Intraoperative Hydroxyethyl Starch and its Effects on Different Fibrinogen Measurements.

BACKGROUND: Intravenous fluids with synthetic colloids such as hydroxyethyl starch (HES) are known to interfere with plasma fibrinogen concentration measurements. The aim of this study was to evaluate the effects of an HES solution on fibrinogen measurements in a clinical setting. METHODS: The study was performed in patients who received at least 1 L of HES during intracranial tumor resection surgery. Blood samples were drawn before the start of surgery (baseline), after infusion of 1 L of HES, and at later time points. The fibrinogen concentration was measured using 3 different methods: (a) enzyme-linked immunosorbent assay (ELISA), (b) Clauss method with a photometric readout, and (c) Clauss method with an electromechanical readout. In addition, the fibrin-based clot quality was evaluated with the thromboelastometric FIBTEM test. RESULTS: Forty patients were enrolled, and 25 patients were included in the analysis. The fibrinogen concentrations at baseline were 2.2, 2.3, and 2.6 g/L and after 1 L of HES 1.6, 1.7, and 1.9 g/L as measured by ELISA, the photometric test, and the electromechanical test, respectively. The electromechanical Clauss test measured significantly higher concentrations at these time points. The relative decrease, however, was comparable between methods (31%, 29%, and 25%, respectively) but significantly lower than the 44% relative decrease with FIBTEM maximum clot firmness. CONCLUSION: Despite providing different fibrinogen concentration values at baseline, the relative decrease in fibrinogen concentration after HES infusion was comparable among the 3 tests. In contrast, fibrin-based clot quality was more affected than fibrinogen concentration tests by HES infusion.

Correction of hypothermic and dilutional coagulopathy with concentrates of fibrinogen and factor XIII: an in vitro study with ROTEM.

BACKGROUND: Fibrinogen concentrate treatment can improve coagulation during massive traumatic bleeding. The aim of this in vitro study was to determine whether fibrinogen concentrate, or a combination of factor XIII and fibrinogen concentrates, could reverse a haemodilution-induced coagulopathy during hypothermia. METHODS: Citrated venous blood from 10 healthy volunteers was diluted in vitro by 33% with 130/0.42 hydroxyethyl starch (HES) or Ringer's acetate (RAc). The effects of fibrinogen concentrate corresponding to 4 gram per 70 kg, or a combination of the same dose of fibrinogen with factor XIII (20 IU per kg), were measured using rotational thromboelastometry (ROTEM). The blood was analysed at 33°C or 37°C with ROTEM EXTEM and FIBTEM reagents. Clotting time (CT), clot formation time (CFT), alpha angle (AA) and maximal clot formation (MCF) were recorded. RESULTS: Fibrinogen with or without factor XIII improved all ROTEM parameters in either solution irrespective of temperature, with the exception of EXTEM-AA and EXTEM-CFT in HES haemodilution. Fibrinogen increased FIBTEM-MCF more in the samples diluted with RAc than HES, particularly in presence of factor XIII. CONCLUSIONS: Fibrinogen improved in vitro haemodilution-induced coagulopathy at both 33°C and 37°C, though more efficiently after crystalloid than HES haemodilution. Factor XIII had an additional effect on FIBTEM-MCF, but only after crystalloid dilution.

Fibrinogen and FXIII dose response effects on albumin-induced coagulopathy.

OBJECTIVES: Natural colloid albumin induces a lesser degree of dilutional coagulopathy than synthetic colloids. Fibrinogen concentrate has emerged as a promising strategy to treat coagulopathy, and factor XIII (FXIII) works synergistically with fibrinogen to correct coagulopathy following haemodilution with crystalloids. Our objectives were to examine the ability of fibrinogen and FXIII concentrates to reverse albumin-induced dilutional coagulopathy. METHODS: High and low concentrations of both fibrinogen and FXIII were used to reverse coagulopathy induced by 1:1 dilution in vitro with 5% albumin of blood samples from healthy volunteers, monitored by rotational thromboelastometry (ROTEM). RESULTS: Haemodilution with albumin significantly attenuated EXTEM maximum clot firmness (MCF), alpha angle (AA), clotting time (CT) and clot formation time (CFT), and FIBTEM MCF (p < 0.001). Following haemodilution, both doses of fibrinogen significantly corrected all ROTEM parameters (p ≤ 0.02), except the lower dose did not correct AA. Compared to the lower dose, the higher dose of fibrinogen significantly improved FIBTEM MCF and EXTEM MCF, AA and CFT (p < 0.001). The lower dose of FXIII did not significantly correct any of the ROTEM parameters, and the high dose only improved EXTEM CT (p = 0.004). All combinations of high/low concentrations of fibrinogen/FXIII significantly improved all ROTEM parameters examined (p ≤ 0.001). Fibrinogen concentration generally had a greater effect on each parameter than did FXIII concentration; the best correction of ROTEM parameters was achieved with high-dose fibrinogen concentrate and either low- or high-dose FXIII. CONCLUSIONS: Fibrinogen concentrate successfully corrected initiation, propagation and clot firmness deficits induced by haemodilution with albumin, and FXIII synergistically improved fibrin-based clot strength.

Free oscillation rheometry monitoring of haemodilution and hypothermia and correction with fibrinogen and factor XIII concentrates.

BACKGROUND: Haemodilution and hypothermia induce coagulopathy separately, but their combined effect on coagulation has not been widely studied. Fibrinogen concentrate can correct dilutional coagulopathy and has an additional effect when combined with factor XIII concentrate. However, their effect on dilutional coagulopathy concomitant with hypothermia has not been studied previously. Free oscillation rheometry - FOR (Reorox®) - is a novel viscoelastic haemostatic assay that has not been studied in this context before. METHODS: Blood from 10 healthy volunteers was diluted by 33% with hydroxyethyl starch or Ringer's acetate solutions. Effects of fibrinogen added in vitro with and without factor XIII were studied at 33°C and 37°C. Coagulation velocity (coagulation time) and clot strength (elasticity) were assessed with FOR. Coagulation was initiated in vitro with thromboplastin alone, or thromboplastin plus a platelet inhibitor. RESULTS: Hydroxyethyl starch increased the coagulation time and decreased clot strength significantly more than Ringer's acetate solution, both in the presence and absence of a platelet inhibitor. There was a significant interaction between haemodilution with hydroxyethyl starch and hypothermia, resulting in increased coagulation time. After addition of fibrinogen, coagulation time shortened and elasticity increased, with the exception of fibrinogen-dependent clot strength (i.e., elasticity in the presence of a platelet inhibitor) after hydroxyethyl starch haemodilution. Factor XIII had an additional effect with fibrinogen on fibrinogen-dependent clot strength in blood diluted with Ringer's acetate solution. Hypothermia did not influence any of the coagulation factor effects. CONCLUSIONS: Both haemodilution and mild hypothermia impaired coagulation. Coagulopathy was more pronounced after haemodilution with hydroxyethyl starch than with Ringer's acetate. Addition of fibrinogen with factor XIII was unable to reverse hydroxyethyl starch induced clot instability, but improved coagulation in blood diluted with Ringer's acetate solution. Fibrinogen improved coagulation irrespective of hypothermia.

Albumin-induced coagulopathy is less severe and more effectively reversed with fibrinogen concentrate than is synthetic colloid-induced coagulopathy.

BACKGROUND: Synthetic colloids cause dilutional coagulopathy. The aims of our study were to determine whether the natural colloid albumin induces a lesser degree of coagulopathy compared to synthetic colloids, and the comparative effectiveness of fibrinogen concentrate to reverse coagulopathy following dilution with these solutions. METHODS: Coagulation was assessed with rotational thrombelastometry after stimulation with tissue factor (EXTEM) and in the presence of a platelet inhibitor (FIBTEM). With EXTEM, clotting time (CT), clot formation time CFT), alpha angle (AA) and maximum clot firmness (MCF) were recorded. With FIBTEM, only MCF was recorded. These parameters were assessed ex vivo in blood from 10 healthy volunteers; diluted 1:1 with either saline, Ringer's acetate, buffered/unbuffered hydroxyethyl starch, buffered/unbuffered dextran (synthetic colloids) or 5% albumin. Samples were analyzed before/after addition of fibrinogen concentrate. RESULTS: FIBTEM MCF decreased significantly upon dilution (> 50% reduced) with all colloid solutions (p ≤ 0.02), although a significantly greater coagulopathic effect was seen for samples diluted with synthetic colloids versus albumin (p ≤ 0.001). A significant reduction in the platelet component of clot strength (EXTEM MCF - FIBTEM MCF) was seen for samples diluted with synthetic colloids (p < 0.001) but not albumin (p = 0.10). Following addition of fibrinogen, FIBTEM MCF, EXTEM MCF and AA were significantly higher, and CFT was significantly shorter in samples diluted with albumin versus those treated with synthetic colloids (p ≤ 0.001). CONCLUSION: Hemodilution using albumin induced a lesser degree of coagulopathy compared with the synthetic colloids. In addition, albumin-induced coagulopathy was more effectively reversed following addition of fibrinogen concentrate compared with coagulopathy induced by synthetic colloids.