Case Presentation: A 54-year-old woman with hyperlipidemia and prior transient ischemic attack (TIA) 2 months ago presented to our hospital with vaginal bleeding after an intentional overdose of a study drug of clopidogrel versus placebo. She was diagnosed with possible TIA 2 months prior after presenting with right-sided weakness and dysarthria resolving after 4 hours. She was enrolled in the Platelet-Oriented Inhibition in New TIA (POINT) trial, which seeks to determine if clopidogrel prevents major ischemic events within 90 days of a TIA. In the current episode, she presented with vaginal bleeding and hematuria 12 hours after taking 30 study drug pills following a domestic argument and binge drinking. She was also on aspirin 162 mg daily and atorvastatin. She denied suicidality. Labs revealed a platelet count of 245 x 103/mm3 and normal hemoglobin and INR. The POINT study team unblinded the study drug, which was clopidogrel. Platelet function assay was abnormal with prolongation of closure times above 300 seconds. On hospital day 3, the patient's vaginal bleeding resolved, her blood counts were stable, and she was discharged to psychiatry. Discussion: Clopidogrel is a common antiplatelet agent for acute coronary syndrome, peripheral vascular disease, and prevention of thrombotic events. It had the sales among prescription drugs in the United States in 2011. It prevents platelet aggregation by blocking binding of ADP to its receptors. This inhibition is irreversible and lasts for the life span of platelets (7—10 days). The drug's half-life is 6 hours, but its active metabolite has a half-life of 30 minutes. There is little literature regarding overdose on clopidogrel. A PubMed search revealed only a case report by Kocabay et al. (2006). In that case, a 49-year-man took 1650 mg of clopidogrel in a suicidal gesture. The authors treated the patient with activated charcoal. As in our case, platelet count and hemoglobin were normal and remained so. They performed platelet aggregation tests showing decreased aggregation fractions, which slowly recovered over 7 days. Our patient took 2250 mg of clopidogrel, higher than the Kobacay case or typical doses of 75—600 mg. Supportive care is advocated for cases of overdose. The manufacturer's site mentions that 'platelet transfusion may restore clotting ability.' Our toxicologists and hematologists also recommended serial monitoring of complete blood counts. There are no published data on using of either platelet function assays or aggregation studies in overdose. Conclusions: Clopidogrel is commonly prescribed, and clinicians may encounter overdose. The inhibition of platelet aggregation is irreversible, lasting for the life span of platelets. There is little guidance regarding measures to take in cases of clopidogrel overdose. A supportive approach is recommended, with platelet transfusions for bleeding and serial monitoring of blood counts.
Thoreson Liviya, Worsham Anthony; CLOPIDOGREL OVERDOSE: A CASE REPORT AND LITERATURE REVIEW [abstract]. Journal of Hospital Medicine 8 Suppl 1 :815. [http://www.shmabstracts.com/abstract.asp?MeetingID=793&id=104408]