title: Aspirin resistance following pediatric cardiac surgery.
abstract: BACKGROUND
  Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels.
  
  
  METHODS
  This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained.
  
  
  RESULTS
  101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (p<0.01). High risk aspirin-treated subjects who experienced thrombosis had higher POD#5 uTxB2. This finding did not reach statistical significance (p=0.07). Elevated pre-operative C-reactive protein (CRP) was independently associated with thrombosis (p<0.02) in all subjects and in high risk subjects (p=0.01). Inflammatory markers were not affected by aspirin.
  
  
  CONCLUSIONS
  Aspirin inhibited ex-vivo platelet function with a low incidence of resistance. Elevated POD#5 uTxB2 and pre-operative CRP were correlated with thrombosis in aspirin treated subjects. Further studies are needed to determine whether children with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center 601 Elmwood Avenue Rochester, New York 14642, USA. Jill_Cholette@urmc.rochester.edu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Cholette
authors.forename: Lara
authors.initials: L
authors.lastname: Mamikonian
authors.forename: George M
authors.initials: GM
authors.lastname: Alfieris
authors.forename: Neil
authors.initials: N
authors.lastname: Blumberg
authors.forename: Norma B
authors.initials: NB
authors.lastname: Lerner
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004351:Drug Resistance; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood; D016015:Logistic Models; D009518:New York; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013488:Suppositories; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D013488:Suppositories; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D002097:C-Reactive Protein; D001241:Aspirin