ROLE OF NURSE SPECIALISTS

A key role for nurse specialists in caring for patients withbeta-thalassemia, SCD, or MDS is identifying and monitoringthose at risk for iron overload. Once blood transfusionsare initiated, a patient should be provided with a chartfor tracking the number of RBC units transfused, sinceiron overload can occur after only 10 transfusions. A baselineserum ferritin level should also be recorded, as consistentlyhigh levels can be an indication for treatment with ironchelatingagents.1 Samples of both charts are downloadableat www.ironoverloadnurses.com.

Iron Chelation Therapy
Iron chelation therapy, which removes excess iron fromplasma and cells in organs, has been in use for more than40 years.3 The rationale for use of an iron chelator is tomaintain safe levels of NTBI5; however, to work effectively,chelator levels must be maintained at pharmacologicallyactive concentrations1 or NTBI returns to cause oxidativedamage. Therefore, patient adherence to therapy is criticalfor the effective management of iron overload. Two drugsare currently approved by the US Food and DrugAdministration (FDA) for iron chelation therapy: deferoxaminemesylate (Desferal®) and deferasirox (Exjade®).Deferoxamine mesylate: Introduced in the 1960s,deferoxamineis indicated for the treatment of acute ironintoxication and of chronic iron overload due to transfusiondependentanemias. Iron chelation with deferoxamine iscurrently the reference standard to which new chelatingagents are compared.1 Doses are administered intravenouslyor subcutaneously using a small portable pump capable ofproviding continuous infusions 8 to 24 hours/day 5 to 7days per week, due to its short plasma half-life. The durationof infusion must be individualized. For patients withbeta-thalassemia in particular, the introduction of deferoxaminemeant survival improved significantly beyondinfancy or childhood; for the first time, conditions related


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TABLE 2. Overview of Iron Overload Test

METHOD ADVANTAGES DISADVANTAGES
Serum ferritin
  • Noninvasive
  • Easy to assess
  • Inexpensive
  • Can be performed frequently, allowing regular monitoring
  • Positive correlation with morbidity and mortality
  • Allows longitudinal follow-up
  • Indirect measurement of iron burden
  • Levels are influenced by many factors, including nutrition, infection, and inflammation
  • Serial measurement and/or combination with other indicators is required


Liver biopsy
  • Validated reference standard
  • Direct measurement that provides accurate information
  • Allows non-heme storage iron to be measured
  • Allows accurate assessment of disease progression
  • Positive correlation with morbidity and mortality
  • Invasive, painful, potentially serious complications
  • Requires skilled professional personnel and standardized laboratory procedures
  • Small biopsy may not be representative of tissue iron distribution
  • Spurious measurements may occur as a result of certain hepatic diseases
  • Poorly correlated with cardiac iron
  • Difficult follow-up
MRI
  • Noninvasive
  • Able to analyze whole organ
  • Pathologic status of the liver can be assessed in parallel
  • Allows longitudinal follow-up of patients
  • Requires imager with a dedicated imaging method
  • Indirect measurement of LIC
SQUID
  • Noninvasive
  • Measurement may be repeated frequently
  • Linear correlation with LIC assessed by biopsy
  • Limited availability
  • High cost
  • Indirect measurement of LIC
  • Complex procedure requiring trained personnel
  • Underestimates LIC versus biopsy

LIC = liver iron concentration; MRI = magnetic resonance imaging; SQUID = super conducting quantum interference device.
Source: Cappellini5; www.irontoxicity.com.19

CASE 1: In Betathalassemia, Low Liver Iron Does Not Necessarily Indicate That Cardiac Iron is Not Present

to iron overload, such as heart disease, could be prevented.1The safety of deferoxamine is well established. The majorityof patients do not experience complications even afterdecades of use; for this reason, some individuals may preferto start chelation therapy on deferoxamine rather thandeferasirox.1 In addition to injection-site soreness and otherreactions related to infusion (eg, itching, erythema, andinduration), adverse events include allergic reactions, cardiovascular(tachycardia, hypotension, shock), hematologic,musculoskeletal, nervous system, special senses (eg, highfrequencysensorineural hearing loss and/or tinnitus),respiratory, and urogenital. Deferoxamine is contraindicatedin patients with severe renal disease or anuria, since thedrug and the iron chelate are excreted primarily by thekidney.23

Deferasirox: Approved by the FDA in 2005, deferasiroxis an orally administered iron chelating agent indicated forthe treatment of chronic iron overload due to blood transfusionsin patients 2 years of age and older.21 Results ofphase II and III deferasirox clinical trials have shown adose-dependent efficacy across a range of anemias21,24-28;the drug is well tolerated and safe, including in pediatricpatients with beta-thalassemia.25 Five-year safety data arenow available.29 Common adverse events include gastrointestinalupset, diarrhea, nausea, vomiting, abdominalpain, and skin rash.21 Deferasirox may cause serious renal,hepatic, and cytopenic adverse reactions, including multiorgandysfunction and fatalities in patients. These eventsare more frequently observed in patients with advancedage, high-risk MDS, thrombocytopenia, or underlyingrenal or hepatic impairment. Deferasirox is contraindicatedin patients with creatinine clearance <40 mL/min or serumcreatinine >2 times the age-appropriate upper limit ofnormal, in patients with poor performance status and highriskMDS or advanced malignancies, in patients with plateletcounts <50 x 109L, and in patients with hypersensitivityto deferasirox or any of its components.21