Perioperative management of coagulation

Summary

Guidelines of official societies for diagnosis and therapy of intraoperatively occurring hypocoagulability rely mainly on data of patients receiving whole blood transfusions. They recommend -provided that laboratory evaluation shows deficiency (values >1.5 fold normal)- administration of fresh frozen plasma, cryoprecipitate and platelet concentrates (platelet count <50 000 or <100 000/μl).

This article describes the pathogenesis of coagulopathy in the light of the special intraoperative setting, emphasizes recent changes of blood component preparation, transfusion triggers, effects of volume therapy and challenges standard laboratory assays as reliable guide for intraoperative hemostatic therapy. The role of thrombelastographic monitoring is discussed as well as an alternative strategy to compensate deficiencies by the use of coagulation factor concentrates instead of or in addition to transfusion of FFP, a new concept which is illustrated by the presentation of an actual case report.

Keywords

Haemostasis - laboratory testing - PT - aPTT - fibrinogen - haemorrhage - volume therapy - thrombelastography/ thrombelastometry - TEG - ROTEM

• References

• 1 Allen GA, Wolberg AS, Oliver JA. et al. Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system. J Thromb Haemost 2004; 2: 402-13.
• 2 American Society of Anesthesiologists Task Force on Blood Component Therapy.. Practice guidelines for blood component therapy. Anaesthesiology 1996; 84: 732-47.
• 3 Erber WN. Massive blood transfusion in the elective surgical setting. Transfus Apher Science 2002; 27: 83-92.
• 4 Brecher ME, Monk T, Goodnough LT. A standardized method for calculating blood loss. Transfusion 1997; 37: 1070-4.
• 5 British Committee for standards in haematology, blood transfusion task force.. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. British J Haematol 2004; 126: 11-28.
• 6 Burns ER, Goldberg SN, Wenz B. Paradoxic effect of multiple mild coagulation factor deficiencies on the prothrombin time and activated partial thromboplastin time. Am J Clin Pathol 1993; 100: 94-8.
• 7 Cammerer U, Dietrich W, Rampf T. et al. The predictive value of modified computerized thrombelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 2003; 96: 51-7.
• 8 Chandler WL, Patel MA, Gravelle L. et al. Factor XIIIA and clot strength after cardiopulmonary bypass. Blood Coag Fibrinol 2001; 12: 101-8.
• 9 Chau TN, Chan YW, Patch D. et al. Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding. Gut 1998; 43: 267-71.
• 10 Chowdhury P, Saayman A, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Brit J Haematol 2004; 125: 69-73.
• 11 Ciavarella D, Reed RL, Counts RB. et al. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Brit J Haematol 1987; 67: 365-8.
• 12 Counts RB, Haisch C, Simon TL. et al. Hemostasis in massively transfused trauma patients. Ann Surg 1979; 190: 91-9.
• 13 Dara SI, Rana R, Afessa B. Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med 2005; 33: 2667-71.
• 14 Davidson SJ, Burman JF, Philips SM. et al. Correlation between thrombin potential and bleeding after cardiac surgery. Blood Coagul Fibrinol 2003; 14: 175-9.
• 15 De Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation : a comparative review. Crit Care Med 2001; 29: 1261-7.
• 16 Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rev Rep 2004; 3: 324-30.
• 17 Fenger-Eriksen C, Anker-Moller E, Heslop J. et al. Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate. Br J Anaesth 2005; 94: 324-9.
• 18 Fries D, Haas T, Velik-Salchner C. et al. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy, a porcine model. Br J Anaesth. 2006 (in Review).
• 19 Fries D, Innerhofer P, Klingler A. et al. The effect of the combined administration of colloids and lactated Ringer’s solution on the coagulation system: an in vitro study using thrombelastograph coagulation analysis. Anesth Analg 2002; 94: 1280-7.
• 20 Fries D, Innerhofer P, Reif C. et al. The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model. Anest Analg 2006; 102: 347-51.
• 21 Fries D, Krimer A, Klingler A. et al. Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. Br J Anaesth 2005; 95: 172-7.
• 22 Gajic O, Rana R, Mendez JL. et al. Acute lung injury after blood transfusion in mechanically ventilated patients. Transfusion 2004; 44: 1468-74.
• 23 Garrioch MA. The body’s response to blood loss. Vox Sang 2004; (Suppl1) 87 S74-76.
• 24 Gerlach R, Tölle F, Raabe A. et al. Increased risk for postoperative hemorrhage after intracranial surgery in patients with decreased factor XIII activity. Implications of a prospective study. Stroke 2002; 33: 1618-23.
• 25 Girulami A, Randi ML, Gavasso S. et al. The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probably due to associated risk factors: a study of prevalence in 21 patients and a review of the literature. J Thromb Thrombol 2004; 17: 139-43.
• 26 Gottumukkala VN, Sharma SK, Philip J. Assessing platelet and fibrinogen contribution to clot strength using modified thrombelastography in pregnant women. AnesthAnalg 1999; 89: 1453-5.
• 27 Greinacher A, Warketin TE. Recognition, treatment, and prevention of heparin-induced thrombocytopenia: Review and update. Thromb Res. 2005 Aug 31 (epub ahead of print).
• 28 Gurbel PA, Bliden KP, Gyer K. et al. Platelet reactivity in patients and recurrent events post-stenting. J Am Coll Cardiol 2005; 46: 1820-6.
• 29 Hardy JF, Moerloose P, Samama M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anesth 2004; 51: 293-310.
• 30 Harrison P. The role of PFA-100 testing in the investigation and management of haemostatic defects in children and adults. Br J Haematol 2005; 130: 3-10.
• 31 Hartert H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschrift 1948; 26: 577-83.
• 32 Hedin A, Hahn R. Volume expansion and plasma protein clearance during intravenous infusion of 5% albumin and autologous plasme. Clin Science 2005; 108: 217-24.
• 33 Hellstern P, Haubelt H. Indications for plasma transfusion. Thromb Res 2002; 107: 19-22.
• 34 Hippala S, Myllyä HJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360-5.
• 35 Hippala ST. Dextran and hydroxyethyl starch interfere with fibrinogen assays. Blood Coag Fibrinol 1995; 6: 743-6.
• 36 Hirshberg A, Dugas M, Banez EI. et al. Minimizing dilutional coagulopathy in exsanguinating hemorrhage : A computer simulation. J Trauma 2003; 54: 454-63.
• 37 Ho AM, Karmakar MK, Dion PW. Are we giving enough coagulation factors during major trauma resuscitation ?. Am J Surg 2005; 190: 479-84.
• 38 Horsey PJ. Multiple trauma and massive transfusion. Anaesthesia 1997; 52: 1027-29.
• 39 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: 858-65.
• 40 Iwata H, Kaibara M, Dohmae N. et al. Purification, identification, and characterization of elastase on erythrocyte membrane as factor IX-activating enzyme. Biochem Biophys Res Comm 2004; 316: 65-70.
• 41 Karkouti K, Wijeysundera DN, Yau TM. et al. The independent association of massive blood loss with mortality in cardiac surgery. Transfusion 2004; 44: 1453-62.
• 42 Kitchens CS, Alving BM, Kessler CM. Consultative Hemostasis and Thrombosis. Philadelphia: W. B. Saunders, Elsevier Science; 2002: 27-36.
• 43 Kitchens CS. To bleed or not to bleed? is that the question for PTT. J Thromb Haemost 2005; 3: 2607-11.
• 44 Koscielny J, Ziemer S, Radtke H. et al. A practical concept for preoperative identification of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10: 195-204.
• 45 Kushimoto S. Implications of excessive fibrinolysis and α-plasmin inhibitor deficiency in patients with severe head injury. Neurosurgery 2001; 49: 1084-90.
• 46 Lang T, Bauters A, Braun SL. et al. Multi-centre investigation on reference ranges for ROTEM thrombelastometry. Blood Coagul Fibrinol 2005; 16: 301-10.
• 47 Levi M, Peters M, Büller HR. Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: A systematic review. Crit Care Med 2005; 33: 883-90.
• 48 Lucas CE, Ledgerwood AM, Saxe JM. et al. Plasma supplementation is beneficial for coagulation during severe hemorrhagic shock. Am J Surg 1996; 171: 399-404.
• 49 Luddington RJ. Thrombelastography/thrombelastometry. Clin Lab Haematol 2005; 27: 81-90.
• 50 MacLeod JB, Lynn M, McKenney MG. et al. Early coagulopathy predicts mortality in trauma. J Trauma 2003; 55: 39-44.
• 51 Mallett SV, Cox DJ. Thrombelastography. Br J Anaesth 1992; 69: 307-13.
• 52 Malone DL, Dunne J, Tracy JK. et al. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma 2003; 54: 898-907.
• 53 Mannucci PM, Federici AB, Sirchia G. Hemostasis testing during massive blood replacement. A study of 172 cases. Vox Sang 1982; 42: 113-23.
• 54 Martini WZ, Chinkes DL, Pusateri AE. et al. Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs. AJP-Endo 2005; 289: 930-4.
• 55 Mayer AS, Brun NC, Begtrup K. et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005; 352: 777-85.
• 56 McCrath DJ, Cerboni E, Frumento RJ. et al. Thrombelastography maximum amplitude predicts postoperative thrombotic complications including myocarial infarction. Anesth Analg 2005; 100: 1576-83.
• 57 McLoughlin TM, Fontana JL, Alving B. et al. Profound normovolemic hemodilution: Hemostatic effects in patients and in a porcine model. Anest Analg 1996; 83: 459-65.
• 58 Miller BE, Guzzetta NA, Tosone SR. et al. Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thrombelastography. Anesth Analg 2000; 90: 1324-30.
• 59 Miller E, Mochizuki T, levy JH. et al. Predicting and treating coagulopathies after cardiopulmonary bypass in children. AnestAnalg 1997; 85: 1196-202.
• 60 Mittermayr M, Margreiter J. Corinna Velik-Salchner et al. Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (ROTEM): an in vitro study. Br J Anaesth 2005; 95: 310-6.
• 61 Monroe DM, Hoffman M. What does it take to make the perfect clot?. Arterioscler Thromb Vasc Biol 2006; 26: 1-8.
• 62 Murray D, Pennell BJ, Weinstein SL. et al. Packed red cells in acute blood loss : Dilutional coagulopathy as a cause of surgical bleeding. Anesth Analg 1995; 80: 336-42.
• 63 Nielsen VG, Cohen BM, Cohen E. Effects of coagulation factor deficiency on plasma coagulation kinetics determined via thrombelastography: critical roles of fibrinogen and factors II, VII, X and XII. Acta Ansesthesiol Scand 2005; 49: 222-31.
• 64 Nuttall G, Oliver WC, Santrach Pj. et al. Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology 2001; 94: 773-81.
• 65 Oshita K, Az-ma T, Osawa Y. et al. Quantitative measurement of thrombelastography as a function of platelet count. Anesth Analg 1999; 89: 296-9.
• 66 Ramsay MA, Randall HB, Burton EC. Intravascular thrombosis and thrombembolism during liver transplantation: Antifibrinolytic therapy indicated?. Liver Transplantation 2004; 10: 310-4.
• 67 Reed RL, Ciavarella D, Heimbacg DM. et al. Prophylactic platelet administration during massive transfusion. A prospective randomized, doubleblind clinical study. Ann Surg 1979; 190: 91-9.
• 68 Reiss RF. Hemostatic defects in massive transfusion: Rapid diagnosis and management. Am J Crit Care 2000; 9: 158-65.
• 69 Rivard GE, Brummel-Ziedins KE, Mann KG. et al. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assayed by thrombelastography. J Thromb Haemost 2005; 3: 2039-43.
• 70 Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. Br J Anaesth 2001; 86: 575-8.
• 71 Shore-Lesserson L, Manspeizer HE, DePerio M. et al. Thrombelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88: 312-9.
• 72 Singbartl K, Innerhofer P, Radvan J. et al. Hemostasis and hemodilution: a mathematical guide for clinical practice. AnesthAnalg 2003; 96: 929-35.
• 73 Sorensen B, Fenger-Eriksen C, Ingerslev J. Recombinant factor VIIa fails to correct coagulopathy induced by haemodilution with coloid. Br J Anaesth 2005; 94: 862-3.
• 74 Spahn DR, Rossaint R. Coagulopathy and blood component transfusion in trauma. Br J Anaesth 2005; 95: 130-9.
• 75 Spiel AO, Mayr FB, Firbas C. et al. Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans. J Thromb Haemost 2006; 4: 411-7.
• 76 Stanworth SJ, Brunskill SJ, Hyde CJ. et al. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol 2004; 126: 139-52.
• 77 Stanworth SJ, Wash TS. Fresh frozen plasma: Friend or faux pas in critical illness ?. Crit Care Med 2005; 33: 2714-6.
• 78 Stein SC, Young GS, Talucci RC. et al. Delayed brain injury after head trauma: significance of coagulopathy. Neurosurgery 1992; 30: 160-5.
• 79 Ti LK, Cheong KF, Chen FG. Prediction of excessive bleeding after coronary artery bypass graft surgery: the influence of timing and heparinase on thrombelastography. J Cardiothorac Vasc Anesth 2002; 16: 545-50.
• 80 Toh CH, Downey C. Back to the future: testing in disseminated intravascular coagulation. Blood Coag Fibrinol 2005; 16: 535-42.
• 81 Tripodi A, Salerno F, Chantarangkul V. et al. Evidence of normal thrombin generation in cirhhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41: 553-8.
• 82 Tuman KJ, McCarthy RJ, Djuric M. et al. Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thrombelastographic Assay. J Cardiothorac Vasc Anesth 1994; 8: 144-9.
• 83 Valeri CR, Cassidy G, Pivacek LE. et al. Anemiainduced increase in bleeding time: implications for treatment of nonsurgical blood loss. Transfusion 2001; 41: 977-83.
• 84 Vorweg M, Hartmann B, Knüttgen D. et al. Management of fulminant fibrinolysis during abdominal aortic surgery. J Cardiothorac Vasc Anesth 2001; 6: 764-7.
• 85 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: 1564-9.