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Standard-of-Care Clinical Practice Guidelines (2012)

Standard of Care Guidelines 2012:

▶ Contents
▶ 1: Introduction
▶ 2: DNA Testing
▶ 3: Diagnosis
▶ 4: Transfusion
▶ 5: Chelation
▶ 6: Imaging
▶ 7: Chelation Toxicity
▶ 8: Liver & Gallbladder
▶ 9: Endocrine
▶ 10: Cardiac
▶ 11: Pulmonary Care
▶ 12: Pain Syndrome
▶ 13: HCT
▶ 14: Acute Infection
▶ 15: Dental
▶ 16: Nutrition
▶ 17: Vaccinations
▶ 18: Fertility & Pregnancy
▶ 19: Thal Intermedia
▶ 20: Hb H Disease
▶ 21: Thal Research
▶ 22: Psychosocial
▶ 23: Genetic testing
▶ 24: Clinical & Lab timetable
▶ 25: Authors
▶ 26: Support
▶ 27: References

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Thalassemia Standard-of-Care Guidelines (mobile optimized)


LIC is one way to determine total body iron content. While liver biopsy determination of LIC has been recommended for years, recent progress with MRI imaging provides an expedient and noninvasive way to directly measure LIC, as well as iron concentration in multiple organs. A FerriScan is a commercially available and validated system for quantitative MRI measurements of iron. The SQUID is also an effective way to noninvasively monitor LIC. The LIC is reported in wet weight and dry weight. The LIC in patients with thalassemia should always be maintained below 7,000 µg/g dry weight and 1,100 µg/g wet weight in order to avoid iron-induced organ damage.

Serum ferritin is a convenient way to monitor iron overload. The magnitude and direction of change in ferritin is a reasonable predictor of the magnitude and direction of change in total body iron. While there is about a 70 percent correlation of ferritin with LIC in population studies, there is tremendous scatter in the relation, so ferritin is a poor marker of absolute iron content in an individual patient.

The intermittent measurement of LIC by biopsy, MRI, or SQUID, in addition to measurement of ferritin with each transfusion, is the recommended way to follow change in iron burden in chronically transfused patients. It is important to use the average change of 3 to 5 ferritin measurements to determine the direction of change in iron. Because of the sensitivity of ferritin levels to inflammation, vitamin C, and iron, changes between two consecutive measures can be very misleading. If there seems to be little change in ferritin, in spite of good compliance with chelation, change in iron status should be verified by liver iron measurement before making drastic changes in chelation therapy.

The availability of noninvasive ways to directly measure iron in several organs has led to a better understanding of how iron is stored in the body and differences in iron storage among individual patients. It was once thought that liver iron correlated with heart iron, but due to further research, it is now clearly understood that iron transport into and removal from various organs occurs at different rates. We also know that ferritin levels can be misleading and that periodic direct measurement of liver iron can be of great benefit in monitoring patients. New iron measurement techniques have had a direct impact on management of iron overload. For example, it is now known that a patient can almost completely empty the liver of iron and reduce ferritin to very low levels even though significant amounts of iron may remain in the heart. This means that patients with such iron levels must cautiously proceed with chelation to empty the heart, when they might otherwise have considered stopping or reducing chelation treatment.

Recommendations for LIC goals are changing. The recommendations in Table 5.1 are based on previously published results and may need modification as new data is published. Some leading experts suggest that these recommendations should be modified and lower liver and ferritin levels should be used to increase dosing. In fact, there is emerging data that some complications such as endocrine dysfunction may respond to lowering iron levels to near normal. Since recommendations are evolving, we have included the standard accepted guidelines. Lower LIC and ferritin levels, as indicators for dose adjustment, should only be attempted by providers who are very familiar with the toxicities of over-chelation and can serially monitor liver tissue iron. Such levels should not be attempted using ferritin monitoring alone.

6.1 Monitoring the efficacy of chelation therapy in the presence of iron cardiomyopathy

Cardiomyopathy is the most life-threatening of the iron-related complications. The heart often remains iron-free for many years. Once cardiac iron loading starts, it progresses very rapidly, since the presence of iron in the heart increases the rate of influx of iron. Removal of iron from the heart progresses very slowly with a half-life of approximately 17 months. Even though there is no linear correlation between LIC and cardiac iron, the heart often does not really began to unload until the LIC drops to very low levels. The cornerstone of effective treatment of iron cardiomyopathy is continual exposure to chelation. This can reduce cardiac arrhythmias and dysfunction even before the heart begins to unload iron. The actual dose of chelator depends primarily on the LIC and must be reduced as the LIC approaches normal in order to avoid symptoms of over-chelation. (Also see Section 7.7, on over-chelation.) However, in the presence of cardiac iron, and especially if there is cardiac dysfunction, chelation cannot be stopped.

In the presence of cardiac symptoms (arrhythmia or decreased left ventricular ejection fraction) the patient must be exposed to chelator 24 hours per day, 7 days per week. This treatment is considered to be emergent. Multiple drug therapy—in particular, therapy involving deferiprone—should be considered in this circumstance. Other cardiac medications may be recommended by the cardiologist. Patients whose cardiac T2* is less than 10 ms and who do not have cardiomyopathy should receive maximum therapy (see Table 5.1). Consultation with an iron chelation specialist is strongly recommended in the management of all patients with an abnormal cardiac T2*. Since several patients may have low body iron and high cardiac iron, iron chelation therapy decisions may be complex. Liver iron measurements should also be closely monitored with each cardiac T2*. It is very important to note that other things, such as myocarditis, vitamin B1 deficiency, and vitamin D deficiency can also affect cardiac function and need to be explored, particularly if there is no cardiac iron and function remains abnormal.

Northern California Comprehensive Thalassemia Center
UCSF Benioff Children's Hospital Oakland
747 52nd Street, Oakland CA 94609   •   Phone: (510) 428-3347   •   Fax: (510) 450-5647
© 2003-2012 Children's Hospital & Research Center Oakland
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