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

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

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

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

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

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.

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

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.

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

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

References Cappellini, M. D., & Fiorelli, G. (2008). Glucose-6-phosphate dehydrogenase deficiency. Lancet 371(9606), 64-74. doi:10.1016/S0140-6736(08)60073-2 Carter, S. M. (2009). Glucose-6-Phosphate Dehydrogenase Deficiency. Medscape Reference WebMD LLC. Retrieved from http://emedicine.medscape.com/article/200390-overview G6PD Deficiency. (2010). In g6pddeficiency.org. Retrieved from http://g6pddeficiency.org/index.php Harmening, D.M. (2009). Hemolytic Anemias: Intracorpuscular Defects: II. Hereditary Enzyme Deficiencies. Clinical Hematology and Fundamentals of Hemostasis 5th Edition (197-200). Philadelphia, PA: F. A. Davis. McQueen, N. L. (2011). Hemolytic Anemias Due to Other Intracorpuscular Defects [PowerPoint slides]. Retrieved from http://instructional1.calstatela.edu/nmcquee/MICR410/

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