Martyn Hooper

Pernicious Anaemia Society

Changing the way in which Pernicious Anaemia is Treated – Part Two

by on Jul.22, 2014, under Pernicious Anaemia Society

Now here’s a story to ponder – and it’s not an isolated case.  A man with Pernicious Anaemia is receiving an injection of B12 every three months (this is the ‘normal’ treatment regimen in the UK).  After a month he starts experiencing the symptoms of B12 Deficiency.  He gets that strange tiredness, he becomes irritable, he forgets words, his family notice the changes in his personality.  He struggles on until the time has come for his injection.  So, he makes an appointment to see the practice nurse, arranged to take a morning off work  and dutifully turns up at the local health centre where he rolls up his left sleeve to save the nurse’s time.

It’s a Friday. He is summoned into the nurse’s room, take a seat and presents his arm to the nurse.  She checks his records and shakes her head.

“You have to have the injection every three months” she says.

“Yes” he replies

“But it’s only 11 weeks and five days”

“But I can’t come on Monday as it’s a bank holiday and you are closed”

“Well you’ll have to come back on Tuesday” says the nurse as she puts the injection back in the fridge.

Think that’s unusual?  It’s not, it happens all too frequently.  Just like patients who are told that, because their B12 levels are now normal or high (well they would be – after all the injections are supposed to do just that)  their injections will now be stopped all together.  That happens so often that it is almost normal to get two or three reports every week.  And then there’s the case I am dealing with at the moment – a pregnant lady whose injections have been stopped because “you have too much B12 and it will harm the baby”.

Let’s take another scenario – let’s go to the far east.  We walk into a shopping centre and are greeted by advertisements for a brand of B12 injection.  We go to a supermarket and choose five ampoules of B12 in the form of Methylcobalamin and take them to the checkout.  The ampoules are cheap and you hand over a few coins and return home where you take a clean single-use syringe and inject the contents of the ampoule using a small needle – there’s no need to find a vein or a muscle – you just inject the B12 under your skin in the top of your thigh.  And then you carry on with your life.

These two situations reveal just how disparate the treatment of Pernicious Anaemia is.  And because there is such a variation in how patients’ B12 Deficiency is treated it causes unnecessary suffering (to various degrees), patient frustration and, perhaps more importantly health inequality.

Let’s try to clarify what is going on by looking at what we know and what we don’t know for sure.  And I’ll start with what we don’t know.

Firstly we don’t know why some patients need more frequent replacement therapy injections than others.  There are doctors who know that some of their patients need more frequent treatment than others because when their additional injections are sanctioned the patient ceases to make frequent return journeys to the doctors practice and go about their daily lives as best they can.  Some doctors notice a marked improvement in their patient once treatment is prescribed according to the patient’s needs.  However, and this is the tricky bit – the science behind all of this is simply not there.  Nobody has fully investigated why some patients need more frequent injections than others.  Instead doctors assume that because some patients manage perfectly well on an injection every three months (in the UK that is) then every patient should be able to benefit fully from an injection every twelve weeks and that this is perfectly adequate.  Because the science to explain different patient needs is not there they look at the lowest denominator as being the norm rather than the other way around.  Instead of taking the twelve weekly regimen as the norm they should, perhaps, think of a monthly injection as the norm and if patients can and do manage perfectly well on a three monthly treatment regime then all is well and good.  The problem centres around the fact that there is simply no decent scientific data or evidence that will explain why some patients need more frequent injections than others.  And here’s an interesting fact – it is often the case that it is not the patient who notices that he or she is experiencing the original symptoms of PA (irritability, mood swings, tiredness etc) but the family, friends and work colleagues of the patient who begin to notice changes in the behaviour of the patient.  And this is especially true when it involves patients who are dependent on others for their care – children and those with special needs.

That isn’t to say that the whole of the medical profession is ignoring this issue.  I know of several doctors who hold various hypotheses as to why different patients have different needs.  Some believe it is due to molecular imperfections at cell level; or perhaps it is all due to faulty cell receptors; or maybe it’s to do with gut bacteria; or perhaps it’s to do with the way in which the patient turns the artificial B12 into the biologically active form.  There are lots of theories, but sadly no hard and reliable research findings that would give a credible explanation of what is going on.  And because there is this lack of scientific evidence doctors are left with only two options: either they can prescribe more frequent injections an in so doing fail to practice their art based on scientific knowledge or they make the only other option which is to assume, and it’s a big assume, that the patient is ‘imagining’ their need.  I had this last week when a caller to the office told me that her doctor had told her that if he gave her more injections then she would soon return and ask for more; “the more I give you the more you will want them” the patient was told.  I get this all the time.

So now let’s look at what we do know.  Well, the first startling fact is that when the 1ml of 1mg/ml of Hydroxocobalamin was introduced in the UK as the B12 of choice in 1963 the British National Formulary (BNF which sets out the guidelines for treating all manner of diseases) stated that the injection was to be given every month.  In 1974 that was changed to ever two months and, in Thatcher’s Britain, in 1984 it was changed to “every 12 weeks”.  And I mention Margaret Thatcher for a very good reason.  Every month she used to visit a doctor in Harley Street to receive a vitamin B12 injection – even though she didn’t have Pernicious Anaemia.

We also know that there is great dissatisfaction among patients with Pernicious Anaemia in the UK.  Over 2/3 of respondents to the Pj0182630A Society’s survey stated that they were ‘dissatisfied’ with their current treatment; and you have to remember that a great many of the 1/3 who were happy with their treatment were either being allowed more frequent injections by their doctor or were buying B12 from other sources and treating themselves with or without their doctors approval or knowledge.  10% of respondents to the survey were using Methylcobalamin as their choice of injection even though it isn’t licensed in the UK.

So what about these alternative sources of B12 Injections?  Where are patients finding injectable B12 and perhaps more importantly why are they being forced into by-passing their doctors?  The answer lies partly with what I have said above – that the science to explain why some patients need more frequent replacement therapy than others is not there and unfortunately the lowest treatment regimen is taken as the norm, and partly in the British Medicines Act of 1968 that states that any medical product that is delivered to the patient parenterally (via an injection) can only be obtained via a doctor;s prescription.  That’s why you cannot walk into a pharmacy (or supermarket) in the UK and simply buy injectable B12.

So, patients who have Pernicious Anaemia who live in the UK and who cannot convince their doctor that they would benefit from more frequent replacement therapy injections of B12 either and experience the return of their symptoms before, sometimes long before their prescribed injection either suffer needlessly or obtain injectable B12 from other sources.  And some of these sources are very dubious indeed.

I’ll start with the safest sources of injectable B12 – those prescribed by a doctor and dispensed by a pharmacist.  And yes it does happen in the UK – there are GPs who are willing to depart from the guidelines for treating Pernicious Anaemia as set out in the BNF and will treat their patient according to his or her individual need.  Unfortunately we in the Pernicious Anaemia Society don’t get to hear about these cases very often for a very good reason.  Obviously, if a patient is receiving their replacement therapy B12 when they want it they are unlikely to seek help from a patient support group.  This is the same reason why we have so few members who manage perfectly well on the three monthly regimen – they have no need for extra support and just go about their daily lives with their condition not affecting them in any way.  However, we do get patients who are receiving their injections whenever they want them (usually every four or five weeks) but who contact the society because they are still experiencing their symptoms to some degree.  Just why these patients should experience the symptoms of B12 deficiency when they are getting so many injections remains a mystery.  I know of at least two doctors who inject themselves twice or three times a day – perhaps the patients on monthly injections need them even more frequently; what is certain is that the evidence to support this is solely anecdotal and lacks any scientific explanation.  Prescribing injections to patients more frequently than the guidelines suggest does, unfortunately, have consequences for medical professionals who are investigated by the organisations responsible for overseeing quality and ‘good practice’.  And this is why doctors are reluctant to prescribe more frequent injections than mentioned in the BNF.

The next safest option open to patients whose National Health Service doctors refuse to prescribe more frequent injections is to turn to the private sector.  Here, the patient can pay for his or her extra B12 which is often offered in different forms, cyanocobalamin, hydroxocobalamin or the increasingly popular methylcobalamin.  Some patients report responding better to one or the other various types of cobalamin though why this is so is again unexplained.  Interestingly 10% of respondents to the survey used methylcobalamin which is not licensed for use in the UK.  And it can be expensive – especially if the compounding pharmacy where it is made opens up its operation to third party quality assurance agencies.

The third option available to UK patients is to buy their injections from pharmacies in mainland Europe.  This will usually be in the form of cyanocobalamin.  The patient then injects him or herself or gets a family member or friend to inject them.  In the best case scenario the person carrying out the injection will have received appropriate instruction, will use established hygiene practices and also use a lockable sharps bin.  Unfortunately, best practice is not followed.

Methylcobalamin Injection

Methylcobalamin Injection

And now we get to the more worrying options of by-passing normal medical practice and sourcing B12 from what could be rather risky and potentially dangerous places.

Internet ‘Pharmacies’ have become an increasingly popular source for patients buying additional B12.  The interesting point here is that individual suppliers are being championed and recommended by individuals and so in the process some are trusted more than others.  The internet has shrunk the world and so it is not surprising that enterprising individuals are capitalising on the fact that many patients cannot get the treatment that they need.  This sector continues to grow and now there are elements of price cutting and other promotions as the competition increases.  These ‘pharmacies’ do not only supply injections of B12, they also offer various other forms of B12 including sub-lingual drops, lozenges and sprays (the B12 gets into the patient’s bloodstream via a membrane under the tongue), nasal drops, trans-dermal patches and even anal suppositories.  The amazing thing about all of this is that nobody has evaluated the efficacy of these alternative treatments.  The problem faced by anyone carrying out any evaluation will be how the products efficacy could be measured; they will all raise the patient’s serum B12, but will they make him or her feel better?  I won’t go any further into this because it’s an enormous question that involves some highly complex biochemistry.  One sub-lingual spray has been evaluated in a laboratory and shown to replenish B12 levels and is becoming increasingly popular as it’s available in high street health food stores.

Intravenous Drips of a ‘cocktail’ of vitamins including B12 are another option for patients who are not benefiting from the normal treatment regimen.  This is the increasingly popular choice of ‘celebrities’ and there has been much press coverage of various people from the world of entertainment receiving these bagfuls of vitamins and minerals in various combinations.  And I know that this is a popular treatment for more and more of the PA Society’s members.  Alarmingly though, they are being offered by people, entrepreneurs, who are not medically qualified or trained.  Even some hairdressers and beauty parlours are offering this procedure and these institutions are not subject to any regulations.

All of the above alternative sources of replacement B12 are readily available to anyone with a computer and internet connection and there is now a growing demand for their services.  That demand is being enthusiastically met by health food shops and internet providers.  It really is time for the whole issue of a ‘one size fits all’ treatment regimen to be thoroughly investigated.  The way in which Pernicious Anaemia is currently treated is by far the single biggest cause of complaint by our members.  It’s hard to get your head around the fact that in the UK patients with Pernicious Anaemia were better treated in the 1960s than they are now.

 

 

 

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Changing the way in which Pernicious Anaemia is Treated – Part One

by on Jul.13, 2014, under Pernicious Anaemia Society

So here we are – seven years after we began the campaign to get someone who knows what they are doing to review the way in which PA is diagnosed we now have a new set of Guidelines produced by the British Committee for Standards in Haematology that acknowledges that there are serious problems with the way in which Pernicious Anaemia is diagnosed.  It’s strange to reflect that during the campaigning to get the way PA is diagnosed looked at it one of the options we used to put forward to doctors was that we wished that medical professionals would go back to how they used to diagnose the disease basing their decision on the patient’s symptoms rather than on the result of a blood test.  We were told that that would never happen.  However, the very first Recommendation states that “the Clinical Picture is More Important than the test result” so in effect the new guidelines are retrospective in that they are now telling doctors to listen to the patient rather than concentrate solely on the test result.

It took seven years of hard work to get our concerns listened to – five years of building up a good name and presenting our evidence in a calm and rational manner but five years on those doors that we were knocking on started to open.  Our paper that showed the results of our survey of over 1,300 members experiences in getting diagnosed was carefully analysed and presented using the preferred format of a respectable health journal and the results showed just how the poor diagnostic procedure currently used was effecting the everyday lives of people.  So, the battle to prove that the society (and me) were not dangerous nutcases finally paid off and thankfully we are now being asked our opinion on various aspects of B12 – we were even sent a copy of the draft guidelines to comment on.

Now we have had to ask ourselves ‘where do we go next’.  It wasn’t a difficult question to answer.  Ever since its inception the society has identified two key areas that are badly in need of reform.  The first concerned the problems with the way in which PA is diagnosed and, as we have seen from the new Guidelines, those issues have now been addressed.  And so now it is time for the society (and me) to start work on the second problem we face as patients – the ridiculous way in which replacement therapy B12 is provided, not only in the UK but throughout the world.  And this is where I start to outline just how big a problem this is; not only for patients but also for their families and friends.

Let’s first of all go back to the early 1920′s.  If you were one of the unfortunate people to have been diagnosed as having Pernicious Anaemia the term ‘pernicious’ meaning ruinous, deadly, fatal, would tend to concentrate your attention.  Despite whatever your doctor would try to help you, the prognosis was not good and you would die following a long drawn out but inevitable journey.  Your family and friends would only be able to make you as comfortable as possible and would have to look on helplessly as you began your final journey.  Then, in the middle of the 1920′s it was discovered by doctors in the USA that eating liver, and lots of it, could keep you alive.  Liver and other offal, preferably eaten raw, would mean that you could spend the rest of your life looking forward to your next dinner and hopefully a novel way of being served your lifesaver portion (they used to liquidise liver, make liver soup and all manner of other ways of trying to add a little variety into the patient’s diet).  Now this would be bad enough if you happened to like liver, especially raw, but even if you couldn’t stand the stuff it would, presumably, be better than the alternative – death.  Fast forward to the second half of the 1940′s and liver extract injections became available.  Highly concentrated liver could be injected directly into the patient who could then join in with the rest of humanity and look forward to a less strict diet.  Now, notice that nobody was told how much liver the hapless patient had to eat.  He or she would eat and ingest as much liver as he or she could bear.  You see, there’s no danger of overdosing on liver, not even the greatest fans of liver have ever been told to take it easy and try to cut down on their intake.  Imagine somebody telling someone who enjoyed liver to try and have it just three times a week.  It didn’t happen.  And no doubt, though I haven’t been able to find any evidence of this, some patients needed liver, preferably raw, more often than others.  While some patients would manage to stay alive on just one or two delicious platefuls of raw liver a week, others might need it twice a day.  Now, imagine if you can that you are a doctor in the 1930′s and you had one patient whose family made sure that the he or she consumed liver at least once a day.  As a doctor you would presumably congratulate both the patient and the family on their enthusiasm for the only treatment available at the time which was keeping the patient alive.  You may wonder at the resolve of the patient and marvel at his or her enthusiasm for all things offal but you would never suggest that he or she limits the amount of liver being eaten.  There was, however, a problem although this was not known at the time.  Liver is high in Vitamin A (Retinol), which had been identified as early as 1013 but was not named until 1920 and much later it was discovered that taking too much Vitamin A causes weak bones.  At the time that liver was being used to treat, though not cure Pernicious Anaemia this link between too much Vitamin A and Osteoporosis was not known and patients were free to bulk up on as much liver as they could manage.  In 1948 two independent teams, one in the US and one in the UK identified a new vitamin, vitamin B12.

B12 Molecule

The Chemical Composition of B12

From just after the Second World War and the late 1950′s concentrated liver injections were used to keep patients alive and then, following the discovery of the molecular structure of B12 in the mid 1950s by Dorothy Hodgkin (who was awarded the Nobel Prize in Medicine for this exceptional discovery) industrial scale production of artificial B12 began and this became available to correct the B12 Deficiency in patients with Pernicious Anaemia from the late 1950′s and early 1960′s.

The chemical composition of B12 is the most complex of all of the vitamins. and even today just what it does and what it is capable of is still a mystery to the dedicated team of expert doctors and scientists who have dedicated their lives to studying it.  And now that we’ve had a brief history of the vitamin it’s now time to turn our attention to the purpose of this story – why there is an urgent need for there to be a review of how patients with Pernicious Anaemia receive this lifesaving little molecule.

 

 

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Blossom the Cow & Bringing About Change

by on Jul.11, 2014, under Pernicious Anaemia Society

Well, that was a fine first half of the year.  Two incredibly important milestones were reached and they both occurred within two weeks of each other.

The Strategic Plan of the Society, that was written five years ago, stated quite clearly that there were serious problems surrounding Pernicious Anaemia.  Firstly there was the problem with the way in which the disease is diagnosed.  New Guidelines on diagnosing and treating PA were due to be produced in June 2012 but, following a highly successful meeting at the Department of Health in May 2012 those new guidelines were postponed and after two years the new guidelines were produced in May of this year (2014).  Most importantly those new guidelines included recently published research papers that provided the evidence, the scientific evidence, that the current assay used to determine the B12 status in patients was seriously flawed.  And just before the new guidelines were issued (we were shown the new guidelines in draft form which I commented on) our own research into patients’ experiences in getting diagnosed was eventually published in the British Journal of Nursing.  This paper, designed and analysed by three doctors, provided statistical evidence – credible statistical evidence – of what was previously only anecdotal evidence as told over and over again on the society’s online forum.  And so, these two events, the new guidelines and our own paper together have shown just how poor is the diagnostic process for determining B12 Deficiency and whether that deficiency was due to the quite specific disease called Pernicious Anaemia.  It took five years for us to be acknowledged as a credible patient support group by senior figures in the world of medicine; five long years of knocking on doors and writing to newspapers and magazines before finally we secured that meeting at the department of Health in May 2012.  And then it took another two years for the new guidelines to be produced.  And if there’s one thing I have learned from that experience it’s that changes in medicine don’t happen overnight.

However, whilst the new guidelines acknowledge the fact that patients and doctors are being let down badly by the current test they failed to address the second problem that was highlighted by the original Strategic Plan – that there are serious problems with the way in which patients are treated.  Instead of acknowledging this problem (and we made sure that this was a major subject of discussion during the May 2012 meeting) the new guidelines simply refer the matter to the British National Formulary for them to deal with.  And so whilst the new guidelines dealt with, or at least acknowledged that there are serious issues with the current test to determine B12 status, the second of our problems was not dealt with at all other than acknowledging that any neurological involvement should be treated by an injection every other day (something that was already in the BNF guidelines) but added that the writing group of the guidelines couldn’t see any reason this should continue after three weeks.  This is annoying because, more than anything else, it was a recommendation or suggestion that was, as far as I can determine, not based on any scientific basis – it’s more an opinion than a hard scientifically based judgement.

And so we still have the problem that the current treatment regimen in the UK for treating Pernicious Anaemia is nothing short of a farce and remains the single most common cause of complaint to the society.

Let’s take a look at events in the past week.  On Wednesday (today is Friday) I received an email from a member who is in her fourth month of pregnancy.  The email was not hysterical in nature but calmly enquired whether it was normal for patients who were pregnant to have their replacement therapy injection of B12 stopped “in case too much would harm the baby”.  This is not the first time we have heard of this by a long shot but what struck me as odd about this request was the casual nature of the question.  It was as if the writer had found the fact that her injections had been stopped a trifle odd and it had obviously been niggling her.  And so she took the step of seeking assurance from the society that her doctor was in order and that she should stop worrying.  We responded immediately telling her that her injections should never be stopped (as per the new guidelines) and that there was no danger of overdosing on B12 and that if anything she would need adequate levels to ensure the baby was not born deficient.  She was told all this and a copy of the leaflet on Pregnancy and PA was attached.  It was just another ordinary request for information from a patient whose health and that of her new baby were at serious risk of being compromised because of the confusion among some medical professionals about vitamin B12.  I wonder what the atmosphere was like at her next visit to her doctor?

This was not an isolated incidence, some of the horror stories that we here in the society’s office on a daily basis make this request seem almost routine, but I mention it because it happened at the same time as another incident that proves the need for a serious overhaul of the current treatment of Pernicious Anaemia.

In the north of England there’s a GP who, for many years, has treated all manner of symptoms with regular doses of vitamin B12.  He is adored by his patients, admired by his colleagues who are often truly amazed at the outcome of his treatments and he is very unpopular with his local Primary Care Trust who are deeply suspicious of his liberal prescribing of a harmless vitamin, and the Medical Practitioners Tribunal Service (part of the General Medical Council) have, through the Interim Order Panel recently renewed  an order that restricts the doctor from prescribing B12 for anything other than Pernicious Anaemia.  The doctor hasn’t done anyone any harm, has offended nobody and delighted thousands.  And so why is the GMC taking this action?  It’s simple – the scientific evidence on the benefits of B12 in treating all manner of other conditions is simply not there.  Just as the society only had anecdotal evidence from the online forum that there was serious issues with the diagnosing of PA so too the doctor only has his case histories of the benefits he has brought to patients with a wide range of problems.  Yes, there is some, and I mean some science as to what B12 does, and certainly the doctor is not alone in the medical profession who has discovered the incredible benefits that B12 can give to people, but that science is very small compared to other investigations carried out in laboratories.  His case studies are well recorded and read like a book of miracles, but until the science is there to explain the benefits of B12 people like him will always be on the defensive.

Blossom was a cow whose hide hangs on the wall of the St George’s Medical School Library (now in Tooting south London).  And you may be wondering why the hide of a dead cow should adorn the walls of a medical school library.  Well, she played an important tole in the development of medicine.  Edward Lister was a family doctor who had become aware of the fact that milkmaids who had caught cowpox were usually immune from the much nastier smallpox.  At this time (the 1790s) it was said that 60% of the population caught smallpox and that 20% died of it.  Small pox was a nasty and often deadly disease.  Jenner made the connection between the immunity of milkmaids to smallpox – and following the advice of his teacher – “don’t think, act” – Jenner scraped pus from the cowpox blisters of Sarah Nelmes a milkmaid who has spent many an intimate hour with Blossom the cow.  He then inoculated James Phipps, an eight year old son of his gardener in both his arms.  The boy became mildly ill but did not go on to develop smallpox – he was immune.  Now, why am I telling you this?  Because the science behind the experiment was not known.  There was no scientific hypothesis or explanation – it was just well known that milkmaids caught cowpox but didn’t go on to develop the much more serious smallpox.  Jenner didn’t have the scientific background to justify the experiment, all he did was find out if the old wives’ tale that milkmaids were immune to smallpox was true – and it was.  Of course, it could have all gone tragically wrong and a certain gardener could have found himself with one less mouth to feed and medicine has moved on a long way from the time when doctors could carry out such experiments that are based on no more than hearsay and a hunch and that is why doctors who use B12 so liberally are viewed at best as curiosities and at worse as quacks, but there’s a whole world of difference between injecting boys  with pus from blisters and using an incredibly safe and cheap vitamin – nobody has ever reported that any treatment involving B12 has caused any harm, at least as far as I’m aware.  The science isn’t there but it works and if they neglected to provide patients with this harmless vitamin then surely they could be seen as guilty of failing in their calling to ease and prevent patients’ suffering.  Of course the real heroine of all this is Blossom – a bovine whose contribution to the development of Immunology is thankfully recorded on the wall of a library.

So, this week we have had a pregnant woman whose life-saving injections have been stopped and a GP being told he can’t prescribe any more B12 – there’s something sadly and badly wrong with the way vitamin B12 is provided.  It’s a mess!

Tomorrow I will explain how the society is going about changing how we are treated for the better – a treatment regimen based on the needs of the individual who is offered a choice of how he or she receives that treatment.

 

 

 

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Awareness Week

by on Jun.27, 2014, under Pernicious Anaemia Society

Now that the new website is up and running and in safe hands it is time to turn our attention to our Awareness Week that will take place in October of this year.

Yesterday we applied for a grant to have a series of posters professionally designed and printed and I have written to several MP’s who are sympathetic to our cause asking them to arrange a series of events in the Palace of Westminster.  These events will include the following:

Parliamentary Reception – the last one we held was six years ago and was not successful as we had statistical evidence about how poor the current diagnosis and treatment of PA is – this time we will be able to make a presentation.

Prime Minister’s QuestionsHouses of Parliament and the Thames

Early Day Motion

Adjournment Debate

Questions to the Secretary of State for Health

Hopefully, really hopefully a Westminster Hall Debate.

We will be asking all of our members to write to their MP requesting that he or she attends the reception, signs any Early Day Motion, takes part in any debates and is made aware of the problems that we face in getting an accurate and timely diagnosis with treatment based on the individual’s needs.  Already there is a link on the website so that members can quickly find out who their MP is and how to contact them.  We will be providing a downloadable pro-forma letter that will make the whole campaign as easy as possible.

Between now and October me and the other volunteers will be busy making all of the necessary arrangements.

More on this as it happens.

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The Worst Six Months in the Society’s History

by on Jun.26, 2014, under Other, Pernicious Anaemia Society

Today the new website has gone live and hopefully that event marks the end of the worst six months in the history of the society.

It was just before Christmas 2013 that the company that had looked after all aspects of the website went into administration and we were left without any paid support.  It has taken six months to raise the necessary funds to make all manner of changes to the website that included changing servers, domain names and a host of other complicated stuff.

It is easy to forget just how big the website is and how much of a role it plays in patient’s lives.  The new website features a special section especially designed and built for medical professionals.  For the first time doctors will now be able to download a unique fact sheet that contains all of the latest developments in diagnosing and treating Pernicious Anaemia.  It is fully referenced and gives details of how the current test used to determine B12 status and whether any deficiency is caused by PA is not fit for purpose and it also tells of what we as a society are doing to make others aware of this.

Sadly, the Forum has now been suspended.  Two of the most knowledgeable moderators resigned earlier in the year and the sheer number of members posting questions made it impossible to moderate effectively.  We now have links to Health Unlocked:

“HealthUnlocked is a social network designed for people who care about their health and the health of others. With hundreds of dedicated communities run by patient charities and health organizations and a million users visiting monthly it’s the fastest growing hub for health support and information

So, with the website management going into freefall and the hugely popular forum being suspended the last six months have been one long headache as we searched for solutions to the problems.  Hopefully the second half of 2014 will be a lot less complicated than the first six months.

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Summary of New Guidelines on B12 and Folic Acid by the BCSH

by on Jun.15, 2014, under Pernicious Anaemia Society

I thought I had posted these over a month ago.  Ah well, better late than neverl

SUMMARY
OF THE
DRAFT GUIDELINES
FOR THE
DIAGNOSIS AND TREATMENT OF COBALAMIN & FOLATE DISORDERS
ISSUED BY
THE BRITISH COMMITTEE FOR STANDARDS IN HAEMATOLOGY
JANUARY 2014

This is a summary of the main conclusions and recommendations of the recently updated guidelines on diagnosing and treating Vitamin B12 and Folic Acid deficiency.
The report was published in January 2014 and is a thorough evaluation of how Vitamin B12 and folic acid deficiency is diagnosed and treated that takes into consideration the large number of research papers that have been published since the last guidelines were issued in 1994.

These new guidelines were originally intended to be published in June 2012 but were postponed following a meeting between the society and representatives of the Department of Health although whether the postponement was solely due to that meeting is not confirmed.

The full Draft guidelines contains 9,950 words and so this summary concentrates on the main issues addressed by the report and doesn’t include any references to the papers.

The complete report will be available here when it is published in full and not as a draft.
Please note that because this is a draft report some of the content may change before publication though that seems unlikely.

Medical professionals associated with the PA Society all welcome the new recommendations and are generally pleased with the result. The main conclusion of the report is that there are several issues surrounding the current Combined Binding Luminescence Assay that is used to determine B12 status and that research is needed to address these problems. However, all who have had sight of the report are disappointed that the single most common cause of complaint by members (the frequency of replacement therapy injections) is not addressed at all but refers the reader to the British National Formulary.
Summary of Key Recommendations:

• The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status since there is no ‘gold standard’ test to define deficiency.

• Serum cobalamin remains the first line test currently, with additional second line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Plasma homocysteine may be helpful as a second line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited.

• Serum holotranscobalamin has the potential as a first line test, but an indeterminate ‘grey area’ may still exist.

• Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established.

• In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment.

• Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue.

• Serum folate offers equivalent diagnostic capability to red cell folate and is the first line test of choice to assess folate status.

A. Tests to confirm/diagnose cobalamin deficiency
The grades are based on recommendations 1=strongly recommended – read as recommended; 2=weak – read as suggest.
The Quality of available evidence is given as A, B or C. A=strong evidence; B=moderate evidence and C=more research is needed.
Recommendations
• A blood film showing oval macrocytes and hypersegmented neutrophils in the presence of an elevated MCV may alert the clinician to the presence of underlying cobalamin or folate deficiency (Grade 2B)

• Cobalamin and folate assays should be assessed concurrently due to the close relationship in metabolism (Grade 1A)

• The writing group recommends adoption of reporting for cobalamin assay results in pmol/L (Grade 2C)

• A serum cobalamin cut-off level of either 148 pmol/L (200 ng/L) or one derived from a local reference range should be used as evidence of cobalamin deficiency in the presence of a strong clinical suspicion (Grade 2B)

• The report providing the result of a serum cobalamin assay should include the following
o The interpretation of the result should be considered in relation to the clinical circumstances
o Falsely low serum cobalamin levels may be seen in the presence of folate deficiency or technical issues
o Neurological symptoms due to cobalamin deficiency may occur in the presence of a normal MCV (Grade 2C)

• Plasma tHcy and/or plasma MMA, depending on availability, may be considered as supplementary tests to determine biochemical cobalamin deficiency in the presence of clinical suspicion of deficiency but an indeterminate serum cobalamin level (Grade 2B)
o Although plasma tHcy is a sensitive marker of cobalamin deficiency, plasma MMA is more specific
o Both assays have to be interpreted in relation to renal function

• Holotranscobalamin is suggested as a suitable assay for assessment of cobalamin status in a routine diagnostic laboratory in the future (Grade 1B)
B. Tests to determine the aetiology of cobalamin deficiency
Recommendations
• All patients with anaemia, neuropathy or glossitis, and suspected of having pernicious anaemia, should be tested for anti-intrinsic factor antibody regardless of cobalamin levels (Grade 1A).

• Patients found to have a low serum cobalamin level in the absence of anaemia, and who do not have food malabsorption or other causes of deficiency, should be tested for IFAB to clarify whether they have an early/latent presentation of pernicious anaemia (Grade 2A).

• Anti-gastric parietal cell antibody testing for diagnosing pernicious anaemia is not recommended (Grade 1A).

C. Treatment of cobalamin deficiency
Recommendations
• Treatment of established cobalamin deficiency should follow the schedules in the British National Formulary (Grade 1A).

• Initial treatment with oral cobalamin may not be appropriate in pernicious anaemia, but may be considered in maintenance or correction of suboptimal levels in asymptomatic patients (Grade 2C).

D. Recommendations on the clinical approach to investigation and treatment of cobalamin associated disorders
Recommendations
• Patients suspected of having pernicious anaemia should be tested for intrinsic factor antibody. Patients found to be positive should have lifelong therapy with cobalamin (Grade 1A).

• Patients negative for intrinsic factor antibody, with no other causes of deficiency, may still have pernicious anaemia as a result of poor sensitivity of the test and should be treated as anti-intrinsic factor antibody negative pernicious anaemia. Lifelong therapy should be continued in the presence of an objective clinical response. (Grade 2A)

Recommendation
• Serum cobalamin level of greater than 148 pmol/L (200 ng/l) in the presence of a strong clinical suspicion of cobalamin deficiency should be evaluated further with MMA, tHcy or HoloTC and a trial of hydroxocobalamin given to ascertain any clinical improvement (Grade 1C).

• In patients with serum cobalamin levels of ‘subclinical deficiency’ on two occasions, an empirical trial of treatment with oral cyanocobalamin (50 g daily for four weeks) should be given. Strict instructions should be given to patients to seek immediate medical attention if symptoms of neuropathy develop. The cobalamin level should be rechecked after 3 months, and second line tests considered if there is no improvement (Grade 2c).

• No definitive advice can be given on the desirable frequency of monitoring of serum cobalamin in patients with type II diabetes mellitus, but it is recommended that serum cobalamin is checked in the presence of strong clinical suspicion of deficiency (Grade 2B).

• If serum cobalamin levels are reduced, patients should have tests for anti-intrinsic factor antibody since the concurrence of pernicious anaemia with diabetes should be considered. If positive, the patient should have lifelong treatment with replacement cobalamin. If negative, the reduced level may be purely as a result of metformin, although underlying AbNegPA cannot be excluded. Treatment with oral cobalamin may be considered (50 g for one month), with subsequent monitoring of serum cobalamin after six months and then at yearly intervals is suggested (Grade 2C).
• Currently no recommendations can be given on prophylactic administration with oral cobalamin in patients taking metformin.

• Asymptomatic women taking oral contraception or HRT with mildly reduced serum cobalamin (110-148 pmol/L; 150-200 ng/L) do not require further investigation but should be advised to review their dietary intake of cobalamin rich foods, and cobalamin supplements may be considered.
Grade 1B)

• Serum cobalamin levels fall during pregnancy and are less reliable in determining underlying deficiency (Grade 1A).

• During pregnancy, in the presence of strong suspicion of underlying deficiency , a short course of empirical hydroxocobalamin should be given, with further investigations post-partum (Grade 2C)

• HoloTC may be more reliable than serum cobalamin in determining deficiency in pregnancy, and is recommended as the test of choice, if available (Grade 1B).

• Vegetarians, particularly strict vegans, should be considered for monitoring of their cobalamin level according to clinical assessment (Grade 2C).

• Dietary alterations or oral supplementation may be considered according to the clinical situation (Grade 2C), particularly during pregnancy and breast-feeding.

• Patients who have had bariatric surgery should have their cobalamin status monitored and are likely to need cobalamin supplementation via a route depending upon the type of surgery (Grade 1B).

• Patients with food-bound cobalamin malabsorption may benefit from low dose oral replacement (Grade 2B).

INFANTS
• In the presence of clinical suspicion of underlying cobalamin deficiency, even in the presence of normal serum cobalamin levels, further biochemical tests including MMA and tHcy are recommended (Grade 1B). The role of HoloTC in this context is undefined. Further investigation to define any possible genetic abnormalities should be referred to a specialist centre.

• No specific recommendation can be made regarding treatment since each case has to be judged individually.
Tests to diagnose folate deficiency
Recommendations
• A serum folate level less than 7 nmol/L (3 µg/L) is indicative of folate deficiency (Grade 1B).

• Routine red cell folate testing is not necessary since serum folate alone is sufficient in most cases (Grade 1A).

• In the presence of strong clinical suspicion of folate deficiency, despite a normal serum level, a red cell folate may be undertaken, having ruled out cobalamin deficiency (Grade 2B).

• Plasma tHcy can be measured to confirm suspected folate deficiency only in special circumstances; a level above 15 µmol/L could be indicative of folate deficiency but must be assessed in relation to local reference ranges (Grade 2B).
B. Clinical approach to investigation and treatment of folate associated disorders
Recommendation
• Folate status is generally checked in clinical situations similar to those of cobalamin deficiency (Grade 1A).

• Consultation of the British National Formulary and Summary of Product Characteristics is recommended for clarifying any suspicion of low serum folate levels associated with prescribed medications.
Recommendations for future research
In the absence of anaemia or objective clinical signs of cobalamin deficiency, the significance of a low serum cobalamin/folate level can be difficult to determine.
A prospective study on the natural history of subclinical cobalamin deficiency or LCUS with or without abnormal homocysteine/methylmalonic acid is required.
Research on the clinical utility of more sensitive and specific tests is needed.
Research on ways of assessing adequate replacement would be of benefit in titrating the treatment with clinical efficacy.
Recommendations for audit
Laboratory performance of serum cobalamin assay in relation to UK NEQAS .
Clinical reason for serum cobalamin request as specified on request forms.
Haemoglobin concentration and mean cell volume, if available, taken at same time as serum cobalamin in the deficiency level and 25% below the local laboratory reference range cut off level.
Clinical audit investigating deficiency states in relation to local reference ranges.
Establishment of clinical cut-off points for deficiency with holotranscobalamin assay.
End of Summary

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The Petitions

by on Jun.15, 2014, under Pernicious Anaemia Society

Today I have submitted two new Petitions or more correctly two new E-Petitions.  One is to the UK Government and one to the Welsh Government.  Both call on the relevant authorities to change the way patients with Pernicious Anaemia are currently treated with the (usually) hopeless one-size-fits-all injection every three months to a regimen where the patients gets to choose the way in which he or she will receive their replacement therapy injection (nurse administered injection, self-administered injection, nasal spray, sub-lingual drops, sub-lingual spray, anal suppositories or skin patch) that is based on the need of the individual patient.

Both have now to be approved.  I’ll keep you posted!

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The ‘Complaint’

by on Jun.15, 2014, under Pernicious Anaemia Society

It was an all too familiar story.  The patient telephoned to say that because she had asked for more frequent injections the GP had checked her B12 status which was unsurprisingly high.  And then, again all too familiarly, her injections have been stopped altogether.  It is now over a year since she had her last B12 injection and she has developed neurological symptoms.

So, I offered to write to the Medical Director of her NHS Trust.  That was a month ago.  I wrote and reminded the Doctor that patients with Pernicious Anaemia need injections for life and that I was extremely concerned about the neurological involvement.  Now what usually happens is that the Medical Director will contact the GP practice and remind the doctors that injections should never be stopped.  Then the patient is called in to the practice and the injections are resumed.

Yesterday I received a letter from the Medical Director stating that he had referred my letter to the ‘Complaints Department’ and that they would contact me soon.

Ho Hum!  Let’s wait and see what happens now.  It wasn’t a complaint but a letter to raise awareness of bad medicine.  I’ll keep you informed.

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Freezer Bought

by on May.25, 2014, under Pernicious Anaemia Society

Yesterday I bought a new upright freezer that will be used to store the samples of urine and pooh that are required for the research taking place into why some patients need more frequent than others.  A large box of sample containers arrived on Friday so everything is starting to take shape.

The only thing holding us up is Ethics Approval which will hopefully be granted on the 9th June.  When the ethics committee gives the ok I will then be writing to various doctors surgeries asking them to identify patients who manage perfectly well on a 1mg injection of B12 every three months.  This is because whilst we have plenty of volunteers who need more frequent injections that one every twelve weeks, we are struggling to get the necessary number of patients to take part in the research who need more frequent injections.

The project will be coordinated at the office end by a medical student.

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DOCTORS -the BBC’s Daytime TV Drama

by on May.23, 2014, under Pernicious Anaemia Society

DoctorsAnd so it begins!  It has been months since I was contacted by one of the writers of the BBC’s increasingly popular daytime drama ‘Doctors’ who wanted to know about how Pernicious Anaemia affects patients.  And yesterday saw the storyline about a patient with Pernicious Anaemia begin.

I don’t know why one of the writers contacted me, after all there is a qualified doctor who acts as an adviser to the show, but I remember being able to tell the caller that we were aware that many of our members waited many years for a correct diagnosis and that there were problems with the current test used to assess the patient’s B12 status.  I remember also telling him that the range of symptoms was wide and varied and can lead to severe and irreversible nerve damage.

So – based on just one episode how accurate was the show’s depiction of diagnosing and treating PA?

The Gaffes:

Let’s start with the bad points.  Firstly the doctor not only ordered a full blood count but also asked for the patient’s B12 and folate to be examined.  That doesn’t always happen and actually runs contrary to NICE’s Clinical Knowledge Summary that states that B12 status in patients shouldn’t be assessed unless there is sign of enlarged red blood cells (macrocytosis).  Still, there is some evidence that as the PAS raises awareness of the problems with patients receiving a quick and accurate diagnosis more and more primary care doctors are requesting the patients B12 and folate is assessed as well as the full blood count.

Secondly – the diagnosis and treatment.  Well the doctor suspected anaemia due to the patient’s mucous membrane around her eyelids seemed pale which was a good thing, however we know that patients with B12 deficiency may not always have anaemia – a small but interesting point.  And then there was the treatment – not a small interesting point but a large, very large piece of misinformation.  The doctor told Stevie (let’s get familiar) that her treatment would be an injection every three months until her “blood returned to normal”.  There was no mention of loading doses and of course, pernicious anaemia needs to be treated for life and NOT until the patient’s blood returns to normal. Surely the writers would know that B12 replacement therapy would have to be for life.  Surely the doctor acting as medical adviser would know this and would have corrected the script.  So what is going on?  I think, and it’s only my theory – I have no inside knowledge – I think that the writers have deliberately written this huge error into the script to show how badly patients with PA are treated, will I hope that is what has happened – only time will tell.

And then there was the casual referral to a haematologist which only happens in the UK if the patient displays any neurological involvement.  Now, Stevie has told the doctor that she has burning feet and prickly feet so the GP may have suspected neurological involvement but I don’t think so.  I remember telling the writer that not all doctors make the link between neurological symptoms and B12 deficiency and I suspect that this may be part of the plot – that Stevie’s condition (and career) worsens before the link is made.  If the doctor had suspected neurological damage then he should have prescribed an injection every other day until there was no further improvement.

Thirdly – the symptom of shortage of breath (or more accurately The Sighs).  Was Stevie’s breathing problems due to shock or because of her Pernicious Anaemia?  Had the writer exaggerated the problems that patients who have Pernicious Anaemia have in breathing normally or was her breathlessness due to her being in shock – that wasn’t made clear.

The Good Bits:

There were plenty of good bits.  Firstly the acknowledgement that Pernicious Anaemia, if left undiagnosed and untreated can and does lead to mental disturbances – that was good.  Secondly her erratic behaviour in the weeks previous to her being diagnosed was pointed out as was her forgetfulness – all strong indicators of PA.  Then there was the tiredness and let’s remember that Stevie is in danger of seeing her business fold because of her incapacity to work – something that is much more common that is generally supposed.  Another positive point is that Stevie is relatively young which runs contrary to what most medical professionals believe – that PA is mostly to be found in the elderly or very elderly.

Finally, one last but very good point – the laboratory telephoned the doctor just a few hours after Stevie had her blood taken to make him aware that the patient’s B12 level was dangerously low.  The hospital laboratory that received my first blood tests did the same with my doctors.

 

The Future.  So, as the plot unfolds and the story progresses what is going to happen?  Will the doctor make the link between Stevie’s neurological issues and her PA?  Will she manage perfectly well on an injection every three months?  Will the doctor prescribe more frequent injections if she needs them?  Will Stevie resort to alternative sources of the injections if he doesn’t?  Will she make a full recovery or will she still be symptomatic for the rest of her life?  We’ll have to keep watching!

 

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