Zusammenfassung
In den letzten Jahren konnte ein verbessertes Verständnis traumaassoziierter Gerinnungsstörungen (traumainduzierte Koagulopathie) durch eine Reihe neuer wissenschaftlicher Erkenntnisse erreicht werden. Neben dem Gewebetrauma scheinen auch Schock und Minderperfusion für die Entwicklung einer Koagulopathie maßgeblich verantwortlich zu sein. Hypoperfusion kann über eine Endothelaktivierung zur Hyperfibrinolyse führen. Additive Effekte wie Hypothermie und Acidose verstärken diese Gerinnungsstörung. Standardgerinnungstests wie Quick-Test und die Bestimmung der aktivierten partiellen Thromboplastinzeit (aPTT) werden zwar häufig zu Therapieentscheidungen herangezogen, sind aber mit Nachteilen behaftet. Die Thrombelastometrie/-graphie scheint den Routinegerinnungtests überlegen zu sein. Da die Prophylaxe der traumainduzierten Koagulopathie einfacher als die Therapie ist, ist eine antizipierende Vorgehensweise notwendig. Während die pathophysiologischen und pharmakologischen Zusammenhänge der geschilderten Therapieoptionen schlüssig sind, fehlt jedoch für die meisten eine evidenzbasierte Bestätigung durch randomisierte, kontrollierte Studien. Zu dem notärztlichen und anästhesiologischen Konzept der „damage control resuscitation“ gehören die Begrenzung der Infusion von kristalloidem und kolloidalem Volumenersatz auf einen mittleren arteriellen Druck (MAP) von ≥65 mmHg (höher bei Schädel-Hirn-Trauma), ein aktives Wärmemanagement, die Verhinderung bzw. der Ausgleich einer Acidose auf einen pH>7,2 bzw. ein „base excess“ (BE)≤−6 mmol/l sowie die frühzeitige und ausreichende Gabe von gerinnungsaktiven Medikamenten. Da Erythrozyten auch einen beträchtlichen Anteil am Gerinnungsprozess haben, sollten bei massiver, nichtgestillter Blutung Hämoglobin- (Hb-)Werte um 6,2 mmol/l (10 g/dl) bzw. ein Hämatokrit (HKT) um 30% angestrebt werden. Ein Fibrinogenmangel entwickelt sich bei schweren Polytraumen früh und muss adäquat ausgeglichen werden. Wenn eine Gerinnungstherapie mit gefrorenem Frischplasma (GFP) durchgeführt wird, müssen ausreichende Mengen (20–30 ml/kgKG) verabreicht werden, um die Gerinnungsfaktoren entsprechend anzuheben. Prothrombinkomplexpräparate (PPSB) können bei schweren Blutungen zur Optimierung der Thrombingenerierung hilfreich sein. Da eine Hyperfibrinolyse nach schwerem Trauma häufiger ist als bislang angenommen, sollte insbesondere bei kreislaufinstabilen Patienten an den Einsatz eines Antifibrinolytikums gedacht werden. Die Thrombozytenzahl sollten bei blutenden Polytraumata 100.000/µl nicht unterschreiten. Bei thrombopathischer, diffuser Blutung kann die Infusion von Desmopressin (DDAVP) indiziert sein. Rekombinanter aktivierter Faktor VII stellt eine Therapieoption dar, allerdings nur bei strenger Indikationsstellung und wenn oben genannte Maßnahmen zur Optimierung der Gerinnungssituation ergriffen wurden.
Abstract
In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure ≥65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH≤7.2 and a base excess (BE) ≤−6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6,2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20–30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/µl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the “off label” use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.
Literatur
Afshari A, Wetterslev J, Brok J et al (2007) Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ 335:1248–1251
Ahonen J, Jokela R, Korttila K (2007) An open non-randomized study of recombinant activated factor VII in major postpartum haemorrhage. Acta Anaesthesiol Scand 51:929–936
Arbeitsgruppe „Perioperative Gerinnung“ der Österreichischen Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin (2009) Gerinnungsmanagement bei traumatisch bedingter Massivblutung. Anasthesiol Intensivmed Notfallmed Schmerzther (in press)
Bartal C, Yitzhak A (2009) The role of thrombelastometrie and recombinant factor VIIa in trauma. Curr Opin Anaesthesiol 22:281–288
Beekley AC (2008) Damage control resuscitation: a sensible approach to the exsanguinating surgical patient. Crit Care Med 36:S267–S274
Boffard KD, Riou B, Warren B et al (2005) Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma 59:8–15
Borgman MA, Spinella PC, Perkins JG et al (2007) The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 63:805–813
Brohi K, Cohen MJ, Davenport RA (2007) Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care 13:680–685
Brohi K, Cohen MJ, Ganter MT et al (2007) Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg 245:812–818
Brohi K, Cohen MJ, Ganter MT et al (2008) Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma 64:1211–1217
Brohi K, Singh J, Heron M et al (2003) Acute traumatic coagulopathy. J Trauma 54:1127–1130
Bundesärztekammer (BÄK) Richtlinien zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Hämotherapie) gemäß §§ 12 und 18 des Transfusionsgesetzes (TFG) v. 19.09.2005. http://www.bundesaerztekammer.de/downloads/Haemo2005.pdf. Gesehen am 13.05.2008
Bundesärztekammer (BÄK). Querschnitts-Leitlinien (BÄK) zur Therapie mit Blutkomponenten und Plasmaderivaten, 4. Aufl. http://www.bundesaerztekammer.de/downloads/2009-02-13_Gesamtdokument.pdf. Gesehen am 08.03.2009
Cannon W, Frawer J, Cowell E (1918) The preventive treatment of wound shock. JAMA 70:618–621
Chowdhury P, Saayman AG, Paulus U et al (2004) Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 125:69–73
Ciavarella D, Reed RL, Counts RB et al (1987) Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Br J Haematol 67:365–368
Cotton BA, Gunter OL, Isbell J et al (2008) Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma 64:1177–1182
Dara SI, Rana R, Afessa B et al (2005) Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med 33:2667–2671
Despotis G, Eby C, Lublin DM (2008) A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery. Transfusion 48 [Suppl 1]:2–30
Dutton RP, McCunn M, Hyder M et al (2004) Factor VIIa for correction of traumatic coagulopathy. J Trauma 57:709–718
Dzik WH (2004) Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep 3:324–330
Engstrom M, Schott U, Romner B et al (2006) Acidosis impairs the coagulation: a thromboelastographic study. J Trauma 61:624–628
Farriols Danés A, Gallur Cuenca L, Rodríguez Bueno S et al (2008) Efficacy and tolerability of human fibrinogen concentrate administration to patients with acquired fibrinogen deficiency and active or in high-risk severe bleeding. Vox Sang 94:221–226
Fergusson DA, Hebert PC, Mazer CD et al (2008) A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358:2319–2331
Fraser I, Porte R, Kouides P et al (2008) A benefit-risk review of systemic haemostatic agents. Part 1: in major surgery. Drug Saf 31:217–230
Fries D, Haas T, Salchner V et al (2005) Gerinnungsmanagement beim Polytrauma. Anaesthesist 54:137–144
Fries D, Innerhofer P, Reif C et al (2006) The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model. Anesth Analg 102:347–351
Fries D, Innerhofer P, Schobersberger W (2009) Time for changing coagulation management in trauma-related massive bleeding. Curr Opin Anaesthesiol 22:267–274
Ganter MT, Cohen MJ, Brohi K et al (2008) Angiopoietin-2, marker and mediator of endothelial activation with prognostic significance early after trauma? Ann Surg 247:320–326
Gonzalez EA, Moore FA, Holcomb JB et al (2007) Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma 62:112–119
Haas T, Fries D, Holz C et al (2008) Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution. Anesth Analg 106:1078–1086, table
Henrich W, Surbek D, Kainer F et al (2008) Diagnosis and treatment of peripartum bleeding. J Perinat Med 36:467–478
Hess JR (2007) Blood and coagulation support in trauma care. Hematology Am Soc Hematol Educ Program 2007:187–191
Hess JR, Brohi K, Dutton RP et al (2008) The coagulopathy of trauma: a review of mechanisms. J Trauma 65:748–754
Hess JR, Dutton RB, Holcomb JB et al (2008) Giving plasma at a 1:1 ratio with red cells in resuscitation: who might benefit? Transfusion 48:1763–1765
Hess JR, Lawson JH (2006) The coagulopathy of trauma versus disseminated intravascular coagulation. J Trauma 60:S12–S19
Hiippala ST (1995) Dextran and hydroxyethyl starch interfere with fibrinogen assays. Blood Coagul Fibrinolysis 6:743–746
Hoffman M (2001) A cell-based model of hemostasis. Thromb Haemost 85:958–965
Holcomb JB (2007) Damage control resuscitation. J Trauma 62 [Suppl 6]:36–37
Holcomb JB, Hess JR (2006) Early massive trauma transfusion: state of the art. J Trauma 60:S1–S2
Holcomb JB, Jenkins D, Rhee P et al (2007) Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma 62:307–310
Holcomb JB, Wade CE, Michalek JE et al (2008) Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg 248:447–458
Jámbor C, Heindl B, Spannagl M et al (2009) Bluttransfusion. Hämostaseologisches Management beim Polytrauma – Stellenwert der patientennahen diagnostischen Methoden. Anasthesiol Intensivmed Notfallmed Schmerzther 44:200–210
Karalapillai D, Popham P (2007) Recombinant factor VIIa in massive postpartum haemorrhage. Int J Obstet Anesth 16:29–34
Kashuk JL, Moore EE, Johnson JL et al (2008) Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma 65:261–270
Kitchens CS (2005) To bleed or not to bleed? Is that the question for the PTT? J Thromb Haemost 3:2607–2611
Kozek-Langenecker S (2007) Monitoring hemostasis in emergency medicine. Yearb Intensive Care Emerg Med 848–859
Kreimeier U, Huber-Wagner S, Körner M et al (2008) Interdisziplinäre Schockraumversorgung. Initiale Versorgung bei Aufnahme in der Klinik. Notfall Rettungsmed 11:399–406
Lee JC, Peitzman AB (2006) Damage-control laparotomy. Curr Opin Crit Care 12:346–350
Lefering R (2008) Das schwere Trauma. Qualitative und quantitative Herausforderung für das Rettungssystem. Notfall Rettungsmed 11:373–376
Levi M (2002) Pro-hemostatic therapy for prevention and treatment of bleeding. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine 2002. Springer, Berlin Heidelberg New York Tokio
Lier H (2008) Hypothermie und die tödliche Triade. Notfall Rettungsmed 11:377–380
Lier H, Kampe S, Schroeder S (2007) Rahmenbedingungen für eine intakte Hämostase. Anaesthesist 56:239–251
Lier H, Krep H, Schroeder S et al (2008) Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia and hypothermia on functional hemostasis in trauma. J Trauma 65:951–960
Luddington RJ (2005) Thrombelastography/thromboelastometry. Clin Lab Haematol 27:81–90
Mackie IJ, Kitchen S, Machin SJ et al (2003) Guidelines on fibrinogen assays. Br J Haematol 121:396–404
MacLeod JB, Lynn M, McKenney MG et al (2003) Early coagulopathy predicts mortality in trauma. J Trauma 55:39–44
MacLoud J (2008) Trauma and coagulopathy. A new paradigm to consider. Arch Surg 143:797–801
Maegele M, Lefering R, Paffrath T et al (2008) Red-blood-cell to plasma ratios transfused during massive transfusion are associated with mortality in severe multiple injury: a retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft fur Unfallchirurgie. Vox Sang 95:112–119
Maegele M, Lefering R, Yucel N et al (2007) Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury 38:298–304
Malone DL, Hess JR, Fingerhut A (2006) Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol. J Trauma 60:S91–S96
Mannucci PM (1997) Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 90:2515–2521
Mannucci PM, Levi M (2007) Prevention and treatment of major blood loss. N Engl J Med 356:2301–2311
Martini WZ (2008) The role of fibrinogen. Symposium: Multiple injury and coagulation. SHOCK, Köln
Martini WZ, Cortez DS, Dubick MA et al (2008) Thrombelastography is better than PT, aPTT and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma 65:535–543
Martini WZ, Dubick MA, Wade CE et al (2007) Evaluation of tris-hydroxymethylaminomethane on reversing coagulation abnormalities caused by acidosis in pigs. Crit Care Med 35:1568–1574
McDonald V, Ryland K (2008) Coagulopathy in trauma: optimising haematological status. J Trauma 10:109–123
McMorrow RC, Ryan SM, Blunnie WP et al (2008) Use of recombinant factor VIIa in massive post-partum haemorrhage. Eur J Anaesthesiol 25:293–298
Plotkin AJ, Wade CE, Jenkins DH et al (2008) A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma 64:S64–S68
Raat NJ, Berends F, Verhoeven AJ et al (2005) The age of stored red blood cell concentrates at the time of transfusion. Transfus Med 15:419–423
Rabinovici R, Frankel H, Kaplan L (2003) Trauma evaluation and resuscitation. Curr Probl Surg 40:599–681
Repine TB, Perkins JG, Kauvar DS et al (2006) The use of fresh whole blood in massive transfusion. J Trauma 60:S59–S69
Rhee P, Koustova E, Alam HB (2003) Searching for the optimal resuscitation method: recommendations for the initial fluid resuscitation of combat casualties. J Trauma 54:S52–S62
Rixen D, Grass G, Sauerland S et al (2005) Evaluation of criteria for temporary external fixation in risk-adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients: „evidence-based medicine“ versus „reality“ in the Trauma Registry of the German Trauma Society. J Trauma 59:1375–1394
Rugeri L, Levrat A, David JS et al (2007) Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost 5:289–295
Sagraves SG, Toschlog EA, Rotondo MF (2006) Damage control surgery – the intensivist’s role. J Intensive Care Med 21:5–16
Samama CM (2008) Prothrombin complex concentrates: a brief review. Eur J Anaesthesiol 25:784–789
Sarani B, Dunkman WJ, Dean L et al (2008) Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med 36:1114–1118
Scalea TM, Bochicchio KM, Lumpkins K et al (2008) Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients. Ann Surg 248:578–584
Shafi S, Elliott AC, Gentilello L (2005) Is hypothermia simply a marker of shock and injury severity or an independent risk factor for mortality in trauma patients? Analysis of a large national trauma registry. J Trauma 59:1081–1085
Singbartl K, Innerhofer P, Radvan J et al (2003) Hemostasis and hemodilution: a quantitative mathematical guide for clinical practice. Anesth Analg 96:929–935, table
Sirker A, Malik N, Bellamy M et al (2008) Acute myocardial infarction following tranexamic acid use in a low cardiovascular risk setting. Br J Haematol 141:907–908
Spahn DR, Cerny V, Coats TJ et al (2007) Management of bleeding following major trauma: a European guideline. Crit Care 11:R17
Spahn DR, Rossaint R (2005) Coagulopathy and blood component transfusion in trauma. Br J Anaesth 95:130–139
Spahn DR, Tucci MA, Makris M (2005) Is recombinant FVIIa the magic bullet in the treatment of major bleeding? Br J Anaesth 94:553–555
Spinella PC, Perkins JG, McLaughlin DF et al (2008) The effect of recombinant activated factor VII on mortality in combat-related casualties with severe trauma and massive transfusion. J Trauma 64:286–293
Steuernagel C (o J) Bleeding Card. http://www.card.haemostase.info/. Gesehen 22.08.2009
Stinger HK, Spinella PC, Perkins JG et al (2008) The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital. J Trauma 64 [Suppl 2]:79–85
Tanaka KA, Taketomi T, Szlam F et al (2008) Improved clot formation by combined administration of activated factor VII (NovoSeven) and fibrinogen (Haemocomplettan P). Anesth Analg 106:732–738, table
The CRASH-2 Trial Collaborators (2006) Improving the evidence base for trauma care: progress in the international CRASH-2 trial. PLoS Clin Trials 1:e30
Tieu BH, Holcomb JB, Schreiber MA (2007) Coagulopathy: its pathophysiology and treatment in the injured patient. World J Surg 31:1055–1064
Tsuei BJ, Kearney PA (2004) Hypothermia in the trauma patient. Injury 35:7–15
Weeterings C, de Groot PG, Adelmeijer J et al (2008) The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface. Blood 112:3227–3233
Weinberg JA, McGwin G Jr, Marques MB et al (2008) Transfusions in the less severely injured: does age of transfused blood affect outcomes? J Trauma 65:794–798
Williams TM, Sadjadi J, Harken AH et al (2008) The necessity to assess anticoagulation status in elderly injured patients. J Trauma 65:772–776
Wilson RF, Dulchavsky SA, Soullier G et al (1987) Problems with 20 or more blood transfusions in 24 hours. Am Surg 53:410–417
Ying CL, Tsang SF, Ng KF (2008) The potential use of desmopressin to correct hypothermia-induced impairment of primary haemostasis – An in vitro study using PFA-100((R)). Resuscitation 76:129–133
Yucel N, Lefering R, Maegele M et al (2006) Trauma Associated Severe Hemorrhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma. J Trauma 60:1228–1236
Zufferey P, Merquiol F, Laporte S et al (2006) Do antifibrinolytics reduce allogenic blood transfusion in orthopedic surgery? Anesthesiology 105:1034–1046
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H. Lier und H. Schöchl haben Reisekostenerstattung und Vortragshonorare von der Firma CSL Behring erhalten.
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Lier, H., Krep, H. & Schöchl, H. Gerinnungsmanagement bei der Polytraumaversorgung. Anaesthesist 58, 1010–1026 (2009). https://doi.org/10.1007/s00101-009-1595-z
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DOI: https://doi.org/10.1007/s00101-009-1595-z