title: Perioperative management of aspirin resistance after off-pump coronary artery bypass grafting: possible role for aprotinin.
abstract: BACKGROUND
  Aspirin is the only drug proven to reduce saphenous vein graft (SVG) failure, but aspirin resistance (ASA-R) frequently occurs after off-pump coronary artery bypass grafting (OPCAB). The factors, mechanism, and best means for preventing and/or treating ASA-R have not been established. This study hypothesizes that thrombin production during OPCAB stimulates this acquired ASA-R.
  
  
  METHODS
  A nonrandomized prospective cohort of 255 patients (n=465 SVG) who underwent OPCAB with varied use of aprotinin (21%) and different SVG preparation techniques (standard, 56% vs. low-pressure, 44%) was analyzed. A surplus SVG segment was obtained to assess endothelial integrity. ASA-R was determined at baseline, after surgery, and on Days 1 and 3 by three assays. The effects of aprotinin on thrombin responsiveness were analyzed by means of whole-blood aggregometry, SVG tissue factor (TF) activity, and transcardiac thrombin production (i.e., F1.2 levels in aorta versus coronary sinus). SVG patency was assessed on Day 5 with multichannel CT angiography.
  
  
  RESULTS
  ASA-R developed in 42 percent of patients after OPCAB. Multivariate analysis showed that ASA-R, endothelial integrity, and target size independently predicted early SVG failure. Aprotinin use was associated with: 1) reduced postoperative ASA-R (15%); 2) decreased platelet (PLT) response to thrombin; 3) reduced TF activity within SVG segments; 4) decreased transcardiac thrombin gradient; and 5) improved SVG patency.
  
  
  CONCLUSIONS
  ASA-R is a common post-OPCAB event whose frequency may be reduced by intraoperative use of aprotinin, possibly via TF and thrombin suppression. Improved perioperative PLT function after OPCAB may also inadvertently enhance the clinical relevance of these potential antithrombotic effects.
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. rposton@smail.umaryland.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Poston
authors.forename: Junyan
authors.initials: J
authors.lastname: Gu
authors.forename: Charles
authors.initials: C
authors.lastname: White
authors.forename: Jean
authors.initials: J
authors.lastname: Jeudy
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.forename: James
authors.initials: J
authors.lastname: Brown
authors.forename: James
authors.initials: J
authors.lastname: Gammie
authors.forename: Richard N
authors.initials: RN
authors.lastname: Pierson
authors.forename: Linda
authors.initials: L
authors.lastname: Romar
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
mesh_terms: D007611:Aprotinin / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D047549:Coronary Artery Bypass, Off-Pump / Q000009:adverse effects; D004351:Drug Resistance / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects; D006490:Hemostatics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019990:Perioperative Care / Q000379:methods*; D015539:Platelet Activation; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D006490:Hemostatics; D013925:Thromboplastin; D007611:Aprotinin; D001241:Aspirin