Viscoelastic haemostatic assays and fibrinogen concentration tests during haemodilution: The effects of fibrinogen and factor XIII

Abstract: Background: The efficacy of concentrates of fibrinogen and factor XIII in hypothermia and haemodilution has not yet been completely investigated. Clauss methods have not previously been evaluated perioperatively. Methods: Coagulation was assessed with rotational thromboelastometry (ROTEM) or free oscillation rheometry (FOR) in vitro and different fibrinogen measurement methods in observational studies. Results: Haemodilution with human albumin (HA) impaired clot strength (EXTEM MCF, maximal clot formation) less than the synthetic colloids hydroxyethyl starch (HES) or dextran (p<0.001), but equal with crystalloid fluids (normal saline, NA, or Ringer’s acetated solution, RA). Addition of fibrinogen improved fibrinogen dependent clot strength (FIBTEM MCF) better after haemodilution with HA than synthetic colloids (p<0.001), but less than or equal with crystalloids. In haemodilution with HA, fibrinogen improved ROTEM parameters dose-dependently (p<0.001). Factor XIII (FXIII) had no effect alone, but an additional effect to that of fibrinogen on clot strength, FIBTEM-MCF (p<0.02). Hypothermia at 33°C and haemodilution with HES, but not RA, interacted to impair fibrinogen-dependent clot strength measured with FOR Fibscreen2 G′max (p<0.001), and clot velocity measured with FOR Fibscreen1 COT2 or ROTEM EXTEM CFT (p=0.035 and p<0.001). Fibrinogen (+/-FXIII) improved coagulation independently of temperature (33° or 37°C). After infusion of 1000 ml of HES to patients, fibrinogen measured with two Clauss methods and one immunological method decreased to the same extent (29, 27, and 31%), whereas fibrinogen-dependent clot strength (ROTEM FIBTEM MCF) decreased more (44%, p>0.001). Finally, when comparing seven different Clauss methods during cardiac surgery, within-method variability was low, but between-method variability was high (mean difference >0.5 g/l).No differences between pre- and post-weaning from cardiopulmonary by-pass was seen. Conclusion: Fibrinogen concentrate improved coagulation better after haemodilution with HA than synthetic colloids, but equal with or less than after crystalloid haemodilution. FXIII had an additional effect to that of fibrinogen. Hypothermia and haemodilution with HES interacted to impair coagulation. Fibrinogen+/-FXIII improved coagulation also at 33°C. Clauss methods after in vivo HES haemodilution did not overestimate fibrinogen; however, fibrinogen-dependent clot strength decreased more than fibrinogen concentration. Clauss methods varied considerably between methods. These findings support the use of fibrinogen concentrate after resuscitation with HA, also at hypothermia, but question the use of colloids, especially HES, in resuscitation. Clauss fibrinogen methods need to improve.