caa a22 4500 475824725 CHVBK 20180406123828.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1023/A:1018758308979 doi (NATIONALLICENCE)springer-10.1023/A:1018758308979 A Pharmacodynamic Study of Clopidogrel in Chronic Hemodialysis Patients [Elektronische Daten] [James Kaufman, Louis Fiore, James Hasbargen, Theresa O'Connor, Gilles Perdriset] Combination antiplatelet agents, particularly aspirin and ticlopidine, have found increased use in the prevention of arterial thrombosis. Clopidogrel, a thienopyridine derivative, like ticlopidine was recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of ischemic events in patients with myocardial infarction, stroke, or peripheral arterial disease and appears to have much less hematologic toxicity than ticlopidine has. Thrombosis of hemodialysis access grafts is a major cause of morbidity in this patient population. Combination antiplatelet agents may be particularly useful in the prevention of hemodialysis access graft thrombosis. In preparation for such a study, we have performed a pharmacodynamic study of the platelet inhibitory effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic hemodialysis patients were studied. Baseline platelet aggregation studies were performed, after which the subjects were begun on clopidogrel 75 mg daily. Platelet aggregation studies were repeated after 14 days of therapy. Drug was stopped and a final set of platelet aggregation studies were performed 7 days later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation, we used ADP as the agonist in the platelet aggregation studies. We also measured the time required to achieve hemostasis after removing the dialysis needles at the termination of a dialysis session. Patients were carefully monitored for any adverse reaction to clopidogrel. Fourteen days' treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to 23% with ADP 2 μM ( P=0.0113), from 59 to 38% with ADP 5 μM ( P=0.0166), and from 66 to 44% with ADP 10 μM ( P=0.0172). This inhibition of platelet aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel administration did not affect the time required to achieve hemostasis after removal of the dialysis needles. No adverse reactions were noted. No patient had evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits ADP-induced platelet aggregation in subjects receiving chronic maintenance hemodialysis. The magnitude of inhibition is similar to that reported in nonuremic subjects with atherosclerosis. This inhibition is reversible within 7 days of discontinuing the drug. No adverse reactions to the drug were noted in this short-term (14-day) trial. Kluwer Academic Publishers, 2000 clopidogrel nationallicence pharmacodynamics nationallicence hemodialysis nationallicence platelet aggregation nationallicence Kaufman James Renal Section, VA Boston Healthcare System, Boston, Massachusetts, USA aut Fiore Louis Hematology Section, VA Boston Healthcare System, Boston, Massachusetts, USA aut Hasbargen James Renal Section, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA aut O'Connor Theresa West Haven Cooperative Studies Program Coordinating Center, West Haven, Connecticut, USA aut Perdriset Gilles Sanofi Recherche, Gentilly, France aut Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/2(2000-10-01), 127-131 0929-5305 10:2<127 2000 10 11239 https://doi.org/10.1023/A:1018758308979 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018758308979 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kaufman James Renal Section, VA Boston Healthcare System, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Fiore Louis Hematology Section, VA Boston Healthcare System, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Hasbargen James Renal Section, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA aut NATIONALLICENCE 700 1- O'Connor Theresa West Haven Cooperative Studies Program Coordinating Center, West Haven, Connecticut, USA aut NATIONALLICENCE 700 1- Perdriset Gilles Sanofi Recherche, Gentilly, France aut NATIONALLICENCE 773 0- Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/2(2000-10-01), 127-131 0929-5305 10:2<127 2000 10 11239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer