Embed Size (px)
Citation preview
University of New MexicoUNM Digital Repository
Hospital Medicine Internal Medicine
5-19-2013
Clinical vignette: Clopidogrel overdose: a casereport and literature reviewLiviya Thoreson
Anthony Worsham
Follow this and additional works at: https://digitalrepository.unm.edu/hostpitalmed_pubs
This Presentation is brought to you for free and open access by the Internal Medicine at UNM Digital Repository. It has been accepted for inclusion inHospital Medicine by an authorized administrator of UNM Digital Repository. For more information, please contact [email protected].
Recommended CitationThoreson 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]
Russian Roulette with Clopidogrel Clopidogrel Overdose: A Case Report and Literature Review
Liviya Thoreson, D.O. Anthony Worsham, M.D.
Department of Internal Medicine
INTRODUCTION:
CASE INFORMATION
DISCUSSION
REFERENCES
• A 54-year-old woman with hyperlipidemia and prior transient ischemic attack (TIA) two months prior presented to our hospital with vaginal bleeding and hematuria. Admitted to having intentionally overdosed on a study drug 12 hours earlier. • She was diagnosed with possible TIA two 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, a large ongoing, multi-centered, double-blinded, randomized controlled study, which seeks to determine if clopidogrel prevents major ischemic events within 90 days of a TIA.
• Consumed 30 study drug pills (placebo vs clopidogrel) following a domestic argument and binge drinking. She was also on aspirin 162 mg daily and atorvastatin. She denied suicidality.
• The POINT study team unblinded the study drug, which was clopidogrel.
• Platelet count of 245 x 103/mm3 and normal hemoglobin and INR. • Platelet function assay was abnormal with prolongation of closure times above 300 sec.
• On hospital day 3, the patient’s vaginal bleeding resolved, her blood counts were stable, and she was discharged to Psychiatry.
CONCLUSIONS
Clopidogrel is a thienopyradine which prevents ADP from binding to the P2Y12 receptor; by doing so, it inhibits platelet activation and therefore, platelet aggregation. This inhibition is irreversible and lasts for the lifespan of platelets (7-10 days). Clopidogrel is a pro-drug with a half-life of 6 hours, but its active metabolite has a half-life of 30 minutes. There is little literature regarding overdose and no published data on using either platelet function assays or aggregation studies in overdose. Only two case reports could be found documenting clopidogrel overdoses.
http://www.pointtrial.org
Becker RC, Bassand JP, Budaj A,, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J (2011) 32 (23): 2933-2944
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329-39.
Claua LB, Lópeza JG, Caballero G. Pulmonary Haemorrhage and Haemothorax After Massive Ingestion of Clopidogrel as a Suicide Attempt. Arch Bronconeumol. 2009 Nov;45(11):570-1
Geiger, Joreg, et al. Monitoring of Clopidogrel Action: Comparison of Methods. Clinical Chemistry (2005) 51:6 957–965
Kocabay, G, Okcular I, Akkaya V, Guler K. Suicide attempt with clopidogrel. Hum Experim Tox 2006; 25: 731-734
L’Allier P, Ducrocq G, Pranno N, et al. Clopidogrel 600-Mg Double Loading Dose Achieves Stronger Platelet Inhibition Than Conventional Regimens. J Am Coll Cardiol. 2008;51(11):1066-1072
Mayo Clinic, Jacksonville http://www.mayomedicallaboratories.com/articles/hottopics/transcripts/2011/12-plavix/index.html, Accessed on January 5, 2012
Wallentin, Lars. P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. European Heart Journal (2009) 30, 1964–1977 doi:10.1093/eurheartj/ehp296
Our patient took 2,250 mg of clopidogrel, a higher dose than either the Kobacay or Claua cases and almost twice that of a “double loading dose” which can be used prior to angioplasty. Despite this, she was mildly symptomatic with vaginal bleeding and mild hematuria, but within 3 days of observation and conservative management, recovered completely.
University of New MexicoSchool of MedicineDepartment of Internal MedicineMSC10 55501 University of New MexicoAlbuquerque, NM 87131
HISTORY:
LABS:
HOSPITAL COURSE:
Case One:Kocabay et al (2006), Turkey49 yo M, Suicide Attempt- Overdosed on 1,650 mg clopidogrel- Asymptomatic & No Bleeding- Normal vitals & lab results- Platelet Aggregation Tests over 7 daysshowed decreased aggregation fractions which recovered over the week.
Case Two:Claua et al (2009), Spain49 yo F, Suicide Attempt- Overdosed on 1,875 mg clopidogrel- HR 101, BP 150/95, RR 22 O2- Hgb= 10.4 & Hct= 31- CT Chest: Pulmonary hemorrhage
and hemothorax- Required thoracentesis (200mL) +
transfusions- Recovered & discharged after 11 days
CASE REPORTS
• Clopidogrel is an antiplatelet agent commonly prescribed for acute coronary, peripheral vascular disease and prevention of thrombotic events. As it was among the highest of prescription drug sales in the US in 2011, hospitalists should be prepared to encounter and manage overdoses.
• Here we describe an unusual case of a clopidogrel overdose and the discovery that despite its frequent use, the literature is quite barren of case reports and discussion regarding the monitoring and management of potentially fatal hemorrhage.
• Clopidogrel is very commonly prescribed, ranked amongst the highest of prescription drug sales in 2011. • Given its popularity, the lack of reported overdoses in the literature is surprising.
• There still remains very little guidance regarding management and monitoring of clopidogrel overdose.
From what we learned in our case and from the related literature review, we propose that in situations of clopidogrel overdose, a conservative approach be taken:
• Serial monitoring of blood counts• Platelet & RBC transfusions, if needed• Platelet testing/ functional monitoring is probably unnecessary in most cases
ADP attached to P2Y12 Receptor
Fibrin Polymers
Von Willebrand Factor on GPIb Receptor &GPVI receptor bound to collagen
SIMPLIFIED DIAGRAM OF AGGREGATED PLATELETS
Exposed Subendothelial Collagen
VWF bound between two GPIIb/IIIa receptors
Fibrinogen connecting two GPIIb/IIIa receptors
Clopidogrel, ticlopidine, prasugrel, ticagrelor, cangrelor & elinogrel are all antagonists at this same site.
(505) [email protected]
