A 59-year-old woman, diagnosed with chronic myelogenous leukemia (chronic phase) and treated with interferon-α for 13 years, developed renal failure. Renal biopsy showed thrombotic thrombocytopenic purpura, but intensive therapy including plasma exchange and steroid administration was not effective. The activity of von Willebrand factor-cleaving protease was detectable at the intermediate level (15–46%) during the clinical course, suggesting that this case was not compatible with the previously reported pattern of idiopathic or drug-induced thrombotic thrombocytopenic purpura, but with the pattern associated with malignant disease or immunological disorders. Further studies to determine the effects of interferon-α on endothelial cells in chronic myelogenous leukemia patients are needed.

1.
Jonasch E, Haluska FG: Interferon in oncological practice: Review of interferon biology, clinical applications, and toxicities. Oncologist 2001;6:34–55.
2.
Tothova E, Kafkova A, Stecova N, Fricova M, Guman T, Svorcova E: Immune-mediated complications during interferon alpha therapy in chronic myelogenous leukemia. Neoplasma 2002;49:91–94.
3.
Medina PJ, Sipols JM, George JN: Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2001;8:286–293.
4.
Pisoni R, Ruggenenti P, Remuzzi G: Drug-induced thrombotic microangiopathy: Incidence, prevention and management. Drug Saf 2001;24:491–501.
5.
Al-Zahrani H, Gupta V, Minden MD, Messner HA, Lipton JH: Vascular events associated with alpha interferon therapy. Leuk Lymphoma 2003;44:471–475.
6.
Zuber J, Martinez F, Droz D, Oksenhendler E, Legendre C; Groupe D’stude Des Nephrologues D’ile-de-France (GENIF): Alpha-interferon-associated thrombotic microangiopathy: A clinicopathologic study of 8 patients and review of the literature. Medicine (Baltimore) 2002;81:321–331.
7.
Badid C, McGregor B, Faivre JM, Guerard A, Juillard L, Fouque D, Laville M: Renal thrombotic microangiopathy induced by interferon-alpha. Nephrol Dial Transplant 2001;16:846–848.
8.
Cardineau E, Le Goff C, Henri P, Reman O, Lobbedez T, Hurault de Ligny B, Leporrier M, Ryckelynck JP: Nephropathies caused by interferon alpha: Apropos of 2 cases. Rev Med Interne 1995;16:691–695.
9.
Harvey M, Rosenfeld D, Davies D, Hall BM: Recombinant interferon alpha and hemolytic uremic syndrome: Cause or coincidence? Am J Hematol 1994;46:152–153.
10.
Honda K, Ando A, Endo M, Shimizu K, Higashihara M, Nitta K, Nihei H: Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia. Am J Kidney Dis 1997;30:123–130.
11.
Jadoul M, Piessevaux H, Ferrant A, Cosyns JP, van Ypersele de Strihou C: Renal thrombotic microangiopathy in patients with chronic myelogenous leukaemia treated with interferon-alpha 2b. Nephrol Dial Transplant 1995;10:111–113.
12.
Kobayashi H, Utsunomiya Y, Miyazaki Y, Tokutome G, Kawamura T, Hashimoto T, Sakai T, Takahashi S, Tojyo A, Asano S: Case of chronic myelogenous leukemia with hemolytic-uremic-syndrome like kidney during long-term interferon-alpha therapy. (Japanese, abstract in English) Nippon Naika Gakkai Zasshi 1997;86:1259–1261.
13.
Lacotte L, Thierry A, Delwail V, Dreyfus B, Guilhot F: Thrombotic thrombocytopenic purpura during interferon alpha treatment for chronic myelogenous leukemia. Acta Haematol 2000;102:160–162.
14.
Lipton JH, Minden M: CML may not be part of HUS. Am J Hematol 1995;49:100–101.
15.
Magee CC, Abraham K, Farrell J, Dorman T, Walshe JJ: Renal thrombotic microangiopathy associated with interferon-alpha treatment of chronic myeloid leukemia. Am J Kidney Dis 2000;36:E5.
16.
Ohashi N, Yonemura K, Sugiura T, Isozaki T, Togawa A, Fujigaki Y, Yamamoto T, Hishida A: Withdrawal of interferon-alpha results in prompt resolution of thrombocytopenia and hemolysis but not renal failure in hemolytic uremic syndrome caused by interferon-alpha. Am J Kidney Dis 2003;41:E10.
17.
Rachmani R, Avigdor A, Youkla M, Raanani P, Zilber M, Ravid M, Ben-Bassat I: Thrombotic thrombocytopenic purpura complicating chronic myelogenous leukemia treated with interferon-alpha: A report of two successfully treated patients. Acta Haematol 1998;100:204–206.
18.
Ravandi-Kashani F, Cortes J, Talpaz M, Kantarjian HM: Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia: Coincidence or true side effect? Cancer 1999;85:2583–2588.
19.
Schlaifer D, Dumazer P, Spenatto N, Mignon-Conte M, Brousset P, Lumbroso C, Cooper M, Muller C, Huguet F, Attal M, Laurent G, Pris J: Hemolytic-uremic syndrome in a patient with chronic myelogenous leukemia treated with interferon alpha. Am J Hematol 1994;47:254–255.
20.
Shammas F, Meyer P, Heikkila R, Apeland T, Goransson L, Berland J, Kjellevold K: Thrombotic microangiopathy in a patient with chronic myelogenous leukemia on hydroxyurea. Acta Haematol 1997;97:184–186.
21.
Vacher-Coponat H, Opris A, Daniel L, Harle JR, Veit V, Olmer M: Thrombotic microangiopathy in a patient with chronic myelocytic leukaemia treated with alpha-interferon. Nephrol Dial Transplant 1999;14:2469–2471.
22.
Studt JD, Kremer Hovinga JA, Alberio L, Bianchi V, Lammle B: Von Willebrand factor-cleaving protease (ADAMTS-13) activity in thrombotic microangiopathies: Diagnostic experience 2001/2002 of a single research laboratory. Swiss Med Wkly 2003;133:325–332.
23.
Saigo K, Jiang M, Tanaka C, Fujimoto K, Kobayashi A, Nozu K, Iijima K, Ryo R, Sugimoto T, Imoto S, Kumagai S: Usefulness of automatic detection of fragmented red cells using a hematology analyzer for diagnosis of thrombotic microangiopathy. Clin Lab Haematol 2002;24:347–351.
24.
Kinoshita S, Yoshioka A, Park YD, Ishizashi H, Konno M, Funato M, Matsui T, Titani K, Yagi H, Matsumoto M, Fujimura Y: Upshaw-Schulman syndrome revisited: A concept of congenital thrombotic thrombocytopenic purpura. Int J Hematol 2001;74:101–108.
25.
Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, Krause M, Scharrer I, Aumann V, Mittler U, Solenthaler M, Lammle B: von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998;339:1578–1584.
26.
Talpaz M, McCredie KB, Mavligit GM, Gutterman JU: Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood 1983;62:689–692.
27.
Creput C, Auffret N, Samuel D, Jian R, Hill G, Nochy D: Cutaneous thrombotic microangiopathy during treatment with alpha-interferon for chronic hepatitis C. J Hepatol 2002;37:871–872.
28.
Iyoda K, Kato M, Nakagawa T, Kakiuchi Y, Sugiyasu Y, Fujii E, Fujimoto K, Michida T, Kaneko A, Hayashi N, Yamamoto K, Kurosawa K, Ikeda M, Masuzawa M: Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C. J Gastroenterol 1998;33:588–592.
29.
Ubara Y, Hara S, Takedatu H, Katori H, Yamada K, Yoshihara K, Matsushita Y, Yokoyama K, Takemoto F, Yamada A, Takagawa R, Endo Y, Hara M, Koida I, Kumada H: Hemolytic uremic syndrome associated with beta-interferon therapy for chronic hepatitis C. Nephron 1998;80:107–108.
30.
Stratta P, Canavese C, Dogliani M, Thea A, Degani G, Mairone L, Vercellone A: Hemolytic-uremic syndrome during recombinant alpha-interferon treatment for hairy cell leukemia. Ren Fail 1993;15:559–561.
31.
George JN, Sadler JE, Lammle B: Platelets: Thrombotic thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program) 2002;1:315–334.
32.
Tsai HM, Lian EC: Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998;339:1585–1594.
33.
Matsumoto M, Yagi H, Ishizashi H, Wada H, Fujimura Y: The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Semin Hematol 2004;41:68–74.
34.
van der Plas RM, Schiphorst ME, Huizinga EG, Hene RJ, Verdonck LF, Sixma JJ, Fijnheer R: von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood 1999;93:3798–3802.
35.
George JN, Vesely SK, Terrell DR: The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry: A community perspective of patients with clinically diagnosed TTP-HUS. Semin Hematol 2004;41:60–67.
36.
Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockhammer G, Gabl C, Dirnhofer S, Clausen J, Gastl G: Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet 2000;355:1688–1691.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.