Transcript Final Case Study - Cal State LA

CASE STUDY 1
MICR 410 - HEMATOLOGY
SPRING, 2011
HIBA ALLO
CHRISTINA CASTRO
CLAIRE ENDO
ADRIAN VALONES
CASE SUMMARY
John, a 4 year old boy, complains of
weakness, fatigue, and dyspnea
(labored breathing).
 Parents encounter bouts of fatigue,
but have never consulted a physician.
 Parents are from Greece.
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Significance: Greeks have a genetic
predilection for certain diseases
http://www.inmagine.com/unx202/u14837207-photo
KEY INFORMATION POINTING TO DIAGNOSIS

Patient presents with anemia. Weakness, fatigue, and
dyspnea are symptoms of anemia.
http://www.med.cmu.ac.th/dept/pediatrics/06-interest-cases/ic-52/case52-page-1.HTM
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CBC
Low RBC, Hemoglobin, and HCT 
 Hypochromic, Microcytic
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Anemia
Peripheral Blood Smear
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Poikilocytosis, Polychromasia and Target Cells (dominant)
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NOTE: Target Cells are also found in Hemoglobinopathies, Iron Deficiency
Anemia, & Thalassemia
KEY INFORMATION POINTING TO
DIAGNOSIS
 Additional
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lab test confirming the diagnosis:
Hemoglobin Electrophoresis & Iron Panel
 Hemoglobin
Electrophoresis Results Abnormal
HbA levels are low
 8% Hb Bart’s and 24% Hb H are abnormally present
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 Iron
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Studies are normal
α-Thalassemia is commonly found in Mediterranian
people (Greeks and Sardinians)
THE DIAGNOSIS FOR CASE 1
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R/O Iron Deficiency Anemia
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Iron panel normal
R/O Hemoglobinopathies & β-Thalassemia
 Alpha chains decreased: low Hgb A 66% (95-98%)
 β and ϒ chains in excess: Hgb H 24%, Hgb Bart’s 8%
 Hgb S, SC, C: No sickle cells or crystals present
Diagnosis: Hemoglobin H Disease (Alpha Thalassemia)
PATHOPHYSIOLOGY OF HB H DISEASE
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Patients with Deletional Hb H Disease
lack 3 of the α-globin genes
Patients with Non-deletional Hb H
Disease lack 2 of the α-globin genes and 1
of the present genes is abnormal
Gene deletion results in excess γ
andβchains
Excess γ4 tetreamers form in the fetus
Excess β4 tetreamers form in adults
Hb H (β4) ranges from 5 to 30% of Hb in
patients with the disease (24% in this
case)
Hb H has a high affinity for oxygen
resulting in a left shift of the O2
dissociation curve where less O2 is
delivered to the tissues
https://aspirusgmi.dnadirect.com/grc/patient-site/alpha-thalassemia-carrier-screening/genetics-of-alpha-thalassemia.html?w3bz10N81iH6NK6Ms-JpoqO
Left
Shift
Abn Hb
PATHOPHYSIOLOGY OF HB H DISEASE
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Hb H forms an intracellular
precipitate
As RBCs age they contain more
precipitated Hb H due to
attachment to the cell membrane
Precipitates make Hb H RBCs
more rigid leading to culling in
the spleen
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http://emedicine.medscape.com/article/958850-overview
Hb H Disease is mainly a hemolytic
disorder
Precipitates may also cause
ineffective erythropoiesis
http://bloodjournal.hematologylibrary.org/content/105/2.cover-expansion
DIAGNOSTIC TESTS FOR HB H DISEASE
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Hemoglobin electrophoresis is used to
quantify and identify hemoglobin
types
Iron Panel
Zhou S et al. J. Biol. Chem. 2006;281:32611-32618
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Brilliant Cresyl Blue Stain can
display Hb H inclusions
http://bloodjournal.hematologylibrary.org/content/105/2.cover-expansion
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High Performance Liquid
Chromatography can quickly separate
different hemoglobins
http://www.med.cmu.ac.th/dept/pediatrics/06-interest-cases/ic-52/case52-page-1.HTM
THERAPY AND PROGNOSIS FOR HB H DISEASE
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Therapy
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For severe anemia: blood transfusions
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Monitor for Hemochromatosis
Splenectomy
 Hematopoietic Stem Cell Transplantation
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Requires bone marrow transplant
 Only used in severe cases
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Avoid certain medications sulfa drugs, analgesics
 Avoid mothballs and fava beans: causes severe
anemia
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Prognosis
Proper care reduces medical complications
 Good prognosis with treatment
 Nondeletional Hb H Disease has more severe
complications than Deletional Hb H Disease
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PREVENTION OF HB H DISEASE
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Family history – genetic counseling
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Likelihood of Hgb Bart’s (Hydrops Fetalis)
Prenatal Testing
Amniocentesis & Chorionic Villus Sampling
 Ultrasound Monitoring of Hydrophobic Changes
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Preimplantation Genetic Diagnosis (PGD)
Embryos grown in vitro
 Increase chance of a healthy child
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TAKE HOME MESSAGE
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The diagnosis is Hemoglobin H (alpha thalassemia)
Typical symptoms
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The cause of the disease
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Intermittent blood transfusions for severe anemia
Splenectomy then bone marrow transplant in severe cases
Dietary restriction & avoiding certain medications
Prognosis
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CBC, Iron Panel & Hemoglobin electrophoresis
Treatment
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3 Alpha chain gene deletions
Diagnostic tests
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Fatigue, weakness & dyspnea
Prognosis is good with proper medical care
Prevention is genetic counseling with family history,
prenatal testing & PGD
REFERENCES
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Cheerva, A.C. and Coppes, M.J. (2011). Hemoglobin H Disease
(Alpha Thalassemia). Retrieved from
http://emedicine.medscape.com/article/955496-overview
Chui, D. H. K. et al. (2003). Hemoglobin H Disease: not
necessarily a benign disorder. Blood, 101(3), 791-800.
Harmening, D. (2008). Clinical Hematology and Fundamentals of
Hemostasis. (5th ed.). Baltimore, MD: F.A. Davis Company.
Knapp, A. et al. (2010). Evidence Review: Hemoglobin H Disease.
Retrieved from
http://www.hrsa.gov/heritabledisorderscommittee/reports/
hemogolbinh.pdf
London Fertility Centre. Information Sheet for Thalassemias and
Preimplantation Genetic Diagnosis. Retrieved from
http://www.fertilityplus.org.uk/data/documents/PGDTHALINFOSHEET74%20V4%2007%2010%2010.pdf