Hemolytic Anemia due to
membrane defect
Nada Mohamed Ahmed ,
MD, MT (ASCP)i
OBJECTIVES
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Normal structure of RBCs
Definition
Causes
Mechanism
Symptoms
Lab findings
HEMOLYTIC ANEMIA
Intracorpuscular
Extracorpuscular
OUTSIDE THE RED CELL
WITHIN THE RED CELL
Hereditary
Acquired
1. Warm Ab
1. Membrane defects
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Hereditary stomatocytosis
-G6PD
PNH
3. -Hemoglobin defects
-.Hemoglbinopathies(sickle cell disorders)
- Hb SS, CC, SC & S-B- Thalassemias
NON-IMMUNE
1. Hypersplenism
2. Cold Ab
2. Infections
(Malaria),,
3. Transfusion
reactions
3-mechanical
trauma to RBCs
4. Drug
associated
4. Liver dz (Spur
cell)
Membrane defects
- Hereditary pyropoikilocytosis
2. Enzyme defects
AUTOIMMUNE
Definition of Membrane defects
Hemolytic anemia
• Defects due to abnormalities in
membrane proteins or lipids.
• Defects alter membrane’s stability,
shape, deformability and
permeability.
• Hemolysis occurs extravascularly.
normal Structure of RBC membrane :
Structure of RBC membrane:
–Lipid bilayer(43%)
–Membrane proteins (49%)
–Carbohydrate (8%).
Continued…
• Glycophorins are the most abundant integral membrane
glycoproteins in erythrocytes.
• Glycophorins constitute more than 60 percent of the net negative
surface charge of red cells.
• GPC, which participates in a complex with protein 4.1 plays a
critical role in regulating the stability, deformability, and shape of
the membrane.
• Glycophorins serve as receptors for several infectious agents,
including Plasmodium falciparum. The glycophorins carry a number
of blood group antigens, including MN, Ss, Gerbich.
Continued…
• The functions of spectrin and ankyrin are to maintain
cellular shape, regulate the lateral mobility of integral
membrane proteins, and provide structural support for the
lipid bilayer.
• Band-3 :
Regulates metabolic pathways by sequestering enzymes
of glycolysis such as glyceraldehyde 3 phosphate dehydrogenase
and aldolase.
Conditions Associated with Membrane Defects
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1-Hereditary spherocytosis
2-Hereditary elliptocytocytosis
3-Hereditary poikilocytosis
4-hereditary stomatocytosis
Disorders
 1-Hereditary spherocytosis (HS)
 Defect in ankyrin & spectrin
 Results in the formation of fragile spherocytic red
cells.
 Spherocyte becomes less flexible and more
permeable to Na+
Clinical Findings
Varies in severity
Compensated hemolytic disease
No anemia
Intermittent (not happened
regularly) jaundice
• Splenomegaly
• Cholelithiasis: pigment bile stones
from increased bilirubin breakdown
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Lab Features
• CBC
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Mild anemia
MCV is usually normal (77-87fL)
MCH normal
MCHC is >36% (This is the only condition
in which an MCHC can be truly increased.)
• RBC morphology
– Spherocyte
– Varying degrees of polychromasia,
anisocytosis and poikilocytosis
Lab Features
• Bone Marrow
– Normoblastic erythroid hyperplasia
– Increased iron storage
• Chemistry
– Increased
• Bilirubin
• Fecal urobilinogen
• LD
– Decreased
• Haptoglobin
Special Diagnostic tests for HS
• Osmotic fragility - ↑
– Cells are incubated in decreasing concentrations
of NaCl. Spherocytes lyse sooner than normal
red cells.
• Autohemolysis test
– Red cells are incubated at 37̊ C for 48 hours.
Degree of hemolysis is increased when
spherocytes are present.
• Red cell membrane studies
– Membrane proteins are analyzed using gel
electrophoresis.
Disorders
• 2-Hereditary elliptocytosis
– A defect of one of the skeletal proteins (GPC
deficiency)
– Results in the formation of fragile , deformable RBCs
(elliptocytic )red cells that are sensitive to mechanical
stress.
– More permeable to Na+
– Tends to affect blacks, especially in Africa
Lab Features
• CBC
– Mild anemia
– Hgb level increased
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• RBC morphology
– Elliptocytes or ovalocytes
Hereditary Elliptocytosis
Disorders
• 3-Hereditary poikilocytosis (HP)
– Deficiency of α-spectrin and a mutant spectrin leads to
disruption of skeletal lattice and cell destabilization
– Cells fragment when heated
– Presents in infancy or early childhood
Clinical Findings
• Hyperbilirubinemia
Lab Features
• CBC
– MCV decreased (25-55 fL)
• RBC morphology
– Extreme erythrocyte morphologies
• Fragments, elliptocytes, triangulocytes etc
4-Hereditary Stomatocytosis Syndromes
– Disorders of membrane action permeability
• Hereditary stomatocytosis (stoma= mouth)
– In this disorder the RBC is abnormally
permeable to sodium and potassium.
– The net gain of sodium is more than the net
loss of potassium.
– Therefore water rushes in and the RBCs are
swollen and less deformable and are culled in
the spleen.
Hereditary stomatocytosis
The anemia may be mild to
moderate with polychromasia.
Stomatocytes (RBCS with mouthlike areas of central pallor) are
seen
Lab Features
• Anemia is mild to moderate
• Increased bilirubin
• MCV increased
CASE study 1
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14 YR old female present with anemia, jaundice
stable.pallor+,icterus+,splenomegaly +
- cholilithiasis
Lab; elevated ,LDH, S.Bilirubin
Peripheral smear shows-
• What the type of hemolytic anemia ?
• Name of special test used to diagnose it?