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Transfusional risk of HHV-8 infection
THE LANCET
group should do the same and implement accepted guidelines of care which will ultimately improve outcome. *J J Craig, V H Patterson, R S Cooke, L G Rocke, C S McKinstry Departments of *Neurology, Neurosurgery, and Accident and Emergency, Royal Victoria Hospital, Belfast BT12 6BA, UK
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van Gijn J. Slip-ups in diagnosis of subarachnoid haemorrhage. Lancet 1997; 349: 1492. Fodden DI, Peatfield RC, Milsom PL. Beware the patient with a headache in the accident and emergency department. Arch Emerg Med 1989; 6: 7–12. Mayer PL, Awad IA, Todor R, et al. Misdiagnosis of symptomatic cerebral aneurysm-prevalence and correlation with outcome at four institutions. Stroke 1996; 27: 1558–63. Neil-Dwyer G, Lang D. ‘Brain attack’— aneurysmal subarachnoid haemorrhage: death due to delayed diagnosis. J R Coll Physicians 1997; 31: 49–52. Linn FHH, Wijdicks EFM, van der Graf Y, et al. Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage. Lancet 1994; 344: 590–93.
Transfusional risk of HHV-8 infection SIR—David J Blackbourn and colleagues,1 reporting the presence of human herpesvirus eight (HHV-8) sequences in a blood donor, suggested that the virus could be transmitted by blood transfusions. Indeed, HHV-8, which is present in a high percentage of cases of Kaposi sarcoma, has been found in the peripheral blood mononuclear cells (PBMCs) of healthy individuals, and the fact that some individuals may carry this agent without symptoms2 raises the possibility that HHV-8, like hepatitis virus and HIV, could be transmitted by blood transfusion. HHV-8 prevalence data in blood donors have been limited by the lack of a specific and validated serological assay, and by the difficulty in undertaking large-scale PCR studies. However, HHV-8, being a transmissible agent, must be present in at least a small proportion of the general population and thus in blood donors. Although it is reassuring that epidemiological studies have shown that the AIDS-associated Kaposi sarcoma is rare in patients who were HIV-infected through transfusion or intravenous drug use, and that Kaposi sarcoma cases fail to emerge in recipients of blood products, the possibility of HHV-8 transmission through transfusion cannot be excluded. For this reason, we looked for the presence of HHV-8 DNA sequences in PBMCs of 19 patients who had received a large number of blood components during their life: ten had homozygous thalassaemia and nine
Vol 350 • July 19, 1997
had sickle-cell disease. They had received a mean total of 326·2 whiteblood-cell-reduced packed red cells per patient (total 6525, range 50–700), and 12 were male. Mean age was 21 years (range 4·56). No patient was infected with HIV; four were positive for antibody to hepatitis C virus; eight had a positive marker of GBV-C/hepatitis G virus infection (viral RNA or anti-E2 antibody). The lymphocyte samples studied were coded for blind analysis and tested in duplicate by PCR according to a previously described procedure,3 with a specific primer pair (KS1 and KS2) amplifying a sequence of 233 base pairs designated KS330233, that specifically hybridised to the internal probe KSS.4 Controls included lymphocyte samples from 17 HHV-8 DNA-positive AIDS patients with Kaposi sarcoma and four HHV-8 DNA positive healthy HIV-negative homosexual men (positive controls), and lymphocyte samples of 15 healthy HIV-negative individuals at low risk of HIV infection (negative controls). The 19 multiply-transfused recipients were all negative for HHV-8 DNA by PCR. Positive and negative controls gave results as expected. With respect to transfusional risk of HHV-8 infection, the at-risk recipients are mainly immunodepressed patients, or individuals likely to be immunodepressed later in life, who could, at some point, develop HHV-8linked Kaposi sarcoma. Most individuals known to have received cellular components from hepatitis viruses or HIV-infected donors became infected. Our failure to detect HHV-8 DNA sequences in our patients suggests that HHV-8 is not transmitted with a high frequency in individuals receiving white-blood-cell-reduced components. Our patients, having received only such products over their whole life, could not reflect the transfusional risk of HHV-8 infection through non-white-blood-cell-reduced products. One can only suppose that if HHV-8 is highly cell-associated, it could lose its efficacy for transfusional transmission after filtration done for white-blood-cell reduction. Before having more data on HHV-8 prevalence in blood donors and on the parenteral risk of HHV-8 transmission, white-blood-cell reduction seems a prudent preventive measure. Recently, the French Ministry of Health decided that all transfused individuals would henceforth receive only such cellular products. *Jean-Jacques Lefrère, Martine Mariotti, Robert Girot, Pascale Loiseau, Patrick Hervé *Institut National de la Transfusion Sanguine, 75012 Paris, France; Hôpital Tenon, Paris; and Etablissement de Transfusion de l’AP-HP, Paris
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2
3
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Blackbourn DJ, Ambroziak J, Lennette E, Adams M, Ramachandran B, Levy JA. Infectious human herpesvirus 8 in a healthy North American blood donor. Lancet 1997; 349: 609–11. Moore PS, Chang Y. Detection of herpesvirus-like DNA sequence in Kaposi’s sarcoma in patients with and those without HIV infection. N Engl J Med 1995; 332: 1181–85. Lefrère JJ, Mehohas MC, Mariotti M, Meynard JL, Thauvin M, Frottier J. Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi’s sarcoma in human immunodeficiency virus (HIV)-positive subjects with a known date of HIV seroconversion. J Infect Dis 1996; 174: 283–87. Chang Y, Cesarman F, Pessin MS, et al. Identification of new human herpes viruslike DNA sequences in AIDS-associated Kaposi sarcoma. Science 1994; 266: 1865–69.
Accuracy of DINAMAP monitors SIR—Eoin O’Brien and Neil Atkins (April 5, p 1026)1 question the accuracy of DINAMAP blood pressure technology, particularly, the accuracy of the DINAMAP model 8100 as a device for the measurement of diastolic pressure. DINAMAP monitors use the oscillometric technique and achieve accuracy through patented technologies, which include step deflation and rejection of artifact. Johnson & Johnson Medical Inc, (JJMI) Patient Monitoring tests the accuracy of all our DINAMAP monitors with the ANSI/AAMI SP 101992 Standard.2 Pressure from a catheter placed in the central aorta is used as the reference standard. If proper care is taken in establishing this measurement system,3 invasive blood pressure is regarded as the gold standard for blood-pressure monitoring. The choice of measurement site (central aorta, brachial artery, or radial artery) will affect the measured value but not the accuracy of the technique. We have consistently met AAMI requirements for accuracy (5 [SD 8] mm Hg) for all our monitors. JJMI provides summaries of the results of these studies to its customers on request. Previous, independent studies compared the accuracy of DINAMAP monitors with blood-pressure measurements from invasive lines in adult, paediatric, and neonatal patients, and found that the DINAMAP was an accurate and reliable means for measurement of non-invasive blood pressure.4,5 O’Brien and Atkins refer to comparisons of DINAMAP with the auscultatory method (mercury sphygmomanometer), and state that the DINAMAP is inferior to auscultatory measurements. O’Brien
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group should do the same and implement accepted guidelines of care which will ultimately improve outcome. *J J Craig, V H Patterson, R S Cooke, L G Rocke, C S McKinstry Departments of *Neurology, Neurosurgery, and Accident and Emergency, Royal Victoria Hospital, Belfast BT12 6BA, UK
1
2
3
4
5
van Gijn J. Slip-ups in diagnosis of subarachnoid haemorrhage. Lancet 1997; 349: 1492. Fodden DI, Peatfield RC, Milsom PL. Beware the patient with a headache in the accident and emergency department. Arch Emerg Med 1989; 6: 7–12. Mayer PL, Awad IA, Todor R, et al. Misdiagnosis of symptomatic cerebral aneurysm-prevalence and correlation with outcome at four institutions. Stroke 1996; 27: 1558–63. Neil-Dwyer G, Lang D. ‘Brain attack’— aneurysmal subarachnoid haemorrhage: death due to delayed diagnosis. J R Coll Physicians 1997; 31: 49–52. Linn FHH, Wijdicks EFM, van der Graf Y, et al. Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage. Lancet 1994; 344: 590–93.
Transfusional risk of HHV-8 infection SIR—David J Blackbourn and colleagues,1 reporting the presence of human herpesvirus eight (HHV-8) sequences in a blood donor, suggested that the virus could be transmitted by blood transfusions. Indeed, HHV-8, which is present in a high percentage of cases of Kaposi sarcoma, has been found in the peripheral blood mononuclear cells (PBMCs) of healthy individuals, and the fact that some individuals may carry this agent without symptoms2 raises the possibility that HHV-8, like hepatitis virus and HIV, could be transmitted by blood transfusion. HHV-8 prevalence data in blood donors have been limited by the lack of a specific and validated serological assay, and by the difficulty in undertaking large-scale PCR studies. However, HHV-8, being a transmissible agent, must be present in at least a small proportion of the general population and thus in blood donors. Although it is reassuring that epidemiological studies have shown that the AIDS-associated Kaposi sarcoma is rare in patients who were HIV-infected through transfusion or intravenous drug use, and that Kaposi sarcoma cases fail to emerge in recipients of blood products, the possibility of HHV-8 transmission through transfusion cannot be excluded. For this reason, we looked for the presence of HHV-8 DNA sequences in PBMCs of 19 patients who had received a large number of blood components during their life: ten had homozygous thalassaemia and nine
Vol 350 • July 19, 1997
had sickle-cell disease. They had received a mean total of 326·2 whiteblood-cell-reduced packed red cells per patient (total 6525, range 50–700), and 12 were male. Mean age was 21 years (range 4·56). No patient was infected with HIV; four were positive for antibody to hepatitis C virus; eight had a positive marker of GBV-C/hepatitis G virus infection (viral RNA or anti-E2 antibody). The lymphocyte samples studied were coded for blind analysis and tested in duplicate by PCR according to a previously described procedure,3 with a specific primer pair (KS1 and KS2) amplifying a sequence of 233 base pairs designated KS330233, that specifically hybridised to the internal probe KSS.4 Controls included lymphocyte samples from 17 HHV-8 DNA-positive AIDS patients with Kaposi sarcoma and four HHV-8 DNA positive healthy HIV-negative homosexual men (positive controls), and lymphocyte samples of 15 healthy HIV-negative individuals at low risk of HIV infection (negative controls). The 19 multiply-transfused recipients were all negative for HHV-8 DNA by PCR. Positive and negative controls gave results as expected. With respect to transfusional risk of HHV-8 infection, the at-risk recipients are mainly immunodepressed patients, or individuals likely to be immunodepressed later in life, who could, at some point, develop HHV-8linked Kaposi sarcoma. Most individuals known to have received cellular components from hepatitis viruses or HIV-infected donors became infected. Our failure to detect HHV-8 DNA sequences in our patients suggests that HHV-8 is not transmitted with a high frequency in individuals receiving white-blood-cell-reduced components. Our patients, having received only such products over their whole life, could not reflect the transfusional risk of HHV-8 infection through non-white-blood-cell-reduced products. One can only suppose that if HHV-8 is highly cell-associated, it could lose its efficacy for transfusional transmission after filtration done for white-blood-cell reduction. Before having more data on HHV-8 prevalence in blood donors and on the parenteral risk of HHV-8 transmission, white-blood-cell reduction seems a prudent preventive measure. Recently, the French Ministry of Health decided that all transfused individuals would henceforth receive only such cellular products. *Jean-Jacques Lefrère, Martine Mariotti, Robert Girot, Pascale Loiseau, Patrick Hervé *Institut National de la Transfusion Sanguine, 75012 Paris, France; Hôpital Tenon, Paris; and Etablissement de Transfusion de l’AP-HP, Paris
1
2
3
4
Blackbourn DJ, Ambroziak J, Lennette E, Adams M, Ramachandran B, Levy JA. Infectious human herpesvirus 8 in a healthy North American blood donor. Lancet 1997; 349: 609–11. Moore PS, Chang Y. Detection of herpesvirus-like DNA sequence in Kaposi’s sarcoma in patients with and those without HIV infection. N Engl J Med 1995; 332: 1181–85. Lefrère JJ, Mehohas MC, Mariotti M, Meynard JL, Thauvin M, Frottier J. Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi’s sarcoma in human immunodeficiency virus (HIV)-positive subjects with a known date of HIV seroconversion. J Infect Dis 1996; 174: 283–87. Chang Y, Cesarman F, Pessin MS, et al. Identification of new human herpes viruslike DNA sequences in AIDS-associated Kaposi sarcoma. Science 1994; 266: 1865–69.
Accuracy of DINAMAP monitors SIR—Eoin O’Brien and Neil Atkins (April 5, p 1026)1 question the accuracy of DINAMAP blood pressure technology, particularly, the accuracy of the DINAMAP model 8100 as a device for the measurement of diastolic pressure. DINAMAP monitors use the oscillometric technique and achieve accuracy through patented technologies, which include step deflation and rejection of artifact. Johnson & Johnson Medical Inc, (JJMI) Patient Monitoring tests the accuracy of all our DINAMAP monitors with the ANSI/AAMI SP 101992 Standard.2 Pressure from a catheter placed in the central aorta is used as the reference standard. If proper care is taken in establishing this measurement system,3 invasive blood pressure is regarded as the gold standard for blood-pressure monitoring. The choice of measurement site (central aorta, brachial artery, or radial artery) will affect the measured value but not the accuracy of the technique. We have consistently met AAMI requirements for accuracy (5 [SD 8] mm Hg) for all our monitors. JJMI provides summaries of the results of these studies to its customers on request. Previous, independent studies compared the accuracy of DINAMAP monitors with blood-pressure measurements from invasive lines in adult, paediatric, and neonatal patients, and found that the DINAMAP was an accurate and reliable means for measurement of non-invasive blood pressure.4,5 O’Brien and Atkins refer to comparisons of DINAMAP with the auscultatory method (mercury sphygmomanometer), and state that the DINAMAP is inferior to auscultatory measurements. O’Brien
217