Inherited red cell membrane defects include hereditary
spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis,
and pyropoikilocytosis. In each abnormalities of the red cell membrane
result in hemolysis.
Hereditary spherocytosis is characterized by numerous spherocytes on
the PBS (right).
Spherocytes have reduced surface membrane area relative to the RBC
volume. Spherocytes are osmotically fragile compared to normal RBCs.
Spherocytes, being less flexible than normal RBCs, are destroyed in
the spleen, often causing splenomegaly.
Hereditary spherocytosis is most common in people of northern
European ancestry. Although a spectrin deficiency is seen in nearly
all HS patients, it is thought that the principle defect is an abnormality
of the membrane protein ankyrin.
Defects in vertical stabilization* of the phospholipid
bilayer of the RBC membrane cause separation of the spectrin - phospholipid
bilayer. Portions of the phospholipid bilayer form vesicles and are
lost from the RBC surface resulting in decreased surface area and
Defects may be in 1) the actin - spectrin - band 3 complex; 2) the
spectrin - 4.1 -glycophorin complex or 3) the connection between the
bilayer and spectrin.
Usually the osmotic fragility test results are graphed
and reported as shown below.
Normal osmotic fragility is seen at top right.
Abnormal lysis of RBCs in mildly hypotonic solutions is seen at lower
right (hereditary spherocytosis).
In other cases the defects are found in the horizontal junctions
between the a-spectrin and b- spectrin dimers or between spectrin, actin
and band 4.1.
These protein interactions normally maintain the structural strength
and lateral stability of the RBC.
Defects of the junctions between the a-spectrin and b- spectrin dimers
or between spectrin, actin and band 4.1 may cause the RBC cytoskeleton
to loose its lateral integrity.
Such defects result in RBC shape alterations as in hereditary elliptocytosis
or to fragmentation of the RBC as in hereditary pyropoikilocytosis.
Hereditary elliptocytosis is usually inherited as an
autosomal dominant trait. The defect is a structural abnormality of
spectrin or a deficiency of the RBC membrane protein 4.1, without anemia
and usually with no splenomegaly and only mild hemolysis. Most patients
The PBS shows large numbers of elliptocytes and/or ovalocytes. The
number of elliptocytes does not correlate with the severity of the hemolysis.
Osmotic fragility is usually normal. Reticulocytes are mildly increased
(<5%) and haptoglobin levels low.
RBC hemolysis occurs in the spleen, thus splenectomy corrects the hemolysis,
but not the RBC membrane defect.
Hereditary stomatocytosis is an autosomal dominant disorder,
in which a membrane abnormality leads to increased permeability to sodium.
This causes water to move into the RBC decreasing the mean corpuscular
The PBS shows RBCs with narrow mouth-like areas of hypochromia. These
RBCs are known as stomatocytes.
A mild hemolytic anemia and splenomegaly are typical clinical findings.
Acquired stomatocytosis may be seen in liver disease and hyperalimentation
Severe hemolysis, bizarre poikilocytosis, and RBC fragmentation
are the hallmarks of hereditary pyropoikilocytosis, a rare autosomal
A structural abnormality of spectrin is present in which RBCs fragment
when heated to only 45°C. Normal RBCs fragment at 49°C.
Match patient A, B, and C with test results 1, 2, and 3 shown at
A. a 14 year lold boy who has lost blood from an auto accident
is brought into the ER where Dr. Isbit Sloe orders an osmotic fragility
test. The Hct is .44 L/L and the MCV 89fL.
B. a 12 year old girl who has always been a bit pale is seen
in the clinic with a Hct of .32 L/L; MCV 90fL. Dr. Lisa Rotblut orders
an osmotic fragility test.
C. a 15 year old boy is found to be mildly anemic in a camp
physical. His Dad and several relatives also are repoorted to be anemic.
His Hct is .34 L/L and the MCV 75 fL. Dr. I.M.A. Payne orders an osmotic
A. A = #1; B = #2; C = #3
B. B = #1; C = #2; A = #3
C. C = #1; A = #2; B = #3
D. A = #2; B = #3; C = #1
E. A = #2; B = #1; C = #3
Under no circumstances should you share any material downloaded from Student Source course websites with individuals outside the class. Under no circumstances should you repost material downloaded from Student Source to other websites. Some of our pages are restricted to UVa School of Medicine users and require an Oasis account for access.