CASE STUDYMICR 410 - HEMATOLOGY

SPRING, 2011

Case 3Benjamin Haro, John Kang, Annelise Lupica

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 SpreadCase summary 5

Key Information pointing to Diagnosis 15

Diagnosis 5

Pathophysiology of the disease 25

Diagnostic tests 10

Therapy 5

Prognosis 5

Prevention 5

Take home message 5

Are all questions addressed? 10

Appearance 5

Presentation skills (individual) 5

Total 100