Thrombotic thrombocytopenic purpura, a life-threatening multisystem disease, has been infrequently associated with use of ticlopidine, a platelet anti-aggregating agent.
To review 60 cases of ticlopidine-associated thrombotic thrombocytopenic purpura.
Medical records, published case reports, and case reports submitted to the U.S. Food and Drug Administration.
Instances of ticlopidine-associated thrombotic thrombocytopenic purpura were identified.
Ticlopidine had been prescribed for less than 1 month in 80% of the patients, and normal platelet counts had been found within 2 weeks of the onset of thrombotic thrombocytopenic purpura in most patients. Mortality rates were higher among patients who were not treated with plasmapheresis than among those who underwent plasmapheresis (50% compared with 24%; P < 0.05).
Ticlopidine use may be associated with the development of thrombotic thrombocytopenic purpura, usually within 1 month of initiation of therapy. The onset of ticlopidine-associated thrombotic thrombocytopenic purpura is difficult to predict, despite close monitoring of platelet counts.
- 1. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med. 1991; 325:398-403. Google Scholar
- 2. Rose M, Rowe JM, Eldor A. The changing course of thrombotic thrombocytopenic purpura. Blood Rev. 1993; 7:94-103. Google Scholar
- 3. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991; 325:393-7. Google Scholar
- 4. Torok TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United States-analysis of national mortality data, 1968-1991. Am J Hematol. 1995; 50:84-90. Google Scholar
- 5. Rose M, Eldor A. High incidence of relapse in thrombotic thrombocytopenic purpura. Clinical study of 38 patients. Am J Med. 1987; 83:437-44. Google Scholar
- 6. Gordon LI, Kwaan HC. Cancer- and drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol. 1997; 34:140-7. Google Scholar
- 7. Wysowski DK, Bacsanyi J. Blood dyscrasias and hematologic reactions in ticlopidine users [Letter]. JAMA. 1996; 276:952. Google Scholar
- 8. Kovacs MJ, Soong PY, Chin-Hee IH. Thrombotic thrombocytopenic purpura associated with ticlopidine. Ann Pharmacother. 1993; 27:1060-1. Google Scholar
- 9. Page Y, Tardy B, Zeni F, Comtet C, Terrana R, Bertrand JC. Thrombotic thrombocytopenic purpura related to ticlopidine. Lancet. 1991; 337:774-6. Google Scholar
- 10. Capra R, Marciano N, Fieni F, Capucci M, Ferremi P, Orlandini A. Cerebral hemorrhage and thrombotic thrombocytopenic purpura during ticlopidine treatment: case report. Acta Neurol Belg. 1992; 92:83-7. Google Scholar
- 11. Kodama K, Nomura T, Yasui K, Matsuo T. [Thrombotic thrombocytopenia purpura after administration of ticlopidine.] Rinsho Ketsueki. 1996; 37:1334-6. Google Scholar
- 12. Ariyoshi K, Shinohara K, Ruirong X. Thrombotic thrombocytopenic purpura caused by ticlopidine, successfully treated by plasmapheresis [Letter]. Am J Hematol. 1997; 54:175-6. Google Scholar
- 13. Kupfer Y, Tessler S. Ticlopidine and thrombotic thrombocytopenic purpura [Letter]. N Engl J Med. 1997; 337:1245. Google Scholar
- 14. Ellie E, Durrieu C, Besse P, Julien J, Gbipki-Benissan G. Thrombotic thrombocytopenic purpura associated with ticlopidine [Letter]. Stroke. 1992; 23:922-3. Google Scholar
- 15. Gachet C, Stierle A, Cazenave JP, Ohlmann P, Lanza F, Bouloux C, et al. The thienopyridine PCR 4099 selectively inhibits ADP-induced platelet aggregation and fibrinogen binding without modifying the membrane glycoprotein IIb-IIIa complex in rat and in man. Biochem Pharmacol. 1990; 40:229-38. Google Scholar
- 16. Savi P, Laplace MC, Maffand JP, Herbert JM. Binding of [3H]-2-methylthio ADP to rat platelets-effect of clopidogrel and ticlopidine. J Pharmacol Exp Ther. 1994; 269:772-7. Google Scholar
- 17. de Maat MP, Arnold AE, van Buuren S, Wilson JH, Kluft C. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris. Thromb Haemost. 1996; 76:166-70. Google Scholar
- 18. Piovella F, Ricetti MM, Samaden A, Custodi P, Montecchio GP. Ticlopidine normalized abnormally high platelet fibronectin levels in retinopathic diabetics. Blood. 1985; 66:311. Google Scholar
- 19. Defreyn G, Bernat A, Delebassee D, Maffrand JP. Pharmacology of ticlopidine: review. Semin Thromb Hemost. 1989; 15:159-66. Google Scholar
- 20. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989; 321:501-7. Google Scholar
Author, Article, and Disclosure Information
From Northwestern University and Chicago Veterans Affairs HealthCare System-Lakeside Division, Chicago, Illinois.
Acknowledgments: The authors thank Drs. Diane Wysowski and Janos Bacsanyi of the U.S. Food and Drug Administration for providing information on retrieval of reports and for review of the manuscript; Drs. Dave Aboulafia, Harvey Einhorn, James Grossman, Robert Hecht, Chitra Raman, Tariq Mahmood, Peter Townley, Michael Voralia, and Walter Kahr, as well as Hal Lieberman, Nurit Begani, and Dr. Josh Levy and the staff of HemaCare Corp., Sherman Oaks, California, for contributing case histories and helpful comments; Dr. James George, for helpful comments; and our index patient, for her assistance and interest.
Corresponding Author: Charles Bennett, MD, PhD, Veterans Affairs Medical Sciences Building, #205, 400 East Ontario, Chicago, IL 60611.
Current Author Addresses: Dr. Bennett and Mr. Weinberg: Veterans Affairs Medical Sciences Building, #205, 400 East Ontario, Chicago, IL 60611.