Comparison of the coagulation profile following treatment of major surgical haemorrhage with fresh frozen plasma or fibrinogen concentrate.

In a parallel-assignment, single-blinded study, we measured the detailed coagulation profile of 20 patients randomised to receive infusions of fresh frozen plasma (FFP) or fibrinogen concentrate during surgery associated with major surgical haemorrhage - Extent 4 Thoraco-abdominal Aortic Aneurysm repair.Ten patients received FFP; ten fibrinogen concentrate, infused to achieve plasma fibrinogen concentration around 1.5g.l-1. There were pre-defined haemoglobin and ROTEM cutoffs for red cell and platelet administration. Blood samples were taken at up to twelve pre-defined timepoints before, during, and after surgery. Measurements included coagulation and anticoagulant factor concentrations, thrombin generation, activated protein C concentrations and thromboelastography.Intraoperative blood loss was between 2750ml and 16,500ml. During surgery, plasma fibrinogen concentration was slightly lower in the FFP group but maintained or restored to ~1.5g.l-1. When blood loss exceeded ~4000ml, most factor concentrations and conventional tests were superior in the FFP group. Mean(SD) prothrombin time (15.8(2.3) vs. 26.3(5.1) and activated partial thromboplastin time (42.8(8.6) vs. 60.4(15.8) seconds; p<0.001. Protein C and activated protein C (aPC) concentrations trended higher in the FFP group: Protein C 59.7(18.4) vs. 30.0(10.6) % normal; p<0.001, aPC 6.9(5.5) vs. 3.1(2.3) ng.ml-1; p=0.001. Differences in peak thrombin generation two hours postoperatively in the FFP group did not meet statistical significance: (224.3(54.8) vs. 133.0(66.0) nM; p=0.004.In this exploratory cohort, both FFP and fibrinogen concentrate administration achieved low-normal plasma fibrinogen concentrations. Although coagulation factor concentrations and thrombin generation were lower in the fibrinogen concentrate group at blood losses above 4000ml, this was not associated with worse surgical haemostasis or observed bleeding complications.