Viscoelastic haemostatic assays and fibrinogen concentration tests during haemodilution

Abstract

BackgroundThe efficacy of concentrates of fibrinogen and factor XIII in hypothermia and haemodilution has not yet been completely investigated. Clauss fibrinogen measurement may overestimate fibrinogen concentrations during in vitro haemodilution with hydroxyethyl starch (HES).MethodsCoagulation was assessed with viscoelastic haemostatic assays [rotational thromboelastometry (ROTEM) or free oscillation rheometry (FOR)] in vitro. Fibrinogen measurement methods were compared in observational studies.ResultsHaemodilution with human albumin (HA) decreased the clot strength of ROTEM assay with tissue factor activation [EXTEM maximal clot formation (MCF)] less than the synthetic colloids HES or dextran (P < 0.001), but equal with crystalloid fluids [normal saline (NA) or Ringer's acetated solution (RA)]. Addition of fibrinogen increased the clot strength of ROTEM assay with tissue factor activation and platelet inhibitor cytochalasin D, i.e. fibrinogen‐dependent clot strength (FIBTEM MCF) more after haemodilution with HA than synthetic colloids (P < 0.001), but less than or equal with crystalloids. In haemodilution with HA, fibrinogen increased coagulation as measured with ROTEM 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 decrease fibrinogen‐dependent clot strength measured with FOR (Fibscreen2 G′max, P < 0.001), and clot velocity measured with FOR (Fibscreen1 coagulation time 2, P = 0.035) or ROTEM (EXTEM clot formation time, P < 0.001). Fibrinogen (±FXIII) increased 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 difference between pre‐ and post‐weaning from cardiopulmonary by‐pass was seen.ConclusionFibrinogen concentrate increased coagulation more 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 decrease coagulation. Fibrinogen ± FXIII increased coagulation also at 33°C. Two Clauss methods after in vivo HES haemodilution did not overestimate fibrinogen; however, fibrinogen‐dependent clot strength decreased more than fibrinogen concentration. Between‐method variability with seven Clauss methods was high. 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.