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

BackgroundFibrinogen 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.MethodsCitrated 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.ResultsFibrinogen 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.ConclusionsFibrinogen 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.

• Publication year

  2014

• Venue

  Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

• Publication date

  2014-12-16

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s13049-014-0073-zPMID 25510409PMCID 4272532
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients.

  2014cited by this paper
• Free oscillation rheometry monitoring of haemodilution and hypothermia and correction with fibrinogen and factor XIII concentrates

  2013influential reference
• Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates.

  2013cited by this paper
• Rotational thromboelastometry and multiple electrode platelet aggregometry in four patients with abnormal routine coagulation studies before removal of epidural catheters after major surgery: a case series and research study

  2013cited by this paper
• The effect of fibrinogen concentrate and factor XIII on thromboelastometry in 33% diluted blood with albumin, gelatine, hydroxyethyl starch or saline in vitro.

  2013cited by this paper
• The Impact of Hematocrit on Fibrin Clot Formation Assessed by Rotational Thromboelastometry

  2012cited by this paper
• Acute traumatic coagulopathy

  2012cited by this paper
• Low-dose desmopressin improves hypothermia-induced impairment of primary haemostasis in healthy volunteers

  2012cited by this paper
• Effects of In vitro hemodilution, hypothermia and rFVIIa addition on coagulation in human blood.

  2012cited by this paper
• Low‐dose desmopressin improves hypothermia‐induced impairment of primary haemostasis in healthy volunteers *

  2011cited by this paper
• Potential of whole blood coagulation reconstitution by desmopressin and fibrinogen under conditions of hypothermia and acidosis – an in vitro study using rotation thrombelastometry

  2011cited by this paper
• Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis: a systematic review

  2011cited by this paper
• Effects on coagulation of balanced (130/0.42) and non-balanced (130/0.4) hydroxyethyl starch or gelatin compared with balanced Ringer's solution: an in vitro study using two different viscoelastic coagulation tests ROTEMTM and SONOCLOTTM.

  2010cited by this paper
• Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution

  2010cited by this paper
• Mild and moderate hypothermia increases platelet aggregation induced by various agonists: a whole blood in vitro study

  2010cited by this paper
• In vitro , study

  2010cited by this paper
• In vitro factor XIII supplementation increases clot firmness in Rotation Thromboelastometry (ROTEM®)

  2010cited by this paper
• Critical Factors Contributing to the Thromboelastography Trace

  2010cited by this paper
• Expressiveness of global coagulation parameters in dilutional coagulopathy.

  2010cited by this paper
• Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine Emergency Presentation and Management of Acute Severe Asthma in Children

  2009cited by this paper
• Hydroxyethyl starch interferes with human blood ex vivo coagulation, platelet function and sedimentation.

  2009cited by this paper
• Role of fibrinogen‐, factor VIII‐ and XIII‐mediated clot propagation in gelatin haemodilution

  2009cited by this paper
• [''R"--project for statistical computing].

  2008cited by this paper
• The In Vitro Effects of Fibrinogen Concentrate, Factor XIII and Fresh Frozen Plasma on Impaired Clot Formation After 60% Dilution

  2008cited by this paper
• Hypothermia and Acidosis Synergistically Impair Coagulation in Human Whole Blood

  2008cited by this paper
• Rheometry and associated techniques for blood coagulation studies.

  2008cited by this paper
• Simultaneous Inference in General Parametric Models

  2008cited by this paper
• A Thromboelastometric Evaluation of the Effects of Hypothermia on the Coagulation System

  2008cited by this paper
• The Effect of Fibrinogen Substitution on Reversal of Dilutional Coagulopathy: An In Vitro Model

  2006cited by this paper
• Fibrinogen Concentrate Reverses Dilutional Coagulopathy Induced In Vitro by Saline but Not by Hydroxyethyl Starch 6%

  2006cited by this paper
• Colloids decrease clot propagation and strength: role of factor XIII‐fibrin polymer and thrombin–fibrinogen interactions

  2005cited by this paper
• Multi-centre investigation on reference ranges for ROTEM thromboelastometry

  2005cited by this paper
• A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function.

  2004influential reference
• Different effects of abciximab and cytochalasin D on clot strength in thrombelastography

  2004cited by this paper
• Effect of in vitro hemodilution with hydroxyethyl starch and dextran on the activity of plasma clotting factors

  2003cited by this paper
• The Effect of Graded Hypothermia (36°C–32°C) on Hemostasis in Anesthetized Patients Without Surgical Trauma

  2003cited by this paper
• The effect of graded hypothermia (36 degrees C-32 degrees C) on hemostasis in anesthetized patients without surgical trauma.

  2003cited by this paper
• Acute traumatic coagulopathy.

  2003cited by this paper
• The Effects of Hydroxyethyl Starches of Varying Molecular Weights on Platelet Function

  2001cited by this paper
• Comparative efficacy of fibrinogen and platelet supplementation on the in vitro reversibility of competitive glycoprotein IIb/IIIa receptor-directed platelet inhibition.

  2001cited by this paper
• Haemodilution-Induced Enhancement of Coagulation is Attenuated in Vitro by Restoring Antithrombin III to Pre-Dilution Concentrations

  2001cited by this paper
• Hypothermia-Induced Coagulopathy during Hemorrhagic Shock

  2000cited by this paper
• LINEAR AND NONLINEAR MIXED-EFFECTS MODELS

  1998cited by this paper
• In Vitro Hypothermia Enhances Platelet GPIIb‐IIIa Activation and P‐Selectin Expression

  1998cited by this paper
• Haemodilution induces a hypercoagulable state.

  1996cited by this paper
• Controlling the false discovery rate: a practical and powerful approach to multiple testing

  1995cited by this paper
• The impact of hypothermia on dilutional coagulopathy.

  1993cited by this paper

• Factor XIII Supplementation in Postpartum Hemorrhage: From Biological Rationale to Clinical Implementation.

  2025cites this paper
• The effect of leukoreduction and prolonged storage on coagulation in cold‐stored whole blood: An in vitro study

  2025cites this paper
• In Vivo Effects of Balanced Crystalloid or Gelatine Infusions on Functional Parameters of Coagulation and Fibrinolysis: A Prospective Randomized Crossover Study

  2022cites this paper
• Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: Results from a laboratory sub-study of the FEISTY trial

  2022cites this paper
• The impact of crystalloid versus colloid on coagulation as measured by thromboelastometry in term parturients: an in vitro study

  2021cites this paper
• Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study

  2021cites this paper
• In-vitro assessment of the effects of fibrinogen, recombinant factor VIIa and factor XIII on trauma-induced coagulopathy.

  2020cites this paper
• Effects of balanced hydroxyethyl starch 6% (130/0.4) and albumin 5% on clot formation and glycocalyx shedding: Subgroup analysis of a prospective randomized trial.

  2019cites this paper
• Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study

  2019cites this paper
• Biomimetic Strategies to Treat Traumatic Brain Injury by Leveraging Fibrinogen.

  2019cites this paper
• How do external factors contribute to the hypocoagulative state in trauma-induced coagulopathy? – In vitro analysis of the lethal triad in trauma

  2018cites this paper
• Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study

  2018cites this paper
• Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma

  2017cites this paper
• Monitoring the coagulation status of trauma patients with viscoelastic devices

  2017cites this paper
• The Effects of Temperature on Clot Microstructure and Strength in Healthy Volunteers

  2016cites this paper
• Fibrinogen supplementation ex vivo increasesclot firmness comparable to platelet transfusion in thrombocytopenia.

  2016cites this paper
• Clinical Management of Severe Bleeding in Trauma Patients

  2016cites this paper
• In vitro effects of different sources of fibrinogen supplementation on clot initiation and stability in a model of dilutional coagulopathy

  2016cites this paper
• Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs

  2015cites this paper
• Viscoelastic haemostatic assays and fibrinogen concentration tests during haemodilution

  2015cites this paper
• Fluids and coagulation.

  2015cites this paper
• Viscoelastic haemostatic assays and fibrinogen concentration tests during haemodilution: The effects of fibrinogen and factor XIII

  2014cites this paper