Erworbene Gerinnungsstörungen in der Intensivmedizin

Störungen der Gerinnungsfunktion sind in der Intensivmedizin bei vielen Patienten zu beobachten. Dabei liegen diesen Gerinnungsstörungen nur selten angeborene hämatologische oder hämostaseologische Erkrankungen zugrunde. Dieser Übersichtsartikel beschäftigt sich mit erworbenen Gerinnungsstörungen in der Intensivmedizin.

Kernaussagen

• Zu den klinisch wichtigsten erworbenen Gerinnungsstörungen in der Intensivmedizin zählen:

  • die Verlust- und Dilutionskoagulopathie

  • die Trauma-induzierte Koagulopathie

  • die disseminierte intravasale Gerinnung und Verbrauchskoagulopathie, insbesondere die Sepsis-induzierte Koagulopathie

  • die Heparin-induzierte Thrombopenie Typ II

  • die Koagulopathie bei Leberinsuffizienz

• Für eine zielgerichtete Therapie der genannten Gerinnungsstörungen ist das Verständnis der pathophysiologischen Hämostasestörung notwendig.

• Das dynamische Geschehen vieler Gerinnungsstörungen mit äußerst unterschiedlichen klinischen Ausprägungen wird nur durch engmaschige Gerinnungstests, idealerweise mit Point-of-Care-Verfahren, erfasst.

• Eine „blinde“ Therapie mit Substraten und Faktoren der Gerinnung kann nicht nur zu unnötigen und kostenintensiven, sondern auch risikoreichen Substitutionen führen.

Schlüsselwörter

disseminierte intravasale Gerinnung - Koagulopathie - erworbenes von-Willebrand‐Syndrom - Blutungsrisiko - thromboembolische Komplikation - Hämostasestörung

Publication History

Article published online:
04 June 2024

• Literatur

• 1 Das Gerinnungskompendium. Barthels M. 2. Stuttgart: Thieme; 2013
• 2 Physiologie des Menschen: mit Pathophysiologie. Schmidt RF, Lang F. 30. Heidelberg: Springer; 2007
• 3 Valeri CR, Cassidy G, Pivacek LE. et al. Anemia-induced increase in the bleeding time: implications for treatment of nonsurgical blood loss. Transfusion 2001; 41: 977-983 DOI: 10.1046/j.1537-2995.2001.41080977.x. (PMID: 11493727)
• 4 Escolar G, Garrido M, Mazzara R. et al. Experimental basis for the use of red cell transfusion in the management of anemic thrombocytopenic patients. Transfusion 1988; 28: 406-411 DOI: 10.1046/j.1537-2995.1988.28588337325.x. (PMID: 3420667)
• 5 Deutsche Gesellschaft für Unfallchirurgie e. V.. S3-Leitlinie Polytrauma/Schwerverletzten-Behandlung. AWMF-Registernummer 187–023. Version 4.0. 31.12.2022 Accessed March 28, 2024 at: https://register.awmf.org/de/leitlinien/detail/187–023
• 6 Kietaibl S, Ahmed A, Afshari A. et al. Management of severe peri-operative bleeding: guidelines from the European Society of Anaesthesiology and Intensive Care. Second update 2022. Eur J Anaesth 2023; 40: 226-304 DOI: 10.1097/EJA.0000000000001803. (PMID: 36855941)
• 7 Innerhofer P, Fries D, Margreiter J. et al. The effects of perioperatively administered colloids and crystalloids on primary platelet-mediated hemostasis and clot formation. Anesth Analg 2002; 95: 858-865 DOI: 10.1097/00000539-200210000-00012. (PMID: 12351257)
• 8 Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg 2012; 73: 60-66 DOI: 10.1097/TA.0b013e31825b5c10. (PMID: 22743373)
• 9 Innerhofer P, Fries D, Mittermayr M. et al. Reversal of trauma- induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open- label, randomised trial. Lancet Haematol 2017; 4: e258-e271 DOI: 10.1016/S2352-3026(17)30077-7. (PMID: 28457980)
• 10 Rossaint R, Afshari A, Bouillon B. et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care 2023; 27: 80 DOI: 10.1186/s13054-023-04327-7. (PMID: 36859355)
• 11 Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360-365 DOI: 10.1097/00000539-199508000-00026. (PMID: 7542432)
• 12 Innerhofer N, Treichl B, Rugg C. et al. First-line administration of fibrinogen concentrate in the bleeding trauma patient: searching for effective dosages and optimal post-treatment levels limiting massive transfusion-further results of the RETIC study. J Clin Med 2021; 10: 3930 DOI: 10.3390/jcm10173930. (PMID: 34501379)
• 13 Görlinger K, Dirkmann D, Weber CF. et al. Algorithmen in der Hämotherapie. Anästh Intensivmed 2011; 52: 98-159
• 14 Danés AF, Cuenca LG, Bueno SR. et al. 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 DOI: 10.1111/j.1423-0410.2007.01024.x. (PMID: 18179679)
• 15 Wray JP, Bridwell RE, Schauer SG. et al. The diamond of death: Hypocalcemia in trauma and resuscitation. Am J Emerg Med 2021; 41: 104-109 DOI: 10.1016/j.ajem.2020.12.065. (PMID: 33421674)
• 16 Bundesärztekammer. Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten –Gesamtnovelle 2020. Accessed March 28, 2024 at: https://www.bundesaerztekammer.de/fileadmin/user_upload/_old-files/downloads/pdf-Ordner/MuE/Querschnitts-Leitlinien_BAEK_zur_Therapie_mit_Blutkomponenten_und_Plasmaderivaten-Gesamtnovelle_2020.pdf
• 17 Lier H, Krep H, Schöchl H. Gerinnungsmanagement bei der Polytraumaversorgung. Anaesthesist 2009; 58: 1010-1026 DOI: 10.1007/s00101-009-1595-z. (PMID: 19816662)
• 18 Ditzel jr. RM, Anderson JL, Eisenhart WJ. et al. A review of transfusion- and trauma-induced hypocalcemia: is it time to change the lethal triad to the lethal diamond?. J Trauma Acute Care Surg 2020; 88: 434-439 DOI: 10.1097/TA0000000000002570. (PMID: 31876689)
• 19 Moore EE, Moore HB, Kornblith LZ. et al. traumainduced coagulopathy. Nat Rev Dis Primers 2021; 7: 30 DOI: 10.1038/s41572-021-00264-3. (PMID: 33927200)
• 20 Duque P, Calvo A, Lockie C. et al. Pathophysiology of trauma-induced coagulopathy. Transfus Med Rev 2021; 35: 80-86 DOI: 10.1016/j.tmrv.2021.07.004. (PMID: 34610877)
• 21 Moore HB, Gando S, Iba T. et al. Defining trauma-induced coagulopathy with respect to future implications for patient management: communication from the SSC of the ISTH. J Thromb Haemost 2020; 18: 740-747 DOI: 10.1111/jth.14690. (PMID: 32112533)
• 22 Roberts I, Shakur H, Afolabi A. CRASH-2 collaborators. 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 DOI: 10.1016/S0140-6736(11)60278-X. (PMID: 21439633)
• 23 Lester ELW, Fox EE, Holcomb JB. et al. The impact of hypothermia on outcomes in massively transfused patients. J Trauma Acute Care Surg 2019; 86: 458-463 DOI: 10.1097/TA.0000000000002144. (PMID: 30444856)
• 24 Reynolds BR, Forsythe RM, Harbrecht BG. et al. Hypothermia in massive transfusion: have we been paying enough attention to it?. J Trauma Acute Care Surg 2012; 73: 486-491 (PMID: 11816725)
• 25 De Robertis E, Kozek-Langenecker SA, Tufano R. et al. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding. Minerva Anestesiol 2015; 81: 65-75 (PMID: 24608516)
• 26 Taylor jr. FB, Toh CH, Hoots WK. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86: 1327-1330 (PMID: 11816725)
• 27 Levi M, van der Poll T. A short contemporary history of disseminated intravascular coagulation. Semin Thromb Hemost 2014; 40: 874-880 DOI: 10.1055/s-0034-1395155. (PMID: 25377321)
• 28 Thachil J. Disseminated intravascular coagulation: a practical approach. Anesthesiology 2016; 125: 230-236 DOI: 10.1097/ALN0000000000001123. (PMID: 27031011)
• 29 Toshiaki I, Jerrold HL. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Anesthesiology 2020; 132: 1238-1245 DOI: 10.1097/ALN.0000000000003122. (PMID: 32044801)
• 30 Tsantes AG, Parastatidou S, Tsantes EA. et al. Sepsis-induced coagulopathy: an update on pathophysiology, biomarkers, and current guidelines. Life (Basel) 2023; 13: 350 DOI: 10.3390/life13020350. (PMID: 36836706)
• 31 Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol 2021; 113: 45-57 DOI: 10.1007/s12185-020-03029-y. (PMID: 33161508)
• 32 Franchini M. Haemostasis and pregnancy. Thromb Haemost 2006; 95: 401-413 DOI: 10.1160/TH05-11-0753. (PMID: 16525566)
• 33 Erez O, Mastrolia SA, Thachil J. Disseminated intravascular coagulation in pregnancy: insights in pathophysiology, diagnosis and management. Am J Obstet Gynecol 2015; 213: 452-463 DOI: 10.1016/j.ajog.2015.03.054. (PMID: 25840271)
• 34 Adelborg K, Larsen JB, Hvas AM. Disseminated intravascular coagulation: epidemiology, biomarkers, and management. Br J Haematol 2021; 192: 803-818 DOI: 10.1111/bjh.17172. (PMID: 33555051)
• 35 Sakuragawa N, Hasegawa H, Maki M. et al. Clinical evaluation of low-molecular-weight heparin (FR-860) on disseminated intravascular coagulation (DIC)—A multicenter co-operative double-blind trial in comparison with heparin. Thromb Res 1993; 72: 475-500 DOI: 10.1016/0049-3848(93)90109-2. (PMID: 8128454)
• 36 Thachil J. Disseminated intravascular coagulation: a practical approach. Anesthesiology 2016; 125: 230-236 DOI: 10.1097/ALN0000000000001123. (PMID: 27031011)
• 37 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 DOI: 10.1001/jama.286.15.1869. (PMID: 11597289)
• 38 Papageorgiou C, Jourdi G, Adjambri E. et al. Disseminated intravascular coagulation: an update on pathogenesis, diagnosis, and therapeutic strategies. Clin Appl Thromb Hemost 2018; 24 (Suppl. 9) 8S-28S DOI: 10.1177/1076029618806424. (PMID: 30296833)
• 39 WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 2017; 389: 2105-2116 DOI: 10.1016/S0140-6736(17)30638-4. (PMID: 28456509)
• 40 East JM, Cserti-Gazdewich CM, Granton JT. Heparin-induced thrombocytopenia in the critically Ill patient. Chest 2018; 154: 678-690 DOI: 10.1016/j.chest.2017.11.039. (PMID: 29253554)
• 41 Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Semin Thromb Hemost 2015; 41: 49-60 DOI: 10.1055/s-0034-1398381. (PMID: 25590528)
• 42 Fiorenza MA, Frazee EN, Personett HA. et al. Assessment of a modified 4T scoring system for heparin-induced thrombocytopenia in critically ill patients. J Crit Care 2014; 29: 426-431 DOI: 10.1016/j.jcrc.2013.12.010. (PMID: 24462656)
• 43 Wiegele M, Gütl M, Heil S. et al. Empfehlung der Arbeitsgruppe Perioperative Gerinnung der ÖGARI zum Thema: Heparin-induzierte Thrombozytopenie Typ 2 (HIT II) Version 1.1 vom 11.08.2019, Gültigkeit bis 31.12.2021. Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin Accessed February 24, 2024 at: https://www.oegari.at/web_files/cms_daten/agpg-heparin_induzierte_thrombozytopenie_typ2–2019-v1_1.pdf
• 44 Stravitz RT, Lisman T. Rebalanced hemostasis in patients with acute liver failure. Semin Thromb Hemost 2015; 41: 468-473 DOI: 10.1055/s-0035-1550430. (PMID: 26049071)
• 45 Metze M, Petros S. Spezielles Blutungsmanagement bei Lebererkrankungen. In: Eckart J, Forst H, Briegel J. Intensivmedizin. Kompendium und Repetitorium zur interdisziplinären Weiter- und Fortbildung. 85. Erg.-Lfg.. Landsberg am Lech: Ecomed; 2018. Kap. V – 6.2 1-33
• 46 Tripodi A, Salerno F, Chantarangkul V. et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41: 553-558 DOI: 10.1002/hep.20569. (PMID: 15726661)
• 47 Nadim MK, Durand F, Kellum JA. et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 2016; 64: 717-735 DOI: 10.1016/j.jhep.2015.10.019.
• 48 Götz M, Biecker E, Dechêne A. et al. Addendum zur S2k-Leitlinie Gastrointestinale Blutungen der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). Z Gastroenterol 2022; 60: 1139-1145 DOI: 10.1055/a-1788-3501.
• 49 Ribic C, Crowther M. Thrombosis and anticoagulation in the setting of renal or liver disease. Hematology Am Soc Hematol Educ Program 2016; 2016: 188-195 DOI: 10.1182/asheducation-2016.1.188. (PMID: 27913479)
• 50 Horiuchi H, Doman T, Kokame K. et al. Acquired von Willebrand syndrome associated with cardiovascular diseases. J Atheroscler Thromb 2019; 26: 303-314 DOI: 10.5551/jat.RV17031.
• 51 Crow S, Chen D, Milano C. et al. Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. Ann Thorac Surg 2010; 90: 1263-1269 DOI: 10.1016/j.athoracsur.2010.04.099. (PMID: 20868825)
• 52 Tiede A, Rand JH, Budde U. et al. How I treat the acquired von Willebrand syndrome. Blood 2011; 117: 6777-6785 DOI: 10.1182/blood-2010-11-297580. (PMID: 21540459)