THE LANCET
deterioration, with urea and creatinine peaking at 19·1 mmol/L and 461 µmol/L, respectively. Renal function improved to baseline values 10 days after the patient’s readmission. Haematological profiles were normal, from a raised eosinophil count of 1·0⫻109/L, from a total white cell count of 7·5⫻109/L and from a C-reactive protein with a maximum concentration of 147 mg/L (local upper limit of normal=10 mg/L). Thrombocytopenia is a recognised side-effect of ticlopidine and is reversible if the drug is promptly withdrawn. We recommend routine haematological monitoring of all patients taking this medication, and evaluation of renal function should also be considered. Both in our patient and in the case first described2 a florid, urticarial type rash was present, and nausea and weakness were prominent symptoms. These findings in a patient taking ticlopidine should prompt immediate cessation of therapy and a thorough evaluation of renal function.
NALIGN and CLUSTAL programs from PC/GENE 6.85 software. Haemate-P and Feiba Immuno TIM 4 sequences showed 90–95% and 95–97% homology with those reported by Leary et al4 and Linnen et al,5 respectively. Sequence comparison between Haemate-P and Feiba Immuno TIM 4 revealed 92% homology. The differences found in HGV detection in coagulation factors may depend on the procedures used for purification of concentrates. Coagulation-factor concentrates positive for HGV may transmit HGV infection to recipients. If so, patients who received these concentrates should be tested for HGV, although the clinical significance of HGV infection remains to be proven. Elena R García-Trevijano, Juan M López-Alcorocho, Manuel Quintana, Fernando Hernández,*Vicente Carreño * Hepatology Unit, Fundación Jiménez Díaz and Fundación para el Estudio de las Hepatitis Virales, Madrid 28040, Spain; and Haemophilia Unit, Sistema Hospitalario “La Paz”, Instituto Nacional de la Salud, Madrid
*M Virdee, J Collinson, R H Stables Royal Brompton Hospital, London SW3 6NP, UK
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Elsman P, Zijlstra F. Ticlopidine and renal function. Lancet 1996; 348: 273–74. Rosen H, El-Hennawy AS, Greenberg S, Chen C, Nicastri AD. Acute interstitial nephritis associated with ticlopidine. Am J Kidney Dis 1995; 25: 934–36.
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HGV in coagulation-factor concentrates SIR—Since the development of effective methods for virus elimination from coagulation factor concentrates, viral hepatitis in haemophiliacs has decreased. However, some cases of hepatitis are probably transmitted by coagulation factors which are not contaminated with hepatitis A-E viruses.1 A new hepatitis-associated virus, HGV,2 has been isolated which seems to be transmitted by blood products.3 We looked for HGV in 14 different commercial coagulationfactor concentrates: Kogenate and Poliglobin N (Bayer); Haemate-P, Beriate-P, and Factor IX-P (Berhing); Monoclate and Mononine (Armour); Fanhdi and Flebogamma IV (Grifols); Hyland Recombinante, Hyland Hemofil M, Hyland Proplex-T, and Hyland Autoplex-T (Baxter); and Feiba Immuno TIM 4 (Immuno), which differ in their methods of purification. Serum samples from healthy donors as well as water and a recombinant coagulation factor (Hyland Recombinante), were included as negative controls. HGV RNA was detected by specific RT-PCR,2 with primer pairs derived from the NS3 region of the HGV genome and primers from the 5' non-coding region. The specificity of HGV-RNA detection was assured by cloning and sequencing the PCR products and at least three clones were obtained from each positive sample. Analysis of HGV RNA showed that two (Haemate-P, batch J6 and Feiba Immuno TIM 4 batch J1) (14%) of the coagulation-factor concentrates were positive for HGBV-C RNA by both NS3 and 5' non-coding-region-derived primers. Two other batches of Haemate-P (J7 and J8) and one of Feiba Immuno TIM 4 (J2) were tested, only the Haemate-P batch J7 was positive. All samples were tested four times in a blind fashion by different workers obtaining identical results. To determine the specificity of HGV detection and homology between the HGV sequences from the coagulationfactors concentrates, the amplified products corresponding to the NS3 and 5' non-coding-region from different positive batches were cloned and sequenced. Alignment and comparison of the nucleotide sequences obtained from different clones and batches were carried out using the
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Hanley JP, Jarvis LM, Andrews J, et al. Investigation of chronic hepatitis C infection in individuals with haemophilia: assessment of invasive and non-invasive methods. Br J Haematol 1996; 94: 159–65. Simons JN, Leary TP, Dawson GJ, et al. Isolation of novel virus-like sequences associated with human hepatitis. Nat Med 1995; 1: 564–69. Nübling CM, Lower J. GB-C genomes in a high-risk group, in plasma pools, and in intravenous immunoglobulin. Lancet 1996; 347: 68. Leary TP, Muerhoff AS, Simons JM, et al. Sequence and genomic organization of GBV-C: a novel member of the Flaviviridae associated with human non-A-E hepatitis. J Med Virol 1996; 48: 60–67. Linnen J, Wages J, Zhang-Keck ZY, et al. Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 1996; 271: 505–08.
GBV-C/HGV infection and aplastic anaemia SIR—Whether the known hepatitis viruses are responsible for hepatitis-associated aplastic anaemia remains unclear. Zaidi1 and Byrnes2 and their colleagues (Aug 17, pp 471, 472) report two patients with aplastic anaemia that occurred after overt hepatitis. After extensive mircobiological and virological tests, only GBV-C/HGV RNA, a newly discovered flavivirus, was detected in their serum samples at initial presentation (before any blood transfusion). These workers therefore concluded that GBV-C/HGV could be responsible for both hepatitis and aplastic anaemia. Although their findings are interesting and the speculated association of GBV-C/HGV with aplastic anaemia may be true, some controversial issues should be addressed. First, the prevalence of GBV-C/HGV viraemia in blood donors and in healthy adults without any identifiable risk factor is around 1–2%,3 and the presence of GBV-C/HGV RNA in one spot-serum sample is insufficient to establish acute infection. Instead, one has to document seroconversion of viral RNA. Thus the findings that initial serum samples taken before any blood transfusion were already positive for GBV-C/HGV RNA undermine the conclusion that GBVC/HGV was the causal agent of both the hepatitis and subsequent aplastic anaemia in these patients. Second, the clinical significance of GBV-C/HGV remains uncertain. For example, although GBV-C/HGV infection has been incriminated in fulminant hepatic failure of unknown aetiology,4 its causal relation has been questioned.5 Furthermore, our data suggested that GBV-C/HGV does not cause important hepatitis, or perhaps could only be associated with certain hepatic damage with manifestations and severity different from those caused by classic hepatitis viruses such as hepatitis A-E.3 Therefore, unless a seroconversion for GBV-C/HGV RNA or reliable serological markers and the culprit virus in liver cells or blood cells can
Vol 348 • October 12, 1996