 |
 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
16 May 2000 | Volume 132 Issue 10 | Pages 794-799
Background: Thrombotic thrombocytopenic purpura (TTP) affects 1 in 1600 to 1 in 5000 patients who receive ticlopidine, but little is known about the pathogenesis of this complication.
Objective: To investigate whether von Willebrand factor (vWF), which has been associated with idiopathic TTP, is involved in the pathogenesis of ticlopidine-associated TTP.
Design: Case series.
Setting: Three tertiary care, university-affiliated medical centers.
Patients: Seven patients who developed TTP 2 to 7 weeks after initiation of ticlopidine therapy. Controls were 7 consecutive patients without thrombocytopenia who had been receiving ticlopidine for 3 to 5 weeks and 10 randomly selected hospitalized patients.
Measurements: Platelet-bound vWF in patients' EDTA-anticoagulated whole blood samples; vWF proteinase activity in patients' plasma samples; inhibitory activity of IgG isolated from patients' plasma samples against the proteinase from the controls' plasma samples; and vWF multimeric patterns in patients' EDTA-anticoagulated plasma samples.
Results: Binding of vWF to single platelets was increased in the three patients tested during the most thrombocytopenic phase of TTP episodes. Initial plasma samples from all seven patients lacked the largest vWF multimers and were severely deficient in vWF metalloproteinase. IgG molecules, isolated from plasma samples of five patients, inhibited metalloproteinase in plasma samples from the controls. In patients examined, these abnormalities resolved upon the remission that accompanied plasma exchange and discontinuation of ticlopidine therapy.
Conclusion: In the patients who developed ticlopidine-associated TTP, autoantibodies to the vWF metalloproteinase were formed; this led to the same type of vWF abnormalities observed in patients with idiopathic acute TTP. The findings suggest that failure to process large and unusually large vWF multimers in vivo caused binding of vWF to platelets, systemic platelet thrombosis, and TTP.
Author and Article Information
From Albert Einstein College of Medicine, Bronx, New York; Baylor College of Medicine and Rice University, Houston, Texas; and Case Western Reserve University, Cleveland, Ohio.
Grant Support: By grants HL62131 (H-MT) and HL18584 and HL 54169 (JLM) from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
Requests for Single Reprints: Han-Mou Tsai, MD, Division of Hematology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.
Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.
Current Author Addresses: Dr. Tsai: Division of Hematology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.
Drs. Rice and Moake: Department of Medicine/Hematology-Oncology, The Methodist Hospital, 6565 Fannin, MS 902-Main, Houston, TX 77030.
Dr. Sarode: Blood Bank/Pathology, University Hospitals of Cleveland, 11100 Euclid Avenue, RB&C-568, Cleveland, OH 44106.
Dr. Chow: Cox Laboratory for Biomedical Engineering, Rice University, 6100 South Main, Houston, TX 77005.
Author Contributions: Conception and design: H.-M. Tsai, L. Rice, T.W. Chow, J.L. Moake.
Analysis and interpretation of the data: H.-M. Tsai, L. Rice, T.W. Chow, J.L. Moake.
Drafting of the article: H.-M. Tsai, L. Rice, J.L. Moake.
Critical revision of the article for important intellectual content: H.-M. Tsai, L. Rice, R. Sarode, J.L. Moake.
Final approval of the article: H.-M. Tsai, L. Rice, R. Sarode, T.W. Chow, J.L. Moake.
Provision of study materials or patients: H.-M. Tsai, R. Sarode, J.L. Moake.
Statistical expertise: H.-M. Tsai, R. Sarode,
Obtaining of funding: H.-M. Tsai
Administrative, technical, or logistic support: H.-M. Tsai, T.W. Chow, J.L. Moake
Collection and assembly of data: H.-M. Tsai, T.W. Chow, J.L. Moake. BRIEF COMMUNICATION
Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  C. L. Bennett, B. Kim, A. Zakarija, N. Bandarenko, D. K. Pandey, C. G. Buffie, J. M. McKoy, A. D. Tevar, J. F. Cursio, P. R. Yarnold, et al. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura: A Report From the SERF-TTP Research Group and the RADAR Project J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1138 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Levy, D. G. Motto, and D. Ginsburg ADAMTS13 turns 3 Blood, July 1, 2005; 106(1): 11 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M-A von Mach, A Eich, L S Weilemann, and T Munzel Subacute coronary stent thrombosis in a patient developing clopidogrel associated thrombotic thrombocytopenic purpura Heart, February 1, 2005; 91(2): e14 - e14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zakarija, N. Bandarenko, D. K. Pandey, A. Auerbach, D. W. Raisch, B. Kim, H. C. Kwaan, J. M. McKoy, B. P. Schmitt, C. J. Davidson, et al. Clopidogrel-Associated TTP: An Update of Pharmacovigilance Efforts Conducted by Independent Researchers, Pharmaceutical Suppliers, and the Food and Drug Administration Stroke, February 1, 2004; 35(2): 533 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Olszewski and J. M. Shapiro Thrombotic Thrombocytopenic Purpura Associated with Abacavir in a Patient with HIV Infection J Intensive Care Med, May 1, 2003; 18(3): 156 - 159. [Abstract] [PDF]
|
|
|
|
 |
|
 H.-M. Tsai Advances in the Pathogenesis, Diagnosis, and Treatment of Thrombotic Thrombocytopenic Purpura J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1072 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-M. Tsai Platelet Activation and the Formation of the Platelet Plug: Deficiency of ADAMTS13 Causes Thrombotic Thrombocytopenic Purpura Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 388 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Spiera, R. S. Berman, A. J. Werner, and H. Spiera Ticlopidine-Induced Lupus: A Report of 4 Cases Arch Intern Med, October 28, 2002; 162(19): 2240 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Sadler A new name in thrombosis, ADAMTS13 PNAS, September 3, 2002; 99(18): 11552 - 11554. [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. George, J. E. Sadler, and B. Lammle Platelets: Thrombotic Thrombocytopenic Purpura Hematology, January 1, 2002; 2002(1): 315 - 334. [Abstract] [Full Text]
|
|
|
|
|
|
P. M. Mannucci, M. T. Canciani, I. Forza, F. Lussana, A. Lattuada, and E. Rossi Changes in health and disease of the metalloprotease that cleaves von Willebrand factor Blood, November 1, 2001; 98(9): 2730 - 2735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Veyradier, B. Obert, A. Houllier, D. Meyer, and J.-P. Girma Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases Blood, September 15, 2001; 98(6): 1765 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. McCrae, J. B. Bussel, P. M. Mannucci, G. Remuzzi, and D. B. Cines Platelets: An Update on Diagnosis and Management of Thrombocytopenic Disorders Hematology, January 1, 2001; 2001(1): 282 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Salliere, K. B. Kassler-Taub, A. E. Trontell, P. K. Honig, J. Z. Brooker, R. T.F. Cheung, M. R. Goldstein, C. L. Bennett, J. M. Connors, J. L. Moake, et al. Clopidogrel and Thrombotic Thrombocytopenic Purpura N. Engl. J. Med., October 19, 2000; 343(16): 1191 - 1194. [Full Text]
|
|
|
|
|
|
C. L. Bennett, J. M. Connors, J. M. Carwile, J. L. Moake, W. R. Bell, S. R. Tarantolo, L. J. McCarthy, R. Sarode, A. J. Hatfield, M. D. Feldman, et al. Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel N. Engl. J. Med., June 15, 2000; 342(24): 1773 - 1777. [Abstract] [Full Text] [PDF]
|
|
Article
