title: Fibrinogen reduction and coagulation in cardiac surgery: an investigational study.
abstract: Fibrinogen as precursor of fibrin plays an essential role in clot formation. There are three main mechanisms associated with a reduction in fibrinogen concentration during cardiac surgery: hemodilution, consumption, and degradation. Moreover, early fibrinogen degradation products (FgDPs) can interfere with normal fibrin formation of intact fibrinogen. The aim of this study was to determine the relative contributions of hemodilution, consumption, and degradation to fibrinogen loss in cardiac surgery and to evaluate the effects fibrinogen degradation products on blood clot formation in vitro. First, fibrin and fibrinogen concentrations, their degradation products, hematocrit, and albumin concentrations were compared in 10 patients before and after isolated coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass. Second, ex-vivo fibrinogen supplementation experiments were performed. Finally, the effects of purified FgDPs on clotting time and clot firmness were established in vitro in whole blood by ROTEM. Fibrinogen plasma concentration decreased 30% during surgery. This drop appears to be mainly caused by hemodilution, as both hematocrit and albumin levels decreased and no relevant increase in D-dimer levels and FgDPs was observed. Furthermore, the coagulation profile normalized after addition of purified fibrinogen. Early FgDPs demonstrated a significant impact on in-vitro whole blood clotting. Although early FgDPs have a pronounced effect on blood clot formation in vitro and therefore may induce or enhance in vivo coagulopathy, the drop of fibrinogen concentration seen after CABG surgery (using tranexamic acid) is primarily caused by hemodilution.
authors.affiliation: aDepartment of Cardiothoracic Surgery, Leiden University Medical Center (LUMC) bProFibrix B.V., Zernikedreef 9, cDepartment of Vascular Surgery and Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Albinusdreef 2, Leiden, The Netherlands.
authors.forename: Chantal L I
authors.initials: CL
authors.lastname: Gielen
authors.forename: Jos
authors.initials: J
authors.lastname: Grimbergen
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Klautz
authors.forename: Jaap
authors.initials: J
authors.lastname: Koopman
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
mesh_terms: D001780:Blood Coagulation Tests / Q000379:methods*; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male
chemical_list: D005340:Fibrinogen