{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:59:52Z","timestamp":1792515592447,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T00:00:00Z","timestamp":1281571200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Introduction<\/jats:title>\n            <jats:p>Hepatitis-associated aplastic anemia is a common syndrome in patients with bone marrow failure. However, hepatitis-associated aplastic anemia is an immune-mediated disease that does not appear to be caused by any of the known hepatitis viruses including hepatitis C virus. In addition, to the best of our knowledge there are no reported cases of patients with chronic hepatitis C virus infection developing aplastic anemia associated with pegylated interferon alpha 2a treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>We report the case of a 46-year-old Greek man who developed severe aplastic anemia during treatment with pegylated interferon alpha 2a for chronic hepatitis C virus infection. He presented with generalized purpura and bruising, as well as pallor of the skin and mucous membranes. His blood tests showed pancytopenia. He underwent allogeneic bone marrow transplantation after completing two courses of immunosuppressive therapy with antithymocyte globulin and cyclosporin A.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The combination of a specific environmental precipitant represented by the hepatitis C virus infection, an altered metabolic detoxification pathway due to treatment with pegylated interferon alpha 2a and a facilitating genetic background such as polymorphism in metabolic detoxification pathways and specific human leukocyte antigen genes possibly conspired synergistically in the development of aplastic anemia in this patient. Our case clearly shows that the causative role of pegylated interferon alpha 2a in the development of aplastic anemia must not be ignored.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-1947-4-268","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T18:20:10Z","timestamp":1281637210000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report"],"prefix":"10.1186","volume":"4","author":[{"given":"Savvas","family":"Ioannou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorios","family":"Hatzis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Vlahadami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Voulgarelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,8,12]]},"reference":[{"key":"1225_CR1","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/S0168-8278(99)80154-8","volume":"30","author":"EASL International Consensus Conference on Hepatitis C","year":"1999","unstructured":"EASL International Consensus Conference on Hepatitis C: Consensus statement. J Hepatol. 1999, 30: 956-961. 10.1016\/S0168-8278(99)80154-8.","journal-title":"J Hepatol"},{"key":"1225_CR2","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1097\/01.smj.0000182873.62872.22","volume":"98","author":"NA Palekar","year":"2005","unstructured":"Palekar NA, Harrison SA: Extrahepatic manifestations of hepatitis C. South Med J. 2005, 98: 1019-1023. 10.1097\/01.smj.0000182873.62872.22.","journal-title":"South Med J"},{"key":"1225_CR3","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/j.0954-6820.1972.tb04823.x","volume":"192","author":"LE Bottiger","year":"1972","unstructured":"Bottiger LE, Westerholm B: Aplastic anaemia. III. Aplastic anaemia and infectious hepatitis. Acta Med Scand. 1972, 192: 323-6. 10.1111\/j.0954-6820.1972.tb04823.x.","journal-title":"Acta Med Scand"},{"key":"1225_CR4","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1182\/blood.V75.8.1646.1646","volume":"75","author":"JY Mary","year":"1990","unstructured":"Mary JY, Baumelou E, Guiguet M: Epidemiology of aplastic anemia in France: A prospective multicentric study. Blood. 1990, 75: 1646-53.","journal-title":"Blood"},{"key":"1225_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2141.1986.tb02893.x","volume":"62","author":"NS Young","year":"1986","unstructured":"Young NS, Issaragrasil S, Chieh CW, Takaku F: Aplastic anaemia in the Orient. Br J Haematol. 1986, 62: 1-6. 10.1111\/j.1365-2141.1986.tb02893.x.","journal-title":"Br J Haematol"},{"key":"1225_CR6","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.3748\/wjg.15.4653","volume":"15","author":"R Gonzalez-Casas","year":"2009","unstructured":"Gonzalez-Casas R, Jones EA, Moreno-Otero R: Spectrum of anemia associated with chronic liver disease. World J Gastroenterol. 2009, 15: 4653-4658. 10.3748\/wjg.15.4653.","journal-title":"World J Gastroenterol"},{"key":"1225_CR7","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1056\/NEJM199704103361504","volume":"336","author":"KE Brown","year":"1997","unstructured":"Brown KE, Tisdale J, Barrett AJ, Dunbar CE, Young NS: Hepatitis-associated aplastic anemia. N Engl J Med. 1997, 336: 1059-1064. 10.1056\/NEJM199704103361504.","journal-title":"N Engl J Med"},{"key":"1225_CR8","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1111\/j.1365-2036.2009.04060.x","volume":"30","author":"R Gonzalez-Casas","year":"2009","unstructured":"Gonzalez-Casas R, Garcia-Buey L, Jones EA, Gisbert JP, Moreno-Otero R: Systematic review: hepatitis-associated aplastic anaemia-a syndrome associated with abnormal immunological function. Aliment Pharmacol Ther. 2009, 30: 436-443. 10.1111\/j.1365-2036.2009.04060.x.","journal-title":"Aliment Pharmacol Ther"},{"key":"1225_CR9","doi-asserted-by":"publisher","first-page":"4588","DOI":"10.1182\/blood-2003-11-3959","volume":"103","author":"J Lu","year":"2004","unstructured":"Lu J, Basu A, Melenhorst JJ, Young NS, Brown KE: Analysis of T-cell repertoire in hepatitis-associated aplastic anemia. Blood. 2004, 103: 4588-4593. 10.1182\/blood-2003-11-3959.","journal-title":"Blood"},{"key":"1225_CR10","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1080\/08916930310001602137","volume":"36","author":"B Conrad","year":"2003","unstructured":"Conrad B: Potential mechanisms of interferon-alpha induced autoimmunity. Autoimmunity. 2003, 36: 519-523. 10.1080\/08916930310001602137.","journal-title":"Autoimmunity"},{"key":"1225_CR11","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1016\/S0301-472X(99)00109-5","volume":"27","author":"LC Platanias","year":"1999","unstructured":"Platanias LC, Fish EN: Signaling pathways activated by interferons. Exp Hematol. 1999, 27: 1583-1592. 10.1016\/S0301-472X(99)00109-5.","journal-title":"Exp Hematol"},{"key":"1225_CR12","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.2174\/092986706778773059","volume":"13","author":"S Russmann","year":"2006","unstructured":"Russmann S, Grattagliano I, Portincasa P, Palmieri VO, Palasciano G: Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research. Curr Med Chem. 2006, 13: 3351-3357. 10.2174\/092986706778773059.","journal-title":"Curr Med Chem"},{"key":"1225_CR13","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1053\/jhep.2002.32672","volume":"35","author":"JY Lau","year":"2002","unstructured":"Lau JY, Tam RC, Liang TJ, Hong Z: Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology. 2002, 35: 1002-1009. 10.1053\/jhep.2002.32672.","journal-title":"Hepatology"},{"key":"1225_CR14","doi-asserted-by":"publisher","first-page":"534","DOI":"10.7326\/0003-4819-136-7-200204020-00011","volume":"136","author":"NS Young","year":"2002","unstructured":"Young NS: Acquired aplastic anemia. Ann Intern Med. 2002, 136: 534-46.","journal-title":"Ann Intern Med"},{"key":"1225_CR15","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1001\/jama.1969.03160110017004","volume":"208","author":"RO Wallerstein","year":"1969","unstructured":"Wallerstein RO, Condit PK, Kasper CK: Statewide study of chloramphenicol therapy and fatal aplastic anemia. JAMA. 1969, 208: 2045-50. 10.1001\/jama.208.11.2045.","journal-title":"JAMA"},{"key":"1225_CR16","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1182\/blood-2006-03-010777","volume":"108","author":"NS Young","year":"2006","unstructured":"Young NS, Calado RT, Scheinberg P: Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006, 108: 2509-2519. 10.1182\/blood-2006-03-010777.","journal-title":"Blood"},{"key":"1225_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.exphem.2006.09.002","volume":"35","author":"C Sugimori","year":"2007","unstructured":"Sugimori C, Yamazaki H, Feng X, Mochizuki K, Kondo Y, Takami A, Chuhjo T, Kimura A, Teramura M, Mizoguchi H, Omine M, Nakao S: Roles of DRB1 *1501 and DRB1 *1502 in the pathogenesis of aplastic anemia. Exp Hematol. 2007, 35: 13-20. 10.1016\/j.exphem.2006.09.002.","journal-title":"Exp Hematol"},{"key":"1225_CR18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1111\/j.1744-313X.2008.00810.x","volume":"35","author":"F Yari","year":"2008","unstructured":"Yari F, Sobhani M, Vaziri MZ, Bagheri N, Sabaghi F, Talebian A: Association of aplastic anaemia and Fanconi's disease with HLA-DRB1 alleles. Int J Immunogenet. 2008, 35: 453-456. 10.1111\/j.1744-313X.2008.00810.x.","journal-title":"Int J Immunogenet"},{"key":"1225_CR19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/00005792-200303000-00003","volume":"82","author":"M Ramos-Casals","year":"2003","unstructured":"Ramos-Casals M, Garc\u00eda-Carrasco M, L\u00f3pez-Medrano F, Trejo O, Forns X, L\u00f3pez-Guillermo A, Mu\u00f1oz C, Ingelmo M, Font J: Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. Medicine (Baltimore). 2003, 82: 87-96. 10.1097\/00005792-200303000-00003.","journal-title":"Medicine (Baltimore)"},{"key":"1225_CR20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/BF01697628","volume":"66","author":"A Gruber","year":"1993","unstructured":"Gruber A, Grillner L, Norder H, Magnius L, Bj\u00f6rkholm M: Severe aplastic anemia associated with seronegative community-acquired hepatitis C virus infection. Ann Hematol. 1993, 66: 157-159. 10.1007\/BF01697628.","journal-title":"Ann Hematol"},{"key":"1225_CR21","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/(SICI)1096-8652(199806)58:2<122::AID-AJH6>3.0.CO;2-U","volume":"58","author":"RL Paquette","year":"1998","unstructured":"Paquette RL, Kuramoto K, Tran L, Sopher G, Nimer SD, Zeldis JB: Hepatitis C virus infection in acquired aplastic anaemia. Am J Hematol. 1998, 58: 122-126. 10.1002\/(SICI)1096-8652(199806)58:2<122::AID-AJH6>3.0.CO;2-U.","journal-title":"Am J Hematol"},{"key":"1225_CR22","first-page":"605","volume":"8","author":"A Hoffmann","year":"1994","unstructured":"Hoffmann A, Kirn E, Krueger GR, Fischer R: Bone marrow hypoplasia and fibrosis following interferon treatment. In Vivo. 1994, 8: 605-612.","journal-title":"In Vivo"},{"key":"1225_CR23","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1002\/ajh.2830190411","volume":"19","author":"KF Mangan","year":"1985","unstructured":"Mangan KF, Zidar B, Shadduck RK, Zeigler Z, Winkelstein A: Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin. Am J Hematol. 1985, 19: 401-413. 10.1002\/ajh.2830190411.","journal-title":"Am J Hematol"},{"key":"1225_CR24","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1097\/00045391-200211000-00011","volume":"9","author":"AK Aslam","year":"2002","unstructured":"Aslam AK, Singh T: Aplastic anemia associated with interferon beta-1a. Am J Ther. 2002, 9: 522-523. 10.1097\/00045391-200211000-00011.","journal-title":"Am J Ther"},{"key":"1225_CR25","doi-asserted-by":"publisher","first-page":"3483","DOI":"10.1182\/blood.V98.12.3483","volume":"98","author":"KA Lee","year":"2001","unstructured":"Lee KA, Kim SH, Woo HY, Hong YJ: Increased frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia. Blood. 2001, 98: 3483-3485. 10.1182\/blood.V98.12.3483.","journal-title":"Blood"},{"key":"1225_CR26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1159\/000087885","volume":"114","author":"B Poonkuzhali","year":"2005","unstructured":"Poonkuzhali B, Shaji RV, Salamun DE, George B, Srivastava A, Chandy M: Cytochrome P4501A1 and glutathione S transferase gene polymorphisms in patients with aplastic anemia in India. Acta Haematol. 2005, 114: 127-132. 10.1159\/000087885.","journal-title":"Acta Haematol"},{"key":"1225_CR27","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1365-2125.1993.tb04222.x","volume":"36","author":"BC Israel","year":"1993","unstructured":"Israel BC, Blouin R, McIntyre W, Shedlofsky S: Effects of interferon-? monotherapy on hepatic drug metabolism in cancer patients. Br J Pharmac. 1993, 36: 229-235.","journal-title":"Br J Pharmac"},{"key":"1225_CR28","first-page":"59","volume":"8","author":"JF Waring","year":"2005","unstructured":"Waring JF, Anderson MG: Idiosyncratic toxicity: mechanistic insights gained from analysis of prior compounds. Curr Opin Drug Discov Devel. 2005, 8: 59-65.","journal-title":"Curr Opin Drug Discov Devel"}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-1947-4-268.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-1947-4-268\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-1947-4-268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-1947-4-268.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T05:52:00Z","timestamp":1630475520000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/1752-1947-4-268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,12]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["1225"],"URL":"https:\/\/doi.org\/10.1186\/1752-1947-4-268","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,12]]},"assertion":[{"value":"11 December 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"268"}}