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HEMOLYTIC ANEMIA Presented by:Ally Dhalla firstname.lastname@example.org Sandeep Gothi email@example.com Ujjwal Patel firstname.lastname@example.org Presented JAN 20 2004
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What is hemolytic anemia? Hemolytic anemia is a disorder in which the red blood cells are destroyed prematurely. RBCs are destroyed faster than the bone marrow can produce them. There are two types of hemolytic anemia: Extrinsic and Intrinsic
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Types of Hemolytic Anemia Extrinsic - red blood cells are produced healthy but are later destroyed by becoming trapped in the spleen, destroyed by infection, or destroyed from drugs that can affect red blood cells. Intrinsic - the destruction of the red blood cells due to a defect within the red blood cells themselves. Intrinsic hemolytic anemia is often inherited, such as sickle cell anemia and Glucose-6-Phosphate Dehydrogenase deficiency. (G6PD)
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What is G6PD? It is an X-linked recessive inheritance. (males usually affected and females are carriers) Risk factors: being black, being male, or having a family history of G6PD deficiency. G6PD enzyme functions in the Pentose-Monophosphate shunt and in the process, catalyzes the reduction of NADP+ to NADPH required in triggering a cascade of events that can detoxify the harmful oxidant H2O2.
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Role of G6PD Responsible for maintaining adequate levels of NADPH inside cell. The oxidation of NADPH back to NADP+ is coupled with the reduction of oxidized glutathione (GSSG) to glutathione (GSH). Thus, NADPH keeps glutathione, a tri-peptide, in its reduced form.
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Role of G6PD Cont’d... Reduced glutathione (GSH) acts as a scavenger for dangerous oxidative metabolites in the cell. GSH converts harmful hydrogen peroxide to water catalyzed by the enzyme, glutathione peroxidase (catalase enzyme also detoxifies H2O2). If H2O2 cannot be detoxified by GSH or catalase, hydroxyl radical formed from H2O2 can be scavenged by Vit C/E.
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G6PD Deficiency Red cells deficient in G6PD are unable to neutralize hydrogen peroxide - H2O2 converts to hydroxyl radicals and this can lead to oxidative damage/toxic injury. Impaired response to oxidizing drugs can also induce hemolytic anemia (Individuals with G6PD deficiency are particularly susceptible)
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Glycolytic Pathway Glucose Glucose-6-phosphate ATP ADP Fructose-6-phosphate hexokinase isomerase Fructose-1,6-bisphosphate ATP ADP Glyceraldehyde- 3-phosphate Dihydroxy- acetone Phosphate PFKinase G-3-P Dehydrogenase NAD+ NADH 1,3-Bisphosphoglycerate Pyruvate NAD+ Fe3+ + O2 O2 + Fe2+ MetHb reductase (2 Net ATP) Drugs H2O2 Know this diagram
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PMP Generation of NADPH Glucose Glucose- 6-phosphate 6-Phosphogluconate Ribose-5-phosphate Fructose-6-phosphate Glyceraldehyde-3-phosphate + Glyceraldehyde- 3-phosphate Pentose Shunt ATP ADP G6P Dehydrogenase NADPH NADP+ GSSG GSH GSH reductase NADPH NADP+ H2O H2O2 O2 Catalase Know this diagram
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Drugs that affect it Drugs that can precipitate this reaction include: · anti-malarial agents · sulfonamides (antibiotic) · aspirin · non-steroidal anti-inflammatory drugs (NSAIDs) · nitrofurantoin · quinidine · quinine · others Also: exposure to certain chemicals such as those in mothballs and flava beans.
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How Drugs Affect G6PD Deficient Individuals? Glucose Glucose- 6-phosphate 6-Phosphogluconate Ribose-5-phosphate Fructose-6-phosphate Glyceraldehyde-3-phosphate + Pentose Shunt G6P Dehydrogenase NADPH NADP+ GSSG GSH GSH reductase NADPH NADP+ H2O ?H2O2 O2 Catalase NAD+ NADH Fe2+ (oxyHb) Fe3+ (metHb) Drugs Glyceraldehyde- 3-phosphate 2 OH Hemolysis Superoxide Desmutase (SOD) (Fe2+) GSH Peroxidase NADPH (O2 )
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What are the symptoms? The most common symptoms include: abnormal paleness or lack of color of the skin jaundice, or yellowing of the skin, eyes, and mouth dark color to urine fever weakness dizziness confusion intolerance to physical activity
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Signs of anemia include: pale skin and fingernails rapid pulse heart murmur Enlarged spleen and liver
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Required Tests Blood tests are taken to measure levels of: red cells, assess size and shape of red cells measure the Hb level determine the number of reticulocytes. Other blood tests may include: Coombs' test (direct and indirect) — checks for hemolytic anemia caused by an abnormal immune reaction. Heinz body presentation — looks for a deficiency in amount of G6PD enzyme, which results in hemolysis if certain medications or foods are ingested.
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Treatments may include Stopping use of offending drug. For more severe cases, treat with: corticosteroids (e.g. prednisone) intravenous immunoglobulin infusions immunosuppressive (e.g. azathioprine (Imuran) and cyclophosphamide (Cytoxan) Vitamin and mineral supplements (e.g. folic acid). Change in diet. If Hb levels ?, treatment may include blood transfusion or splenectomy (surgical removal of the spleen). If physical damage to RBC, then treat w/ blood transfusions or simple iron supplements. Iron - Taken during pregnancy and when iron levels are low. Erythropoietin (Procrit) - To increase RBC production in people w/ kidney problems.
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References Ezra E. W. Cohen, M.D., Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL. 11 Jan 2004
Updated by: Corey Culter, M.D. M.P.H., F.R.C.P.C., Department of Medical Oncology, Dana Farber Cancer INsitiute; Instructor of Medicine, Harvard University, Boston, MA. Review provided by VeriMed Healthcare Network. Source: MEDLINEplus Medical Information. 11 Jan 2004 http://www.hlm.nil.gov/medlineplus/ency/article/000528.htm Ramez A. Ethnasios. An Introduction to G6PD Deficiency. 7 Jan 2004
Peggy Gulley, MD. Hemolytic Anemia Lecture. 9 Jan 2004
Rebecca Elstrom, M.D., Division of Hematology-Oncology, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network. . 11 Jan 2004
Patrick Yorba, MD, Staff Physician, Department of Emergency Medicine, University of Virginia Health Sciences Center. 11 Jan 2004 http://www.emedicinehealth.com/articles/4893-6.asp?pd=1/11/2004%2010:25:15%20PM Faculty of Harvard Medical School © 1996-2003 Aetna I
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Ally Dhalla email@example.com. Sandeep Gothi firstname.lastname@example.org. Ujjwal Patel patel_ujjwal@
Ally Dhalla email@example.com. Sandeep Gothi firstname.lastname@example.org. Ujjwal Patel email@example.com. Presented. JAN 20 2004 ...