1. Case Study MICR 410 - Hematology Spring, 2011
Benjamin Haro, John Kang, Annelise Lupica
Case Study MICR Hematology Spring, 2011

2. Case Summary
25-year-old African American male soldier in the process of being deployed to West Africa, took anti-malarial prophylaxis, primaquine, three days before leaving
Within 24 hours of taking the medication, the patient was hospitalized for fever, chills, and general malaise
His physical exam seemed normal, without acute stress, with no significant family history or drug allergies

3. Key Information Pointing to Diagnosis
Decreased Hemoglobin at 9.1 g/dL
Decreased RBC count at 3x1012/L
Value derived from Hct/RBC=MCV
Bite Cells and spherocytes in peripheral blood
Onset of anemia after administration of primaquine
Blood smear indicating shortened RBC life span, caused by oxidative damage
Positive G6PD deficient spectrophotomertric assay, after the cells had aged

4. The Diagnosis for Case 3
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency)
Also known as Heinz Body Anemia

5. Pathophysiology of G6PD Deficiency
Acute intravascular hemolysis occurs when exposed to acute oxidative stress, such as certain drugs, fava beans, infection, and birth
In normal cells, G6PD catalyzes the first step in the hexose monophosphate shunt
Glucose-6-phosphate is oxidized to 6-phosphogluconate in a coupled reaction in which NADP is reduced to NADPH
NADPH in turn reduces a glutathione aggregate to a glutathione monomer
Because G6PD deficient patients cannot reduce to glutathione, oxidative damage precipitates Heinz bodies

6. Pathophysiology of G6PD Deficiency
G6PD activity is highest in young RBCs and decreases as the cell ages.
Once the cell starts to age enzyme activity decreases and Heinz bodies attach to the RBC membrane.
Heinz bodies lead to decreased RBC survival time.
Normally the bone marrow is able to compensate for the decreased RBC survival time.
Oxidative drugs (anti-malarial) can cause acute oxidative stress and lead to acute intravascular hemolysis.

7. Diagnostic Tests for G6PD Deficiency
CBC
Peripheral Blood Smear (stained with new Methylene Blue)
Spectrophotometric Assay
A measurement of the activity of the G6PD enzyme
Rapid fluorescent spot test (Beutler fluorescent spot test)
Detects the generation of NADPH from NADP

8. Therapy and Prognosis for G6PD Deficiency
Avoid or discontinue use of an oxidant drug
Transfusion after a hemolytic episode
The prognosis for patients with G6PD deficiency is good with no complications as long as the use of oxidant drugs is discontinued.

9. Prevention of G6PD Deficiency
Avoiding oxidant drugs and fava beans (if diagnosed with Favism) can avoid the anemic effects of G6PD Deficiency

10. Take Home Message
The diagnosis is Glucose-6-Phosphate Dehydrogenase Deficiency
Typical symptoms are anemia, bite cells, hemoglobinuria, and jaundice
The cause of the disease is deficiency in G6PD, typical of older RBCs
Diagnostic tests include spectrophotometric assay and rapid fluorescent spot test
Treatment is discontinuation of oxidizing drugs, and transfusion
Prognosis is good if oxidant drugs are discontinued
Prevention is avoidance of oxidant drugs and fava beans

11. References
Cappellini, M. D., & Fiorelli, G. (2008). Glucose-6-phosphate dehydrogenase deficiency. Lancet 371(9606), doi: /S (08)
Carter, S. M. (2009). Glucose-6-Phosphate Dehydrogenase Deficiency. Medscape Reference WebMD LLC. Retrieved from
G6PD Deficiency. (2010). In g6pddeficiency.org. Retrieved from
Harmening, D.M. (2009). Hemolytic Anemias: Intracorpuscular Defects: II. Hereditary Enzyme Deficiencies. Clinical Hematology and Fundamentals of Hemostasis 5th Edition ( ). Philadelphia, PA: F. A. Davis.
McQueen, N. L. (2011). Hemolytic Anemias Due to Other Intracorpuscular Defects [PowerPoint slides]. Retrieved from

12. Point Spread Case summary 5 Key Information pointing to Diagnosis 15
Pathophysiology of the disease 25
Diagnostic tests 10
Therapy
Prognosis
Prevention
Take home message
Are all questions addressed?
Appearance
Presentation skills (individual)
Total
100