title: Normalization of platelet reactivity in clopidogrel-treated subjects.
abstract: BACKGROUND
  Aspirin (ASA) + clopidogrel are commonly used in acute coronary syndrome (ACS), but persistent antiplatelet effects may complicate surgery.
  
  
  RESULTS
  To study the possibility of normalizing platelet reactivity after ASA + clopidogrel treatment, 11 healthy subjects received a 325-mg ASA + clopidogrel loading dose (300 or 600 mg dependent on study arm), followed by 81 mg of ASA + 75 mg of clopidogrel daily for 2 days. Platelet reactivity was assessed by light transmittance aggregometry (LTA) [challenged by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin receptor activating peptide (TRAP)] and flow cytometry for platelet activation by GPIIb/IIIa receptor exposure pretreatment, 4 and 72 h postload. To normalize platelet reactivity, increasing amounts of pooled platelets from five untreated volunteers [volunteers (V)-platelet-rich plasma (PRP)] were added ex vivo to the subject's PRP (S-PRP). At both 4 and 72 h, 40% and 50% V-PRP were needed to overcome platelet disaggregation in the 300 or 600 mg arms, respectively, after ADP challenge; an additional 10% V-PRP fully normalized aggregation. Recovery of function was linear with each incremental increase of V-PRP. ADP-induced GPIIb/IIIa activation showed the same pattern as LTA (r = 0.74). Forty percent V-PRP was required to normalize platelet function to AA, collagen, and TRAP.
  
  
  CONCLUSIONS
  Our results suggest that the pre-operative transfusion of 10 platelet concentrate units (the equivalent of 40% V-PRP) after a 300-mg clopidogrel loading or 12.5 units (50% V-PRP) after a 600 mg loading may adequately reverse clopidogrel-induced platelet disaggregation to facilitate postoperative hemostasis. An additional 2.5 units fully normalized platelet function. The potential clinical implications of our observations could include shorter hospitalizations and reduced bleeding complications. But these observations should be fully explored in an in vivo clinical setting with clopidogrel-treated patients before and after surgery.
authors.affiliation: Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: G
authors.initials: G
authors.lastname: Vilahur
authors.forename: B G
authors.initials: BG
authors.lastname: Choi
authors.forename: M U
authors.initials: MU
authors.lastname: Zafar
authors.forename: J F
authors.initials: JF
authors.lastname: Viles-Gonzalez
authors.forename: D A
authors.initials: DA
authors.lastname: Vorchheimer
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D017713:Platelet Transfusion; D053657:Platelet-Rich Plasma / Q000187:drug effects*; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D018179:Receptors, Thrombin / Q000378:metabolism; D020127:Recovery of Function; D012016:Reference Values; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018179:Receptors, Thrombin; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin