Gerinnungsstörungen in der Herzchirurgie

Zusammenfassung

Blutgerinnungsstörungen und Blutungen im Zuge von herzchirurgischen Eingriffen stellen häufige, aber meist gut beherrschbare perioperative Komplikationen dar. Als Ursache für diese Komplikationen gelten auf der einen Seite chirurgisch bedingte Blutungen, wie sie nach Eingriffen am Herzen oder an den abgehenden großen Gefäßen vorkommen können. Auf der anderen Seite werden Gerinnungsstörungen in Zusammenhang mit der Verwendung der Herz-Lungen-Maschine gebracht. Obwohl heutzutage der Einsatz der extrakorporalen Zirkulation als ein sicheres Verfahren gilt, sind die dabei auftretenden Gerinnungsstörungen und die sogenannte systemische Ganzkörperentzündungsreaktion immer noch gravierende Nachteile. Als Gründe für die postoperativen Blutungen nach herzchirurgischen Eingriffen werden Hämodilution, Thrombozytopenie, Thrombozytendysfunktion, eine gesteigerte fibronolytische Aktivität sowie eine verminderte Gerinnungsaktivität genannt. Die Thrombozytendysfunktion während der extrakorporalen Zirkulation dürfte dabei der Hauptgrund für das perioperative Auftreten einer gestörten Hämostase sein. Zusätzlich verstärkt die weitverbreitete Therapie mit ASS die Blutungsneigung von Herzpatienten und erhöht damit die Notwendigkeit homologer Bluttransfusionen nach herzchirurgischen Eingriffen. Basierend auf vorangegangenen Studien kann gesagt werden, daß die Thrombozytenfunktion während des kardiopulmonalen Bypasses reversibel vermindert ist. Diese Dysfunktion ist charakterisiert durch den vorübergehenden Verlust des Glycoprotein-Ib-Rezeptors (GPIb), der Bindungsstelle für den von-Willebrand-Faktor, welcher essentiell für die erste Phase der Hämostase ist. Im folgenden werden die multifaktoriellen Gründe für die perioperativen Blutgerinnungsstörungen bzw. die Blutungsneigung genannt. Außerdem werden Möglichkeiten und Therapieansätze zur Verminderung dieser hämorrhagischen Diathesen aufgezeigt.

Summary

Coagulation defects and haemorrhage caused by cardic surgery are common incidents perioperatively, but they appeare mostly as manageable complications. One reason for these complications is bleeding due to the surgery following interventions on the heart or big vessels. Other reasons are coagulation defects caused by the use of the heart-lung machine. Although today cardiopulmonary bypass can be considered a safe procedure, the postoperative bleeding diathesis and the systemic inflammatory response are still major drawbacks. The postoperative bleeding is attributed to many causes such as haemodilution, thrombocytopenia, platelet dysfunction, increased fibrinolytic activity and decreased clotting activity. Platelet dysfunction during cardiopulmonary bypass may be the most likely cause for the observed disturbed haemostasis perioperatively. Additionally, the increasing usage of aspirin by cardiac patients amplifies blood loss and the consecutive demand for homologous blood products after cardiac surgery. Based on observations in previous studies, it can be suggested that platelet function is reversibly impaired during cardiopulmonary bypass. This dysfunction is characterized by a temporary loss of glycoprotein Ib receptors (GPIb), the binding site for v. Willebrand factor, which is essential for the first phase of haemostasis.

In the following the multiple causes of bleeding diathesis or haemorrhagia after cardiac surgery are described. Additionally, possibilities of therapeutic approaches in reducing coagulation defects will be discussed.

Schlüsselwörter

Gerinnungsstörung - Herzchirurgie - Herz-Lungen-Maschine - Thrombozyten

Keywords

Coagulation defects - cardiac surgery - cardiopulmonary bypass - platelets

• Literatur

• 1 Woodman RC, Harker LA. Bleeding complications associated with cardiopulonary bypass. Blood 1990; 9: 1680-97.
• 2 Gibbon LH. Application of a mechanical heart and lung apparatus in cardiac surgery. Minn Med 1954; 37: 171-85.
• 3 Esposita RA, Culliford AT, Colvin SB, Thomas SJ, Lackner H, Spencer FC. The role of the activated clotting time in heparin administration and neutralization for cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983; 85: 174-85.
• 4 Hung TC, Hochmuth RM, Joist JH, Sutera SP. Shear-induced aggregation and lysis of platelets. Trans Am Soc Artif Int Organs 1976; 22: 285-91.
• 5 Brown CH, Lemuth RF, Hellums JD, Leverett J, Alfrey CP. Response of human platelets to shear stress. ASAIO Transactions 1975; 21: 35-8.
• 6 Didisheim P, Tirrell MV, Lyons CS. et al. Relative role of surface chemistry and surface texture in blood-material interactions. ASAIO Transactions 1983; 29: 169-76.
• 7 Kroll MH, Schafer AI. Biomechanical mechanism of platelet activation. Blood 1989; 74: 1181-95.
• 8 Mohr R, Golan M, Martinowitz U, Rosner E, Goor DA, Ramot B. Effect of cardiac operation on platelets. J Thorac Cardiovasc Surg 1986; 92: 434-41.
• 9 Hsu LC. Principles of heparin-coating techniques. Perfusion 1991; 6: 209-19.
• 10 Boonstra PW, Gu YJ, Akkerman C, Haan J, Huyzen R, van Oeveren W. Heparin coating of an extracorporeal circuit partly improves hemostasis after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994; 107: 289.
• 11 Zilla P, Fasol R, Groscurth P, Klepetko W, Reichenspurner H, Wolner E. Blood platelets in cardiopulmonary bypass operations. Recovery occurs after initial stimulation, rather than continual activation. J Thorac Cardiovasc Surg 1989; 97: 379.
• 12 Heimark RL, Kurachi K, Fujikawa K, Davie EW. Surface activation of blood coagulation, fibrinolysis and kinin formation. Nature 1980; 286: 456-60.
• 13 Mannhalter C, Baumgartner-Parzer S. Interaktion von Plasmaproteinen mit künstlichen Oberflächen. In: Thrombophilie und Antikoagulation. Tilsner V, Matthias FR. (Hrsg). Basel: Editiones »Roche«; 1994
• 14 Khuri SF, Wolfs JA, Josa M. et al. Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and non-surgical blood loss. J Thorac Cardiovasc Surg 1992; 104: 94-107.
• 15 Stibbe J, Kluft C, Brommer EJP, Gomes M. et al. Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984; 14: 375-82.
• 16 Müller-Berghaus G. Pathophysiologic and biochemical events in dissiminated intravascular coagulation: Dysregulation of procoagulant and anticoagulant pathways. Sem Thromb Hemostas 1989; 15: 58-87.
• 17 Tschaut RJ. (ed) Extracorporale Zirkulation in Theorie und Praxis. Lengerich, Berlin, Düsseldorf, Wien, Zagreb: Pabst; 1999
• 18 Sinclair DG, Haslam PL, Quinlan GJ, Pepper JR, Evans TW. The effects of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability. Chest 1995; 108: 718-24.
• 19 Fosse E, Moen O, Johnson E, Semb G, Brockmeier V, Mollnes TE, Fagerhol MK, Venge P. Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1994; 58: 472-7.
• 20 Westaby S. Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit. Intensiv Care Med 1987; 13: 89-95.
• 21 Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass. Evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 1981; 304: 497-503.
• 22 von Segesser LK, Weiss BM, Pasic M, Leskosek B, von Felten A, Pei P, Turina M. Experimental evaluation of heparin-coated cardiopulmonary bypass equipment with low systemic heparinization and high-dose aprotinin. Thorac Cardiovasc Surgeon 1991; 39: 251-6.
• 23 Moore FD, Warner KG, Assousa S, Valeri CR, Khuri SF. The effects of complement activation during cardiopulmonary bypass. Attenuation by hypothermia, heparin and hemodilution. Ann Surg 1988; 208: 95-103.
• 24 Sakakibara T, Ida T, Mannouji E, Kikuchi T. et al. Posttransfusion graft-versus-host disease following open heart surgery. Report of six cases. J Cardiovasc Surg 1989; 30: 687-91.
• 25 Gombotz H, Rigler B, Matzer Ch, Metzler H, Winkler G, Tscheliessnigg KH. 10 Jahre Herzoperationen bei Zeugen Jehovas. Anästhesist 1989; 38: 585-90.
• 26 Pötzsch B, Madlener K, Seelig C, Riess CF, Greinacher A, Müller-Berghaus G. Monitoring of r-Hirudin Anticoagulation during Cardiopulmonary Bypass – Assessment of the Whole Blood Ecarin Clotting Time. Thromb Haemost 1997; 5: 920-5.
• 27 Nowak G, Bucha E. A new method for the therapeutical monitoring of hirudin. Thromb Haemost 1993; 69: 1306 (abstract).
• 28 Fish KJ, Sarnquist FH, van Steennis C, Mitchell RS, Hilberman M, Jamieson SW, Linet OI, Miller DC. A prospective randomized study of the effects of prostacyclin on platelets and bloodloss during coronary bypass operations. J Thorac Cardiovasc Surg 1986; 91: 436.
• 29 Blauth C, Brady A, Brannan J, Schulenburg WE, Frackowiak R, Taylor KM. A double blind clinical trial of Iloprost during cardiopulmonary bypass. Perfusion 1987; 2: 271.
• 30 Horrow JC, Hlavacek J, Strong MD. et al. Prophylactic tranexamic acid decreases bleeding after cardiac operations. J Thorac Cardiovasc Surg 1990; 99: 24.
• 31 Van der Salm TJ, Ansell JE, Okike ON. et al. The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: a double blind randomized study. J Thorac Cardiovasc Surg 1988; 95: 32.
• 32 Oeveren van W, Jansen NJG, Bidstrup BP, Royston D, Westaby S, Neuhof H, Wildevuur ChRH. Effects of aprotinin on haemostativ mechanism during cardio-pulmonary bypass. Ann Thorac Surgery 1987; 44: 134.
• 33 Havel M, Teufelsbauer H, Knöbl P. et al. Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation. J Thorac Cardiovasc Surg 1991; 101: 922.
• 34 Fremes SE, Wong BI, Lee E. et al. Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding. Ann Thorac Surg 1994; 58: 1580-8.
• 35 Levy JH, Bailey JM, Salmenpera M. Pharmacokinetics of aprotinin in preoperative cardiac surgical patients. Anesthesiology 1994; 80: 1013-8.
• 36 Diefenbach C, Abel M, Limpers B. et al. Fatal anaphylactic shock after aprotinin reexposure in cardiac surgery. Anesth Analg 1995; 80: 830-1.
• 37 De Haan J, Schönberger J, Haan J, van Oeveren W, Eijgelaar A. Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass. J Thoracic Cardiovasc Surg 1993; 106: 1017-23.
• 38 Singer RL, Mannion JD, Bauer TL, Armenti FR, Edie RN. Complications from heparin-induced thrombocytopenia in patients undergoing cardiopulmonary bypass. Chest 1993; 104: 1436-40.
• 39 Benetti FJ, Ballester C. Use of thoracoscopy and a minimal thoracotomy, in mammarycoronary bypass to left anterior descending artery, without extracorporeal circulation. J Cardiovasc Surg 1995; 36: 159-61.