Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study

Abstract

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.

Fig 1. Patient flow diagram.

CABG = coronary artery bypass grafting; AVR = aortic valve replacement; AAR = ascending aorta replacement; HCA = hypothermic circulatory arrest. n indicates number of patients.

Fig 2. Fibrinogen concentration at the sampling points and changes in relation to time point Protamine.

Clauss fibrinogen concentration in all patients during the observation period (upper graph), and relative post-CPB change as percent difference from levels at time point Protamine (lower graph). In the upper graph the light grey shaded area indicates the period of surgery. Time on CPB is shaded dark grey. The red horizontal line indicates Clauss fibrinogen at 1.5 g/L. Note that true time intervals increase between sequence points T1 and T24.

Fig 3. Clauss fibrinogen increase after weaning from CPB, according to surgery type.

Clauss fibrinogen measurements over time, starting at the time point Protomine. The comprehensive plots show all patients, with the three types of surgery represented by different symbols. Predictions based on the fixed effects of the three respective linear mixed-effects models are superimposed.