1. Case Study 1 MICR 410 - Hematology Spring, 2011
Note: Embedded in your PowerPoint, you must address all questions in the case!
HIBA ALLO
CHRISTINA CASTRO
CLAIRE ENDO
ADRIAN VALONES

2. 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.
Significance: Greeks have a genetic predilection for certain diseases
What is the significance if any of knowing the patient’s background?

3. Key Information Pointing to Diagnosis
Patient presents with anemia. Weakness, fatigue, and dyspnea are symptoms of anemia.
CBC
Low RBC, Hemoglobin, and HCT  Anemia
Hypochromic, Microcytic
Peripheral Blood Smear
Poikilocytosis, Polychromasia and Target Cells (dominant)
NOTE: Target Cells are also found in Hemoglobinopathies, Iron Deficiency Anemia, & Thalassemia

4. KEY INFORMATION POINTING TO DIAGNOSIS
Additional 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
Iron Studies are normal
α-Thalassemia is commonly found in Mediterranian people (Greeks and Sardinians)
α-Thalassemia has a 40% incidence in the Greek population

5. The Diagnosis for Case 1 R/O Iron Deficiency Anemia
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)

6. Pathophysiology of Hb H Disease
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
Left Shift
Abn Hb
Nondeletional Hb H disease include Hb H disease with Constant Spring.
The abnormal α-globin genes is result of a point mutation affecting the termination codon of the α2 gene on another chromosome.

7. Pathophysiology of Hb H Disease
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
Hb H Disease is mainly a hemolytic disorder
Precipitates may also cause ineffective erythropoiesis
Lecture material/ text book information/review article/WEB information etc

8. Diagnostic Tests for Hb H Disease
Hemoglobin electrophoresis is used to quantify and identify hemoglobin types
Iron Panel
Brilliant Cresyl Blue Stain can display Hb H inclusions
High Performance Liquid Chromatography can quickly separate different hemoglobins
Zhou S et al. J. Biol. Chem. 2006;281:
High performance liquid chromatography is a newborn screening test required by California state law. Newborns with abnormal hemoglobin such as Bart’s hemoglobin indicate alpha thalassemia.

9. Therapy and Prognosis for Hb H Disease
For severe anemia: blood transfusions
Monitor for Hemochromatosis
Splenectomy
Hematopoietic Stem Cell Transplantation
Requires bone marrow transplant
Only used in severe cases
Avoid certain medications sulfa drugs, analgesics
Avoid mothballs and fava beans: causes severe anemia
Prognosis
Proper care reduces medical complications
Good prognosis with treatment
Nondeletional Hb H Disease has more severe complications than Deletional Hb H Disease
Hb H Disease is primarily preventive and supportive in nature.
Patients with nondeletional Hb H disease have more severe clinical and hematologic features including:
Younger age at diagnosis, higher proportion of patients requiring transfusion, large liver and spleen sizes, higher requirement for splenectomy, higher percentage of growth deficiencies and more are symptomatic at presentation

10. Prevention of Hb H Disease
Family history – genetic counseling
Likelihood of Hgb Bart’s (Hydrops Fetalis)
Prenatal Testing
Amniocentesis & Chorionic Villus Sampling
Ultrasound Monitoring of Hydrophobic Changes
Preimplantation Genetic Diagnosis (PGD)
Embryos grown in vitro
Increase chance of a healthy child

11. Take Home Message Treatment
The diagnosis is Hemoglobin H (alpha thalassemia)
Typical symptoms
Fatigue, weakness & dyspnea
The cause of the disease
3 Alpha chain gene deletions
Diagnostic tests
CBC, Iron Panel & Hemoglobin electrophoresis
Treatment
Intermittent blood transfusions for severe anemia
Splenectomy then bone marrow transplant in severe cases
Dietary restriction & avoiding certain medications
Prognosis
Prognosis is good with proper medical care
Prevention is genetic counseling with family history, prenatal testing & PGD

12. References
Cheerva, A.C. and Coppes, M.J. (2011). Hemoglobin H Disease (Alpha Thalassemia). Retrieved from
Chui, D. H. K. et al. (2003). Hemoglobin H Disease: not necessarily a benign disorder. Blood, 101(3),
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
hemogolbinh.pdf
London Fertility Centre. Information Sheet for Thalassemias and Preimplantation Genetic Diagnosis. Retrieved from