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DOI: 10.5482/HAMO-13-07-0038
The role of fibrinogen in trauma-induced coagulopathy[*]
Die Bedeutung von Fibrinogen bei Trauma-induzierter KoagulopathiePublikationsverlauf
received:
16. Juli 2013
accepted in revised form:
18. Oktober 2013
Publikationsdatum:
27. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034925/201401/lookinside/thumbnails/10-5482-hamo-13-07-0038_de-1.jpg)
Summary
Fibrinogen plays an essential role in clot formation and stability. Importantly it seems to be the most vulnerable coagulation factor, reaching critical levels earlier than the others during the course of severe injury. A variety of causes of fibrinogen depletion in major trauma have been identified, such as blood loss, dilution, consumption, hyperfibrinolysis, hypothermia and acidosis. Low concentrations of fibrinogen are associated with an increased risk of diffuse microvascular bleeding. Therefore, repeated measurements of plasma fibrinogen concentration are strongly recommended in trauma patients with major bleeding. Recent guidelines recommend maintaining plasma fibrinogen concentration at 1.5–2 g/l in coagulopathic patients. It has been shown that early fibrinogen substitution is associated with improved outcome.
Zusammenfassung
Fibrinogen spielt eine wichtige Rolle in der Hämostase und bei der Bildung eines stabilen Blutgerinnsels. Von allen Gerinnungsfaktoren fällt Fibrinogen bei schweren Verletzungen am frühesten unter einen kritischen Schwellenwert. Die Hauptgründe dafür sind Blutverlust, Dilution, Verbrauch, Hyperfibrinolyse, Hypothermie und Azidose. Niedrige Fibrinogenspiegel gehen mit einem erhöhten Risiko von mikrovaskulären Blutungen einher. Daher wird in Patienten mit schweren Blutungen die wiederholte Messung des Fibrinogens empfohlen. Aktuelle Leitlinien empfehlen einen Plasmafibrinogenwert von 1,5–2 g/l in koagulopathischen Traumapatienten. Es konnte gezeigt werden, dass die frühe Fibrinogensubstitution, vorzugsweise mit Fibrinogenkonzentrat, mit einem verbesserten Outcome einhergeht.
* Attributed to Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre Vienna (Head: Prof. Dr. Heinz Redl)
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References
- 1 Adam S, Karger R, Kretschmer V. Influence of different hydroxyethyl starch (HES) formulations on fibrinogen measurement in HES-diluted plasma. Clin Appl Thromb Hemost 2010; 16: 454-460.
- 2 Adam S, Karger R, Kretschmer V. Photo-optical methods can lead to clinically relevant overestimation of fibrinogen concentration in plasma diluted with hydroxyethyl starch. Clin Appl Thromb Hemost 2010; 16: 461-471.
- 3 Bolliger D, Szlam F, Molinaro RJ. et al. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution. Br J Anaesth 2009; 102: 793-799.
- 4 Borgman MA, Spinella PC, Holcomb JB. et al. The effect of FFP:RBC ratio on morbidity and mortality in trauma patients based on transfusion prediction score. Vox Sang 2011; 101: 44-54.
- 5 Brenni M, Worn M, Bruesch M. et al. Successful rotational thromboelastometry-guided treatment of traumatic haemorrhage, hyperfibrinolysis and coagulopathy. Acta Anaesthesiol Scand 2010; 54: 111-117.
- 6 Brohi K, Cohen MJ, Ganter MT. et al. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?. Ann Surg 2007; 245: 812-818.
- 7 Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowledge. Transfus Med Rev 2009; 23: 177-188.
- 8 Carroll RC, Craft RM, Langdon RJ. et al. Early evaluation of acute traumatic coagulopathy by thrombelastography. Transl Res 2009; 154: 34-39.
- 9 Chambers LA, Chow SJ, Shaffer LE. Frequency and characteristics of coagulopathy in trauma patients treated with a lowor high-plasma-content massive transfusion protocol. Am J Clin Pathol 2011; 136: 364-370.
- 10 Chandler WL, Ferrell C, Trimble S, Moody S. Development of a rapid emergency hemorrhage panel. Transfusion 2010; 50: 2547-2552.
- 11 Charbit B, Mandelbrot L, Samain E. et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007; 05: 266-273.
- 12 Chowdhury P, Saayman AG, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125: 69-73.
- 13 Ciavarella D, Reed RL, Counts RB. et al. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Br J Haematol 1987; 67: 365-368.
- 14 Corum LE, Hlady V. The effect of upstream platelet-fibrinogen interactions on downstream adhesion and activation. Biomaterials. 2011 ???? ((AUTOR BITTE ERGÄNZEN)).
- 15 Cosgriff N, Moore EE, Sauaia A. et al. Predicting life-threatening coagulopathy in the massively transfused trauma patient. J Trauma 1997; 42: 857-862.
- 16 Cotton BA, Harvin JA, Kostousouv V. et al. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg 2012; 73: 365-370.
- 17 Counts RB, Haisch C, Simon TL. et al. Hemostasis in massively transfused trauma patients. Ann Surg 1979; 190: 91-99.
- 18 Darlington DN, Kheirabadi BS, Delgado AV. et al. Coagulation changes to systemic acidosis and bicarbonate correction in Swine. J Trauma 2011; 71: 1271-1277.
- 19 Davenport R, Curry N, Manson J. et al. Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2. J Trauma 2011; 70: 90-95.
- 20 Davenport R, Manson J, De’ath H. et al. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med 2011; 39: 2652-2658.
- 21 De Lorenzo C, Calatzis A, Welsch U, Heindl B. Fibrinogen concentrate reverses dilutional coagulopathy induced in vitro by saline but not by hydroxyethyl starch 6%. Anesth Analg 2006; 102: 1194-200.
- 22 Dickneite G, Pragst I, Joch C, Bergman GE. Animal model and clinical evidence indicating low thrombogenic potential of fibrinogen concentrate. Blood Coagul Fibrinolysis 2009; 20: 535-540.
- 23 Dunn EL, Moore EE, Breslich DJ, Galloway WB. Acidosis-induced coagulopathy. Surg Forum 1979; 30: 471-473.
- 24 Dzik WH, Blajchman MA, Fergusson D. et al. Clinical review: Canadian National Advisory Committee on Blood and Blood Products – Massive Transfusion Consensus Conference 2011. Crit Care 2011; 15: 242.
- 25 Fenger-Eriksen C, Anker-Moller E, Heslop J. et al. Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate. Br J Anaesth 2005; 94: 324-329.
- 26 Fenger-Eriksen C, Tonnesen E, Ingerslev J, Sorensen B. Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost 2009; 07: 1099-1105.
- 27 Fenger-Eriksen C, Ingerslev J, Sorensen B. Fibrinogen concentrate – a potential universal hemostatic agent. Expert Opin Biol Ther 2009; 09: 1325-1333.
- 28 Fenger-Eriksen C, Moore GW, Rangarajan S. et al. Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders. Transfusion 2010; 50: 2571-2576.
- 29 Floccard B, Rugeri L, Faure A. et al. Early coagulopathy in trauma patients. Injury 2010; 42: 697-701.
- 30 Fries D, Innerhofer P, Reif C. et al. The effect of fibrinogen substitution on reversal of dilutional coagulopathy. Anesth Analg 2006; 102: 347-351.
- 31 Fries D, Innerhofer P, Perger P. et al. Coagulation management in trauma-related massive bleeding. Anasthesiol Intensivmed Notfallmed Schmerzther 2010; 45: 552-561.
- 32 Fries D, Martini WZ. Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth 2010; 105: 116-121.
- 33 Goodnight SH, Kenoyer G, Rapaport SI. et al. Defibrination after brain-tissue destruction. N Engl J Med 1974; 290: 1043-1047.
- 34 Groner ReplyA, Pereira A. Cryoprecipitate versus commercial fibrinogen concentrate in patients who occasionally require a therapeutic supply of fibrinogen. Haematologica 2007; 92: 846-849 Haematologica 2008; 93: e24–e26.
- 35 Grottke O, Braunschweig T, Henzler D. et al. Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury. Crit Care 2010; 14: R62.
- 36 Haas T, Fries D, Velik-Salchner C. et al. The in vitro effects of fibrinogen concentrate, factor XIII and fresh frozen plasma on impaired clot formation after 60% dilution. Anesth Analg 2008; 106: 1360-1365.
- 37 Hartog CS, Reuter D, Loesche W. et al. Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis. Intensive Care Med 2011; 37: 1725-1737.
- 38 Hess JR, Lawson JH. The coagulopathy of trauma versus disseminated intravascular coagulation. J Trauma 2006; 60 (Suppl. 06) S12-S19.
- 39 Hess JR, Brohi K, Dutton RP. et al. The coagulopathy of trauma. J Trauma 2008; 65: 748-754.
- 40 Hiippala ST, Myllyla GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360-365.
- 41 Hiippala ST. Dextran and hydroxyethyl starch interfere with fibrinogen assays. Blood Coagul Fibrinolysis 1995; 06: 743-746.
- 42 Hunt BJ, Segal H. Hyperfibrinolysis. J Clin Pathol 1996; 49: 958.
- 43 Inaba K, Branco BC, Rhee P. et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg 2010; 210: 957-965.
- 44 Inaba K, Karamanos E, Lustenberger T. et al. Impact of fibrinogen levels on outcomes after acute injury in patients requiring a massive transfusion. J Am Coll Surg 2013; 216: 290-297.
- 45 Johansson PI, Stissing T, Bochsen L, Ostrowski SR. Thrombelastography and tromboelastometry in assessing coagulopathy in trauma. Scand J Trauma Resusc Emerg Med 2009; 17: 45.
- 46 Karlsson M, Ternstrom L, Hyllner M. et al. Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery. Transfusion 2008; 48: 2152-2158.
- 47 Kashuk JL, Moore EE, Sawyer M. et al. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg 2010; 252: 434-442.
- 48 Ketchum L, Hess JR, Hiippala S. Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma. J Trauma 2006; 60 (Suppl. 06) S51-S58.
- 49 Korte WF. XIII in perioperative coagulation management. Best Pract Res Clin Anaesthesiol 2010; 24: 85-93.
- 50 Kozek-Langenecker SA, Afshari A. et al. Management of severe perioperative bleeding. Eur J Anaesthesiol 2013; 30: 270-382.
- 51 Kushimoto S, Shibata Y, Yamamoto Y. Implications of fibrinogenolysis in patients with closed head injury. J Neurotrauma 2003; 20: 357-363.
- 52 Lang T, Johanning K, Metzler H. et al. The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. Anesth Analg 2009; 108: 751-758.
- 53 Lawson JH, Murphy MP. Challenges for providing effective hemostasis in surgery and trauma. Semin Hematol 2004; 41 1 Suppl 1 55-64.
- 54 Levrat A, Gros A, Rugeri L. et al. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth 2008; 100: 792-797.
- 55 Lowe GD, Rumley A, Mackie IJ. Plasma fibrinogen. Ann Clin Biochem 2004; 41 Pt 6 430-440.
- 56 Mackie IJ, Kitchen S, Machin SJ, Lowe GD. Guidelines on fibrinogen assays. Br J Haematol 2003; 121: 396-404.
- 57 Maegele M, Lefering R, Yucel N. et al. Early coagulopathy in multiple injury. Injury 2007; 38: 298-304.
- 58 Martini WZ, Pusateri AE, Uscilowicz JM. et al. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J Trauma 2005; 58: 1002-1009.
- 59 Martini WZ, Holcomb JB. Acidosis and coagulopathy: the differential effects on fibrinogen synthesis and breakdown in pigs. Ann Surg 2007; 246: 831-835.
- 60 Martini WZ. The effects of hypothermia on fibrinogen metabolism and coagulation function in swine. Metabolism 2007; 56: 214-221.
- 61 Martinowitz U, Michaelson M. Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding. J Thromb Haemost 2005; 03: 640-648.
- 62 McLoughlin TM, Fontana JL, Alving B. et al. Profound normovolemic hemodilution. Anesth Analg 1996; 83: 459-465.
- 63 Meyer M. Molecular biology of haemostasis: fibrinogen, factor XIII. Hämostaseologie 2004; 24: 108-115.
- 64 Meyer MA, Ostrowski SR, Windelov NA, Johansson PI. Fibrinogen concentrates for bleeding trauma patients: what is the evidence?. Vox Sang 2011; 101: 185-190.
- 65 Morrison JJ, Ross JD, Dubose JJ. et al. Association of cryoprecipitate and tranexamic acid with improved survival following wartime injury. JAMA Surg 2013; 148: 218-225.
- 66 Mosesson MW. Fibrinogen and fibrin structure and functions. J Thromb Haemost 2005; 03: 1894-1904.
- 67 Nascimento B, Callum J, Rubenfeld G. et al. Clinical review: Fresh frozen plasma in massive bleedings – more questions than answers. Crit Care 2010; 14: 202.
- 68 Nascimento B, Rizoli S, Rubenfeld G. et al. Cryoprecipitate transfusion. Transfus Med 2011; 21: 394-401.
- 69 O’Shaughnessy DF, Atterbury C, Bolton PMaggs, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004; 126: 11-28.
- 70 Park MS, Martini WZ, Dubick MA. et al. Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time. J Trauma 2009; 67: 266-275.
- 71 Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2011; CD000567.
- 72 Practice guidelines for perioperative blood transfusion and adjuvant therapies. Anesthesiology 2006; 105: 198-208.
- 73 Rahe-Meyer N, Sorensen B. For: Fibrinogen concentrate for management of bleeding. J Thromb Haemost 2011; 09: 1-5.
- 74 Rahe-Meyer N, Solomon C, Hanke A. et al. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery. Anesthesiology 2013; 118: 40-50.
- 75 Rourke C, Curry N, Khan S. et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost 2012; 10: 1342-1351.
- 76 Savry C, Quinio P, Lefevre F, Schmitt F. Manageability and potential for haemostasis monitoring by near-patient modified thromboelastometer in intensive care unit. Ann Fr Anesth Reanim 2005; 24: 607-616.
- 77 Schaden E, Hoerburger D, Hacker S. et al. Fibrinogen function after severe burn injury. Burns 2011; 38: 77-82.
- 78 Schlimp CJ, Cadamuro J, Solomon C. et al. The effect of fibrinogen concentrate and factor XIII on thromboelastometry in 33% diluted blood with albumin, gelatine, hydroxyethyl starch or saline in vitro. Blood Transfus 2012; 1-9.
- 79 Schlimp CJ, Voelckel W, Inaba K. et al. Estimation of plasma fibrinogen levels based on hemoglobin, base excess and ISS upon emergency room admission. Crit Care 2013; 17: R137.
- 80 Schöchl H, Frietsch T, Pavelka M, Jambor C. Hyperfibrinolysis after major trauma. J Trauma 2009; 67: 125-131.
- 81 Schöchl H, Forster L, Woidke R. et al. Use of rotation thromboelastometry (ROTEM) to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate. Anaesthesia 2010; 65: 199-203.
- 82 Schöchl H, Nienaber U, Hofer G. et al. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 2010; 14: R55.
- 83 Schöchl H, Nienaber U, Maegele M. et al. Transfusion in trauma. Crit Care 2011; 15: R83.
- 84 Schöchl H, Cotton B, Inaba K. et al. FIBTEM provides early prediction of massive transfusion in trauma. Crit Care 2011; 15: R265.
- 85 Schöchl H, Solomon C, Traintinger S. et al. Thromboelastometric (ROTEM) findings in patients suffering from isolated severe traumatic brain injury. J Neurotrauma 2011; 28: 2033-2041.
- 86 Schöchl H, Voelckel W, Maegele M, Solomon C. Trauma-associated hyperfibrinolysis. Hämostaseologie. 2011 32. ? (AUTOR BITTE PRÜFEn)???.
- 87 Solomon C, Pichlmaier U, Schoechl H. et al. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth 2010; 104: 555-562.
- 88 Solomon C, Rahe-Meyer N, Sorensen B. Fibrin formation is more impaired than thrombin generation and platelets immediately following cardiac surgery. Thromb Res 2011; 128: 277-282.
- 89 Solomon C, Cadamuro J, Ziegler B. et al. A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients. Transfusion 2011; 51: 1695-1706.
- 90 Solomon C, Sorensen B, Hochleitner G. et al. Comparison of whole blood fibrin-based clot tests in thrombelastography and thromboelastometry. Anesth Analg 2012; 114: 721-730.
- 91 Sorensen B, Bevan D. A critical evaluation of cryoprecipitate for replacement of fibrinogen. Br J Haematol 2010; 149: 834-843.
- 92 Spahn DR, Bouillon B, Cerny V. et al. Management of bleeding following major trauma: an updated European guideline. Crit Care 2013; 17: R76.
- 93 Stinger HK, Spinella PC, Perkins JG. et al. The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital. J Trauma 2008; 64 (Suppl. 02) S79-S85.
- 94 Tauber H, Innerhofer P, Breitkopf R. et al. Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma. Br J Anaesth 2011; 107: 378-387.
- 95 Theusinger OM, Wanner GA, Emmert MY. et al. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg 2011; 113: 1003-1012.
- 96 Theusinger OM, Baulig W, Seifert B. et al. Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and freshfrozen plasma. Br J Anaesth 2011; 106: 505-511.
- 97 Toulon P, Ozier Y, Ankri A. et al. Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery. Thromb Haemost 2009; 101: 394-401.
- 98 Velik-Salchner C, Haas T, Innerhofer P. et al. The effect of fibrinogen concentrate on thrombocytopenia. J Thromb Haemost 2007; 05: 1019-1025.
- 99 Von Heymann C, Keller MK. et al. Activity of clotting factors in fresh-frozen plasma during storage at 4 degrees C over 6 days. Transfusion 2009; 49: 913-920.
- 100 Watson GA, Sperry JL, Rosengart MR. et al. Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome. J Trauma 2009; 67: 221-227.
- 101 Weisel JW, Nagaswami C, Vilaire G, Bennett JS. Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. J Biol Chem 1992; 267: 16637-16643.
- 102 Weiss G, Lison S, Glaser M. et al. Observational study of fibrinogen concentrate in massive hemorrhage. Blood Coagul Fibrinolysis 2011; 22: 727-734.
- 103 White NJ, Martin EJ, Brophy DF, Ward KR. Coagulopathy and traumatic shock. Resuscitation 2010; 81: 111-116.
- 104 Wigginton JG, Roppolo L, Pepe PE. Advances in resuscitative trauma care. Minerva Anestesiol 2011; 77: 993-1002.
- 105 Ziegler B, Schimke C, Marchet P. et al. Severe pediatric blunt trauma--successful ROTEMguided hemostatic therapy with fibrinogen concentrate and no administration of fresh frozen plasma or platelets. Clin Appl Thromb Hemost 2013; 09: 453-459.