Trauma-associated hyperfibrinolysis

H. Schöchl; W. Voelckel; M. Maegele; C. Solomon

doi:10.5482/ha-1178

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2012; 32(01): 22-27
DOI: 10.5482/ha-1178

Review

Schattauer GmbH

Trauma-associated hyperfibrinolysis

Trauma-assoziierte Hyperfibrinolyse

H. Schöchl

¹Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria

²Department of Anaesthesiology and Intensive Care Medicine, AUVA Trauma Centre, Salzburg, Austria

,

W. Voelckel

²Department of Anaesthesiology and Intensive Care Medicine, AUVA Trauma Centre, Salzburg, Austria

,

M. Maegele

³Department of Trauma and Orthopedic Surgery, University of Witten/Herdecke, Cologne-Merheim Medical Center (CMMC), Cologne, Germany

,

C. Solomon

⁴Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Salzburg University, Hospital SALK, Salzburg, Austria

› Institutsangaben

Abstract

Summary

Trauma-induced coagulopathy (TIC) has been considered for a long time as being due to depletion of coagulation factors secondary to blood loss, dilution and consumption. Dysfunction of the remaining coagulation factors due to hypothermia and acidosis is assumed to additionally contribute to TIC. Recent data suggest that hyperfibrinolysis (HF) represents an additional important confounder to the disturbed coagulation process. Severe shock and major tissue trauma are the main drivers of this HF. The incidence of HF is still speculative. According to visco-elastic testing of trauma patients upon emergency room admission, HF is present in approximately 2.5–7% of all trauma patients. However, visco-elastic tests provide information on severe forms of HF only. Occult HF seems to be much more common but diagnosis is still challenging. Results from a recent randomized, placebo-controlled trial suggest that the early treatment of trauma patients with tranexamic acid may result in a significant reduction of trauma-associated mortality.

Zusammenfassung

Bislang wurden Trauma-induzierte Gerinnungsstörungen häufig als Kombination aus Verlust und Dysfunktion von Gerinnungsfaktoren verstanden. Azidose und Hypothermie bedingen eine weitere Funktionseinschränkung der verbleibenden Gerinnungsfaktoren. Neue Daten lagen nahe, dass Hyperfibrinolyse den Gerinnungsprozess zusätzlich beeinträchtigt. Als wesentliche Ursachen für profibrinolytische Prozesse werden die Kombination aus schockbedingter Hypoperfusion und substanziellem Gewebetrauma vermutet. Die wahre Inzidenz der Hyperfibrinolyse nach Trauma ist nach wie vor unklar. Anhand thromboelastometrischer/thrombelasto- graphischer Befunde bei Aufnahme im Schockraum wird gemutmaßt, dass 2.5–7% der Schwerverletzten betroffen sind. Viskoelastische Testverfahren erlauben allerdings nur die Diagnose ausgeprägter HF-Formen. Okkulte Hyperfibrinolysen treten vermutlich wesentlich häufiger auf und sind nach wie vor schwierig zu detektieren.Aktuelle Daten einer großen multizentrischen, multinationalen, randomisierten Doppelbildstudie legen nahe, dass die Mortalität von Traumapatienten durch den frühen Einsatz von Tranexamsäure signifikant gesenkt werden kann.

Keywords

Hyperfibrinolysis - trauma - ROTEM - TEG - tranexamic acid

Schlüsselwörter

Hyperfibrinolyse - Trauma - ROTEM→ - TEG→ - Tranexamsäure

Volltext

Referenzen

References
1 Hunt B, Segal H. Hyperfibrinolysis. J Clin Pathol 1996; 49: 958.
2 Porte RJ, Bontempo FA, Knot EAR. et al. Systemic effects of tPA associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation. Transplantation 1989; 47: 978-984.
3 Annecke T, Geisenberger T, Kürzl R. et al. Algorithm-based coagulation management of catastrophic amniotic fluid embolism. Blood Coagul Fibrinolysis 2010; 21: 95-100.
4 Teufelsbauer H, Proidl S, Havel M, Vukovich T. Early activation of haemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis. Thromb Haemost 1992; 68: 250-252.
5 Vorweg M, Hartmann B, Knüttgen D. et al. Management of fulminant fibrinolysis during abdominal aortic surgery. J Cardiothorac Vasc Anesth 2001; 15: 764-767.
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 Gando S, Tedo I, Kubota M. Posttrauma coagulation and fibrinolysis. Crit Care Med 1992; 20: 594-600.
8 Cosgriff N, Moore EE, Sauaia A. et al. Predicting lifethreatening coagulopathy in the massively transfused trauma patient: hypothermia and acidosis revisited. J Trauma 1997; 42: 857-861.
9 Meng ZH, Wolberg AS, Monroe III DM. et al. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J Trauma 2003; 55: 886-891.
10 Brohi K, Cohen MJ, Ganter MT. et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma 2008; 64: 1211-1217.
11 Floccard B, Rugeri L, Faure A. et al. Early coagulopathy in trauma patients: An on-scene and hospital admission study. Injury 2010; 42: 697-701.
12 Schöchl H, Frietsch T, Pavelka M. et al. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 2009; 67: 125-131.
13 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 DOI:10.1213/ANE.0b013e31822c183f.
14 Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care 2007; 03: 680-685.
15 Adelman B, Michelson AD, Losalzo J. et al. Plasmin effect on platelet glycoprotein 1b-von Willebrand factor interactions. Blood 1985; 65: 32-40.
16 Sawamura A, Hayakawa M, Gando S. et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res 2009; 124: 608-613.
17 Hayakawa M, Sawamura A, Gando S. et al. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. Surgery 2011; 149: 221-230.
18 Eeckhoudt S, Latinne D, Lambert C, Hermans C. Diagnosis of hyperfibrinolysis: which test(s) should be used?. J Thromb Haemost. 2009 suppl 2: PPMO-220.
19 Lang T, von Depka M. Possibilities and limitations of thrombelastometry/graphy. Hämostaseologie 2006; 26: S21-S29.
20 Urano T, Sakakibara K, Rydzewski A. et al. Relationship between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1. Thromb Res 1990; 63: 82-86.
21 Smith AA, Jacobson LJ, Miller BI. et al. A new euglobulin clot lysis assay for global fibrinolysis. Thromb Res 2003; 112: 329-337.
22 Schöchl H, Solomon D, Voelckel W. Thromboelastometry in the perioperative setting. Neth J Crit Care 2010; 14: 23-31.
23 Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27: 81-89.
24 Spiel AO, Mayr FB, Firbas C. Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans. J Thromb Haemost 2006; 04: 411-416.
25 Schöchl H, Solomon C, Schulz A. et al. Thromboelastometry (TEM→) Findings in disseminated intravascular coagulation in a pig model of endotoxinemia. Mol Med 2011; 17: 266-272.
26 Franz RC. ROTEM analysis: a significant advance in the field of rotational thrombelastography. S Afr J Surg 2009; 47: 2-6.
27 Robbie LA, Bennett B, Croll AM. et al. Proteins of the fibrinolytic system in human thrombi. Thromb Haemost 1996; 71: 127-133.
28 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.
29 Carroll RC, Craft RM, Langdon RJ. Early evaluation of acute traumatic coagulopathy by thrombelastography. Transl Res 2009; 154: 34-39.
30 Tauber H, Innerhofer P, Breitkopf R. et al. Prevalence and impact of abnormal ROTEM→ assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIATRE-TIC) study’. Br J Anaesth 2011; 10: 378-387.
31 Kashuk J, Moore E, Sawyer M. et al. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg 2010; 252: 434-442.
32 Schöchl H, Solomon D, Traintinger S. et al. Thromboelastometric (ROTEM) findings in patients suffering from isolated severe traumatic brain injury. J Neurotrauma. 2011 doi:10.1089/neu.2010.1744.
33 Goodnight SH, Kenoyer G, Rapaport SI. et al. Defibrination after brain-tissue destruction. N Engl J Med 1974; 290: 1043-1047.
34 Kushimoto S, Shibata Y, Yamamoto Y. Implications of fibrinogenolysis in patients with closed head injury. J Neurotrauma 2003; 20: 357-363.
35 Brenni M, Worn M, Brüesch M. et al. Successful rotational thromboelastometry-guided treatment of traumatic haemorrhage, hyperfibrinolysis and coagulopathy. Acta Anaesthesiol Scand 2010; 54: 111-117.
36 Shakur H, Roberts I, Bautista R. et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376: 23-32.
37 CRASH-2 collaborators. Roberts I, Shakur H, Afolabi A. et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377: 1096-1101.
38 Johansson PI, Ostrowski SR. Acute coagulopathy of trauma: Balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation. Med Hypoth 2010; 75: 564-567.