Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Iron Overload in Chronic Anaemias Thalassemia Center 1 We cope well with iron shortage… Thalassemia Center 2 …but poorly with iron excess. There is no physiologic mechanism to excrete excessive iron Thalassemia Center 3 Blood transfusion overwhelms the iron balance • Normal daily iron flux: 1-2 mg • Each unit of PRBC: 200-250 mg Thalassemia Center 4 Summary: Iron is in a fine balance • In normal circumstances, not much iron enters or leaves the body • The body cannot increase its excretion of iron. • Blood transfusions contain much iron, so patients who need frequent transfusions will build up excess iron. Thalassemia Center 5 Why too much iron is a bad thing Thalassemia Center 6 Free Iron Dying RBC Liver CIRRHOSIS Endocrine organs DIABETES Heart ARRHYTHMIA Thalassemia Center HEART FAILURE 7 Lessons from thalassaemia Thalassemia Center 8 When does iron become a problem? • Tissue damage when total body iron is 7 – 15 grams – After 30-50 units of red blood cells Thalassemia Center 9 How do we know if there’s too much iron? • Serum ferritin concentration • Liver biopsy • Magnetic resonance imaging (MRI) Thalassemia Center 10 Summary: Too much iron is bad • Iron overload caused by transfusions causes malfunction of the liver, heart, and endocrine organs. • Problems may begin after 30 units of RBC (or even earlier) • We use serum ferritin level to estimate iron levels – MRI might be better Thalassemia Center 11 Iron chelation Thalassemia Center 12 What is Chelation Therapy? Toxic Chelator + Metal Non-Toxic Chelator Metal Outside the Body “Chelate” Thalassemia Center 13 How to chelate? – Deferoxamine – Deferiprone (L1) – Deferasirox (ICL670, Exjade) Thalassemia Center 14 Common Side Effects of Deferoxamine • Local reactions – Erythema (localized redness) – Induration (localized swelling) – Pruritus (itchiness) • Ophthalmologic – – – – Reduced visual acuity Impaired color vision Night blindness Increased by presence of diabetes • Hearing loss 15 • Zinc deficiency Thalassemia Center Are we certain it helps? Survival of patients with thalassaemia Thalassemia Center 16 Summary: Iron chelation and deferoxamine • Chelation works by attaching a drug to iron, which allows the body to excrete it. • Deferoxamine is awful stuff… – Inconvenient and uncomfortable to take – Many nasty side effects • …but it works – Enormous extension of lifespan in thalassaemia. Thalassemia Center 17 ICL670: Deferasirox, Exjade Oral, dispersible tablet Taken once daily Highly specific for iron Thalassemia Center 18 ICL670 is Generally Tolerable The most common adverse events were mild and transient: – – – – – Nausea (10%) Vomiting (9%) Abdominal pain (14%) Diarrhea (12%) Skin rash (8%) Rarely required discontinuation of study drug Mild increases in serum creatinine Thalassemia Center 19 What do the experts say? Thalassemia Center 20 Recommended Treatment for Iron Overload • Why: to prevent end-organ complications of iron overload and extend lifespan • Whom: transfusion-dependent patients with expected survival > 1 year • When: after 25 units RBC transfused, ferritin >1000. • How: Desferal by subcutaneous infusion (for now); keep ferritin<1000 Thalassemia Center 21 Summary • Iron overload is an inevitable consequence of chronic RBC transfusion • Iron toxicity affects the function of the liver, heart, and endocrine organs • Chelation therapy should be offered to iron overloaded patients • Desferal is the drug currently STOOD TEST OF TIME ; Exjade is available too. Thalassemia Center 22 Thank you! Thalassemia Center 23