vCJD in the UK
On February 16th 2009 we contacted all members to inform them about a development in relation to vCJD in the UK. At that time a man with haemophilia in the UK, who was in his 70s, died from a cause unrelated to vCJD. A routine autopsy showed evidence of infection with vCJD in some of his tissues at the time of his death. It appeared most likely at that time that the man had been infected with vCJD from a batch of Factor VIII that was known to have included plasma from a donor who later died of vCJD. This was only relevant to persons with haemophilia in Ireland who received plasma derived factor concentrates in the UK (including Northern Ireland) between 1980 and 2001.
Following the autopsy, the Health Protection Agency (HPA) in the UK have carried out a risk assessment in relation to this man's exposure to vCJD. The risk assessment, which was published on June 9th, concluded that there was a very high degree of probability that this man's prion infection was caused by plasma derived Factor VIII (greater than 99% probability). More suprisingly they reached the conclusion that the infection for this individual was more likely to have resulted from the use of non-implicated batch, in other words from a Factor VIII batch that was not made from a plasma pool containing a donation from someone who later went on to die from vCJD). The risk assessment which is a mathematical modelling exercise depends, to a very large degree, on the assumptions they make before the assessment. The major assumption which affects the outcome of this risk assessment is the prevalence of vCJD in the UK (the number of people in the UK who are infected with vCJD). We know that to date there have been 168 cases of vCJD in the UK where they tested tonsils and appendixes which are removed from people in the general population. Tonsils and appendix tissues are among the tissues where you are more likely to find abnormal prions if an individual has been exposed. They found three tonsil/appendixes positive for prions in a total of 12,874 samples tested. From this they reached the tentative conclusion that the prevalence of vCJD in the UK could be as high as 1 in 4,225, in other words, just over 14,200 persons may, according to this risk assessment, have prions in their tissues although they may not develop vCJD. This is the most pessimistic assumption. Most risk assessments in the past have given two ranges of risk based on the most optimistic range of infection in the UK (one in 350,000) or the most pessimistic (one in 4,225). This risk assumption is bassed on an assumed prevalence of one in 10,000, so they are taking a very pessimistic view.
Based on the assumption, if we look at plasma derived factor concentrates which were used in the UK between 1980 and 2001, typically they would have been made from plasma pools containing up to 20,000 donations. If they assume that one in 10,000 of the population was carrying the abnormal prion, it is a fair assumption, according to this risk assessment, to assume that each pool would contain two infected donations. If we look at the implicated batches which are known to have contained plasma from a donor who later died from vCJD, it is assumed that these pools contained two infected donations plus an additional (known) donor, to give a total of three. Clearly the risk from these implicated batches was slightly higher. This man who died in his 70s used over 400,000 IU's of Factor VIII concentrate in his life and only 9,000 IU's came from known implicated batches. In excess of 390,000 IU's came from non-implicated batches. Therefore, they are making the assumption that, given the fact that every batch is thought to have theoretically contained two infected donations, on the balance of probabilities these prions in his tissues resulted from the use of a non-implicated batch.
It is worth re-iterating a number of points in relation to vCJD and haemophilia in the UK. Every person who lived in the UK from 1980-1996 has a continuing risk of developing vCJD. This risk is very low and there may well be less than 50 cases over the next 50 years. According to the 2004 UK risk assessment, people who received blood or blood products including people with haemophilia, have a slightly increased risk of developing vCJD over and above this background risk (at the time in 2004, they put the increased risk as 1% above the background risk). It is important to note that this man in the UK did not develop vCJD and died from an unrelated cause. It is important to note that this man in the UK did not develop vCJD and died from an unrelated cause. It is also important to note that to date 802 persons with haemophilia in the UK have received factor concentrate that was manufactured from known implicated batches (where a donor whose plasma went into making the batch later died of vCJD). To date none of these persons with haemophilia have developed vCJD. Plasma derived Factor VIII and Factor IX concentrates from the UK were never imported into Ireland, although a number of Irish people with haemophilia did receive treatment in the UK between 1986 and 2001. In addition a number of individuals with rarer bleeding disorders used treatment in Ireland which was manufactured from UK plasma during that time. All of these people have been individually contact in the past by the National Centre for Hereditary Coagulation Disorders and given the information they require in relation to this issue. As a result of this latest risk assessment in the UK there is no need for any change in practice or policy in Ireland. It is also worth noting that the current generations of plasma derived factor concentrates which are used, some of which are used for the treatment of von Willebrands Disease in Ireland) in general have a much higher clearance of prions than those which we used in the 1980's and 1990's.
In the meantime the Food and Drug Administration (FDA) in the U.S.A. have also updated their risk assessment in June 2009, where they looked at the potential risk of vCJD for United States users of US licensed plasma derived products. Theri risk primarily comes from the number of people who were donors in the USA who may have been exposed to the BSE agent during travel or residence in the UK, France or certain other European countries. Unlike the UK they give two sets of figures where they base their assumptions on a very low or very high prevalence. They estimate the risk of developing vCJD to vary from one in 12,000 to one in 12 million. I believe this very broad range demonstrates the enormous amount of uncertainty in this area and the huge affect the assumed prevalence of vCJD in the UK has on these mathematical calculations.
Brian O'Mahony
Click here to view a presentation on vCJD
