title: Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery.
abstract: BACKGROUND
  Drugs that act on the platelet P2Y12 receptor are responsible for postoperative bleeding in cardiac surgery. However, protease-activated receptor (PAR) that reacts to thrombin stimulation might still be active in patients treated with P2Y12 inhibitors. Preoperative platelet function testing could possibly guide the timing of surgery. We investigated the association between P2Y12 receptor and PAR inhibition and bleeding after cardiac surgery.
  
  
  METHODS
  A retrospective cohort study of 361 patients undergoing cardiac surgery and treated with P2Y12 anti-platelet agents was undertaken. All patients received a preoperative multiplate electrode aggregometry testing of platelet P2Y12 receptor activity (ADPtest) and PAR reactivity with thrombin receptor-activating peptide (TRAP) stimulation. ADPtest and TRAPtest data measured before surgery were analysed for association with postoperative bleeding (ml per 12 h) and severe postoperative bleeding.
  
  
  RESULTS
  Both the ADPtest and the TRAPtest were significantly (P=0.001) associated with postoperative bleeding. A threshold of 22 U for the ADPtest yielded a negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 20%, and a threshold of 75 U for the TRAPtest yielded an NPV of 95% and a PPV of 23%. In the subgroup of patients with ADPtest <22 U, TRAPtest ≥75 U was not associated with severe bleeding (NPV of 100% and PPV of 37%).
  
  
  CONCLUSIONS
  In patients taking P2Y12 receptor inhibitors, residual platelet reactivity to thrombin stimulation limits the risk of severe postoperative bleeding.
authors.affiliation: Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy cardioanestesia@virgilio.it.
authors.forename: M
authors.initials: M
authors.lastname: Ranucci
authors.affiliation: Department of Cardiac Anesthesia, Policlinico Tor Vergata, University of Rome Tor Vergata, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Colella
authors.affiliation: Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Baryshnikova
authors.affiliation: Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Di Dedda
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D010979:Platelet Function Tests; D019106:Postoperative Hemorrhage / Q000097:blood / Q000139:chemically induced*; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D044462:Receptors, Proteinase-Activated / Q000097:blood; D058925:Receptors, Purinergic P2Y12 / Q000097:blood; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D044462:Receptors, Proteinase-Activated; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin
keywords: blood, loss; blood, platelets; surgery, cardiovascular