1. Iron overload in Sickle Cell disease
Dr Doreen Mutua
Pediatric Hematologist/Oncologist

2. Transfusion in Sickle Cell Disease
Transfusions usually fall into two categories:
Episodic, acute transfusions to stabilize or reverse complications. E.g. acute splenic sequestration, transient red cell aplasia, Hyperhemolysis (infection, acute chest syndrome, malaria).
Long-term, prophylactic transfusions to prevent future complications. Eg. Stroke prevention

3. Transfusion related iron overload
Each unit of PRBC mg of iron

5. Liver Biopsy: Gold standard
The “Gold Standard”
Advantages: Correlates well with total body iron burden
Allows for assessment of liver histology,
Predictor of risk for cardiac disease, endocrine complications and death
Disadvantages: Invasive, Potentially risky
Speaker Notes
Liver Iron Content (LIC), also referred to as hepatic iron concentration, was measured in one study in 48 patients with thalassemia major and iron overload (1). Patients had undergone successful bone marrow transplant to correct their thalassemia and received phlebotomy to correct existing iron overload. LIC was determined by biopsy and total body iron stores were calculated based on the total amount of blood that needed to be removed to establish a non-overloaded state (quantitative phlebotomy).
As you can see, iron content of liver biopsy samples rose commensurately with total body iron stores in these patients with cirrhosis; serum ferritin levels in the same patients did not show a strong correlation with total body iron stores (1).
Reference
1. Angelucci E, Brittenham GM, McLaren CE, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med. 2000;343:
Direct measurement of iron content

6. Magnetic Resonance Imaging
Several imaging techniques are used to estimate liver and cardiac iron deposition
Non invasive
Correlates well with liver iron concentration by biopsy
Disadvantages: Expensive, variety of techniques and analytical programs may limit comparability, cardiac disease may be present when liver iron levels are low
Speaker Notes
Another method for measuring iron content is through magnetic resonance imaging or MRI. Because of the magnetic properties of iron, MRI is highly sensitive and specific for showing the concentration and distribution of iron throughout the body, or, as mentioned before, in the liver as an indication of total body iron, or iron content of other organ systems. This allows diagnosis of iron overload. (1)
Here is an image of the liver in a patient with significant iron overload (2). This is a processed image consisting of two images, a T2 weighted anatomical picture with an R2 map of the liver superimposed. Unlike liver biopsy, MRI can assess iron overload throughout the liver and does not require a tissue sample. MRI is the only option for monitoring cardiac iron overload, for example, over an extended period of time, because repeated liver biopsies are risky and are performed only when absolutely necessary.
Reference
1. Siegleman ES, Mitchell DG, Semelka RC. Abdominal iron deposition: metabolism, MR findings, and clinical importance. Radiology 1996;199:13-22.
2. Clark PR, et al. Magn Reson Med. 2003;49:
Bright = high iron concentration; dark areas = low iron concentration

7. What is Chelation Therapy?
Toxic
Metal
Chelator +
Speaker Notes
Chelation therapy involves the use of a drug that is capable of binding with a metal in the body to form what is called a chelate. By doing so, the metal loses its toxic effect, or physiological activity, and is then more readily removed from the body. Chelation therapy is generally reserved for the forms of iron overload in which phlebotomy cannot mobilize iron stores adequately or cannot be tolerated because of concurrent anemia.
Non-Toxic
Metal
Chelator
Outside the Body
“Chelate”

8. Available options for Iron chelation therapy

9. Thank you!