Gerinnungsprobleme in der Intensivmedizin

Störungen des Gerinnungssystems und konsekutive hämorrhagische oder thromboembolische Komplikationen sind in der Intensivmedizin ebenso häufige wie ernsthafte Probleme. Ihre frühzeitige Erkennung, korrekte diagnostische Einordnung und gezielte Behandlung sind entscheidende Faktoren für das Outcome.

Kernaussagen

• Häufige Ursachen einer Gerinnungsstörung im klinischen Alltag sind die Antikoagulation und die Thrombozytenhemmung. Ebenfalls nicht selten ist sie Folge einer Erkrankung, u. a. Leber- und Nierenerkrankungen, hämatologische Erkrankungen oder ein Schock.

• Die „Lethal Triade“ (Hypothermie, Azidose, Koagulopathie) führt zu einer Gerinnungsstörung, die chirurgische Maßnahmen, eine hämostaseologische Substitution und eine kardiozirkulatorische Stabilisierung erfordert.

• Das Auftreten diffuser Blutungen ist das wichtigste Leitsymptom einer akuten Koagulopathie.

• Quick und PTT sind schnell und überall verfügbare Globaltests der Gerinnung. Wegen der unterschiedlichen Empfindlichkeit für direkte orale Antikoagulanzien (DOAK) büßen diese Globaltests eine breite diagnostische Aussagekraft aber zusehends ein.

• Therapie der Wahl bei akuter, massiver Blutung ist neben Massivtransfusionen eine frühzeitig Substitution von Fibrinogen und Thrombozyten.

• Klinisch eindeutige Zeichen einer DIC bei Sepsis sind Hautnekrosen und digitale Nekrosen an Händen und Füßen, seltener auch von Ohren, Nase und Mamillen. Der Kern der Therapie einer septischen DIC ist die Antikoagulation mit Heparin (UFH oder NMH).

• Vor allem Autoantikörper gegen die Faktoren des intrinsischen Systems – am häufigsten Faktor VIII (Hemmkörper-Hämophilie), seltener auch gegen Faktor IX und XI – können zu schweren Blutungskomplikationen führen. Diagnostik und Therapie dieser erworbenen Blutungsneigung sind jedoch außerordentlich aufwendig.

• Literatur

• 1 Hoffman M, Monroe 3rd DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-965
• 2 Krumrei NJ, Park MS, Cotton BA. et al. Comparison of massive blood transfusion predictive models in the rural setting. Journal of Trauma and Acute Care Surgery 2012; 72: 211-215
• 3 Nunez TC, Voskresensky IV, Dossett LA. et al. Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)?. Journal of Trauma 2009; 66: 346-352
• 4 Yucel N, Lefering R, Maegele M. et al. Trauma Associated Severe Hemorrhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma. Journal of Trauma 2006; 60: 1228-1236 ; discussion 1236–1227
• 5 McLaughlin DF, Niles SE, Salinas J. et al. A predictive model for massive transfusion in combat casualty patients. Journal of Trauma 2008; 64: S57-63 ; d63
• 6 Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet 2000; 356: 1318-1321
• 7 Subherwal S, Bach RG, Chen AY. et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation 2009; 119: 1873-1882
• 8 Levine GN, Bates ER, Bittl JA. et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. Circulation 2016;
• 9 Kirchhof P, Benussi S, Kotecha D. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;
• 10 Pisters R, Lane DA, Nieuwlaat R. et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093-1100
• 11 O'Brien EC, Simon DN, Thomas LE. et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J 2015;
• 12 Hijazi Z, Oldgren J, Lindback J. et al. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 2016; 387: 2302-2311
• 13 Müller MC, Meijers JC, Vroom MB. et al. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care 2014; 18: R30
• 14 Young T, Tang H, Hughes R. Vena caval filters for the prevention of pulmonary embolism. Im Internet: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006212.pub4/abstract
• 15 Douketis JD, Spyropoulos AC, Spencer FA. et al. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest 2012; 141: e326S-e350S
• 16 Korte W, Cattaneo M, Chassot PG. et al. Peri-operative management of antiplatelet therapy in patients with coronary artery disease. Thromb Haemost 2011; 105: 743-749
• 17 Falck-Ytter Y, Francis CW, Johanson NA. et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy and prevention of thrombosis: american college of chest physicians evidence-based clinical practice guidelines. Chest 2012; 141: e278S-e325S
• 18 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest 2012; 141: e195S-e226S
• 19 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; 5: 266-273
• 20 Schlembach D, Mortl MG, Girard T. et al. Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland). Anaesthesist 2014; 63: 234-242
• 21 Kozek-Langenecker S, Sorensen B, Hess JR. et al. Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review. Crit Care 2011; 15: R239
• 22 Estcourt LJ, Stanworth SJ, Doree C. et al. Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database Syst Rev 2015; 11: CD010983
• 23 Maegele M, Schochl H, Cohen MJ. An update on the coagulopathy of trauma. Shock 2014; 41 (Suppl. 01) 21-25
• 24 Davenport RA, Brohi K. Coagulopathy in trauma patients: importance of thrombocyte function?. Curr Opin Anaesthesiol 2009; 22: 261-266
• 25 Besser MW, Ortmann E, Klein AA. Haemostatic management of cardiac surgical haemorrhage. Anesthesia 2015; 70 (Suppl. 01) 87-95
• 26 Thachil J. Disseminated Intravascular Coagulation: A Practical Approach. Anesthesiology 2016;
• 27 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
• 28 Spahn DR, Bouillon B, Cerny V. et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 2013; 17: R76
• 29 Moore HB, Moore EE, Liras IN. et al. Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients. J Am Coll Surg 2016; 222: 347-355
• 30 Warren BL, Eid A, Singer P. et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286: 1869-1878
• 31 Gando S, Saitoh D, Ishikura H. et al. A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis. Crit Care 2013; 17: R297
• 32 Eichacker PQ, Natanson C, Danner RL. Surviving sepsis – practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med 2006; 355: 1640-1642
• 33 Marti-Carvajal AJ, Sola I, Gluud C. et al. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. Cochrane Database Syst Rev 2012; 12: CD004388
• 34 Yamakawa K, Aihara M, Ogura H. et al. Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis. J Thromb Haemost 2015; 13: 508-519
• 35 Dickneite G, Herwald H, Korte W. et al. Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions. Thromb Haemost 2015; 113: 686-697
• 36 Weber CF, Sanders JO, Friedrich K. et al. Stellenwert der Thrombelastometrie für das Monitoring von Faktor XIII. Prospektive Observationsstudie bei neurochirurgischen Patienten. Hämostaseologie 2011; 31: 111-117
• 37 Wettstein P, Haeberli A, Stutz M. et al. Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding. Anesth Analg 2004; 99: 1564-1569
• 38 Godje O, Gallmeier U, Schelian M. et al. Coagulation factor XIII reduces postoperative bleeding after coronary surgery with extracorporeal circulation. Thorac Cardiovasc Surg 2006; 54: 26-33
• 39 Karkouti K, von Heymann C, Jespersen CM. et al. Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: a randomized, placebo-controlled, multicenter clinical trial. J Thorac Cardiovasc Surg 2013; 146: 927-939
• 40 Tengborn L, Baudo F, Huth-Kuhne A. et al. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG 2012; 119: 1529-1537
• 41 Stemberger M, Mohnle P, Tschop J. et al. Successful bleeding control with recombinant porcine factor VIII in reduced loading doses in two patients with acquired haemophilia A and failure of bypassing agent therapy. Haemophilia 2016; 22: e472-474
• 42 Zipfel PF, Wolf G, John U. et al. Novel developments in thrombotic microangiopathies: is there a common link between hemolytic uremic syndrome and thrombotic thrombocytic purpura?. Pediatr Nephrol 2011; 26: 1947-1956
• 43 Wurzner R, Riedl M, Rosales A. et al. Treatment of enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome (eHUS). Semin Thromb Hemost 2014; 40: 508-516
• 44 Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood 2015; 125: 3860-3867