Paroxysmal Nocturnal Hemoglobinuria Flashcards
Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that results from acquired mutations in the ______________ gene.
phosphatidylinositol glycan complementation group A (PIGA)
PNH has an incidence of ______ per million in the
United States
2-5
PNH is the only hemolytic anemia caused by an
_________ (hereditary/acquired) genetic defect
acquired
In PNH, these __________ (transmembrane/GPI-linked) proteins are deficient because of somatic mutations that inactivate PIGA
GPI-linked
What is the function of PIGA?
PIGA is an enzyme that is essential for the synthesis of
certain membrane-associated “complement regulatory
proteins”
PIGA is _________ (X-linked/autosome linked) and dominant in nature.
X-linked
PIGA is subject to lyonization so only a single acquired mutation in the PIGA gene is enough to produce the disease. What is lyonization?
random inactivation of one X chromosome in cells of females
The mutations occur in a ________________,
all of its clonal progeny (red cells, white cells, and platelets) are deficient in GPI-linked proteins.
hematopoietic stem cell
PNH blood cells are deficient in three GPI-linked proteins that regulate complement activity. Name the proteins.
CD55
CD59
C8 binding protein
What is the other name of CD55?
Decaying accelerating factor
What is the other name of CD59?
membrane inhibitor of reactive lysis
What is the function of CD59?
It is a potent inhibitor of C3 convertase that prevents the spontaneous activation of the alternative complement pathway
Most normal individuals have a small number of cells in the bone marrow that have mutations in PIGA similar to those that cause PNH. What is the difference between normal individuals and individuals that actually have PNH?
In PNH, the cells with mutations are increased more than the normal cells due to any cause, such as autoimmune reactions against GPI-linked antigens.
Normal cells have GPI-linked antigens but cells with mutations do not, leading to increased survival of mutated cells.
PNH is frequently associated with _____________ (thalassemia/aplastic anemia)
aplastic anemia
Red cells _________ (sufficient/deficient) in these GPI-linked factors are abnormally susceptible to lysis or injury by complement.
deficient
____________ (Intravascular/Extravascular) hemolysis occurs in PNH
Intravascular
The hemolysis is paroxysmal and nocturnal in only __% of cases
25
Intravascular hemolysis is caused by _____________.
C5-9 membrane attack complex
What happens in 75% of the cases in PNH?
Chronic hemolysis without hemoglobinuria
The tendency for red cells to lyse at night is
explained by a slight ________ (increase/decrease) in blood pH during sleep, which increases the activity of complement
decrease
The anemia in PNH is _________ (mild-moderate/moderate-severe)
mild-moderate
The loss of heme iron in the urine (hemosiderinuria) eventually leads to _____________.
Iron deficiency
___________ (Thrombosis/Infection) is the leading cause of disease-related death in individuals with PNH.
Thrombosis
About 40% of patients suffer from ________ (venous/arterial) thrombosis in PNH
venous
