Zusammenfassung
Polytraumatisierte Patienten entwickeln durch Verlust, Verdünnung und Verbrauch von
Gerinnungskomponenten häufig eine behandlungsbedürftige Gerinnungsstörung. Für das
perioperative Management dieser Koagulopathie sowie die Steuerung der Therapie mit
Blutprodukten und Hämostyptika stehen patientennahe diagnostische Verfahren mit unterschiedlichen
Vor– und Nachteilen zur Verfügung: einerseits die Point–of–Care–Abwandlungen der konventionellen
Laboranalytik (Blutgasanalyse, Quick– und aPTT–Wert, Thrombozytenzahl), anderseits
die komplexeren Vollblutmethoden (Thromelastometrie und Thrombozytenfunktionsdiagnostik).
Angelehnt an die aktuellen Leitlinien der Bundesärztekammer zur Therapie mit Blutkomponenten
und Plasmaderivaten werden Empfehlungen für die Intervention mit Blutprodukten und
hämostatisch wirksamen Medikamenten anhand patientennaher Gerinnungsdiagnostik beim
Polytrauma beschrieben.
Abstract
Massively transfused multiple trauma patients commonly develop a complex coagulopathy
which needs immediate treatment. Near–patient diagnostic methods are available for
the management of this coagulopathy and for the guidance of the therapeutic options
with blood products and haemostatic drugs: conventional laboratory analysis methods
adapted to the point–of–care (POC) situation (blood gas analysis, point of care PT,
APTT and platelet count), and the complex whole blood methods used for near–patient
coagulation monitoring (thrombelastometry and platelet function analysis). Based on
the new Guidelines of the German Medical Association for the use of blood and plasma
derivates, interventions with blood products and haemostatic drugs in multiple trauma
patients are suggested. The diagnostic value of near–patient methods for coagulation
monitoring is discussed.
Schlüsselwörter:
Gerinnungsmanagement - Koagulopathie - Polytrauma - Point–of–Care - patientennahe
Diagnostik
Keywords:
coagulation management - coagulopathy - multiple trauma - point–of–care - near–patient
diagnostics
Kernaussagen
Bei etwa einem Viertel aller polytraumatisierten Patienten treten klinisch relevante
Gerinnungsstörungen auf.
Für die Therapie der Gerinnungsstörung stehen plasmatische und zelluläre Blutprodukte
und Hämostyptika zur Verfügung.
Methoden zur hämostaseologischen Diagnostik sind: Blutgasanalyse, Blutbild (Hämoglobin,
Thrombozytenzahl), Globaltests (Quick, PTT, Fibrinogen), Thrombelastometrie.
Die viskoelastische POC–Analytik liefert Informationen über den zeitlichen Beginn
der Gerinnung und die Gerinnselfestigkeit. Dies betrifft die Interaktion von plasmatischer
Gerinnung, der Thrombozytenfunktion und der Fibrinolyse.
Mithilfe des „Damage Control”–Konzepts konnte sowohl der Verbrauch von Blutprodukten
als auch die Sterblichkeit Schwerverletzter gesenkt werden.
Für die Rahmenbedingungen einer intakten Hämostase: schnellstmögliche Korrektur von
Hypothermie, Azidose, Anämie und Hypokalzämie.
FFP–Transfusion: Früh anfangen und ausreichend große Mengen (15–20 ml/kg) geben.
Fibrinogenkonzentrat: Indikation bei Fg < 150 mg/dl; Dosierung 3–5 g Fibrinogenkonzentrat
PPSB besteht aus den prokoagulatorischen Faktoren II, VII, IX und X und ist bei Verminderung
der Thrombingenerierung eine mögliche Therapieoption, den Prothrombinasekomplex schnell
anzuheben.
Die initiale Dosierung liegt je nach Ausmaß der Gerinnungsstörung bei 20–25 IE/kg
KG.
Indikation für Thrombozytenkonzentrat: Thrombozytenzahl 50–100 /nl bzw. klinisch
relevante Thrombozytenfunktionsstörung
Für die Behandlung der Hyperfibrinolyse steht Tranexamsäure zur Verfügung (10–20
mg/kg KG als Bolus).
Bei Beeinträchtigung der primären Hämostase kann DDAVP hilfreich sein.
Rekombinanter aktivierter Faktor VII (rFVIIa) kann im Einzelfall eine sinnvolle Therapieoption
darstellen, allerdings nur, wenn die Rahmenbedingungen erfüllt sind, ausreichend Gerinnungssubstrat
vorhanden ist und eine strenge Indikationsstellung erfolgt.
Literaturverzeichnis
1
Brohi K, Singh J, Heron M, Coats T..
Acute traumatic coagulopathy.
J Trauma.
2003;
54
1127-1130
2
Sauaia A, Moore FA, Moore EE. et al. .
Epidemiology of trauma deaths: a reassessment.
J Trauma.
1995;
38
185-193
3
Spiess BD, Gillies BS, Chandler W, Verrier E..
Changes in transfusion therapy and reexploration rate after institution of a blood
management program in cardiac surgical patients.
J Cardiothorac Vasc Anesth.
1995;
9
168-173
4
Shore–Lesserson L, Manspeizer HE, DePerio M. et al. .
Thromboelastography–guided transfusion algorithm reduces transfusions in complex cardiac
surgery.
Anesth Analg.
1999;
88
312-319
5
Nuttall GA, Oliver WC, Santrach PJ. et al. .
Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component
utilization after cardiopulmonary bypass.
Anesthesiology.
2001;
94
773-781
6
Coakley M, Reddy K, Mackie I, Mallett S..
Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry
analyzer, the thromboelastogram, and conventional coagulation tests.
J Cardiothorac Vasc Anesth.
2006;
20
548-553
7 Leitlinien der Bundesärztekammer zur Therapie mit Blutkomponenten und Plasmaderivaten
2008.
www.baek.de/page.asp?his=0.6.3288.6716
8
Nuttall GA, Oliver Jr. WC, Beynen FM. et al. .
Intraoperative measurement of activated partial thromboplastin time and prothrombin
time by a portable laser photometer in patients following cardiopulmonary bypass.
J Cardiothorac Vasc Anesth.
1993;
7
402-409
9
Bonik K, Rode MD, Broder M..
Therapie von Fibrinogenmangelzuständen.
Hämostaseologie.
1996;
16
194-199
10
Monroe DM, Hoffman M..
What does it take to make the perfect clot?.
Arterioscler Thromb Vasc Biol.
2006;
26
41-48
11
Zacharowski K, Sucker C, Zacharowski P, Hartmann M..
Thrombelastography for the monitoring of lipopolysaccharide induced activation of
coagulation.
Thromb Haemost.
2006;
95
557-561
12
Lang T, von Depka M..
Diagnostische Möglichkeiten und Grenzen der Thrombelastometrie/–graphie.
Hämostaseologie.
2006;
26
20-29
13
Hartert H..
Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren.
Klin Wochenschrift.
1948;
26
577-583
14
Hett DA, Walker D, Pilkington SN, Smith DC..
Sonoclot analysis.
Br J Anaesth.
1995;
75
771-776
15
Anderson L, Quasim I, Soutar R. et al. .
An audit of red cell and blood product use after the institution of thromboelastometry
in a cardiac intensive care unit.
Transfus Med.
2006;
16
31-39
16
Spalding GJ, Hartrumpf M, Sierig T. et al. .
Cost reduction of perioperative coagulation management in cardiac surgery: value of
"bedside" thrombelastography (ROTEM).
Eur J Cardiothorac Surg.
2007;
31
1052-1057
17
Plotkin AJ, Wade CE, Jenkins DH. et al. .
A reduction in clot formation rate and strength assessed by thrombelastography is
indicative of transfusion requirements in patients with penetrating injuries.
J Trauma.
2008;
64
64-68
18
Rugeri L, Levrat A, David JS. et al. .
Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography.
J Thromb Haemost.
2007;
5
289-295
19
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
20 Schoechl H, Frietsch T, Pavelka M, Jámbor C.. Hyperfibrinolysis following major
trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J
Trauma 2009
21
Kaufmann CR, Dwyer KM, Crews JD, Dols SJ, Trask AL..
Usefulness of thrombelastography in assessment of trauma patient coagulation.
J Trauma.
1997;
42
716-720
22
Toth O, Calatzis A, Penz S, Losonczy H, Siess W..
Multiple electrode aggregometry: A new device to measure platelet aggregation in whole
blood.
Thromb Haemost.
2006;
96
781-788
23
van Werkum JW, Harmsze AM, Elsenberg EH. et al. .
The use of the VerifyNow system to monitor antiplatelet therapy: a review of the current
evidence.
Platelets.
2008;
19
479-488
24
Mammen EF, Comp PC, Gosselin R. et al. .
PFA–100 system: a new method for assessment of platelet dysfunction.
Semin Thromb Hemost.
1998;
24
195-202
25
Jambor C, Weber C, Lau A, Spannagl M, Zwissler B..
Multiple electrode aggregometry for ex vivo detection of the anti–platelet effect
of non–opioid analgesic drugs.
Thromb Haemost.
2009;
101
207-209
26 Jambor C, Weber C, Gerhardt K. et al. .Point of care assessment of aspirin–induced
platelet function inhibition as determined in whole blood by multiple electrode aggregometry
(MEA). Anesth Analg 2009
27
Sibbing D, Braun S, Jawansky S. et al. .
Assessment of ADP–induced platelet aggregation with light transmission aggregometry
and multiple electrode platelet aggregometry before and after clopidogrel treatment.
Thromb Haemost.
2008;
99
121-126
28 Mueller T, Dieplinger B, Poelz W, Haltmayer M.. Utility of the PFA–100 Instrument
and the Novel Multiplate Analyzer for the Assessment of Aspirin and Clopidogrel Effects
on Platelet Function in Patients With Cardiovascular Disease. Clin Appl Thromb Hemost
2008
29
McArthur BJ..
Damage control surgery for the patient who has experienced multiple traumatic injuries.
AORN J.
2006;
84
992-1000
30
Johnson JW, Gracias VH, Schwab CW. et al. .
Evolution in damage control for exsanguinating penetrating abdominal injury.
J Trauma.
2001;
51
261-269
31
Lier H, Krep H, Schroeder S, Stuber F..
Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia,
anemia, and hypothermia on functional hemostasis in trauma.
J Trauma.
2008;
65
951-960
32
Jurkovich GJ, Greiser WB, Luterman A, Curreri PW..
Hypothermia in trauma victims: an ominous predictor of survival.
J Trauma.
1987;
27
1019-1024
33
Valeri CR, Feingold H, Cassidy G. et al. .
Hypothermia–induced reversible platelet dysfunction.
Ann Surg.
1987;
205
175-181
34
Wolberg AS, Meng ZH, Monroe 3rd DM, Hoffman M..
A systematic evaluation of the effect of temperature on coagulation enzyme activity
and platelet function.
J Trauma.
2004;
56
1221-1228
35
Cosgriff N, Moore EE, Sauaia A. et al. .
Predicting life–threatening coagulopathy in the massively transfused trauma patient:
hypothermia and acidoses revisited.
J Trauma.
1997;
42
857-861
36
Blow O, Magliore L, Claridge JA, Butler K, Young JS..
The golden hour and the silver day: detection and correction of occult hypoperfusion
within 24 hours improves outcome from major trauma.
J Trauma.
1999;
47
964-969
37
Hardy JF, De Moerloose P, Samama M..
Massive transfusion and coagulopathy: pathophysiology and implications for clinical
management.
Can J Anaesth.
2004;
51
293-310
38
Hellstern P..
Solvent/detergent–treated plasma: composition, efficacy, and safety.
Curr Opin Hematol.
2004;
11
346-350
39
Chowdhury P, Saayman AG, Paulus U, Findlay GP, Collins PW..
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
40
Ho AM, Dion PW, Cheng CA. et al. .
A mathematical model for fresh frozen plasma transfusion strategies during major trauma
resuscitation with ongoing hemorrhage.
Can J Surg.
2005;
48
470-478
41
Gonzalez EA, Moore FA, Holcomb JB. et al. .
Fresh frozen plasma should be given earlier to patients requiring massive transfusion.
J Trauma.
2007;
62
112-119
42
Kashuk JL, Moore EE, Johnson JL. et al. .
Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood
cells the answer?.
J Trauma.
2008;
65
261-270
43
Sperry JL, Ochoa JB, Gunn SR. et al. .
An FFP:PRBC transfusion ratio >/=1:1.5 is associated with a lower risk of mortality
after massive transfusion.
J Trauma.
2008;
65
986-993
44 Triulzi DJ.. Transfusion–related acute lung injury: an update. Hematology / the
Education Program of the American Society of Hematology American Society of Hematology. 2006:
497-501
45
Heindl B, Spannagl M..
Frischplasma und Faktorenkonzentrate zur Therapie der perioperativen Koagulopathie:
Was ist bekannt?.
Anaesthesist.
2006;
55
928-936
46
Danes AF, Cuenca LG, Bueno SR, Mendarte L Barrenechea, Ronsano JB..
Efficacy and tolerability of human fibrinogen concentrate administration to patients
with acquired fibrinogen deficiency and active or in high–risk severe bleeding.
Vox Sang.
2008;
94
221-226
47
Key NS, Negrier C..
Coagulation factor concentrates: past, present, and future.
Lancet.
2007;
370
439-448
48
Lampl L, Seifried E, Tisch M. et al. .
(Hemostatic disorders following polytrauma – the role of physiologic coagulation inhibitors
during the preclinical phase).
Anasthesiol Intensivmed Notfallmed Schmerzther.
1992;
27
31-36
49
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
50
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
79-85
51
Heindl B, Delorenzo C, Spannagl M..
Hochdosierte Fibrinogengabe zur Akuttherapie von Gerinnungsstörungen bei perioperativer
Massivtransfusion.
Anaesthesist.
2005;
54
787-790
52
Fenger–Eriksen C, Lindberg–Larsen M, Christensen AQ, Ingerslev J, Sorensen B..
Fibrinogen concentrate substitution therapy in patients with massive haemorrhage and
low plasma fibrinogen concentrations.
Br J Anaesth.
2008;
101
769-773
53
Spahn DR, Rossaint R..
Coagulopathy and blood component transfusion in trauma.
Br J Anaesth.
2005;
95
130-139
54
Gottumukkala VN, Sharma SK, Philip J..
Assessing platelet and fibrinogen contribution to clot strength using modified thromboelastography
in pregnant women.
Anesth Analg.
1999;
89
1453-1455
55
Fries D, Innerhofer P, Reif C. et al. .
The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in
vitro model.
Anesth Analg.
2006;
102
347-351
56
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
1194-1200
57
Grundman C, Plesker R, Kusch M. et al. .
Prothrombin overload causes thromboembolic complications in prothrombin complex concentrates:
in vitro and in vivo evidence.
Thromb Haemost.
2005;
94
1338-1339
58
Hellstern P, Halbmayer WM, Kohler M, Seitz R, Muller–Berghaus G..
Prothrombin complex concentrates: indications, contraindications, and risks: a task
force summary.
Thromb Res.
1999;
95
3-6
60
Reed 2nd RL, Ciavarella D, Heimbach DM. et al. .
Prophylactic platelet administration during massive transfusion. A prospective, randomized,
double–blind clinical study.
Ann Surg.
1986;
203
40-48
61
Fergusson DA, Hebert PC, Mazer CD. et al. .
A comparison of aprotinin and lysine analogues in high–risk cardiac surgery.
N Engl J Med.
2008;
358
2319-2331
62
The CRASH–2 Trial Collaborators .
Improving the evidence base for trauma care: progress in the international CRASH–2
trial (the Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage
trial).
PloS Clin Trials.
2006;
27
63
Jámbor C, Görlinger K..
Einsatz von Antifibrinolytika bei Massivtransfusionen.
Anästh Intensivmed.
2007;
48
167-173
64
Mannucci PM..
Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years.
Blood.
1997;
90
2515-2521
65
Burroughs AK, Matthews K, Qadiri M. et al. .
Desmopressin and bleeding time in patients with cirrhosis.
Br Med J (Clin Res Ed).
1985;
291
1377-1381
66
Mannucci PM, Remuzzi G, Pusineri F. et al. .
Deamino–8–D–arginine vasopressin shortens the bleeding time in uremia.
N Engl J Med.
1983;
308
8-12
67
Dilthey G, Dietrich W, Spannagl M, Richter JA..
Influence of desmopressin acetate on homologous blood requirements in cardiac surgical
patients pretreated with aspirin.
J Cardiothorac Vasc Anesth.
1993;
7
425-430
68
Schulman S, Johnsson H..
Heparin, DDAVP and the bleeding time.
Thromb Haemost.
1991;
65
242-244
69
Emeis JJ, van den Eijnden–Schrauwen Y, van den Hoogen CM. et al. .
An endothelial storage granule for tissue–type plasminogen activator.
J Cell Biol.
1997;
139
245-256
70
Eikelboom JW, Bird R, Blythe D. et al. .
Recombinant activated factor VII for the treatment of life–threatening haemorrhage.
Blood Coagul Fibrinolysis.
2003;
14
713-717
71 Bouillon B. et al. .Primary Results of the Efficacy Trial on the Reduction of Mortality
and Ventilator Days of NovoSeven® in Severe Trauma. Presented at the ISICEM 2009,
24–27 March in Brussels.
72
Barletta JF, Ahrens CL, Tyburski JG, Wilson RF..
A review of recombinant factor VII for refractory bleeding in nonhemophilic trauma
patients.
J Trauma.
2005;
58
646-651
73
Boffard KD, Riou B, Warren B. et al. .
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.
2005;
59
8-15
74
Rizoli SB, Boffard KD, Riou B. et al. .
Recombinant activated factor VII as an adjunctive therapy for bleeding control in
severe trauma patients with coagulopathy: subgroup analysis from two randomized trials.
Crit Care.
2006;
10
75
Kluger Y, Riou B, Rossaint R. et al. .
Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain
injury: post hoc analysis of 30 patients from a prospective, randomized, placebo–controlled,
double–blind clinical trial.
Crit Care.
2007;
11
76
O'Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM..
Thromboembolic adverse events after use of recombinant human coagulation factor VIIa.
JAMA.
2006;
295
293-298
77
Sugg RM, Gonzales NR, Matherne DE. et al. .
Myocardial injury in patients with intracerebral hemorrhage treated with recombinant
factor VIIa.
Neurology.
2006;
67
1053-1055
78
Fiedler F..
Rekombinanter Faktor VIIa bei Massivtransfusion: Pro.
Anästh Intensivmed.
2007;
48
174-176
79
Rump G, Frietsch T, Pötzsch B..
Rekombinanter Faktor VIIa bei Massivtransfusionen: Contra.
Anästh Intensivmed.
2007;
48
192-195
80
Martinowitz U, Michaelson M..
Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled
bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.
J Thromb Haemost.
2005;
3
640-648
Dr. med. dr. (MU Budapest) Csilla Jámbor PD Dr. Bernhard Heindl PD Dr. Michael Spannagl Dr. med. Caroline Rolfes Dr. med. Gerhard Klaus Dinges Prof. Dr. med. Thomas Frietsch
Email: csilla.jambor@med.uni-muenchen.de
Email: Bernhard.Heindl@med.uni-muenchen.de
Email: mispannagl@t-online.de
Email: carolinerolfes@gmx.de
Email: Gerhard.Dinges@med.uni-marburg.de
Email: thomas.frietsch@med.uni-marburg.de