Transcript MLAB 13115- Hematology Keri Brophy

MLAB 13115- Hematology
Keri Brophy-Martinez
Fall 2007
Unit 13: Hemolytic Anemias:
Intracorpuscular Defects/
Hemoglobinopathies
THE HEMOGLOBINOPATHIES
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Hemoglobinopathy is a condition in which
abnormal hemoglobins are synthesized in
the bone marrow.
These are qualitative abnormalities in the
hemoglobins that are formed normally but
have abnormal substitutions of an amino acid
in the globin chain. The most common chain
affected is the β chain
Normal Adult Hemoglobin
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Hb A : 95-98%
Hb A2: 2-3%
Hb A1: 3-6%
Hb F: <1%
Sickle Cell Anemia
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Hemoglobin SS (homozygous) α2β2S
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Inheritance of Hgb S gene from both parents.
Valine is substituted for glutamic acid at the sixth position on the β
globin chain in the hemoglobin molecule.
When oxygen tension is lowered or pH decreases, gel polymerization
occurs and leads to sickling of the red cell. Sickled cells cannot flow
freely through the microvasculature of joints and the spleen, furthering
the hypoxic environment. This causes intense pain. Tissue necrosis
occurs and patients infarct their spleen at an early age
(autosplenectomy). RBC’s trapped within spleen.
Note: Symptoms do not appear in infants until after 6 months of age
due to the persistence of Hgb F causing a low level of Hgb S.
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Sickle Cell Anemia
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Occurs with greatest frequency in tropical
Africa. Incidence in African-Americans is
0.26%
Sickle cell carrier state confers an advantage
to Plasmodium falciparum malaria due to
preferential sickling of parasitized cells
Sickle Cell Anemia: Clinical Features
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Hemolytic anemia with jaundice
Organ damage due to ischemia, where the blood
flow is blocked due to abnormally shaped RBC’s.
Bone and joint abnormalities (swelling of joints)
Severe pain
Leg ulcers
Stroke and pulmonary complications
Sickle Cell Anemia: Lab Tests
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CBC and retic
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Hgb: 6 - 8 g/dl
RBC: decreased
Retic: 5-20% (unless in aplastic crisis)
Evaluation of the peripheral smear
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Sickle cells, target cells, red cell fragments,
polychromasia, NRBC’s, Pappenheimer bodies
and Howell-Jolly bodies
Sickle Cell Anemia: Lab Tests
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Hemoglobin electrophoresis on cellulose acetate and citrate
agar gels
Hemoglobins migrate at different speeds when an electrical
charge is applied to a solution. Staining the support media (gel)
allows you to visibly see a pattern of migration. Several
hemoglobins migrate together on cellulose acetate media at pH
8.4, so it is often necessary to perform the electrophoresis on
citrate agar medium at acid pH of 6.0 to 6.5 to separate them.
Refer to page 807, Figure 40-1 in textbook for hemoglobin
electrophoresis migration patterns on cellulose acetate and
citrate agar
Sickle Cell Anemia: Lab Tests
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Measurement of hemoglobins A2 and F
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Hgb A2 level may be slightly increased
Hgb F may persist into adulthood
Sickle Cell Anemia: Treatment
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Prevention of infection
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Hydroxyurea (it is believed to induce production of
Hgb F). Using chemotherapeutic agents
Avoidance of situations that could cause a crisis.
Blood transfusion
Treatment of pain
Median age at death
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Male: 42
Female: 48
Sickle Cell Trait
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(heterozygous) α2β1β16Glu-Val
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Patients inherit a normal β globin gene from one parent and a sickleglobin gene βs from the other parent.
Incidence is 8-10% in African Americans. Genetic counseling is
recommended for people with the trait.
Usually asymptomatic with occasional episodes of hematuria.
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Sickling can occur with drastic reduction of oxygen tension
such as severe respiratory infection, air travel in
unpressurized aircraft, anesthesia or congestive heart
failure.
Exercise that causes a buildup of lactic acid can cause
sickling due to lowered pH.
Hemoglobin C Disease
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(homozygous) α2β26Glu-Lys
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Inheritance of Hgb C gene from both parents
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Lysine is substituted for glutamic at the 6th position on the β
globin chain of the hemoglobin molecule.
In decreased oxygen tension, HbC has decreased solubility
and forms intracellular crystals.
Greatest frequency is in West Africa. Incidence in US among
African Americans is 0.2%.
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Hemoglobin C Disease: Clinical
Features
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Mild chronic anemia with enlarged spleen
and abdominal discomfort
Hemoglobin C Disease: Lab tests
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Mild ↓ H&H
Peripheral smear evaluation
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Normocytic-normochromic red cells
50-90% target cells
Folded cells with HbC crystals intra- or extracellular.
Hemoglobin electrophoresis
Hemoglobin SC Disease
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α2β16Valβ16Glu-Lys
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HbS gene is inherited from one parent and HbC gene is
inherited from the other parent. Incidence in the US African
Americans is 0.12%
Hemoglobin SC Disease: Clinical
Features
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Milder anemia
Increased blood viscosity causes retinal
hemorrhage, kidney necrosis and femoral
head necrosis.
Hemoglobin SC Disease: Lab tests
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Peripheral smear will have target cells,
folded red cells and occasional glove-shaped
intracellular crystals.
Hemoglobin electrophoresis on cellulose
acetate at alkaline pH.
Hemoglobin E Disease
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α2β226Glu-Lys
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Substitution of lysine for glutamic acid at the 26th position on
the β globin chain of the hemoglobin molecule. Occurs with
greatest frequency in the southeast Asia region
Hemoglobin E Disease: Clinical
Features
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Anemia is mild to absent
Target cells might be present
Hemoglobin S/β-Thalassemia
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To be discussed