Dr Rosemary Leonard
The Northern & Shell Building
10 Lower Thames Street
Dear Dr Leonard,
Re: Treating Pernicious Anaemia
You recently stated that patients suffering from Pernicious Anaemia who have received initial loading doses of replacement vitamin B12 need only a top-up injection every three months and that “There is no need to have injections more often” – Daily Express, 21/10/14. This has, as I’m sure you are aware, angered a great many of our members who, just like the teenager in the letter need far more frequent injections than the usually prescribed twelve weekly regime.
My heart goes out to that young lady who will have all manner of problems trying to lead a normal life. This society has to deal continually with the fallout of the current one-size fits all treatment and that includes dealing with school & college problems, matrimonial strife and the abrupt ending of careers.
There are a number of issues surrounding the treatment of Pernicious Anaemia and I would like to share these with you.
Firstly, the current test to ascertain the B12 status of patients is seriously flawed. Here’s what the new Guidelines for Cobalamin and Folate written by the British Committee for Standards in Haematology say:
“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”. 1
And they state:
“Research on discovery of more sensitive and specific tests is needed”2.
Secondly, the current test – the Combined Binding Luminescence Assay – gives false high readings in between 28 and 35% of patients3 leading to all manner of misdiagnosis and unnecessary treatment. 33% of our members waited five years or more to be correctly diagnosed with 44% having originally being diagnosed with some other condition notably Depression, Myalgic Encephalopathy and Multiple Sclerosis4.
Secondly the current threshold for determining any deficiency may be far too low5 and it is interesting to note that the current Recommended Daily Intake of B12 was established in 1948 based on the serum measurements of 7 patients all of whom had been diagnosed as having PA6.
Finally you may be interested to know that the BNF recommended a 1mg/ml injection of Hydroxocobalamin every month during the 1960s which was changed to every two months in 1974 and then to every three months in 1984. By far the biggest cause of concern to our members is the frequency of injections. Some of our members and a great many of patients with Pernicious Anaemia manage perfectly well on a three-monthly injection but for the majority of our members and a sizeable proportion of patients with the condition they need more frequent replacement injections. 64% of patients with Pernicious Anaemia are Unhappy with their treatment7.
And there are several consequences of this.
Firstly, savvy patients source additional injections from various places. These include travelling to the European continent and buying Cyanocobalamin from pharmacies where it is available without prescription; buying Hydroxocobalamin or more likely Methylcobalamin from online ‘pharmacies’ where it is readily available; receiving intravenous ‘infusions’ of high strength Methylcobalamin and then self-injecting up to 15mg a day (popular with ‘celebrities’), and using nasal sprays, skin patches, ointments, sub-lingual lozenges, drops or sprays which have been developed in response to the demand within the market some of which are remarkably potent. All of this is because their doctor will not provide more frequent injections than those recommended by the BNF. Thankfully, some doctors will listen to their patients and allow injections when he or she requires it. Incidentally, it is not always the patient who notices a return of the symptoms after various periods of time – often it is his or her family, friends or work colleagues who notice the changes in the patient.
So why do some patients need far more frequent treatments than others? Nobody knows but this society is currently working with three teams of researchers to find the answer. Each team has its own hypothesis which includes gut bacteria, defective genetic cells or problems with the methylation cycle (you need lots of folic acid in order for Hydroxocobalamin to transform to Methylcobalamin using methyl-folate) and there are a great many other theories that revolve around ‘active B12 (Holotranscobalamin) and the enormous problem with B12 analogues. What is certain is that some patients need more frequent replacement therapy than others regardless of serum B12 status.
I do hope this has helped clarify this sensitive and emotive issue. I would be most grateful if you would point the young girl and her mother in the direction of this society so that I can explain the options available to the patient. I do not only feel sorry and sad for the young lady, I also completely empathise with her. I was in a similar situation to her when I was eventually diagnosed and treated.
Thank you for taking the time to read this letter. If you would like to discuss the problems with the diagnosis and treatment of Pernicious Anaemia further I would be delighted to meet up to do so.
Finally, we, as a society, would be most grateful for any help you or the Daily Express could give to help us achieve our new main objective – to provide patients with Pernicious Anaemia a choice of treatments that would be delivered according to the individual’s need.
1 Devalia, V et al; British Journal of Haematology: Volume 166, Issue 4, Article first published online: 18 JUN 2014
3 Carmel R, Agrawal Y; Failures of Cobalamin Assays in Pernicious Anemia; New Engl Journal of Medicine; 367;4; July 6th 2012
Yang, D, Cook, R; Spurious Elevations of Vitamin B12 in Pernicious Anaemia; New Engl Journal of Medicine; 366;18, May 3rd, 2012
4 Hooper, Hudson, Porter, McCaddon; Patients Journeys; Diagnosis and Treatment of Pernicious Anaemia: British Journal of Nursing, 2014, Vol 23, No 7
5 Smith & Refsum; Do We Need To Reconsider Blood Level of Vitamin B12?; Journal of Internal Medicine, 2012;271(2): 179-182
6Hilko van der Voe et al: A Statistical Method to Base Nutrient Recommendations on Meta-Analysis of Intake and Health-Related Status Biomarkers; Plos One DOI: 10.1371/journal.pone.009317
7 Ibid 4