Paroxysmal Nocturnal Hemoglobinuria –
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Terms in this set (28)
What are the 3 main subtypes of Classical PNH, which includes patients who have
PNH? evidence of PNH in the absence of another bone
marrow failure disorder.
PNH in the context of other primary bone marrow
disorders, such as aplastic anemia or MDS
Subclinical PNH, in which patients have small PNH
clones but no clinical or laboratory evidence of
hemolysis or thrombosis
What mutation is responsible for A somatic mutation of the gene PIGA is responsible
PNH? for disease.
Protein encoded by PIGA is required for GPI anchors,
which are responsible for attachment of proteins to
cell membrane surface.
PNH stem cells have reduced GPI-anchored proteins
(i.e. CD55 and CD59)
CD55 and CD59 inhibit complement activity resulting
in PNH red cells being susceptible to hemolysis
Who should be screened for PNH? Patients with...
1. Coombs-negative hemolytic anemia
2. Aplastic anemia
3. Refractory anemia
4. Thrombosis with coexisting cytopenias
, What is the diagnostic test of choice? Flow cytometry for evaluation of CD55 and CD59
*CD55 is also present on granulocytes and
monocytes
*CD16 on granulocytes
How does eculizumab work? Eculizumab is a monoclonal antibody directed
against C5 that inhibits terminal complement
activation (blocks formation of MAC, protecting PNH
red blood cells from hemolysis
- Prevents cleavage of C5 by C5 convertase
- Effective in reducing intravascular hemolysis
- Does not treat extravascular hemolysis or bone
marrow failure
Hemolysis in PNH results from the Complement activation
increased susceptibility of PNH red
cells to _____________. PNH red cells are more vulnerable to complement-
mediated lysis because of a reduction, or complete
absence, of CD55 and CD59--both of which prevent
formation of MAC.
What is the complement system? Part of the immune system that enhances the ability
of antibodies and phagocytic cells to clear
microbes/damaged cells, promotes inflammation,
and attacks the pathogen's cell membrane.
Consists of a number of small proteins found in the
blood.
Failure of complement regulation on Increased consumption of nitric oxide
the PNH erythrocyte membrane leads
to intravascular hemolysis resulting in
the release of large amounts of free
hemoglobin into the plasma. Free
plasma hemoglobin leads to...
PNH patients have a greater than Kidney
sixfold increased risk of chronic _________
disease. Renal tubular damage is caused by microvascular
thrombosis and accumulation of iron deposits.
Questions With A+ Solutions
Save
Terms in this set (28)
What are the 3 main subtypes of Classical PNH, which includes patients who have
PNH? evidence of PNH in the absence of another bone
marrow failure disorder.
PNH in the context of other primary bone marrow
disorders, such as aplastic anemia or MDS
Subclinical PNH, in which patients have small PNH
clones but no clinical or laboratory evidence of
hemolysis or thrombosis
What mutation is responsible for A somatic mutation of the gene PIGA is responsible
PNH? for disease.
Protein encoded by PIGA is required for GPI anchors,
which are responsible for attachment of proteins to
cell membrane surface.
PNH stem cells have reduced GPI-anchored proteins
(i.e. CD55 and CD59)
CD55 and CD59 inhibit complement activity resulting
in PNH red cells being susceptible to hemolysis
Who should be screened for PNH? Patients with...
1. Coombs-negative hemolytic anemia
2. Aplastic anemia
3. Refractory anemia
4. Thrombosis with coexisting cytopenias
, What is the diagnostic test of choice? Flow cytometry for evaluation of CD55 and CD59
*CD55 is also present on granulocytes and
monocytes
*CD16 on granulocytes
How does eculizumab work? Eculizumab is a monoclonal antibody directed
against C5 that inhibits terminal complement
activation (blocks formation of MAC, protecting PNH
red blood cells from hemolysis
- Prevents cleavage of C5 by C5 convertase
- Effective in reducing intravascular hemolysis
- Does not treat extravascular hemolysis or bone
marrow failure
Hemolysis in PNH results from the Complement activation
increased susceptibility of PNH red
cells to _____________. PNH red cells are more vulnerable to complement-
mediated lysis because of a reduction, or complete
absence, of CD55 and CD59--both of which prevent
formation of MAC.
What is the complement system? Part of the immune system that enhances the ability
of antibodies and phagocytic cells to clear
microbes/damaged cells, promotes inflammation,
and attacks the pathogen's cell membrane.
Consists of a number of small proteins found in the
blood.
Failure of complement regulation on Increased consumption of nitric oxide
the PNH erythrocyte membrane leads
to intravascular hemolysis resulting in
the release of large amounts of free
hemoglobin into the plasma. Free
plasma hemoglobin leads to...
PNH patients have a greater than Kidney
sixfold increased risk of chronic _________
disease. Renal tubular damage is caused by microvascular
thrombosis and accumulation of iron deposits.
