Test 4: Intrinsic hemolytic Anemias: Membrane Defects Flashcards
 The RBC membrane consists of two interrelated parts, the outer ______________ and the protein __________. 
Lipid bilayer,  Skeleton
Part of the RBC membrane that serves as a barrier, and separates the different concentrations from the cellular interior and the exterior blood plasma
Lipid bilayer
The protein portion of the RBC membrane is responsible for…
Shape, structure, deform ability, and allows for movement of ions and material between the cellular interior and the blood plasma
*alos act as receptors, RBC antigens, and enzymes
This is the anchor for different proteins in the plasma membrane
Spectrin
What causes anemias with high absolute reticulocyte counts?
-hemolysis
-acute blood loss
What are the different hemolysis related anemias?
-immune
-hemoglobinopathy
-membrane defect
-enzyme deficiency
-infection (e.g. malaria)
-microangiopathic
hemolytic anemia
Ture or false:
RBCs are removed from circulation after 120 days by hemolysis.
true
Where does intravascular hemolysis occur?
within the lumen of blood vessels
Lysis without phagocytic involvement
Hgb released directly into plasma
______________ hemolysis occurs after decrease
of RBC flexibility
Loss of glycolytic enzymes
Macrophages in spleen and liver (i.e., reticuloendothelial system)
Extravascular
Extravascular hemolysis:
Intramacrophage RBC breakdown occurs following phagocytosis by when the RBC is attacked by lysosomal enzymes. Hemoglobin is broken down into ______, _______, ______.
heme, iron, and globin
Extravascular Hemolysis:
Heme Iron is stored as ___________ or ________ within the macrophage until needed transferrin and cycle continues. 80% of transferrin
-Globin is broken down and returns to the amino acid pool
ferritin or hemosiderin
Intravascular or extravascular hemolysis?
Cell contents are released into the plasma.
Haptoglobin and hemopexin work to
salvage the released Hgb, so the iron is not lost.
Intravascular hemolysis
Intravascular hemolysis
Cell contents are released into the plasma.
___________ and _________ work to salvage the released Hgb, so the iron is not lost.
Haptoglobin and hemopexin
Where does haptoglobin and hemopexin carry the Hgb to?
to the liver to be broken down into bilirubin.
A decrease in serum _________ may be used
to indicate intravascular hemolysis.
haptoglobin
Intravascular hemolysis:
If haptoglonbin is depleted, free Hgb is…
filtered by the renal glomerulus
Definition of membrane defects
Alters the membrane’s stability, shape,
deformability, and/or permeability
How do membrane defects cause anemia?
when rate of hemolysis
surpasses the rate of compensation by
bone marrow
-Increased likelihood of being trapped in spleen
All hemolytic anemias can be classified into what two groups?
Intrinsic hemolytic anemias
Extrinsic hemolytic anemias
_________ hemolytic anemias:
Usually genetic and occur from defects in
RBC membrane, enzymes, or hemoglobin
Intrinsic
_________ hemolytic anemias
Usually are acquired and occur secondary
to a primary stimulus
Extrinsic
___________ Hemolytic Anemia
RBCs themselves are defective; usually
inherited.
Intrinsic
What are three sites of defect with intrinsic hemolytic anemia?
-membrane
-enzymes
-globin chain sequence
Intrinsic Hemolytic Anemia:
Three examples of membrane defects?
Hereditary spherocytosis (HS)
Hereditary elliptocytosis (HE)
Hereditary pyropoikilocytosis (HPP)
Intrinsic Hemolytic Anemia:
Two examples of enzyme defects?
G6PD deficiency
Pyruvate kinase (PK) deficiency
Intrinsic Hemolytic Anemia:
Examples of globin chain sequence defects?
Hemoglobinopathies (Hgb SS, CC, SC, S-Thal, etc.)
What are the peripheral blood smear findings with hemolytic anemia?
may include anything,
depending upon cause & degree of severity: sickled
cells, target cells, nRBCs, spherocytes, schistocytes,
parasites, & polychromasia
RBC, Hgb, Hct Findings in Hemolytic Anemia?
all decreased
MCV with hemolytic anemia?
Variable MCV (can be ↑ due to retic count, or ↓
due to spherocytes)
What is the most useful in the initial evaluation with hemolytic anemia?
↑ retic count
What are the urinalysis findings with hemolytic anemia?
↑urobilinogen in both types; but ↑ plasma
free Hgb in intravascular hemolysis
True or false:
Positive DAT will confirm an immune hemolytic anemia
True
DAT (Direct Coombs Test):
In certain diseases or conditions an individual’s blood may contain
____ antibodies that can specifically bind to antigens on the red
blood cell (RBC) surface membrane.
IgG
-Circulating red blood cells (RBCs) can become coated with IgG alloantibodies and/or IgG autoantibodies. Complement proteins may
subsequently bind to the bound antibodies.
What test is used to detect antibodies or complement proteins that are bound to the surface of red blood cells?
direct Coombs test
A child was seen by her physician and diagnosed with pneumonia. Her mother has brought her to the physician again because the girl’s urine began to darken after the
first visit and now is alarmingly dark. The
girl has no history of anemia, and there is no
family history. A CBC shows a mild anemia,
polychromasia, and a few schistocytes. This anemia could be categorized as:
A. Acquired, intravascular
B. Acquired, extravascular
C. Hereditary, intravascular
D. Hereditary, extravascular
A. Acquired, intravascular
What are the five major sets of RBC Membrane Abnormalities?
- Hereditary Spherocytosis (HS)
- Hereditary Elliptocytosis (HE)
- Hereditary Pyropoikilocytosis (HPP)
- Hereditary Stomatocytosis
- Hereditary Xerocytosis
*NOTE: All diseases are quite heterogeneous in etiology.
What is the prevalence of Hereditary Spherocytosis (HS)?
Prevalence = about 1 in 5000 in people of Northern European (especially Scandinavian) descent are heterozygous
Homozygous condition is not seen. (FYI: numerous
defects, usually autosomal dominant)
Hereditary Spherocytosis (HS)?
What is the mechanism?
molecular defects in the membrane skeletal
proteins (spectrin, ankyrin, protein 4.1, and band 3).
- RBC p.m. buckles, defective area is removed by spleen (so some micro-spherocytes seen in peripheral blood). P.m. fluidity ↓ , & rigidity ensues, causing
eventual pre-mature hemolysis.
Does HS automatically mean decreased MCV?
No!
What is MCHC typically with Hereditary Spherocytosis?
MCHC ↑ in 1/2 to 2/3 of patients due to slight
cell shrinkage from dehydration.
HS is 1st choice for condition with ↑ ______
MCHC (>37)
-Second choice is Sickle Cell Disease (SCD) in crisis
(due to poik) or severe burns.
What is the confirmatory test for HS?
Osmotic Fragility (OF) Test
RBCs in HS have ________ osmotic fragility. Why?
increased***
-reflects shape of RBCs
Spherocytes already at maximum p.m. expansion, so have limited capacity to expand in hypotonic (<
0.85% NaCl) solutions, & will lyse at higher concentrations of saline than normal RBCs would.
Osmotic Fragility Test
In _________ solutions, water enters the RBCs
until equilibrium is achieved, and internal volume is too great….causing hemolysis!
hypotonic
What can increase the accuracy of the Osmotic fragility test?
Incubating the cells at 37 ̊C for 24 hours, before
testing, increases the accuracy of the test.
Increased OF seen in HS & ____________
(cells fatter & have less resistance to
lysis).
stomatocytes
Decreased osmotic fragility is seen in….
thalassemias, Sickle
Cell Disease, any condition with lots of
targets (cells flatter & have more resistance to lysis).
-hypochromic cells are flatter, have more room to expand
