DOCTOR'S VIEW ARCHIVE
Thrombotic thrombocytopenic purpura (TTP) is a serious, potentially fatal condition in which blood clots form in the arteries. The clots block the flow of blood to the organs, especially the brain and kidneys, and damage them. In addition, destruction of red blood cells and platelets within the arteries causes anemia and bleeding. TTP is a very rare condition, occurring in only four out of every million individuals; however, it may occur with increased frequency with pregnancy, AIDS, cancer, vaccinations and treatment with drugs such as cyclosporine (Sandimmune), oral contraceptives, ticlopidine (Ticlid) and some drugs used for treating cancer. A new association of TTP and the drug Plavix (clopidogrel) will be reported in the New England Journal of Medicine, but because of the potential importance to patients of this association, the Journal has posted the study's results on its web site prior to publication.
Clopidogrel was approved in 1997 for the prevention of blood clots that cause heart attacks and strokes. Clopidogrel also is widely used in patients who have received artificial stents in their arteries in order to prevent blood clots within the stents. It works by interfering with the activity of platelets which are crucial to the formation of blood clots. Clopidogrel is similar to another drug, ticlopidine (Ticlid) that previously has been associated with TTP. Clopidogrel has mostly replaced ticlopidine because no blood problems (including TTP) were seen with clopidogrel in studies prior to marketing. Nevertheless, since approval of clopidogrel, twelve cases of TTP with one death have been reported from approximately three million individuals treated world-wide with clopidogrel. Thus, the incidence of TTP associated with clopidogrel is estimated to be 1 case in every 250,000 treated patients. In contrast, the occurrence with ticlopidine is much higher, 1 case in every 1,600-5,000 treated patients. If TTP occurs, it usually does so during the first few weeks of treatment.
Although TTP can be diagnosed with readily-available blood tests, testing of patients taking clopidogrel is not recommended, perhaps because TTP is such a rare side effect, and it is not known if earlier diagnosis (with earlier discontinuation of drug) would be beneficial.
What will (should) be the impact of this association of clopidogrel and TTP on patient care? For patients already taking clopidogrel, the period during which TTP occurs (the first few weeks of use) already has passed so there is little concern that TTP will develop. For patients who are not yet taking clopidogrel it should be stated that for prevention of heart attacks and strokes, aspirin is the preferred drug. Thus, clopidogrel (and ticlopidine), in general, is reserved for patients who cannot take aspirin. Because of the frequent occurrence and seriousness of heart attacks and strokes, the effectiveness of clopidogrel in preventing heart attacks and strokes, and the lack of aspirin-free alternatives to clopidogrel, the benefit of clopidogrel for aspirin-intolerant patients outweighs the very small risk of TTP.