 |
|
Thrombotic Thrombocytopenic Purpura Associated With Ticlopidine in the Setting of Coronary Artery Stents and Stroke Prevention
Charles L. Bennett, MD, PhD;
Charles J. Davidson, MD;
Dennis W. Raisch, PhD;
Peter D. Weinberg;
Richard H. Bennett, MD;
Marc D. Feldman, MD
Arch Intern Med. 1999;159:2524-2528.
Background One of the most unusual causes of thrombotic thrombocytopenic purpura (TTP), a life-threatening disease, is ticlopidine hydrochloride, an antiplatelet agent used to prevent strokes in high-risk populations or following coronary artery stent placement. Recently, Hoffman-LaRoche Pharmaceuticals, following reports of 20 deaths from ticlopidine-associated TTP, updated the information about the hematologic adverse effects of the drug.
Objectives To review our recent findings on ticlopidine-associated hematologic toxic effects, which served as the impetus for the revised warnings, and to discuss the implications of these findings.
Methods Data were obtained from the Food and Drug Administration's MedWatch program, published phase 3 clinical trials and case reports, hematologists, and plasmapheresis centers.
Results No cases of TTP have been reported in phase 3 ticlopidine trials. In contrast, postmarketing surveillance has identified serious adverse drug reactions to ticlopidine, resulting in 259 deaths, with TTP accounting for 40 of these deaths. Detailed information was available on 98 cases of ticlopidine-associated TTP. Compared with 42 patients in the coronary artery stent setting, 56 patients with ticlopidine-associated TTP in the stroke prevention setting were more likely to be women (62.5% vs 28.6%; P = .01). Before the onset of TTP in patients receiving stroke prevention therapy and patients with stent placement, ticlopidine had been used for less than 2 weeks in 5.4% and 2.4%, between 2 and 3 weeks in 17.9% and 21.4%, between 3 and 4 weeks in 30.4% and 38.1%, and between 4 and 12 weeks in 46.4% and 38.1%, respectively. Death occurred in almost 60% of all patients not receiving plasmapheresis compared with 21.9% of patients receiving plasmapheresis for stroke prevention and 14.3% of patients receiving plasmapheresis in the stent setting.
Conclusions Use of ticlopidine requires frequent physician visits and laboratory tests for at least 3 months in the stroke prevention setting, while, with short-term use in the coronary artery stent setting, adverse events are less likely to occur. These factors, as well as competition from clopidogrel bisulfate, a new antiplatelet agent, potentially limit the feasibility of ticlopidine as a stroke prevention agent, while having less impact on its use following coronary artery stent placement.
From the Divisions of Hematology/Oncology (Dr C. L. Bennett and Mr Weinberg) and Cardiology (Dr Davidson), the Institute for Health Services Research and Policy Studies (Dr C. L. Bennett and Mr Weinberg); the Robert H. Lurie Comprehensive Cancer Center (Dr C. L. Bennett), Northwestern University; and the Chicago Veteran Affairs Health Care System (Dr C. L. Bennett), Chicago, Ill; the Department of Pharmacology, University of New Mexico, Albuquerque (Dr Raisch); the Departments of Neurology, the University of Pennsylvania School of Medicine and the Albert Einstein Medical Center, Philadelphia, Pa (Dr R. H. Bennett); and the Division of Cardiology, the University of Texas Health Sciences Center, San Antonio (Dr Feldman).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Internal Medicine Reader's Choice: Continuing Medical Education
Arch Intern Med. 1999;159(21):2605-2606.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Patrono et al.
Chest 2008;133:199S-233S.
ABSTRACT
| FULL TEXT
Thrombotic Thrombocytopenic Purpura: A Moving Target
Sadler
ASH Education Book 2006;2006:415-420.
ABSTRACT
| FULL TEXT
Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Patrono et al.
Chest 2004;126:234S-264S.
ABSTRACT
| FULL TEXT
Antithrombotic Therapy in Patients With Saphenous Vein and Internal Mammary Artery Bypass Grafts: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Stein et al.
Chest 2004;126:600S-608S.
ABSTRACT
| FULL TEXT
How to Establish the Cut-off Values when Estimating Fragmented RBCs by Flow Cytometry
Han et al.
Annals of Clinical & Laboratory Science 2002;32:404-405.
FULL TEXT
Rapid, Sensitive Diagnosis of Hemolytic Anemia Using Antihemoglobin Antibody in Hypotonic Solution
Lee et al.
Annals of Clinical & Laboratory Science 2002;32:37-43.
ABSTRACT
| FULL TEXT
Randomized Comparison of Ticlopidine and Clopidogrel After Intracoronary Stent Implantation in a Broad Patient Population
Taniuchi et al.
Circulation 2001;104:539-543.
ABSTRACT
| FULL TEXT
Incidence of thrombotic occlusion and major adverse cardiac events between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week ticlopidine regimen
Schuhlen et al.
J Am Coll Cardiol 2001;37:2066-2073.
ABSTRACT
| FULL TEXT
Platelet-Active Drugs : The Relationships Among Dose, Effectiveness, and Side Effects
Patrono et al.
Chest 2001;119
:39S-63S.
FULL TEXT
How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome
George
Blood 2000;96:1223-1229.
ABSTRACT
| FULL TEXT
Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel
Bennett et al.
NEJM 2000;342:1773-1777.
ABSTRACT
| FULL TEXT
Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura
Tsai et al.
ANN INTERN MED 2000;132:794-799.
ABSTRACT
| FULL TEXT
|
