Serum ferritin underestimates liver iron in transfusion independent patients

http://www3.interscience.wiley.com/journal/114277527/abstract

Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients
Zahra Pakbaz, MD 1 *, Roland Fischer, PhD 1 2, Ellen Fung, PhD, RD 1, Peter Nielsen, MD, PhD 2, Paul Harmatz, MD 1, Elliott Vichinsky, MD 1
1Children's Hospital & Research Center Oakland, Oakland, California
2University Medical Center Hamburg-Eppendorf, Hamburg, Germany
email: Zahra Pakbaz (zpakbaz@mail.cho.org)

*Correspondence to Zahra Pakbaz, Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609.

Funded by:
 National Institutes of Health; Grant Number: M01RR01271

Keywords
ferritin • liver iron concentration • sickle cell • thalassemia

Abstract
Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID biosusceptometry, were assessed in a convenience sample of transfusion independent thalassemia patients (nTx-Thal, n = 26), regularly transfused thalassemia (Tx-Thal, n = 89), or sickle cell patients (SCD, n = 45) to investigate the severity of iron overload and the relationship between SF and LIC in nTx-Thal compared to SCD and Tx-Thal. SF correlated with LIC (RS = 0.53, P < 0.001), but was found to be a poor predictor for LIC. SF was significantly lower (P < 0.001) in nTx-Thal patients than in other groups, despite similar LIC values. The SF-to-LIC ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients (median of 0.32, 0.87, and 1.2, respectively: P < 0.001). Due to underestimation of LIC by ferritin levels, chelation treatment may be delayed or misdirected in patients with thalassemia intermedia. Pediatr Blood Cancer 2007;49:329-332. © 2007 Wiley-Liss, Inc.

Non-transfusing intermedias should not rely on ferritin tests alone to determine if iron loading is taking place.

Hi Andy,
Thank you for this information. What tests do intermedias depend on then? Squid and Ferriscan arent very widely available I think.
Zahra

Andy,

This is exactly what my haematologist said for Thal Majors, too, when I went to him, asking whether I can cut back on my Kelfer dosage. He said to first estimate actual organ iron in both heart and liver, using the T2/T3 tests before reducing dosage.

Poirot

Hmm, I dont think I understand this article  Can someone explain this in different words? I feel very silly. 

Shorn of the statistics and medicalese, it means that a low serum ferritin number is not necessarily equivalent to low iron levels in your liver and heart. Those need to be tested separately.

Now I understand it. It has been 7 or 9 years ago since I had my last MRI scan  :'(

Dore,

You can also try liver biposies to estimate iron, if you can not do any MRI scans whatsoever.

Poirot

I know, but I am against liver biopsies.  I will wait untill I can have an other MRI.

http://www.thalassemia.com/documents/Zahra.pdf

Many patients with thalassemia intermedia are able to survive without transfusion with relatively low
hemoglobin and it seems that using medications such as decitabin, hydroxyurea and erythropoietin can help to
increase their hemoglobin 1-2 grams. However measuring liver iron concentration (using non-invasive and pain
free SQUID) in 26 thalassemia intermedia patients who were not transfused showed that these patients could
become as iron overloaded as transfused thalassemia patients due to increased iron absorption from their
intestine. This is while these patients had a relatively low serum ferritin. Therefore liver iron concentration needs
to be monitored in these individuals regardless of their serum ferritin and they need to consult with a dietician to
have a low iron diet to avoid iron overload and check their liver iron concentration regularly to seek treatment
before the iron deposition causes complications.

Intermedia patients who do not transfuse need to be aware of this. They can be just as iron overloaded as patients who do not transfuse. If this does prove to be the case in an individual patient, the decision to not transfuse may need to be re-examined, especially for any patient with demonstrated slow physical development. Please do not rely solely on ferritin levels if you do not transfuse. A liver scan is a must.

Another data point for intermedia's, who don't transfuse to not only rely on the serum ferritin levels, but get the LIC (Liver Iron Concentration checked). Check this link out for full details - http://www.haematologica.org/cgi/content/full/92/5/583

Liver iron concentrations and urinary hepcidin in ß-thalassemia

Liver iron concentration in patients with thalassemia intermedia was not significantly different from that in patients with thalassemia major, while the serum ferritin levels were statistically significantly different between the two groups

In conclusion, we suggest that in thalassemia intermedia, an as yet unknown signal from expanded erythropoiesis strongly suppresses hepcidin production, resulting in increased intestinal iron absorption and eventual parenchymal iron overload. The observation that serum ferritin levels underestimate the severity of iron overload has important implications for iron chelation in patients with thalassemia intermedia. In such patients, serum ferritin levels have little value for the monitoring of iron overload and iron chelation, and alternative assessments such as liver iron concentration by biopsy, superconducting quantum-interference device (SQUID) or magnetic resonance imaging should be used. Moreover, hepcidin measurements may be useful as part of the diagnostic and prognostic evaluation of thalassemia syndromes. In the future, it may be possible to use exogenous hepcidin to restore normal iron homeostasis in patients with thalassemia intermedia

Thal (Intermedia) patients do talk about this with your doctor's and be aware that serum ferritin levels are not going to give a complete picture of ferritin levels