HPE CSL Managing Perioperative Bleeding handbook - Page 14

Concentrates / blood products
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acute lung injury in patients in the intensive care unit 15 and of multiple organ failure in patients with critical injuries . 16 In a study of patients undergoing coronary artery bypass , transfusion of FPP correlated with a higher long-term mortality . 17 Finally , FPP showed to be ineffective to correct mildly prolonged coagulation values in non-bleeding patients ; 18 , 19 however , another study showed that plasma therapy reduced mortality rates in cases of massive transfusions when it was implemented at an early stage . 20 These results were not verified by a meta-analysis of randomised controlled trials evaluating FPP for anticoagulation reversal or for the prevention and treatment of bleeding associated with invasive interventions or specific pathologies . 21
Whereas the transfusion of FPP is associated with increased incidence of nosocomial infections in patients undergoing surgery for conditions other than traumatic injuries , 22 goal-directed therapy with coagulation factor concentrates has a lower potential for infectiousness and incidence of multiple organ failure compared with FFP , although no significant differences in mortality rates have been observed with the two approaches . 23 Prothrombin complex concentrates ( PCCs ), traditionally used in the treatment of haemophilia and other congenital bleeding disorders , are recommended in the emergency reversal of vitamin K-dependent oral anticoagulants . 2 A recent systematic review and metaanalysis of randomised and observational studies demonstrated a lower rate of all-cause mortality and risk of posttransfusion volume overload , accompanied by rapid INR reduction , compared with FFP in patients receiving treatment with warfarin who experienced a major bleeding event or who needed urgent surgery . 24 Unlike FPP , PCCs require small infusion volumes and can be promptly administered to patients without the need for blood group matching or thawing , which can be particularly relevant is urgent cases of patients with intracranial haemorrhage who receive oral anticoagulants , 25 but their use is associated with an increased risk of thrombosis and should therefore be carefully analysed for trauma patients .
Fibrinogen supplementation , by contrast , is superior to FPP in the reversal of severe trauma-induced coagulopathy , but because fibrinogen is a critical
haemostatic factor for efficient local clot formation it reaches its critical lower reference values before all the other factors . 26 , 27 Rescue therapy with recombinant activated FVIIa , commonly used in the treatment of haemophilia , may be considered for life-threatening bleeding events that cannot be controlled with standard surgical interventions or coagulation therapy , although its cost and risk of arterial thromboembolic events associated with higher doses , especially among the elderly , should be taken into consideration in treatment decision making . Finally , replacement therapy with FXIII concentrate does not seem to have an effect in reducing transfusion needs . 2 , 4
Conclusions In light of the current evidence in the management of perioperative bleeding , prompt and goal-directed therapy is the key element in the implementation of haemotherapy for patients with coagulopathies . This involves a rapid and comprehensive diagnosis of the existing coagulation deficits and the use of coagulation factor concentrates to restore function . Nevertheless , the question of superiority of factor concentrates versus . allogenic blood products cannot be definitely answered at this time because allogenic blood products are still indicated for particular conditions , mainly for the management of extensive blood loss with massive transfusions , and in situations where the use of factor concentrates cannot correct the underlying pathology . In conclusion , goal-directed therapy with coagulation factor concentrates is preferred , but in some rare cases clinicians may have to resort to allogenic blood products .
References 1 Tanaka KA et al . Blood coagulation : hemostasis and thrombin regulation . Anesth Analg 2009 ; 108 ( 5 ): 1433 – 46 . 2 Rossaint R et al . The European guideline on management of major bleeding and coagulopathy following trauma : fourth edition . Crit Care 2016 ; 20 ( 1 ): 100 . 3 Grottke O et al . Perioperatively acquired disorders of coagulation . Curr Opin Anestesiol 2015 ; 28 ( 2 ): 113 – 22 . 4 Kozek-Langenecker SA et al . Management of severe perioperative bleeding : guidelines from the European Society of Anaesthesiology : First update 2016 . Eur J Anaesthesiol 2017 ; 34 ( 6 ): 332 – 95 . 5 Glance LG et al . Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery . Anesthesiology 2011 ; 114 ( 2 ): 283 – 92 . 6 Koch CG at al . Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting . Crit Care Med 2006 ; 34 ( 6 ): 1608 – 16 . 7 Weber CF , Zacharowski K . Perioperative point of
care coagulation testing . Dtsch Asztebl Int 2012 ; 109 ( 20 ): 369 – 75 . 8 Straub N et al . Cost-effectiveness of POC coagulation testing using multiple electrode aggregometry . Clin Lab 2016 ; 62 ( 6 ): 1167 – 78 . 9 CRASH-2 trial collaborators , 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 ( 9734 ): 23 – 32 . 10 Gayet Ageron A et al . Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage : a meta-analysis of individual patient-level data from 40 138 bleeding patients . Lancet 2018 ; 391 ( 10116 ): 125 – 32 . 11 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 , placebocontrolled trial . Lancet 2017 ; 389 ( 10084 ): 2105 – 16 . 12 Chowdary P et al . 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 ( 1 ): 69 – 73 . 13 Magee G , Zbrozek A . Fluid overload is associated with increases in length of stay and hospital costs : pooled analysis of data from more than 600 US hospitals . Clinicoecon Outcomes Res 2013 ; 5:289 – 96 . 14 Inaba K et al . Impact of plasma transfusion in trauma patients who do not require massive transfusion . J Am Coll Surg 2010 ; 210 ( 6 ): 957 – 65 . 15 Khan H et al . Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients . CHEST 2007 ; 131 ( 5 ): 1308 – 14 . 16 Johnson JL et al . Effect of blood products transfusion on the development of postinjury multiple organ failure . Arch Surg 2010 ; 145 ( 10 ): 973 – 7 . 17 Bjursten H et al . Increased long-term mortality with plasma transfusion after coronary artery bypass surgery . Intensive Care Med 2013 ; 39 ( 3 ): 437 – 44 . 18 Abdel-Wahab OI et al . Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities . Transfusion 2006 ; 46 ( 8 ): 1279 – 85 . 19 Muller MC et al . Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy . J Thromb Haemost 2015 ; 13 ( 6 ): 989 – 97 . 20 Riskin DJ et al . Massive transfusion protocols : the role of aggressive resuscitation versus product ratio in mortality reduction . J Am Coll Surg 2009 ; 209 ( 2 ): 198 – 205 . 21 Yang L et al . Is fresh-frozen plasma clinically effective ? An update of a systematic review of randomized controlled trials . Transfusion 2012 ; 52 ( 8 ): 1673 – 86 . 22 Sarani B et al . Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection . Crit Care Med 2008 ; 36 ( 4 ): 1114 – 18 . 23 Nienaber U et al . The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion . Injury 2011 ; 42 ( 7 ): 697 – 701 . 24 Chai-Adisaksopha C et al . Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal . A systematic review and meta-analysis . Thromb Haemost 2016 ; 116 ( 5 ): 879 – 90 . 25 Imberti D et al . Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage . Blood Transfus 2011 ; 9 ( 20:148 – 55 . 26 Innerhofer P 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 ( 6 ): e258 – 71 . 27 Hiippala ST et al . Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates . Anesth Analg 1995 ; 81 ( 2 ): 360 – 5 .
hospitalpharmacyeurope . com
Concentrates/blood products 14 acute lung injury in patients in the intensive care unit 15 and of multiple organ failure in patients with critical injuries. 16 In a study of patients undergoing coronary artery bypass, transfusion of FPP correlated with a higher long-term mortality. 17 Finally, FPP showed to be ineffective to correct mildly prolonged coagulation values in non-bleeding patients; 18,19 however, another study showed that plasma therapy reduced mortality rates in cases of massive transfusions when it was implemented at an early stage. 20 These results were not verified by a meta-analysis of randomised controlled trials evaluating FPP for anticoagulation reversal or for the prevention and treatment of bleeding associated with invasive interventions or specific pathologies. 21 Whereas the transfusion of FPP is associated with increased incidence of nosocomial infections in patients undergoing surgery for conditions other than traumatic injuries, 22 goal-directed therapy with coagulation factor concentrates has a lower potential for infectiousness and incidence of multiple organ failure compared with FFP, although no significant differences in mortality rates have been observed with the two approaches. 23 Prothrombin complex concentrates (PCCs), traditionally used in the treatment of haemophilia and other congenital bleeding disorders, are recommended in the emergency reversal of vitamin K-dependent oral anticoagulants. 2 A recent systematic review and meta- analysis of randomised and observational studies demonstrated a lower rate of all-cause mortality and risk of post- transfusion volume overload, accompanied by rapid INR reduction, compared with FFP in patients receiving treatment with warfarin who experienced a major bleeding event or who needed urgent surgery. 24 Unlike FPP, PCCs require small infusion volumes and can be promptly administered to patients without the need for blood group matching or thawing, which can be particularly relevant is urgent cases of patients with intracranial haemorrhage who receive oral anticoagulants, 25 but their use is associated with an increased risk of thrombosis and should therefore be carefully analysed for trauma patients. Fibrinogen supplementation, by contrast, is superior to FPP in the reversal of severe trauma-induced coagulopathy, but because fibrinogen is a critical hospitalpharmacyeurope.com haemostatic factor for efficient local clot formation it reaches its critical lower reference values before all the other factors. 26,27 Rescue therapy with recombinant activated FVIIa, commonly used in the treatment of haemophilia, may be considered for life-threatening bleeding events that cannot be controlled with standard surgical interventions or coagulation therapy, although its cost and risk of arterial thromboembolic events associated with higher doses, especially among the elderly, should be taken into consideration in treatment decision making. Finally, replacement therapy with FXIII concentrate does not seem to have an effect in reducing transfusion needs. 2,4 Conclusions In light of the current evidence in the management of perioperative bleeding, prompt and goal-directed therapy is the key element in the implementation of haemotherapy for patients with coagulopathies. This involves a rapid and comprehensive diagnosis of the existing coagulation deficits and the use of coagulation factor concentrates to restore function. Nevertheless, the question of superiority of factor concentrates versus. allogenic blood products cannot be definitely answered at this time because allogenic blood products are still indicated for particular conditions, mainly for the management of extensive blood loss with massive transfusions, and in situations where the use of factor concentrates cannot correct the underlying pathology. In conclusion, goal-directed therapy with coagulation factor concentrates is preferred, but in some rare cases clinicians may have to resort to allogenic blood products. References 1 Tanaka KA et al. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg 2009;108(5): 1433–46. 2 Rossaint R et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care 2016;20(1):100. 3 Grottke O et al. Perioperatively acquired disorders of coagulation. Curr Opin Anestesiol 2015;28(2):113–22. 4 Kozek-Langenecker SA et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol 2017;34(6):332–95. 5 Glance LG et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology 2011;114(2):283–92. 6 Koch CG at al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34(6):1608–16. 7 Weber CF, Zacharowski K. Perioperative point of care coagulation testing. Dtsch Asztebl Int 2012;109(20):369–75. 8 Straub N et al. Cost-effectiveness of POC coagulation testing using multiple electrode aggregometry. Clin Lab 2016;62(6):1167–78. 9 CRASH-2 trial collaborators, 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(9734):23–32. 10 Gayet Ageron A et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 2018;391(10116):125–32. 11 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(10084):2105–16. 12 Chowdary P et al. 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