Paroxysmal Nocturnal Hemoglobinuria –
Questions And Correct Answers
Save
Terms in this set (45)
A 35-year-old woman comes to the Venous thrombosis
physician because of a 2-month
history of progressive fatigue and This patient presents with fatigue, abdominal pain,
intermittent abdominal pain. During jaundice, and dark urine in the morning.
this time, she has noticed that her Investigations show pancytopenia, evidence of
urine is darker when she wakes up in intravascular hemolysis (unconjugated
the morning. Her stool is of normal hyperbilirubinemia, elevated LDH, low haptoglobin),
color. Five months ago, she was and red urine without RBCs in the sediment
diagnosed with type 2 diabetes (consistent with hemoglobinuria). Together with a
mellitus, for which she takes negative Coombs test (indicative of a non-immune
metformin. Physical examination pathology) and normal peripheral blood smear,
shows pallor and jaundice. There is no these features are suggestive of paroxysmal
splenomegaly. Laboratory studies nocturnal hemoglobinuria (PNH).
show:
Hemoglobin 7.5 g/dL
WBC count 3,500/mm3
Platelet count 100,000/mm3
Serum
Creatinine 1.0 mg/dL
Total bilirubin 6.0 mg/dL
Direct bilirubin 0.2 mg/dl
Lactate dehydrogenase 660 U/L
Haptoglobin 18 mg/dL (N=41-165
mg/dL)
Her urine is red, but urinalysis shows
no RBCs. A Coombs test is negative.
Peripheral blood smear shows no
abnormalities. This patient is at
greatest risk for which of the following
complications?
,Venous thrombosis Venous thrombosis is the leading cause of mortality
in PNH. Thrombosis occurs in atypical locations, such
as hepatic veins (Budd-Chiari syndrome), portal
veins, and cerebral veins (headaches, stroke). The
free Hb released during hemolysis scavenges serum
nitric oxide (a vasodilator) and activates the
endothelial lining of the blood vessels, leading to
vasoconstriction and platelet aggregation, and, as a
result, venous thrombosis. Physiologically, membrane
proteins CD55/CD59 protect erythrocytes from
complement-mediated hemolysis; a
glycosylphosphatidylinositol (GPI) anchor keeps
these proteins attached to the surface of the cell.
PNH is caused by an acquired genetic defect that
results in a deficiency of the GPI anchor, leaving
erythrocytes susceptible to complement-mediated
hemolysis.
Budd-Chiari syndrome Posthepatic venous thrombosis
Hepatic vein obstruction that leads to hepatomegaly,
ascites, and abdominal discomfort. It is most
commonly due to a thrombotic occlusion secondary
to a chronic myeloproliferative neoplasm (e.g.,
polycythemia vera), but may be caused by other
conditions associated with hypercoagulable states.
The obstruction of blood flow causes congestion of
the liver with subsequent liver cell damage resulting
in progressive liver failure.
, CD55 and CD59 CD55: decay accelerating factor
A surface protein found on erythrocytes that inhibits
extravascular hemolysis by preventing the assembly
of C3 and C5 convertases. Normally attached to
erythrocytes via a GPI anchor.
CD59: MAC inhibitory protein
A surface protein found on erythrocytes that inhibits
intravascular hemolysis by preventing the production
of the membrane attack complex. Normally attached
to erythrocytes via a GPI anchor.
inactivate complement
Paroxysmal nocturnal hemoglobinuria (PNH) cells
are susceptible to hemolysis because of a loss of the
complement regulatory proteins CD59 and CD55
Cold Agglutinin Disease This is an autoimmune hemolytic anemia caused by
Mycoplasma pneumonia and infectious
mononucleosis. There are painful blue fingers/toes.
In cold agglutinin disease (CAD), immunoglobulin M
autoantibodies fix complement on the surface of red
cells, resulting in extravascular hemolysis by the
reticuloendothelial system
Questions And Correct Answers
Save
Terms in this set (45)
A 35-year-old woman comes to the Venous thrombosis
physician because of a 2-month
history of progressive fatigue and This patient presents with fatigue, abdominal pain,
intermittent abdominal pain. During jaundice, and dark urine in the morning.
this time, she has noticed that her Investigations show pancytopenia, evidence of
urine is darker when she wakes up in intravascular hemolysis (unconjugated
the morning. Her stool is of normal hyperbilirubinemia, elevated LDH, low haptoglobin),
color. Five months ago, she was and red urine without RBCs in the sediment
diagnosed with type 2 diabetes (consistent with hemoglobinuria). Together with a
mellitus, for which she takes negative Coombs test (indicative of a non-immune
metformin. Physical examination pathology) and normal peripheral blood smear,
shows pallor and jaundice. There is no these features are suggestive of paroxysmal
splenomegaly. Laboratory studies nocturnal hemoglobinuria (PNH).
show:
Hemoglobin 7.5 g/dL
WBC count 3,500/mm3
Platelet count 100,000/mm3
Serum
Creatinine 1.0 mg/dL
Total bilirubin 6.0 mg/dL
Direct bilirubin 0.2 mg/dl
Lactate dehydrogenase 660 U/L
Haptoglobin 18 mg/dL (N=41-165
mg/dL)
Her urine is red, but urinalysis shows
no RBCs. A Coombs test is negative.
Peripheral blood smear shows no
abnormalities. This patient is at
greatest risk for which of the following
complications?
,Venous thrombosis Venous thrombosis is the leading cause of mortality
in PNH. Thrombosis occurs in atypical locations, such
as hepatic veins (Budd-Chiari syndrome), portal
veins, and cerebral veins (headaches, stroke). The
free Hb released during hemolysis scavenges serum
nitric oxide (a vasodilator) and activates the
endothelial lining of the blood vessels, leading to
vasoconstriction and platelet aggregation, and, as a
result, venous thrombosis. Physiologically, membrane
proteins CD55/CD59 protect erythrocytes from
complement-mediated hemolysis; a
glycosylphosphatidylinositol (GPI) anchor keeps
these proteins attached to the surface of the cell.
PNH is caused by an acquired genetic defect that
results in a deficiency of the GPI anchor, leaving
erythrocytes susceptible to complement-mediated
hemolysis.
Budd-Chiari syndrome Posthepatic venous thrombosis
Hepatic vein obstruction that leads to hepatomegaly,
ascites, and abdominal discomfort. It is most
commonly due to a thrombotic occlusion secondary
to a chronic myeloproliferative neoplasm (e.g.,
polycythemia vera), but may be caused by other
conditions associated with hypercoagulable states.
The obstruction of blood flow causes congestion of
the liver with subsequent liver cell damage resulting
in progressive liver failure.
, CD55 and CD59 CD55: decay accelerating factor
A surface protein found on erythrocytes that inhibits
extravascular hemolysis by preventing the assembly
of C3 and C5 convertases. Normally attached to
erythrocytes via a GPI anchor.
CD59: MAC inhibitory protein
A surface protein found on erythrocytes that inhibits
intravascular hemolysis by preventing the production
of the membrane attack complex. Normally attached
to erythrocytes via a GPI anchor.
inactivate complement
Paroxysmal nocturnal hemoglobinuria (PNH) cells
are susceptible to hemolysis because of a loss of the
complement regulatory proteins CD59 and CD55
Cold Agglutinin Disease This is an autoimmune hemolytic anemia caused by
Mycoplasma pneumonia and infectious
mononucleosis. There are painful blue fingers/toes.
In cold agglutinin disease (CAD), immunoglobulin M
autoantibodies fix complement on the surface of red
cells, resulting in extravascular hemolysis by the
reticuloendothelial system
