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Fibrinogen reduction and coagulation in cardiac surgery: an investigational study
Chantal L I Gielen1, Jos Grimbergen, Robert J M Klautz
1aDepartment 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.
Insights
Cardiac surgery reduces fibrinogen levels primarily through hemodilution, not consumption or degradation. Early fibrinogen degradation products significantly impact clot formation in vitro, but are not the main cause of fibrinogen loss post-CABG.
Area of Science:
- Cardiovascular Surgery
- Hematology
- Coagulation Science
Background:
- Fibrinogen is crucial for blood clot formation, acting as the precursor to fibrin.
- Cardiac surgery, particularly with cardiopulmonary bypass, can lead to decreased fibrinogen levels via hemodilution, consumption, and degradation.
- Fibrinogen degradation products (FgDPs) may interfere with normal fibrin formation and clot integrity.
Purpose of the Study:
- To quantify the contributions of hemodilution, consumption, and degradation to fibrinogen loss during cardiac surgery.
- To assess the in vitro effects of early fibrinogen degradation products on blood clot formation.
Main Methods:
- Comparison of fibrinogen, fibrin, degradation products, hematocrit, and albumin levels before and after coronary artery bypass graft (CABG) surgery in 10 patients.
- Ex vivo fibrinogen supplementation experiments.
- In vitro assessment of purified FgDPs' effects on clotting time and clot firmness using rotational thromboelastometry (ROTEM).
Main Results:
- Fibrinogen plasma concentration decreased by 30% post-CABG surgery.
- The observed drop in fibrinogen was primarily attributed to hemodilution, indicated by decreased hematocrit and albumin levels, with no significant increase in D-dimer or FgDPs.
- Fibrinogen supplementation normalized the coagulation profile.
- Purified early FgDPs significantly impaired in vitro whole blood clotting, affecting clotting time and clot firmness.
Conclusions:
- Hemodilution is the principal mechanism for fibrinogen reduction following CABG surgery when tranexamic acid is used.
- While early FgDPs significantly impact in vitro clot formation and may contribute to coagulopathy, they are not the primary driver of fibrinogen decrease in this surgical context.
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.
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