HEMOLYTIC ANEMIA

Presented by:Ally Dhalla ally_dhalla@hotmail.comSandeep Gothi deepsand@hotmail.comUjjwal Patel patel_ujjwal@hotmail.com

Presented JAN 20 2004

PHM 226, ExampleInstructor: Dr. Jeffrey Henderson

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

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)

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.

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.

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.

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)

Glycolytic Pathway

Glucose

Glucose-6-phosphate

ATPADP

Fructose-6-phosphate

hexokinase

isomerase

Fructose-1,6-bisphosphate

ATPADP

Glyceraldehyde-3-phosphate

Dihydroxy-acetone Phosphate

PFKinase

G-3-P Dehydrogenase

NAD+ NADH

1,3-Bisphosphoglycerate

Pyruvate

NAD+

Fe3+ + O2O2 + Fe2+

MetHb reductase

(2 Net ATP)

Drugs H2O2

•Know this diagram

PMP Generation of NADPH

GlucoseGlucose-6-phosphate

6-Phosphogluconate

Ribose-5-phosphate

Fructose-6-phosphate

Glyceraldehyde-3-phosphate+

Glyceraldehyde-3-phosphate

Pent

ose

Shun

t

ATPADP

G6PDehydrogenase

NADPH

NADP+

GSSG

GSHGSH reductase

NADPH

NADP+

H2O

H2O2 O2

Catalase

•Know this diagram

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.

How Drugs Affect G6PD Deficient Individuals?

GlucoseGlucose-6-phosphate

6-Phosphogluconate

Ribose-5-phosphate

Fructose-6-phosphate

Glyceraldehyde-3-phosphate+

Pent

ose

Shun

t

G6PDehydrogenase

NADPH

NADP+

GSSG

GSHGSH reductase

NADPH

NADP+

H2O

↑H2O2 O2Catalase

NAD+

NADH

Fe2+ (oxyHb)

Fe3+

(metHb)

Drugs

Glyceraldehyde-3-phosphate

2 OH

Hemolysis

SuperoxideDesmutase(SOD)

(Fe2+)GSH Peroxidase

NADPH

(O2 )

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

Signs of anemia include:

• pale skin and fingernails• rapid pulse• heart murmur• Enlarged spleen and liver

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.

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.

References• Ezra E. W. Cohen, M.D., Section of Hematology/Oncology, Department of Medicine, The University of

Chicago, Chicago, IL. 11 Jan 2004 <http://www.nlm.nih.gov/medlineplus/ency/article/000571.htm >

• 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 <http://www.rialto.com/g6pd/physiolo.htm>

• Peggy Gulley, MD. Hemolytic Anemia Lecture. 9 Jan 2004 <http//:pathology.uthscsa.edu/MSII/Hemo.html>

• Rebecca Elstrom, M.D., Division of Hematology-Oncology, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network. . 11 Jan 2004 <http://www.umm.edu/blood/anehemol.htm>

• 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 InteliHealth Inc. 11 Jan 2004 <http://www.intelihealth.com/IH/ihtIH/WSIHW000/9339/21246.html>

• Images taken from http://health.allrefer.com/health/hemolytic-anemia-pictures-images.html> . 11 Jan 2004