these red blood
cell populations contributes to the variability in
intravascular hemolysis seen in patients.
, Thrombophilia in PNH is related to the PNH clone
degree of hemolysis and thereby
indirectly related to the size of the
_________ _________
Why do PNH patients have a Hypercoagulability mechanism has not been clearly
propensity for thrombosis defined
Name 4 prothrombotic pathways Possible prothrombotic pathways include:
1) Platelet activation by complement components
2)Procoagulable microparticles derived from GPI-
deficient erythrocytes
3) Slowing of the microcirculation because of
vasoconstriction induced by products of hemolysis
4) Intravascular hemolysis exposes red blood cell
phospholipids that may serve to initiate coagulation
Accurate Solutions For Every Question
Save
Terms in this set (85)
Define Paroxysmal nocturnal A rare, clonal HSC disorder that manifests with a
hemoglobinuria chronic intravascular hemolytic anemia from
uncontrolled complement activation, a propensity for
thrombosis, and bone marrow failure.
Triad:
1) Chronic intravascular hemolysis
2) Thrombosis
3) Pancytopenia
Mechanism of hemolysis in PNH? The hemolysis is largely mediated by the alternative
pathway of complement.
Clinical manifestations in PNH are the CD55 and CD59
result of the lack of what 2 specific
cell surface proteins CD55: Decay Accelerating Factor (DAF)
C59: Protectin or MIRL (Membrane Inhibitor of
Reactive Lysis aka MAC inhibitory protein)
Lack of CD55 and CD59, on PNH cells PIGA gene in HSCs, which results in
are the result of a somatic mutation in failure to synthesize the glycosylphosphatidylinositol
the what gene (GPI)
anchor
PIGA = Phosphatidyl Inositol Glycan A (class A)
,Hemolysis in PNH is _______________ Complement (for both spaces)
mediated and is a direct result of the
mutated PNH cells acquiring a
deficiency of _____________ regulatory
proteins.
In PNH, what is the consequence of The first step in biosynthesis of the GPI anchor
the defect of the enzyme encoded by protein (AP) cannot be completed normally (Figure
the mutant PIGA gene 17-4B), and all GPI-anchored proteins are absent on
the surface of progeny cells of all hematopoietic
lineages derived from the
affected stem cell with increased susceptibility to
hemolysis (Figures 17-4C and D)
What is the role of GPI-anchored They attenuate complement activation on the surface
proteins (CD55 and CD59) of erythrocytes.
What is the difference between PNH Depending on the type of mutation in the PIGA gene,
type I, II and II cells various degrees of CD55 and CD59 deficiency can
occur.
Patients with PNH may have in their circulation an
admixture of normal complement-resistant red blood
cells (so-called PNH I cells), as well as mildly (PNH
II) or markedly (PNH III) abnormal complement-
sensitive cells.
What contributes to the variability in The type of mutation in the PIGA gene
intravascular hemolysis seen in PNH
patients. Different types of mutation result in various degrees
of CD55 and CD59 deficiency
Thus, PNH cells may be normal complement-
resistant red blood cells (so-called PNH I cells), as
well as mildly (PNH II) or markedly (PNH III)
abnormal complement-sensitive cells.
The difference in the proportion of these red blood
cell populations contributes to the variability in
intravascular hemolysis seen in patients.
, Thrombophilia in PNH is related to the PNH clone
degree of hemolysis and thereby
indirectly related to the size of the
_________ _________
Why do PNH patients have a Hypercoagulability mechanism has not been clearly
propensity for thrombosis defined
Name 4 prothrombotic pathways Possible prothrombotic pathways include:
1) Platelet activation by complement components
2)Procoagulable microparticles derived from GPI-
deficient erythrocytes
3) Slowing of the microcirculation because of
vasoconstriction induced by products of hemolysis
4) Intravascular hemolysis exposes red blood cell
phospholipids that may serve to initiate coagulation
