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Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2013

Open Access 01-12-2013 | Original research

Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

Authors: Jostein S Hagemo, Jørgen J Jørgensen, Sisse R Ostrowski, Anders Holtan, Yngvar Gundersen, Pär I Johansson, Pål A Næss, Christine Gaarder

Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Issue 1/2013

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Abstract

Background

Impaired haemostasis following shock and tissue trauma is frequently detected in the trauma setting. These changes occur early, and are associated with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC) is not clear. Several studies highlight the crucial role of fibrinogen in posttraumatic haemorrhage. This study explores the coagulation changes in a swine model of early TIC, with emphasis on fibrinogen levels and utilization of fibrinogen.

Methods

A total of 18 landrace pigs were anaesthetized and divided into four groups. The Trauma-Shock group (TS) were inflicted bilateral blast femoral fractures with concomitant soft tissue injury by a high-energy rifle shot to both hind legs, followed by controlled exsanguination. The Shock group (S) was exposed to shock by exsanguination, whereas a third group was exposed to trauma only (T). A fourth group (C) served as control. Physiological data, haematological measurements, blood gas analyses and conventional coagulation assays were recorded at baseline and repeatedly over 60 minutes. Thrombelastometry were performed by means of the tissue factor activated ExTEM assay and the platelet inhibiting FibTEM assay. Data were statistically analysed by repeated measurements analyses method.

Results

A significant reduction of fibrinogen concentration was observed in both the TS and S groups. INR increased significantly in the S group and differed significantly from the TS group. Maximum clot firmness (MCF) of the ExTEM assay was significantly reduced over time in both TS and S groups. In the FibTEM assay a significant shortening of the clotting time and an increase in MCF was observed in the TS group compared to the S group.

Conclusion

Despite a reduction in clotting capability measured by ExTEM MCF and a reduced fibrinogen concentration, extensive tissue trauma may induce an increased fibrin based clotting activity that attenuates the hypocoagulable tendency in exsanguinated animals.
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Literature
1.
go back to reference Brohi K, Cohen MJ, Davenport RA: Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care. 2007, 13: 680-685. 10.1097/MCC.0b013e3282f1e78f.CrossRefPubMed Brohi K, Cohen MJ, Davenport RA: Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care. 2007, 13: 680-685. 10.1097/MCC.0b013e3282f1e78f.CrossRefPubMed
2.
go back to reference Brohi K, Singh J, Heron M, Coats T: Acute Traumatic Coagulopathy. The Journal of Trauma: Injury, Infection, and Critical Care. 2003, 54: 1127-1130. 10.1097/01.TA.0000069184.82147.06.CrossRef Brohi K, Singh J, Heron M, Coats T: Acute Traumatic Coagulopathy. The Journal of Trauma: Injury, Infection, and Critical Care. 2003, 54: 1127-1130. 10.1097/01.TA.0000069184.82147.06.CrossRef
3.
go back to reference Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, Mackway-Jones K, Parr MJ, Rizoli SB, Yukioka T, Hoyt DB, Bouillon B: The Coagulopathy of Trauma: A Review of Mechanisms. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 748-754. 10.1097/TA.0b013e3181877a9c.CrossRef Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, Mackway-Jones K, Parr MJ, Rizoli SB, Yukioka T, Hoyt DB, Bouillon B: The Coagulopathy of Trauma: A Review of Mechanisms. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 748-754. 10.1097/TA.0b013e3181877a9c.CrossRef
4.
go back to reference Hess JR, Lindell AL, Stansbury LG, Dutton RP, Scalea TM: The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center. Transfusion. 2009, 49: 34-39. 10.1111/j.1537-2995.2008.01944.x.CrossRefPubMed Hess JR, Lindell AL, Stansbury LG, Dutton RP, Scalea TM: The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center. Transfusion. 2009, 49: 34-39. 10.1111/j.1537-2995.2008.01944.x.CrossRefPubMed
5.
go back to reference Frith D, GOSLINGS JC, Gaarder C, Maegele M, Cohen MJ, Allard S, Johansson PI, Stanworth , Thiemermann C, Brohi K: Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations. J Thromb Haemost. 2010, 8: 1919-1925. 10.1111/j.1538-7836.2010.03945.x.CrossRefPubMed Frith D, GOSLINGS JC, Gaarder C, Maegele M, Cohen MJ, Allard S, Johansson PI, Stanworth , Thiemermann C, Brohi K: Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations. J Thromb Haemost. 2010, 8: 1919-1925. 10.1111/j.1538-7836.2010.03945.x.CrossRefPubMed
6.
go back to reference Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, Levrat A, Guillaume C, Marcotte G, Vulliez A, Hautin E, David J-S, Négrier C, Allaouchiche B: Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012, 43: 26-32. 10.1016/j.injury.2010.11.003.CrossRefPubMed Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, Levrat A, Guillaume C, Marcotte G, Vulliez A, Hautin E, David J-S, Négrier C, Allaouchiche B: Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012, 43: 26-32. 10.1016/j.injury.2010.11.003.CrossRefPubMed
7.
go back to reference Cohen MJ, Call M, Nelson M, Calfee CS, Esmon CT, Brohi K, Pittet JF: Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann Surg. 2012, 255: 379-385. 10.1097/SLA.0b013e318235d9e6.PubMedCentralCrossRefPubMed Cohen MJ, Call M, Nelson M, Calfee CS, Esmon CT, Brohi K, Pittet JF: Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann Surg. 2012, 255: 379-385. 10.1097/SLA.0b013e318235d9e6.PubMedCentralCrossRefPubMed
8.
go back to reference Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet J-FO: Acute traumatic coagulopathy: initiated by hypoperfusion. Ann Surg. 2007, 245: 812-818. 10.1097/01.sla.0000256862.79374.31.PubMedCentralCrossRefPubMed Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet J-FO: Acute traumatic coagulopathy: initiated by hypoperfusion. Ann Surg. 2007, 245: 812-818. 10.1097/01.sla.0000256862.79374.31.PubMedCentralCrossRefPubMed
9.
go back to reference Gando S: Acute coagulopathy of trauma shock and coagulopathy of trauma: a rebuttal. You are now going down the wrong path. The Journal of Trauma: Injury, Infection, and Critical Care. 2009, 67: 381-383. 10.1097/TA.0b013e3181a84f63.CrossRef Gando S: Acute coagulopathy of trauma shock and coagulopathy of trauma: a rebuttal. You are now going down the wrong path. The Journal of Trauma: Injury, Infection, and Critical Care. 2009, 67: 381-383. 10.1097/TA.0b013e3181a84f63.CrossRef
10.
go back to reference Ostrowski SR, Johansson PI: Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg. 2012, 73: 60-66. 10.1097/TA.0b013e31825b5c10.CrossRefPubMed Ostrowski SR, Johansson PI: Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg. 2012, 73: 60-66. 10.1097/TA.0b013e31825b5c10.CrossRefPubMed
11.
go back to reference Hoffman M, Monroe DM: A cell-based model of hemostasis. Thromb Haemost. 2001, 85: 958-965.PubMed Hoffman M, Monroe DM: A cell-based model of hemostasis. Thromb Haemost. 2001, 85: 958-965.PubMed
12.
go back to reference Fries D, Martini WZ: Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth. 2010, 105: 116-121. 10.1093/bja/aeq161.CrossRefPubMed Fries D, Martini WZ: Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth. 2010, 105: 116-121. 10.1093/bja/aeq161.CrossRefPubMed
13.
go back to reference Stanworth SJ, Hunt BJ: The desperate need for good-quality clinical trials to evaluate the optimal source and dose of fibrinogen in managing bleeding. Critical Care . 2011, 15: 1006-10.1186/cc10510.PubMedCentralCrossRefPubMed Stanworth SJ, Hunt BJ: The desperate need for good-quality clinical trials to evaluate the optimal source and dose of fibrinogen in managing bleeding. Critical Care . 2011, 15: 1006-10.1186/cc10510.PubMedCentralCrossRefPubMed
14.
go back to reference Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Stahel PF, Vincent J-L, Spahn DR: Management of bleeding following major trauma: an updated European guideline. Critical Care. 2010, 14: R52-10.1186/cc8943.PubMedCentralCrossRefPubMed Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Stahel PF, Vincent J-L, Spahn DR: Management of bleeding following major trauma: an updated European guideline. Critical Care. 2010, 14: R52-10.1186/cc8943.PubMedCentralCrossRefPubMed
15.
go back to reference Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper GJ, Perkins JG, Spinella PC, Williams KL, Park MS: Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Transactions of the Meeting of the American Surgical Association. 2008, 126: 97-108.CrossRef Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper GJ, Perkins JG, Spinella PC, Williams KL, Park MS: Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Transactions of the Meeting of the American Surgical Association. 2008, 126: 97-108.CrossRef
16.
go back to reference Sperry JL, Ochoa JB, Gunn SR, Alarcon LH, Minei JP, Cuschieri J, Rosengart MR, Maier RV, Billiar TR, Peitzman AB, Moore EE: An FFP:PRBC transfusion ratio ≥1:1.5 is associated with a lower risk of mortality after massive transfusion. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 986-993. 10.1097/TA.0b013e3181878028.CrossRef Sperry JL, Ochoa JB, Gunn SR, Alarcon LH, Minei JP, Cuschieri J, Rosengart MR, Maier RV, Billiar TR, Peitzman AB, Moore EE: An FFP:PRBC transfusion ratio ≥1:1.5 is associated with a lower risk of mortality after massive transfusion. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 986-993. 10.1097/TA.0b013e3181878028.CrossRef
17.
go back to reference Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. The Journal of Trauma: Injury, Infection, and Critical Care. 2007, 63: 805-813. 10.1097/TA.0b013e3181271ba3.CrossRef Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. The Journal of Trauma: Injury, Infection, and Critical Care. 2007, 63: 805-813. 10.1097/TA.0b013e3181271ba3.CrossRef
18.
go back to reference Chaiwat O, Lang JD, Vavilala MS, Wang J, MacKenzie EJ, Jurkovich GJ, Rivara FP: Early packed red blood cell transfusion and acute respiratory distress syndrome after trauma. Anesthesiology. 2009, 110: 351-360. 10.1097/ALN.0b013e3181948a97.CrossRefPubMed Chaiwat O, Lang JD, Vavilala MS, Wang J, MacKenzie EJ, Jurkovich GJ, Rivara FP: Early packed red blood cell transfusion and acute respiratory distress syndrome after trauma. Anesthesiology. 2009, 110: 351-360. 10.1097/ALN.0b013e3181948a97.CrossRefPubMed
19.
go back to reference Gundersen Y, Vaagenes P, Os Ø, Pillgram Larsen J, Sundnes KO, Opstad PK: Capacity of glycine to modulate early inflammatory disturbances after serious gunshot injuries in the pig. Scand J Clin Lab Invest. 2007, 67: 143-153. 10.1080/00365510600995226.CrossRefPubMed Gundersen Y, Vaagenes P, Os Ø, Pillgram Larsen J, Sundnes KO, Opstad PK: Capacity of glycine to modulate early inflammatory disturbances after serious gunshot injuries in the pig. Scand J Clin Lab Invest. 2007, 67: 143-153. 10.1080/00365510600995226.CrossRefPubMed
20.
go back to reference Martini WZ: Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs. AJP: Endocrinology and Metabolism. 2005, 289: E930-E934. 10.1152/ajpendo.00137.2005. Martini WZ: Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs. AJP: Endocrinology and Metabolism. 2005, 289: E930-E934. 10.1152/ajpendo.00137.2005.
21.
go back to reference Fries D: Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. British Journal of Anaesthesia. 2005, 95: 172-177. 10.1093/bja/aei160.CrossRefPubMed Fries D: Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. British Journal of Anaesthesia. 2005, 95: 172-177. 10.1093/bja/aei160.CrossRefPubMed
22.
go back to reference Tomori T, Hupalo D, Teranishi K, Michaud S, Hammett M, Freilich D, McCarron R, Arnaud F: Evaluation of coagulation stages of hemorrhaged swine: comparison of thromboelastography and rotational elastometry. Blood Coagulation & Fibrinolysis. 2010, 21: 20-27. 10.1097/MBC.0b013e32833113e9.CrossRef Tomori T, Hupalo D, Teranishi K, Michaud S, Hammett M, Freilich D, McCarron R, Arnaud F: Evaluation of coagulation stages of hemorrhaged swine: comparison of thromboelastography and rotational elastometry. Blood Coagulation & Fibrinolysis. 2010, 21: 20-27. 10.1097/MBC.0b013e32833113e9.CrossRef
23.
go back to reference Martini WZ, Cortez DS, Dubick MA, Park MS, Holcomb JB: Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 535-543. 10.1097/TA.0b013e31818379a6.CrossRef Martini WZ, Cortez DS, Dubick MA, Park MS, Holcomb JB: Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. The Journal of Trauma: Injury, Infection, and Critical Care. 2008, 65: 535-543. 10.1097/TA.0b013e31818379a6.CrossRef
24.
go back to reference Fries D: Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy–a porcine model. British Journal of Anaesthesia. 2006, 97: 460-467. 10.1093/bja/ael191.CrossRefPubMed Fries D: Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy–a porcine model. British Journal of Anaesthesia. 2006, 97: 460-467. 10.1093/bja/ael191.CrossRefPubMed
25.
go back to reference White NJ, Martin EJ, Brophy DF, Ward KR: Coagulopathy and traumatic shock: Characterizing hemostatic function during the critical period prior to fluid resuscitation. Resuscitation. 2010, 81: 111-116. 10.1016/j.resuscitation.2009.09.017.PubMedCentralCrossRefPubMed White NJ, Martin EJ, Brophy DF, Ward KR: Coagulopathy and traumatic shock: Characterizing hemostatic function during the critical period prior to fluid resuscitation. Resuscitation. 2010, 81: 111-116. 10.1016/j.resuscitation.2009.09.017.PubMedCentralCrossRefPubMed
26.
go back to reference White NJ, Martin EJ, Shin Y, Brophy DF, Diegelmann RF, Ward KR: Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: a preclinical observational model. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2010, 18: 64-10.1186/1757-7241-18-64.PubMedCentralCrossRefPubMed White NJ, Martin EJ, Shin Y, Brophy DF, Diegelmann RF, Ward KR: Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: a preclinical observational model. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2010, 18: 64-10.1186/1757-7241-18-64.PubMedCentralCrossRefPubMed
27.
go back to reference Fuchs RJ, Levin J, Tadel M, Merritt W: Perioperative coagulation management in a patient with afibrinogenemia undergoing liver transplantation. Liver Transpl. 2007, 13: 752-756. 10.1002/lt.21164.CrossRefPubMed Fuchs RJ, Levin J, Tadel M, Merritt W: Perioperative coagulation management in a patient with afibrinogenemia undergoing liver transplantation. Liver Transpl. 2007, 13: 752-756. 10.1002/lt.21164.CrossRefPubMed
28.
go back to reference Wozasek GE, Simon P, Redl H, Schlag G: Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep. The Journal of Trauma: Injury, Infection, and Critical Care. 1994, 36: 202-207. 10.1097/00005373-199402000-00010.CrossRef Wozasek GE, Simon P, Redl H, Schlag G: Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep. The Journal of Trauma: Injury, Infection, and Critical Care. 1994, 36: 202-207. 10.1097/00005373-199402000-00010.CrossRef
29.
go back to reference Husebye EE, Lyberg T, Opdahl H, Aspelin T, Støen RØ, Madsen JE, Røise O: Intramedullary nailing of femoral shaft fractures in polytraumatized patients. A longitudinal, prospective and observational study of the procedure-related impact on cardiopulmonary- and inflammatory responses. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2012, 20: 2-10.1186/1757-7241-20-2.PubMedCentralCrossRefPubMed Husebye EE, Lyberg T, Opdahl H, Aspelin T, Støen RØ, Madsen JE, Røise O: Intramedullary nailing of femoral shaft fractures in polytraumatized patients. A longitudinal, prospective and observational study of the procedure-related impact on cardiopulmonary- and inflammatory responses. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2012, 20: 2-10.1186/1757-7241-20-2.PubMedCentralCrossRefPubMed
30.
go back to reference Schöchl H, Cotton B, Inaba K, Nienaber U, Fischer H, Voelckel W, Solomon C: FIBTEM provides early prediction of massive transfusion in trauma. Critical Care. 2011, 15: R265-10.1186/cc10539.PubMedCentralCrossRefPubMed Schöchl H, Cotton B, Inaba K, Nienaber U, Fischer H, Voelckel W, Solomon C: FIBTEM provides early prediction of massive transfusion in trauma. Critical Care. 2011, 15: R265-10.1186/cc10539.PubMedCentralCrossRefPubMed
31.
go back to reference Ostrowski SR, Sørensen AM, Larsen CF, Johansson PI: Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2011, 19: 64-10.1186/1757-7241-19-64.PubMedCentralCrossRefPubMed Ostrowski SR, Sørensen AM, Larsen CF, Johansson PI: Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2011, 19: 64-10.1186/1757-7241-19-64.PubMedCentralCrossRefPubMed
32.
go back to reference Velik-Salchner C, Schnürer C, Fries D, Müssigang PR, Moser PL, Streif W, Kolbitsch C, Lorenz IH: Normal values for thrombelastography (ROTEM®) and selected coagulation parameters in porcine blood. Thrombosis Research. 2006, 117: 597-602. 10.1016/j.thromres.2005.05.015.CrossRefPubMed Velik-Salchner C, Schnürer C, Fries D, Müssigang PR, Moser PL, Streif W, Kolbitsch C, Lorenz IH: Normal values for thrombelastography (ROTEM®) and selected coagulation parameters in porcine blood. Thrombosis Research. 2006, 117: 597-602. 10.1016/j.thromres.2005.05.015.CrossRefPubMed
Metadata
Title
Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy
Authors
Jostein S Hagemo
Jørgen J Jørgensen
Sisse R Ostrowski
Anders Holtan
Yngvar Gundersen
Pär I Johansson
Pål A Næss
Christine Gaarder
Publication date
01-12-2013
Publisher
BioMed Central
DOI
https://doi.org/10.1186/1757-7241-21-56

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