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Pathology - Blood Module > Paroxysmal Nocturnal Hemoglobinuria > Flashcards

Paroxysmal Nocturnal Hemoglobinuria Flashcards

1
Q

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that results from acquired mutations in the ______________ gene.

A

phosphatidylinositol glycan complementation group A (PIGA)

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2
Q

PNH has an incidence of ______ per million in the

United States

A

2-5

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3
Q

PNH is the only hemolytic anemia caused by an

_________ (hereditary/acquired) genetic defect

A

acquired

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4
Q

In PNH, these __________ (transmembrane/GPI-linked) proteins are deficient because of somatic mutations that inactivate PIGA

A

GPI-linked

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5
Q

What is the function of PIGA?

A

PIGA is an enzyme that is essential for the synthesis of
certain membrane-associated “complement regulatory
proteins”

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6
Q

PIGA is _________ (X-linked/autosome linked) and dominant in nature.

A

X-linked

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7
Q

PIGA is subject to lyonization so only a single acquired mutation in the PIGA gene is enough to produce the disease. What is lyonization?

A

random inactivation of one X chromosome in cells of females

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8
Q

The mutations occur in a ________________,

all of its clonal progeny (red cells, white cells, and platelets) are deficient in GPI-linked proteins.

A

hematopoietic stem cell

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9
Q

PNH blood cells are deficient in three GPI-linked proteins that regulate complement activity. Name the proteins.

A

CD55
CD59
C8 binding protein

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10
Q

What is the other name of CD55?

A

Decaying accelerating factor

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11
Q

What is the other name of CD59?

A

membrane inhibitor of reactive lysis

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12
Q

What is the function of CD59?

A

It is a potent inhibitor of C3 convertase that prevents the spontaneous activation of the alternative complement pathway

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13
Q

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?

A

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.

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14
Q

PNH is frequently associated with _____________ (thalassemia/aplastic anemia)

A

aplastic anemia

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15
Q

Red cells _________ (sufficient/deficient) in these GPI-linked factors are abnormally susceptible to lysis or injury by complement.

A

deficient

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16
Q

____________ (Intravascular/Extravascular) hemolysis occurs in PNH

A

Intravascular

17
Q

The hemolysis is paroxysmal and nocturnal in only __% of cases

A

25

18
Q

Intravascular hemolysis is caused by _____________.

A

C5-9 membrane attack complex

19
Q

What happens in 75% of the cases in PNH?

A

Chronic hemolysis without hemoglobinuria

20
Q

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

A

decrease

21
Q

The anemia in PNH is _________ (mild-moderate/moderate-severe)

A

mild-moderate

22
Q

The loss of heme iron in the urine (hemosiderinuria) eventually leads to _____________.

A

Iron deficiency

23
Q

___________ (Thrombosis/Infection) is the leading cause of disease-related death in individuals with PNH.

A

Thrombosis

24
Q

About 40% of patients suffer from ________ (venous/arterial) thrombosis in PNH

A

venous

25
Q

Which veins are involved in thrombosis?

A

Hepatic veins
Portal veins
Cerebral veins

26
Q

Few patients eventually develop some bone marrow disorder due to some kind of genetic damage. Name the disorders

A

Acute myeloid leukemia

Myelodysplastic syndrome

27
Q

PNH is diagnosed by ____________ (flow cytometry/gel electrophoresis), which provides a
sensitive means for detecting red cells that are deficient in GPI-linked proteins such as CD59

A

flow cytometry

28
Q

____________ prevents the conversion of C5 to C5a.

A

Eculizumab

29
Q

____________ not only reduces the hemolysis and attendant transfusion requirements, but also lowers the risk of thrombosis by up to 90%

A

Eculizumab

30
Q

What are the drawbacks of C5 inhibitor therapy (Eculizumab)?

A

The high cost ($500,000 per year)

Risk of fatal or serious meningococcal infections

31
Q

What can we give for aplastic anemia in patients with PNH?

A

Immunosuppressants

32
Q

What is the cure for paroxysmal nocturnal hemoglobinuria?

A

Hematopoietic stem cell transplantation

Pathology - Blood Module (20 decks)

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