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

Winstedt, Dag LU (2014) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2014:127.
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... (More)
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. (Less)
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author
supervisor
opponent
  • Jeppsson, Anders, University of Gothenburg, Sahlgrenska Academy
organization
publishing date
type
Thesis
publication status
published
subject
keywords
thrombelastography, fibrinogen, factor XIII, free oscillatioin rheometry, hemodilution, hypothermia
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2014:127
pages
80 pages
publisher
Anaesthesiology and Intensive Care
defense location
Lecture hall F3, SUS Lund
defense date
2014-11-21 13:00
ISSN
1652-8220
ISBN
978-91-7619-056-2
language
English
LU publication?
yes
id
db66db0d-21f5-4867-aaa9-3cd967c746ca (old id 4813146)
date added to LUP
2014-11-25 10:37:44
date last changed
2016-09-19 08:44:50
@phdthesis{db66db0d-21f5-4867-aaa9-3cd967c746ca,
  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.<br/><br>
Methods: Coagulation was assessed with rotational thromboelastometry (ROTEM) or free oscillation rheometry (FOR) in vitro and different fibrinogen measurement methods in observational studies.<br/><br>
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&lt;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&lt;0.001), but less than or equal with crystalloids. In haemodilution with HA, fibrinogen improved ROTEM parameters dose-dependently (p&lt;0.001). Factor XIII (FXIII) had no effect alone, but an additional effect to that of fibrinogen on clot strength, FIBTEM-MCF (p&lt;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&lt;0.001), and clot velocity measured with FOR Fibscreen1 COT2 or ROTEM EXTEM CFT (p=0.035 and p&lt;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&gt;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 &gt;0.5 g/l).No differences between pre- and post-weaning from cardiopulmonary by-pass was seen.<br/><br>
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.<br/><br>
<br/><br>
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.},
  author       = {Winstedt, Dag},
  isbn         = {978-91-7619-056-2},
  issn         = {1652-8220},
  keyword      = {thrombelastography,fibrinogen,factor XIII,free oscillatioin rheometry,hemodilution,hypothermia},
  language     = {eng},
  pages        = {80},
  publisher    = {Anaesthesiology and Intensive Care},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Viscoelastic haemostatic assays and fibrinogen concentration tests during haemodilution: The effects of fibrinogen and factor XIII},
  volume       = {2014:127},
  year         = {2014},
}