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Clinical Management of Iron Overload (PHM 142)

Clinical Management of Iron Overload (PHM 142). Goher Zahoor Radha Luthra Ashutosh Randhawa Jaguar Randhawa. October 17, 2012. GROUP:. PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson. What is Iron Overload?.

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Clinical Management of Iron Overload (PHM 142)

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  1. Clinical Management of Iron Overload (PHM 142) GoherZahoor RadhaLuthra Ashutosh Randhawa Jaguar Randhawa October 17, 2012 GROUP: PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson

  2. What is Iron Overload? Iron Overload in the body is the disease-state characterised by having too much iron stored within the body over an extended period of time Causes: Primary Hemochromatosis (genetic), Secondary Hemochromatosis (Transfusion-Induced), Alcoholic Cirrhosis, Oral Therapy of Iron, African Bantus, etc.. Pap smear Image Source: http://trialx.com/curebyte/2011/07/06/images-related-to-iron-overload/

  3. How is Iron Overload Harmful? Transferrin proteins become saturated as iron absorbed is too high Free iron in the serum is allocated by the body to organs/joints because excretion rate of iron is not sufficient to bring serum iron levels back to normal Haber-Weiss/ Fenton Reaction produces highly oxidatative free-radicals Radicals essentially damage tissues- loss of respective organ/joint functions

  4. Symptoms of Iron Overload Heptomegaly (enlargement of the liver), fatigue, weight loss, bronze skin pigmentation, diabetes mellitus, hypogonadism-impotency, loss of periods in women, cardiac dysfunctions, arthritis etc... Many others as a result of loss in function of Major Body Organs

  5. Diagnosing Iron Overload Blood Tests Ferritin Level (HIGH) Iron Level (HIGH) Transferrin Saturation Level (Low) <30% is normal Hinting Tests Blood Sugar levels, ECGs for electrical activity in heart, Imaging Tests (CT,MRI), and Liver Function Tests.

  6. Causes of Iron Overload Hereditary Hemochromatosis: a genetic disorder in which too much iron is absorbed from food. It is caused mutations in the protein product of the HFE gene: 282 position: Cysteine changed to Tyrosine 63 position: Aspartic acid changed to Histidine Found most commonly in Northern Europeans; 1 in 200 people of Celtic and Nordian ancestry

  7. Causes of Iron Overload Blood transfusions for thalassemia major and sickle cell patients: leads to iron overload occurs after approximately 20 transfusions and serum ferritin levels of about 1,000 μg/L. According to the Ontario Association of Medical Laboratories, serum ferritin levels of 300 μg/L or greater may indicate iron overload.

  8. Causes of Iron Overload Bantu Siderosis - A type of iron overload first observed in people of South Africa - Continued investigation behind cause of this genetic disease, but polymorphism of protein ferroportin is believed to be involved

  9. Causes of Iron Overload Alcoholic Cirrhosis: Chronic liver disease in which normal liver tissue is replaced by scar tissue, regenerative nodules, and fibers; leading to loss of liver function. Dysfunctional liver processes iron improperly, leading to accumulation of iron Cooking in Iron-containing pots: Iron is added to food being cooked

  10. Prevention of Iron Overload People with Hemochromatosis (genetic or otherwise) should follow the guidelines below: Food: - Choose vegetarian sources for protein, instead of meat, as meat contain easily extractable iron sources Ensure all meat products (seafood) is cooked properly to kill all microbes. Patients with iron overload are better hosts for infection as they contain more iron for the agent of infection.

  11. Prevention of Iron Overload People with Hemochromatosis (genetic or otherwise) should follow the guidelines below: Food: - Drink Tea or Coffee after food as caffeine decreases iron absorption.

  12. Prevention of Iron Overload People with Hemochromatosis (genetic or otherwise) should follow the guidelines below: Supplements: Avoid taking Iron and Vitamin C supplements. Ensure Multivitamins do not contain iron or more than 500mg of Vitamin C. Vitamin C increases iron absorption. Regular Iron Checkups: Obtain CBC from doctor. Check for hepatitis and other liver disease to minimize liver damage

  13. Prevention of Iron Overload People with Hemochromatosis (genetic or otherwise) should follow the guidelines below: Alcohol: Avoid or reduce alcohol consumption, as alcohol damages the liver. Females: 1 Drink per day. Males: Less than 2 drinks per day. Alcoholics should seek help from doctors to reduce/eliminate alcohol intake.

  14. Treatment of Iron Overload How do we reduce iron levels? • Phlebotomies

  15. Treatment of Iron Overload Phlebotomy • The primary method of reducing iron levels(esp. in hemochromatosis) • Similar process to blood donation (tourniquet arm, withdraw blood from vein etc.) and risks • 5-10 mL/kg blood removed at a rate of 5-10 mL/minute (about 450 mL average) • Saline replacement solution Image Source: http://trialx.com/curebyte/2011/07/06/images-related-to-iron-overload/

  16. Treatment of Iron Overload Phlebotomy (Frequency) • Blood taken in phlebotomies can be used as blood donations • Weekly phlebotomy if serum ferritin levels too high (male: 300mcg/L or female: 200 mcg/L), for 3 months – 1 year • A phlebotomy every few months to maintain lower iron levels (50 mcg serumferritin/ L or less)

  17. Treatment of Iron Overload Phlebotomy + Anemia • Dangerous to withdraw blood from people with anemia • A better choice: Chelating Agents

  18. Treatment of Iron Overload Chelating Agents • Administered: Orally, subcutaneously, or intravenously • Make chemical bonds to metal ions, with the resulting complex being water soluble • Complex is chemically inactive  flows through the bloodstream  filtered through the kidney  excreted in urine

  19. Treatment of Iron Overload Iron Chelating Agents • Include Deferoxamine, Deferasirox and Deferiprone • Deferoxamine - administered subcutaneously or intravenously. Results in urinary and fecal excretion. Although inconvenient, studies have demonstrated that it is very good at reducing iron overload.

  20. Treatment of Iron Overload Deferasirox (Exjade) – Orally, once daily. Deferiprone – Orally, TID. May cause a drop in white blood cell count (must have blood checked regularly when using this medication)

  21. Treatment of Iron Overload • Iron Chelation Therapy requires follow up and regular monitoring of iron levels!

  22. Patient Education AASLD Practice Guidelines www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Hemochromatosis%202011.pdf • Centers for Disease Control www.cdc.gov/ncbddd/hemochromatosis • Iron Disorders Institute: (888) 565-4766 or (864) 292-1175 www.irondisorders.org • Medline www.nlm.nih.gov/medlineplus - Enter “iron overload” into search field

  23. Summary Iron Overload is the chronic condition of having too much iron stored within the body (caused by modified transferrin activity in most cases) Iron ultimately produces free radicals that damage organ/joint tissues Symptoms: liver enlargement, skin pigmentation, darker stools, impotency, diabetes, arthritis , liver failure, etc... Diagnosis: elevated ferritin and iron levels, along with high transferrin saturation Causes for Iron Overload: Hereditary Hemochromatosis, over 20 Blood transfusions, Bantu Siderosis, Alcoholic Cirrhosis, and cooking in Iron-containing pots Prevention of Iron Overload in patients with a genetic predisposition to Hereditary Hemochromatosis: Food (avoid meat; ensure all seafood is well cooked; drink caffeine), Supplements (avoid vitamin C and iron), Avoid Alcohol, and check blood and liver regularly. Phlebotomies are the primary method of reducing iron levels (removing blood directly from the patient. They should not be performed on anemic patients. To reduce iron levels in anemic patients, iron chelating agents should be used. These agents bind iron, thus forming a complex that is excreted from the body (iron chelating agents include Deferoxamine, Deferasirox and Deferiprone)

  24. References Bacon, B. et al. 2011. “Hemochromatosis (Hereditary Iron Overload) Beyond the Basics”. Retrieved October 9, 2012 from: http://www.uptodate.com/contents/hemochromatosis-hereditary-iron-overload-beyond-the-basics Barton JC, McDonnell SM, Adams PC, et al. 1998. “Management of hemochromatosis. Hemochromatosis Management Working Group”. Ann Intern Med. 129 (11): 932. Dugdale, D.C., et al. 2012. Hemochromatosis. Retrieved October 8, 2012, from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001368/ Fortier, Lori. Nutrition Guidelines for Individuals with Hemochromatosis. Retrieved October 8, 2012 from: http://www.cdnhemochromatosis.ca/assets/pdf/nutrition_guidelines.pdf Gordeuk V.R., Caleffi A., Corradini E., et al. 2003. "Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene“. Blood Cells Mol. Dis.31 (3): 299–304. Porter L. (2012). “What is Iron Overload”. HCSP Fact Sheet. Version 3. 2010. “CDC – Hemochromatosis (Iron Storage Disease) Pathophysiology”. Retrieved October 9, 2012 from: www.cdc.gov/health/diseases.htm Department of Health and Human Services. 2002. “Iron Overload and Hematochromatosis-Information for patients and their Families”. Centers for Disease Control and Prevention. International Association of Sickle Cell Nurses and Physician Assistants. 2008. “Nursing Practice Guidelines: Care of the Patient with Sickle Cell Disease and Iron Overload”. The Aplastic Anemia and MDS International Foundation. July 15, 2011. Iron Chelation Therapy. Retrieved October 11, 2012 from: http://www.aamds.org/node/82

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