Q and A: Ferritin and Desferal in Thalassemia

Two questions re-visited

Your Questions:

What is, in your opinion, a safe Ferritin level for a patient with beta Thalassemia major and what is the best way to inject Desferal?

My Answers:

Safe Ferritin levels:

Ferritin levels are the most commonly measured body iron storage measurements. While it may not be the most ideal measure of iron level in the body, it has continued to be a very useful tool because of the relative ease of measuring it.

It has been a regular practice to use changing patterns of Ferritin levels as an estimated measure of the body iron status. It is important to note that one single measurement of Ferritin level, in itself, is less useful than trends or changes over a period of time. I believe that target Ferritin levels for patients with beta Thalassaemia major should be based on the benefit the target value is expected to bring. That is; the positive effect on the prognosis in terms of reduction in risk of complications and improvement in survival.

• Ferritin levels above 2000 micrograms/Litre for long periods of time are known to increase the risk of iron-induced multi-organ damage.

• Ferritin levels between a 1000 and 2000 micrograms/Litre are better. Although less then that from higher values, there still is an increased risk of organ damage if Ferritin levels remain above a 1000 micrograms/Litre for a long period of time.

• Ferritin levels below a 1000 are, based on current data, better targets because the risk of organ damage are so significantly reduced that it is very close to no additional risk.
  
  
• The high end of normal Ferritin level for the general population is around 150-300 micrograms/Litre dependending on age and gender. It is quite possible to achieve this level. There are several people who have been able to safely reduce their Ferritin levels to this level and maintain it over long periods of time. However, currently there is a bit of concern whether achieving such low Ferritin levels is of significant extra benefit than having a level of less than a 1000 micrograms/Litre. There have been reports of increasing incidence of Desferal side effects in individual who have very low Ferritin levels. The side effects in such patients could perhaps be reduced by using lower doses.

My current practice is to encourage patients with beta Thalassaemia major to first try to get their Ferritin levels to below 2000 micrograms/Litre. Those who can achieve this will be encouraged to lower it further to less than a 1000 micrograms/Litre. Once that is achieved; have it reduced and maintained around 500 micrograms/Litre.

I think it is very important to communicate this entire plan to the patient at the very beginning, so that they can work towards a target and monitor their own progress.

Having said that, from a prognosis point of view maintaining Ferritin levels anywhere below a 1000 micrograms/Litre is considered a good target. The 500 micrograms/Litre is not universally accepted as the best Ferritin level.

A note to readers:
Reductions in Ferritin levels can take time. It requires a lot of effort from the patient as well as their families. It can be achieved with Desferal safely. I would like to remind readers that it is absolutely vital that you discuss with your treating doctor regarding setting targets and planning for lowering your Ferritin levels, especially with respect to your Desferal dosage. No change to treatment should be brought about without consulting your doctor.

Desferal injection techniques:

I have had the experience of helping a fair number of patients with Beta Thalassaemia major in using Desferal injections by different techniques.

• Intravenous injections: I am personally very uncomfortable with patients using Desferal intravenously (direct injection into the blood via a vein) even when given as an infusion. The risk of sudden high doses entering the blood stream and causing major acute side effects is my worst fear with this technique. Desferal maybe used intravenously under close monitoring at a hospital setting. This is because in a hospital it would be easier to deal with potential problems. I personally think that IV Desferal use is too intrusive, invasive, relatively unsafe and potentially troublesome. It is also a lot more challenging for patients to acquire the skills necessary to self administer Desferal IV. I personally don't recommend this method.

• Intravenous via a porta-cath: I have seen some patients who have had subcutaneously implanted catheter ports on their body into which they self inject (as a slow infusion) their Desferal doses. I consider this to be virtually the same as intravenous injection. It is definitely a lot easier in this case to gain IV access for injection, but it is associated with potential side effects as for the IV techniques in addition to complications related to having the catheter itself. I personally don't recommend this technique either. Immediate side effects are common with both these techniques and are not very well tolerated by most patients who have tried it.

• Subcutaneous via pump: This is till date; the most widely used, most widely accepted and most widely studied injection technique. The Desferal dose is prepared in a syringe which is then "loaded" into the pump. The mechanical pump then slowly (over 8-12 hours) injects the medication via a needle inserted just beneath the skin. This is probably the safest way to inject Desferal. Most patients prefer to "wear" the pump at night allowing it to inject the medication when they sleep. The biggest hurdles in this technique are the incidences of local injection site side-effects (swelling, pain, redness, itching…etc) and the need for about 10 hours on average for the injection. Some people, more than others, have serious injection site problems that hinder regular use of Desferal. Even after considering all this, pump is still perhaps the safest, easiest, most effective and most widely accepted injection technique for Desferal use. I generally recommend this technique more than any other (exceptions: read below).

• Subcutaneous as short infusions: The medication is prepared in a syringe. It is attached to tubing at the end of which is a needle ( a butterfly needle). The needle is inserted into the space just below the skin and medication injected slowly over 20-30 minutes. Although originally developed as a 10 minute "bolus" injection, I support the slower injection over 20-30 minutes and prefer to call it "short infusion". The total daily dose is divided into a morning and an evening dose. This is increasingly becoming popular with patients who weren't able to spare "the 10 or so hours" needed for the pump. They have one injection before going to work and one before going to bed. It is effective, generally safe (but less so than the pump) and less time consuming. The local injection site problems are similar to the pump technique. I would recommend this technique for anyone who is unable to use pump.

• Intra muscular injection: Painful and unsafe. I have met people who were on this injection technique in the late 70s (the then commonly used technique). I don't recommend this technique. I believe this technique to be only of historical significance.

Having written all that, I would like to say that it really up to the patient to choose the most appropriate method of Desferal use for himself after consulting with his doctor. I would certainly recommend one or more techniques depending on circumstances, but it is ultimately the choice of the patient which technique he or she wishes to use. There are advantages and disadvantages of each of these techniques and individualized plans must be the right way to go.

I urge everyone to discuss with their doctors before making any changes to their medications. There are ways in which we as clinicians help minimize and control side effects or the severity of it. In case of a medication like Desferal, which I consider to be an essential life-saving medication for patients with Beta Thalassaemia major, it is important to do everything possible to help patients optimize their regular use.

It is not easy for the patients to adhere to this difficult treatment. But when it is an essential treatment, we must find ways and means to persevere.

Getting more involved

The wheels are still turning, apparently. The official wheels turn slow most of the time......but this pace is painfully slow.

Thanks to the administration at a private clinic (Imperial Medicare) I now have an opportunity to see patients at their clinic. This is a less than ideal (it not a free service) but it is a beginning.

Life without bone marrow transplant

When successful, bone marrow transplant can bring an end to the constant need for blood transfusions and over time, reduce the need for iron chelation therapy. Sadly, bone marrow transplant is not a viable option for many. And for many others [including some known to me personally] it not an option they would even consider.
My mentor, from whom I learnt much about the Thalassaemias, would often ask why bone marrow transplant is such an attractive option to some families. Why do we as people with Thalassaemia [their families and medical staff involved in their care] accept the risks involved in the procedure and go through the difficult treatment protocols?
Would we be as willing for bone marrow transplant if our Thalassaemia was better managed?
I recall the many conversations I had with a number of people with Thalassaemia in Melbourne. I saw in them individuals empowered to take hold of their lives, setting goals and carrying on with life with confidence and pride. Never considering themselves as anything less than a most capable and normal person. They were normal people living normal lives, their medical condition being just a part of who they were.
It wasn't denial; they accepted the medical condition they had and put in an effort to make sure that it wouldn't hold them back in life. With this attitude and the amazing support structure they built around themselves they were able to achieve a healthy state of living from where the risks associated with bone marrow transplant were not worth the risk.
Sadly, the same is not true in many other places. Accessibility to care, the immense hardship individual people and their families have to go through to get much needed precious blood, the lack of a decent support structure to assist in the sometimes difficult chelation therapy and the overall poor results of the largely inadequate therapy makes these differences all too obvious.
Optimised blood transfusions beginning early in life has in those centers reduced the bony changes that are still so visible on our faces. "They look like normal people" said this friend of mine with Thalassaemia upon meeting a middle aged woman with Thalassaemia from another country. And how true his statement was! The disappointment was not hidden in his voice when he later said "My face tells others that I have Thalassaemia". True again. His under-transfused body was trying to make more blood by expanding his facial bones causing tell tale facial features to appear. If we were to offer optimized (and personalized) blood transfusion regimes to cases with Thalassaemia in Maldives, we will be able to minimize the physical deformity associated with the condition. Accepting the fact that our blood donor pool is small and finding others ways of getting blood {say for example getting Red Cross in other countries to donate blood to us} would make it possible to provide adequate transfusions.
But perhaps the most significant difference that I noticed was that the chelation therapy was very well accepted as a part of the treatment in Melbourne. People used their pumps [yes they use pump and needles] diligently. One young girl from Melbourne said, "This is what will keep me well till you can find a cure". Another said, "I have blood to keep me going just the same way as my car needs petrol to run and it is Desferal that keeps my body’s engines in tip-top shape to work".
They keep themselves well by pumping iron out. Chelation is such an essential part of management that much of the treating physician’s time and effort is spent on that aspect of care. Again, we are failing very badly indeed in this aspect. Compliance with Desferal therapy is so very poor in a large number of people that accumulating iron slowly but surely poisons the body organs.
This is in my opinion why bone marrow transplant is such an attractive treatment option for our cases. Not requiring difficult and time consuming treatment on a regular basis is a blessing for anyone. What we at times fail to bring into the equation are the risks associated.
For those who do not have the bone marrow transplant option on the table; there is still life. These people from Melbourne with the medical condition have shown me this.