Iron Overload, Liver and Heart Function

[Francine S]

Hello,
It's been some time since I've written about my mother (not sure if my Jan 13 postings are still available). She has MDS (RCMD), has been diagnosed for about a year now (but has had the disease for at least a yr before this) and is 85. She is transfusion dependent (2 units every 2 wks). Her serum ferritin (iron) is in 4000 range. I read in earlier postings that this may not be excessive on the scale of regularly transfused patients but of course requires iron chelation therapy. She was prescribed Exjade, stalled about a month before taking it. After about 13 days of Exjade she voluntarily stopped it because of 2 incidents of diarrhea (1 not too bad, 1 severe). After getting a blood profile, 2 of her 3 liver enzymes were elevated (apologies but I can't find lab results right now!). 1 elevated 2x above Upper Limit Ref Range, the other slightly elevated, the 3rd normal range. Her Hematologist said to stop Exjade for 4 wks and then he'll run another blood profile and see if her liver enzyme levels had decreased. I asked how Exjade could elevate her liver enzymes after just 13 days of use - could it be the iron overload damaging her liver? He would not commet - just said she had to stop the Exjade.
In the meantime, she's had fluid retention in her legs for some time now and was prescribed furosemide (Lasix). She tends to skip 1-2 days/wk for various reasons but last week, did not take it for almost a week. Her legs are terribly swollen, to the point where it's difficult for her to walk. I'm concerned that this is due to a combination of her not being compliant with the diuretic but also that the iron overload is affecting her heart, putting her into some level of heart failure.
I am trying to get a sense of to what extent an iron level in 4000 range can affect liver and cardiac function. Her kidney lab results were normal.
Also I'm wondering if Desferal might be a better option for her than Exjade. Her Hematologist said that Desferal has the same effect on the liver that Exjade does. But at this point, would slightly elevated liver enzymes be better than the side effects of iron in the 4000 range? I'm not clear on what extent Exjade can affect the liver. I've read in other postings on MarrowForums that it has affected kidney function in some MDS patients. Has anyone had this issue of water retention in the legs and/or impaired liver function when taking Exjade? Sorry for this long-winded posting!
Thank you,

[Marlene]

Desferal, IMO, is probably safer in the long run. You can look up the side effects and warning at these links:

http://www.rxlist.com/exjade-drug.htm

http://www.rxlist.com/desferal-drug.htm

Hopefully, they did not start her on a "full" dose right out of the gate. Your liver and kidneys, as you age, may not be able to clear the drugs as quickly as a younger person so you would have to reduce the dose.

I assume your mom's FE was normal before her diagnosis. If it was, then, a FE of 4000 should not pose a big problem at this time. It usually takes years for the iron to do damage. We've been told that the first signs of damage to show up are usually related to the pancreas, meaning sugar issues. However, everyone is different. But, the elderly and very young are more sensitive. John's Fe was 4600 when he started chelation. It's taken years to get it down. Mostly because he could never get to a full dose of either drug. John took anti-oxidants to help counter the effects of the iron.

Low blood counts can also strain the heart and if your blood volume is low, your body hangs on to more fluid to make up for the missing blood. All this can contribute to edema.

Is she under the care of Internist also? Someone who will look beyond the MDS/iron to see if something else is going on.

[Neil Cuadra]

Originally Posted by Francine S

It's been some time since I've written about my mother (not sure if my Jan 13 postings are still available).

For future refererence, Francine, you can look up your previous posts by going to your profile page and clicking "Find all posts by Francine S" or "Find all threads started by Francine S".

You can get to your profile page by clicking Quick Links in the menu bar and picking My Profile. You can get to any member's profile by clicking on their user name next to a post.

You created your Vidaza for my 85 yr old mother with MDS? thread in November 2008. It doesn't look like you posted in January.

[Helen Robinson]

Francine

My husband had liver problems with Exjade which he started at a lower dose. Because of the holidays he did not have a weekly blood test and within a month he had hepatitis. When his liver counts were normal he tried again at an even lower dose and the count shot up in a week. His liver is sensitive but his counts are normal while using desferal. He is so determined to control the iron that he chelates both day and night for three doses. That way he avoids leaving the canula in for more than two days when he often had bad staph infections.

Your Mum is not young and would probably have trouble managing the chelation on here own. We know of a lady aged 88 with a ferritin of 14,000. They give her an infusion weekly at the hospital but it is obviously not enough.

It is very hard to manage meds if you are elderly and we will all be there one day.

best wishes

Helen

[Birgitta-A]

Hi Francine,
It is very difficult to know if your mother's elevated liver tests depend on the increased ferritin level or an adverse effect of Exjade. You know the liver has very great capacity - we manage well with 1/3 of the liver, so elevated liver tests are really not dangerous.

As Marlene wrote a ferritin level of 4000 is not very high and will probably not give any symptoms except eventually elevated liver tests. The first symptom of high ferritin is often symptoms from the heart and that kind of symptoms can take years to develope.

I looked at a lot of reports about iron overload from the big conference ASH 2008 and wellknown clinics had patients with a ferritin value of 22 000.

Your mother perhaps has svollen legs because of heart problems that have nothing to do with iron overload - of cause it is important that she takes Lasix, that ske obviously needs.

Desferal under the skin is quite difficult to take during long time - I get it through a port-a-cath (a small device of titanium) inplanted on my chest. I get my transfusions through the port too without any complications since Aug 2007.
Kind regards
Birgitta-A
70 yo, dx MDS Interm-1 May 2006, transfusion dependent, Desferal and Ferriprox (not approved in the US) for iron overload, Neupogen 2 injections/week for low white blood cells, asymptomatic

[Francine S]

Thank you Marlene, Helen and Birgitta for your timely and helpful responses! I am taking off shortly to accompany my mom at her Hematologist visit. Will follow up when I return.
Neil: Thanks for educating me on how the website works!

[Francine S]

Hi Everyone,
Just a follow-up since I attended my mom's Hematologist/Oncologist appt on 26 May. He feels that the edema in her legs is not due to iron overload hurting her heart but rather a cardiac problem not related to her MDS. I asked if my mom's blood volume was low: he said "no". I recall that her General Practioner ( I think an Internal Medicine specialist) said that she's got a leaky heart valve. Maybe the leakiness is getting worse in combination with her not being compliant with the diuretic. Her GP told her she must never miss taking the diuretic so she is being compliant now. He said the leg swelling should be reduced in 10 days. If it's not, I will see that she returns to the GP or perhaps sees a cardiologist.
Re. her liver function, she will get blood tests next week. Her Hematologist said that as long as the liver enzyme levels have decreased, even if they're not back to normal, he would start her back on Exjade. Her liver function tests were always normal before taking Exjade. He started her on the 20 mg/kg dose and said if she tolerates that, it would be increased to the max, 30 mg/kg. My read of the Exjade prescribing info is that a 20 mg/kg dose only results in a "steady state" of no change in ferritin levels for routine transfusion patients. But a 30 mg/kg dose results in a decrease in ferritin levels. Your comments about the effects of iron overload upon the organs take years to develop have made me less worried now. After reading that Desferal requires daily infusions, I think that would be very hard for my mom, at her age. Thank you all again for your comments and insight.

[Marlene]

Since he put her back on Exjade, make sure they run a weekly chem panel (kidney & liver) for at least the next month. IMO, I really believe he should wait until they normalize before trying again especially since iron, at this point, is not life threatening. What's the rush?

If she has a central line in, then the desferral is a lot easier to do. I'm sure home health care can set her up to do it like Helen's husband did. They can also do a dose when she gets a transfusion.

And yes, you are correct regarding the dosing.

BTW...Lasix does deplete potassium and some B vitamins.

Marlene