Correspondence

Ticlopidine and Thrombotic Thrombocytopenic Purpura

N Engl J Med 1997; 337:1245October 23, 1997

Article

To the Editor:

Ticlopidine hydrochloride (Ticlid) is a potent platelet-antiaggregating agent that has been used in the United States since 1991 to reduce the risk of thrombotic stroke in patients with aspirin intolerance. Recently, it has been demonstrated to decrease the incidence of cardiac events and reocclusion after the placement of a coronary-artery stent.1 We report two cases of fulminant thrombotic thrombocytopenic purpura that developed within three weeks of the initiation of ticlopidine therapy after coronary-stent placement.

A 47-year-old woman presented in September 1996 with a 48-hour history of increasing confusion, icterus, and nausea. Three weeks before admission she had undergone coronary-artery stenting and was given ticlopidine (250 mg orally twice daily) and enteric-coated aspirin (325 mg orally daily). Over a 48-hour period, her platelet count dropped from 87,000 to 2000 per cubic millimeter and her hemoglobin level decreased from 12.7 to 8.3 g per deciliter. A peripheral-blood smear revealed severe thrombocytopenia and microangiopathic changes. Despite receiving packed red cells, platelets, and plasmapheresis, the patient died.

A 42-year-old woman presented in July 1997 with icterus and mild confusion and a 24-hour history of bloody urine, nausea, vomiting, and headache. Two and a half weeks earlier she had undergone coronary-artery stenting and was given ticlopidine (250 mg orally twice daily) and enteric-coated aspirin (325 mg orally daily). Ten days before admission, the complete blood count was normal, with a platelet count of 214,000 per cubic millimeter and a hemoglobin level of 13 g per deciliter. On admission the patient had a platelet count of 2000 per cubic millimeter and a hemoglobin level of 9.5 g per deciliter. The peripheral-blood smear revealed microangiopathic changes. The blood urea nitrogen level was 41 mg per deciliter, and the creatinine concentration was 1.4 mg per deciliter. The patient was given 6 units of platelets during preparation for plasmapheresis but died within six hours.

Thrombotic thrombocytopenic purpura is a multisystemic disease of unknown cause that is characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and neurologic abnormalities. Fever and renal impairment frequently occur. Prior reports have linked ticlopidine with thrombotic thrombocytopenic purpura2,3 and other hematologic abnormalities in elderly women. Blood dyscrasias occur more frequently in women.4 Our report associates ticlopidine with thrombotic thrombocytopenic purpura in younger women. In both patients the disease developed within three weeks after the initiation of therapy with ticlopidine, despite frequent blood counts. The course was fulminant and rapidly fatal despite treatment with plasmapheresis in one of the patients.

Yizhak Kupfer, M.D.
Sidney Tessler, M.D.
953 49th St., Brooklyn, NY 11219

4 References

1. 1

   Schomig A, Neumann F-J, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996;334:1084-1089
   Full Text | Web of Science | Medline

2. 2

   Page Y, Tardy B, Zeni F, Comtet C, Terrana R, Bertrand JC. Thrombotic thrombocytopenic purpura related to ticlopidine. Lancet 1991;337:774-776
   CrossRef | Web of Science | Medline

3. 3

   Kovacs MJ, Soong PY, Chin-Yee IH. Thrombotic thrombocytopenic purpura associated with ticlopidine. Ann Pharmacother 1993;27:1060-1061
   Web of Science | Medline

4. 4

   Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis and aplastic anemia. Vol. 18 of Monographs in epidemiology and biostatistics. New York: Oxford University Press, 1991.
   

Citing Articles (15)

Citing Articles

1. 1

   Karen K. Swisher, Deirdra R. Terrell, Sara K. Vesely, Johanna A. Kremer Hovinga, Bernhard Lämmle, James N. George. (2009) Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. Transfusion 49:5, 873-887
   CrossRef

2. 2

   2006. Ticlopidine. , 3424-3427.
   CrossRef

3. 3

   Sidney C. Smith, Ted E. Feldman, John W. Hirshfeld, Alice K. Jacobs, Morton J. Kern, Spencer B. King, Douglass A. Morrison, William W. O’Neill, Hartzell V. Schaff, Patrick L. Whitlow, David O. Williams, Elliott M. Antman, Sidney C. Smith, Cynthia D. Adams, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Jonathan L. Halperin, Loren F. Hiratzka, Sharon Ann Hunt, Alice K. Jacobs, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel. (2006) ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. Journal of the American College of Cardiology 47:1, e1-e121
   CrossRef

4. 4

   Imran Masood. (2005) Comparative Effect of Antiplatelet Therapy in Retinal Vein Occlusion Evaluated by the Particle-counting Method Using Light Scattering. American Journal of Ophthalmology 140:1, 167
   CrossRef

5. 5

   Masahito Kawata, Emi Kuramoto, Toshio Kataoka, Atsushi Saito, Kazumasa Adachi, Akira Matsuura, Susumu Sakamoto. (2005) Comparative Inhibitory Effects of Cilostazol and Ticlopidine on Subacute Stent Thrombosis and Platelet Function in Acute Myocardial Infarction Patients With Percutaneous Coronary Intervention. International Heart Journal 46:1, 13-22
   CrossRef

6. 6

   Anna M. Wodlinger, John A. Pieper. (2003) The role of clopidogrel in the management of acute coronary syndromes. Clinical Therapeutics 25:8, 2155-2181
   CrossRef

7. 7

   Patrick J. Medina, James M. Sipols, James N. George. (2001) Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Current Opinion in Hematology 8:5, 286-293
   CrossRef

8. 8

   Sidney C. Smith, James T. Dove, Alice K. Jacobs, J. Ward Kennedy, Dean Kereiakes, Morton J. Kern, Richard E. Kuntz, Jeffery J. Popma, Hartzell V. Schaff, David O. Williams, Raymond J. Gibbons, Joseph P. Alpert, Kim A. Eagle, David P. Faxon, Valentin Fuster, Timothy J. Gardner, Gabriel Gregoratos, Richard O. Russell, Sidney C. Smith. (2001) ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines). Journal of the American College of Cardiology 37:8, 2239
   CrossRef

9. 9

   Chung-Wei Yang, Yung-Chang Chen, Po Dunn, Ming-Yang Chang, Ji-Tseng Fang, Chiu-Ching Huang. (2001) TICLOPIDINE-INDUCED THROMBOTIC THROMBOCYTOPENIC PURPURA: TWO CASE REPORTS TREATED WITH PLASMA EXCHANGE PLUS STEROIDS. Renal Failure 23:6, 851-856
   CrossRef

10. 10

    William C. Dillon, George J. Eckert, James C. Dillon, Michael E. Ritchie. (2000) Incidence of thrombocytopenia following coronary stent placement using abciximab plus clopidogrel or ticlopidine. Catheterization and Cardiovascular Interventions 50:4, 426-430
    CrossRef

11. 11

    Jens Markus Chemnitz, Armin Schulz, Aida Salameh, Christof Scheid, Ralf Müller, Andreas Draube, Volker Diehl, Dietmar Söhngen. (2000) Thrombotisch-thrombozytopenische Purpura (Moschcowitz-Syndrom), verursacht durch Ticlopidin. Medizinische Klinik 95:2, 96-100
    CrossRef

12. 12

    Jörg Carlsson, Sinisa Miketic, Rolf Bätge, Petra Riedel, Günther Rahlf, Ulrich Tebbe. (2000) Ticlopidin-assoziierte thrombotisch-thrombozytopenische Purpura (Morbus Moschcowitz). Medizinische Klinik 95:1, 44-48
    CrossRef

13. 13

    J. MOORE, L. COYLE, J. ISBISTER, J. ROCHE. (1999) Bilateral knee osteonecrosis in a patient with thrombotic thrombocytopenic purpura. Australian and New Zealand Journal of Medicine 29:1, 88-89
    CrossRef

14. 14

    (1998) More about Thrombotic Thrombocytopenic Purpura. New England Journal of Medicine 338:8, 548-548
    Full Text

15. 15

    &NA;. (1997) Ticlopidine. Reactions Weekly &NA;:675, 12
    CrossRef