CASE STUDY 1MICR 410 - HEMATOLOGYSPRING, 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. Significance: Greeks have a genetic

predilection for certain diseaseshttp://www.inmagine.com/unx202/u14837207-photo

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

http://www.med.cmu.ac.th/dept/pediatrics/06-interest-cases/ic-52/case52-page-1.HTM

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)

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)

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

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

• 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

http://emedicine.medscape.com/article/958850-overview

http://bloodjournal.hematologylibrary.org/content/105/2.cover-expansion

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

http://bloodjournal.hematologylibrary.org/content/105/2.cover-expansion

Zhou S et al. J. Biol. Chem. 2006;281:32611-32618

http://www.med.cmu.ac.th/dept/pediatrics/06-interest-cases/ic-52/case52-page-1.HTM

THERAPY AND PROGNOSIS FOR HB H DISEASE

Therapy 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

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

TAKE HOME MESSAGE 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

REFERENCES 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/PGD-THALINFOSHEET74%20V4%2007%2010%2010.pdf