Vox Sanguinis (2015) 108, 432–433 © 2015 International Society of Blood Transfusion DOI: 10.1111/vox.12241
LETTER
Variant CJD and blood transfusion J. P. Wallis Department of Haematology, Freeman Hospital, Newcastle upon Tyne, UK
Dear Editor, The recently published histological study of surgically removed appendix tissue raised the possibility of silent carriers of the disease affecting 1 in 2000 UK donors [1]. Davidson et al. [2] report on the characteristics of patients with clinical vCJD who had previously received blood transfusion but where the donors have not themselves gone on to develop clinical vCJD. On the basis of a higher-than-expected mean age of these cases, they suggest an association between transfusion and vCJD. However, they do not adjust for factors affecting the likelihood of prior transfusion. From our study in 1994 of point incidence of transfusion and subsequent survival, I have estimated the prevalence of prior transfusion by age (Table 1) [3]. To allow for the effect of repeated transfusion and the observed 80% 5-year survival, I have applied a correction factor of 05 to the data. My figures are similar to other surveys of prior transfusion prevalence [4]. I have excluded neonatal transfusion as practice markedly changed during the previous 2 decades. The Table 1 shows the estimated prevalence of prior transfusion in quintiles from 10 to 60 years. This increases because the cumulative likelihood of having received transTable 1 Estimates of expected prevalence of prior transfusion in patients with clinical vCJD
Age group 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–60 Total
432
Transfusion prevalence per 100 in 1994 027 094 179 300 404 518 659 859 1088 1467
vCJD clinical cases
Estimated cases with prior transfusion
0 25 44 44 32 19 6 2 4 1 177
0 024 079 132 127 098 042 016 048 009 575
fusion increases with time at risk and because transfusion point incidence rises with age. Using the known age distribution of the 177 vCJD cases, I have estimated that 575 cases would be expected to have had prior transfusion. Davidson et al. find 14 cases who had definitely been transfused. Of these, three were from donors who subsequently developed vCJD and are excluded, one was transfused immediately prior to diagnosis, leaving 10 cases. One was transfused as a neonate, a period I have excluded leaving 9. Four were from a period before records of donors were available, and not knowing their age at transfusion, I cannot know whether they should be included in an analysis of transfusion after the age of 10 years. A figure of between 5 and 9 remaining cases having received transfusion in the last 10–20 years prior to diagnosis is close to 575 as estimated above. Older patients with clinical vCJD are more likely to have been transfused, and the mean age will be higher than the whole cohort. Based on the age-adjusted transfusion prevalence, the mean age of cases that might have received an unlinked prior transfusion is 334 years. This compares with the observed figure given by Davidson et al. of 355 years. The prevalence of transfusion in females is almost twice that in males between the ages of 30 and 60. Four of six vCJD patients with prior transfusion were female. The observations of Davidson et al. given the analysis above would suggest no significant excess of prior transfusion amongst vCJD cases during the recent epidemic, and no unexpected age or sex distribution in vCJD cases with prior transfusion.
References 1 Gill ON, Spencer Y, Richard-Loendt A, et al.: Prevalent abnormal prion protein in human appendices after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 2013; 347:f5675 2 Davidson LR, Llewelyn CA, Mackensie JM, et al.: Variant CJD and blood transfusion: are there additional cases? Vox Sang 2014; 107:220–225 3 Wallis JP, Wells AW, Matthews JN, et al.: Long-term survival after blood transfusion: a population based study in the North of England. Transfusion 2004; 44:1025–1032 4 Kamper-Jørgensen M, Edgren G, Rostgaard K, et al.: Blood transfusion exposure in Denmark and Sweden. Transfusion 2009; 49:888–894
Received: 20 October 2014, accepted 1 December 2014, published online 6 March 2015
Letter to the Editor 433
J. P. Wallis, Department of Haematology Freeman Hospital Newcastle upon Tyne
© 2015 International Society of Blood Transfusion Vox Sanguinis (2015) 108, 432–433
NE7 7DN UK E-mail: [email protected]
Copyright of Vox Sanguinis is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
LETTER
Variant CJD and blood transfusion J. P. Wallis Department of Haematology, Freeman Hospital, Newcastle upon Tyne, UK
Dear Editor, The recently published histological study of surgically removed appendix tissue raised the possibility of silent carriers of the disease affecting 1 in 2000 UK donors [1]. Davidson et al. [2] report on the characteristics of patients with clinical vCJD who had previously received blood transfusion but where the donors have not themselves gone on to develop clinical vCJD. On the basis of a higher-than-expected mean age of these cases, they suggest an association between transfusion and vCJD. However, they do not adjust for factors affecting the likelihood of prior transfusion. From our study in 1994 of point incidence of transfusion and subsequent survival, I have estimated the prevalence of prior transfusion by age (Table 1) [3]. To allow for the effect of repeated transfusion and the observed 80% 5-year survival, I have applied a correction factor of 05 to the data. My figures are similar to other surveys of prior transfusion prevalence [4]. I have excluded neonatal transfusion as practice markedly changed during the previous 2 decades. The Table 1 shows the estimated prevalence of prior transfusion in quintiles from 10 to 60 years. This increases because the cumulative likelihood of having received transTable 1 Estimates of expected prevalence of prior transfusion in patients with clinical vCJD
Age group 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–60 Total
432
Transfusion prevalence per 100 in 1994 027 094 179 300 404 518 659 859 1088 1467
vCJD clinical cases
Estimated cases with prior transfusion
0 25 44 44 32 19 6 2 4 1 177
0 024 079 132 127 098 042 016 048 009 575
fusion increases with time at risk and because transfusion point incidence rises with age. Using the known age distribution of the 177 vCJD cases, I have estimated that 575 cases would be expected to have had prior transfusion. Davidson et al. find 14 cases who had definitely been transfused. Of these, three were from donors who subsequently developed vCJD and are excluded, one was transfused immediately prior to diagnosis, leaving 10 cases. One was transfused as a neonate, a period I have excluded leaving 9. Four were from a period before records of donors were available, and not knowing their age at transfusion, I cannot know whether they should be included in an analysis of transfusion after the age of 10 years. A figure of between 5 and 9 remaining cases having received transfusion in the last 10–20 years prior to diagnosis is close to 575 as estimated above. Older patients with clinical vCJD are more likely to have been transfused, and the mean age will be higher than the whole cohort. Based on the age-adjusted transfusion prevalence, the mean age of cases that might have received an unlinked prior transfusion is 334 years. This compares with the observed figure given by Davidson et al. of 355 years. The prevalence of transfusion in females is almost twice that in males between the ages of 30 and 60. Four of six vCJD patients with prior transfusion were female. The observations of Davidson et al. given the analysis above would suggest no significant excess of prior transfusion amongst vCJD cases during the recent epidemic, and no unexpected age or sex distribution in vCJD cases with prior transfusion.
References 1 Gill ON, Spencer Y, Richard-Loendt A, et al.: Prevalent abnormal prion protein in human appendices after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 2013; 347:f5675 2 Davidson LR, Llewelyn CA, Mackensie JM, et al.: Variant CJD and blood transfusion: are there additional cases? Vox Sang 2014; 107:220–225 3 Wallis JP, Wells AW, Matthews JN, et al.: Long-term survival after blood transfusion: a population based study in the North of England. Transfusion 2004; 44:1025–1032 4 Kamper-Jørgensen M, Edgren G, Rostgaard K, et al.: Blood transfusion exposure in Denmark and Sweden. Transfusion 2009; 49:888–894
Received: 20 October 2014, accepted 1 December 2014, published online 6 March 2015
Letter to the Editor 433
J. P. Wallis, Department of Haematology Freeman Hospital Newcastle upon Tyne
© 2015 International Society of Blood Transfusion Vox Sanguinis (2015) 108, 432–433
NE7 7DN UK E-mail: [email protected]
Copyright of Vox Sanguinis is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
