vCJD-related abnormal prion protein in a person with haemophilia – an update
Following the finding of evidence of the abnormal prion protein that causes variant Creutzfeldt-Jakob Disease (vCJD) in a haemophilia patient at post mortem, a risk assessment of the possible routes of exposure for this individual has been published by the Department of Health .
The vCJD-related abnormal prion protein was detected only in the individual's spleen but the finding was the first of the agent in a haemophilia patient .
To date, no haemophilia or bleeding disorder patients have been diagnosed with or died from clinical vCJD.
The investigations into the possible routes of infection considered, assuming that the abnormal prion protein did indicate vCJD infection, four possible infection routes: dietary exposure to BSE; surgical procedures; transfusions with several units of red cells; and treatment with large amounts of UK sourced Factor VIII. This included two batches of Factor VIII 8Y that were sourced from plasma pools which included plasma from a single donor who later developed clinical vCJD.
The calculations involved in this risk assessment depend on the likely prevalence of subclinical vCJD infections among the UK population, the infectivity of plasma products and blood components – both of which are subject to great uncertainties - and the number of donors contributing to the plasma pools. The risk assessment concludes that in scenarios based on current evidence, the most likely source of this patient's infection was treatment with UK sourced clotting factors.
This haemophilia patient had been treated in the 1990s with over 390,000 units of UK-sourced Factor VIII, including over 9,000 units from two implicated batches of Factor VIII 8Y (linked to a donor who later developed clinical vCJD).
The risk assessment concluded that, based on plausible assumptions, the patient was more likely to have been infected by a batch of Factor VIII that was not sourced from a pool containing plasma from the donor known to have vCJD (a non-implicated batch), than by one of the two implicated batches that were linked to this donor.
This is because far more units of non-implicated than implicated batches were administered to this patient. Each batch of plasma product is sourced from many thousands of donors (around 20,000), any one of whom could have had an asymptomatic abnormal prion protein infection. The relative risks from implicated and non-implicated batches will only be clarified further by long-term follow-up of patients.
The CJD Incidents Panel considered the risk assessment, together with other information, and concluded that this evidence confirms its existing advice to patients already notified as at increased risk of vCJD. There is therefore currently no reason to change that advice, nor to notify any new groups of patients. There is no change in the public health vCJD “at risk” status of any patients with bleeding disorders.
All patients with bleeding disorders  who have been treated with UK-sourced pooled factor concentrates or antithrombin  between 1980 and 2001  are classified as “at risk of vCJD for public health purposes”. Special infection control precautions and other safety measures apply to these patients.
All haemophilia centre doctors were informed of the Panel's decision on Tuesday, 9 June, 2009 and were asked to send a letter to their patients who have been notified as at increased risk of vCJD. Further information is available at
1. vCJD risk assessment calculations for a patient with multiple routes of exposure. Department of Health, 9 June 2009. Available at:
2. HPA. Post mortem finding of asymptomatic variant Creutzfeldt-Jakob Disease abnormal prion protein in a person with haemophilia, Health Protection Report [serial online] 2009; 3 (10): news. Available at:
3. Defined here as congenital and acquired haemophilia (Haemophilia A and Haemophilia B), Von Willebrand Disease, other congenital bleeding disorders and congenital antithrombin III deficiency.
4. ie clotting factors and antithrombin made from pooled plasma. These include factor VIII, factor IX, factor VII, factor XI, factor XIII and prothrombin complex concentrates as well as antithrombin.
5. The start date of 1980 is when BSE is thought to have entered the human food chain. The end date of 2001 is the last possible expiry date of any product manufactured by the UK fractionators that was sourced from UK donors until 1998.
Variant CJD and plasma products Introduction
Earlier notification of patients who had received implicated plasma products
Asymptomatic vCJD abnormal prion protein in a haemophilia patient
Introduction Certain plasma products, manufactured using plasma from donors who later developed vCJD, may have exposed people who received them to infectivity and an increased risk of developing vCJD. The level of risk is unknown, and likely to be very low. The risk in such circumstances is in addition to a general risk for many people in the UK from past exposure to the BSE agent from eating beef and beef products.
The conclusions of a vCJD Blood Risk Assessment carried out by Det Norske Vertis Consulting have been accepted by the Spongiform Encephalopathy Advisory Committee (SEAC), the Committee on the Microbiological Safety of Blood and Tissue (now the Advisory Committee on the Safety of Blood Tissues and Organs - SaBTO), and by the Committee on Safety of Medicines.
As a consequence, all patients with bleeding disorders 1 who have been treated with UK-sourced pooled factor concentrates or antithrombin 2 between 1980 and 2001 3 are classified as at risk of vCJD for public health purposes. These patients should follow advice to reduce the risk of spreading vCJD to other patients.
Please also see Information leaflets for patients and healthcare professionals.
Earlier notification of patients who had received implicated plasma products In 2004 the HPA, the UK Haemophilia Centre Doctors' Organisation (UKHCDO) and colleagues notified patients who had received plasma products manufactured using plasma from donors who had subsequently developed vCJD. That notification dealt with plasma donations which had been used to manufacture factor VIII, factor IX, antithrombin, intravenous immunoglobulin G, albumin, intramuscular human normal immunoglobulin and anti-D.
Patients treated with these plasma products were managed according to an assessment of potential vCJD infectivity carried out by the Health Protection Agency with the CJD Incidents Panel.
The UKHCDO and patient representatives, the CJD Incidents Panel and UK Health Departments agreed that it was likely that many patients with bleeding disorders would have had sufficient exposure to these implicated plasma products to put them 'at risk of vCJD for public health purposes'. It was also thought likely that further batches of UK-sourced plasma products would be implicated in the future as more cases of vCJD arose.
In 2004 all patients with bleeding disorders were told whether they had received UK-sourced pooled factor concentrate or antithrombin between 1980 and 2001. Those who had were informed that special precautions needed to be taken to reduce the chance of any further spread of vCJD and were asked to follow public health advice.
Asymptomatic vCJD abnormal prion protein in a haemophilia patient A person with haemophilia was recently found to have evidence of the agent (abnormal prion protein) that causes vCJD only in his spleen at post mortem.
The post mortem was carried out as part of a study jointly co-ordinated by the UK Haemophilia Centre Doctors Organisation and the National CJD Surveillance Unit. This was the first time that vCJD abnormal prion protein had been found in a patient with haemophilia.
Up to the present, no haemophilia or bleeding disorder patient has been diagnosed with or died from clinical vCJD This haemophilia patient had been treated with several batches of UK-sourced clotting factor Factor VIII. This includes two batches of Factor VIII manufactured using plasma from a single donor who developed clinical vCJD 6 months after donating the plasma. These batches are called 'implicated' batches because they are linked to a donor who subsequently developed vCJD.
The haemophilia patient was in his 70s when he died of a condition unrelated to vCJD, 11 years and one month after receiving the second batch of implicated Factor VIII. He had no signs or symptoms of vCJD or other neurological disease when alive.
The patient had also received several transfusions of red cells, and had undergone surgical procedures in the past. A recent statistical assessment of the available information has concluded that the most likely source of vCJD infection was treatment with UK plasma-sourced clotting factors.
The risk assessment, together with other information, has been considered by the CJD Incidents Panel. The Panel has concluded that this evidence confirms its existing advice to patients already notified as at increased risk of vCJD. There is therefore currently no reason to change that advice, or to notify any new groups of patients.
There is no change in the pubic health vCJD 'at risk' status of any patients with bleeding disorders.
The CJD Incidents Panel keeps all new information about potentially infected products under close and regular review and advises doctors and their patients about the implications of all new evidence as it emerges.
Patients who are unsure about their vCJD at risk status, or who would like more information, should contact their haemophilia centre.
1. Defined here as congenital and acquired haemophilia (Haemophilia A and Haemophilia B), Von Willebrand Disease, other congenital bleeding disorders and congenital antithrombin III deficiency. 2. ie. clotting factors and antithrombin made from pooled plasma. These include factor VIII, factor IX, factor VII, factor XI, factor XIII and prothrombin complex concentrates as well as antithrombin. 3. The start date of 1980 is when BSE is thought to have entered the human food chain. The end date of 2001 is the last possible expiry date of any product manufactured by the UK fractionators that was sourced from UK donors until 1998.
Last reviewed: 10 June 2009
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)
Sunday, June 07, 2009
L-TYPE-BSE, H-TYPE-BSE, C-TYPE-BSE, IBNC-TYPE-BSE, TME, CWD, SCRAPIE, CJD, NORTH AMERICA