title: Efficacy of fibrinogen concentrate compared with cryoprecipitate for reversal of the antiplatelet effect of clopidogrel in an in vitro model, as assessed by multiple electrode platelet aggregometry, thromboelastometry, and modified thromboelastography.
abstract: OBJECTIVE
  The management of dual-antiplatelet therapy when patients present for surgical revascularization is a clinical challenge. Whether increasing fibrinogen levels can restore hemostasis in this context is not established but may represent increased platelet glycoprotein fibrinogen binding, altered adenosine diphosphate (ADP)-dependent platelet activation, or an increase in formation of soluble fibrin as a component of whole blood clot.
  
  
  METHODS
  The study hypothesis was that fibrinogen concentrate would normalize in vitro hemostatic parameters after clopidogrel loading. The effect was compared with cryoprecipitate.
  
  
  METHODS
  University Hospital
  
  
  METHODS
  Elective coronary catheter studies
  
  
  METHODS
  Assessment of platelet aggregation was made using whole blood platelet impedance. Viscoelastic assessment also was made using whole blood rotational thromboelastometry and modified thromboelastography. Twenty patients presenting for cardiac catheterization on dual-antiplatelet therapy were studied. Whole blood was titrated with increasing amounts of cryoprecipitate and fibrinogen concentrate. Samples then were diluted 40% with normal saline and further titrated.
  
  
  RESULTS
  The principal finding of the study was that fibrinogen supplementation primarily improved assays of fibrin formation. Improvement in platelet aggregation response to ADP and TRAP was not observed. Neither cryoprecipitate nor fibrinogen concentrate, at the concentrations used, were able to improve the amplitude at 30 minutes (A30) in the modified TEG-ADP assay. Furthermore, they produced comparable amplitudes at 30 minutes despite a twofold difference in fibrinogen supplementation.
  
  
  CONCLUSIONS
  Fibrinogen supplementation may play a role in the hemostatic resuscitation of patients on dual-antiplatelet therapy, but there is no evidence in this in vitro study that there is a specific platelet effect involved that would allow for platelet substitution.
authors.affiliation: Department of Anaesthesia, University of Sydney, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia. Electronic address: bruce.cartwright@sydney.edu.au.
authors.forename: Bruce Lloyd
authors.initials: BL
authors.lastname: Cartwright
authors.affiliation: Department of Anaesthesia, University of Sydney, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Kam
authors.affiliation: Department of Anaesthesia, University of Sydney, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia.
authors.forename: Kenny
authors.initials: K
authors.lastname: Yang
mesh_terms: D006328:Cardiac Catheterization / Q000009:adverse effects / Q000639:trends; D000077144:Clopidogrel; D005169:Factor VIII / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods; D013916:Thrombelastography / Q000379:methods*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; C026912:cryoprecipitate coagulum; D005169:Factor VIII; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: cardiac surgery; clopidogrel; cryoprecipitate; fibrinogen concentrate; hemostasis