Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

Henry, DA; Moxey, AJ; Carless, PA; O’Connell, Dianne; McClelland, Brian; Henderson, KM; Sly, K; Laupacis, Andreas; Fergusson, Dean

doi:10.1002/14651858.cd001886

Cited by 173 publications

(282 citation statements)

References 144 publications

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“…8 Also, an updated Cochrane systematic review by Henry et al reported this amount as 380 ml for aprotinin and 260 ml for tranexamic acid. 5 In addition, a head-to-head comparison by Isgro showed that topical aprotinin is equally effective as systemic aprotinin for the reduction of perioperative blood loss. 18 The second reason supporting the topical use of antifibrinolytics is based on the observation that the pericardium acts as a natural barrier that minimizes the rate of systemic absorption and side effects of pharmacological agents applied locally into the pericardial cavity.…”

Section: Discussionmentioning

confidence: 99%

“…Antifibrinolytic agents (aprotinin, tranexamic acid, and e-aminocaproic acid) have been shown to inhibit fibrinolysis and, thus, reduce bleeding in cardiac surgery. 5 However, recent studies on large numbers of patients have raised growing concerns about the serious adverse effects observed following systemic administration of antifibrinolytic agents. These complications include increased mortality, 6 renal toxicity, 5,7,8 anaphylactic reactions, 9 graft vessel occlusion, 10 the risk of myocardial infarction (in high-risk cardiac surgery) following aprotinin use, 11 and, because of its mechanism of action, the potential risk of thromboembolic events after tranexamic acid administration.…”

Section: Introductionmentioning

confidence: 99%

“…5 However, recent studies on large numbers of patients have raised growing concerns about the serious adverse effects observed following systemic administration of antifibrinolytic agents. These complications include increased mortality, 6 renal toxicity, 5,7,8 anaphylactic reactions, 9 graft vessel occlusion, 10 the risk of myocardial infarction (in high-risk cardiac surgery) following aprotinin use, 11 and, because of its mechanism of action, the potential risk of thromboembolic events after tranexamic acid administration. 12 Due to the natural barrier properties of the pericardium, which prevents free diffusion of substances, recent experimental studies have shown that local application of different medications into the pericardial cavity can lead to desirable therapeutic efficacy without significant systemic absorption.…”

Section: Introductionmentioning

confidence: 99%

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Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis

Abrishami

Chung

Wong

2009

Can J Anesth/J Can Anesth

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Purpose This systematic review aimed to evaluate the efficacy and safety of topical application of antifibrinolytic drugs to reduce postoperative bleeding and transfusion requirements in patients undergoing on-pump cardiac surgery. Methods We searched The Cochrane Library, MED-LINE, EMBASE and SCI-EXPANDED for all randomized controlled trials on the topic. Trial inclusion, quality assessment, and data extraction were performed independently by two authors. Standard meta-analytic techniques were applied. Results Eight trials (n = 622 patients) met our inclusion criteria. The medication/placebo was applied into the pericardial cavity and/or mediastinum at the end of cardiac surgery. Seven trials compared antifibrinolytic agents (aprotinin or tranexamic acid) versus placebo. They showed that, on average, topical use of antifibrinolytic agents reduced the amount of 24-h postoperative chest tube (blood) loss by 220 ml (95% confidence interval: -318 to -126, P \ 0.00001, I 2 = 93%) and resulted in a saving of 1 unit of allogeneic red blood cells per patient (95% confidence interval: -1.54 to -0.53, P \ 0.0001, I 2 = 55%). The incidence of blood transfusion was not significantly changed following topical application of the medications. One study comparing topical versus intravenous administration of aprotinin found comparable results between the two methods of administration for the abovementioned outcomes. No adverse effects were reported following topical use of the medications. Conclusion This review suggests that topical application of antifibrinolytics can reduce postoperative bleeding and transfusion requirements in patients undergoing on-pump cardiac surgery. These promising findings need to be confirmed by more trials with large sample size using patient-related outcomes and more assessments regarding the systemic absorption of the medications. RésuméObjectif Le but de cette e´tude me´thodique e´tait d'e´valuer l'efficacite´et l'innocuite´de l'application topique d'agents anti-fibrinolytiques afin de re´duire les saignements et les besoins transfusionnels postope´ratoires chez les patients subissant une chirurgie cardiaque avec circulation extracorporelle. Méthode Nous avons fouille´les bases de donne´es suivantes afin d'extraire toutes les e´tudes randomise´es contrôle´es traitant de cette question : The Cochrane Library, MEDLINE, EMBASE et SCI-EXPANDED. L'inclusion des e´tudes, l'e´valuation de la qualite´et l'extraction des donne´es ont e´te´re´alise´es de façon inde´-pendante par deux auteurs. Des techniques de me´ta-analyse standard ont e´te´utilise´es. Résultats Huit e´tudes (n = 622 patients) ont satisfait aǹ os crite`res d'inclusion. Le me´dicament/placebo a e´teá pplique´dans la cavite´pe´ricardique et/ou dans le me´dia-stin a`la fin de la chirurgie cardiaque. Sept e´tudes ont compare´des agents anti-fibrinolytiques (aprotinine ou acide tranexamique) a`un placebo. Ces e´tudes ont montre´que, en moyenne, l'application topique d'agents

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis

Abrishami

Chung

Wong

2009

Can J Anesth/J Can Anesth

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“…Although aprotinin appears to be effective at reducing bleeding, its use has been associated with an increased risk of death and renal compromise when compared to the lysine analogs. 25,26 TXA decreases bleeding in various settings including multisystem trauma, orthopedic surgery, spine surgery, cardiopulmonary bypass, and liver transplantation. 7,27-31 It has not been well studied in patients undergoing liver resection, and it is rarely used in that setting.…”

Section: Introductionmentioning

confidence: 99%

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

Karanicolas

Lin

Tarshis

et al. 2016

HPB

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“…PCC prothrombin complex concentrate, P-gp P-glycoprotein, RBC red blood cell (DDAVP) have not been studied in TSOAC-associated bleeding. When used to reduce blood loss in the perioperative setting, these agents have not been shown to increased thrombotic risk but do reduce bleeding [42,43]. In the event of severe or life-threatening bleeding, nonspecific hemostatic agents PCC (50 U/kg) or APCC (80 U/kg) may be considered based on methodologically limited data.…”

Section: Approach To the Patient With Tsoac-associated Major Bleedingmentioning

confidence: 99%

Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents

Siegal

2015

J Thromb Thrombolysis

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Target-specific oral anticoagulants (TSOACs) dabigatran, rivaroxaban and apixaban are approved for the prevention and treatment of thromboembolism in several clinical settings. Bleeding is the major complication of anticoagulant therapy, including TSOACs, and anticoagulant reversal strategies are highly desired for the management of anticoagulant-associated major bleeding in addition to maximum supportive care and procedural/surgical intervention. Unlike VKAs for which vitamin K and coagulation factor replacement with prothrombin complex concentrate (PCC) can restore hemostasis, there are no clinically available agents proven to reverse TSOAC anticoagulant effect and ameliorate TSOAC-related major bleeding. This narrative review critically evaluates the evidence for TSOAC reversal using non-specific reversal agents PCC, activated PCC (APCC) and recombinant activated factor VII (rVIIa) which have been assessed primarily using in vitro experiments, animal models and healthy human volunteers. Aripazine is a novel agent undergoing clinical development for non-specific anticoagulant reversal, including TSOACs. Data are presented regarding specific reversal agents idarucizumab (dabigatran) and andexanet alfa (oral factor Xa inhibitors) currently being evaluated in clinical trials. A practical approach to management of patients with TSOAC-associated bleeding is also provided. There is an urgent need for clinical studies that evaluate the efficacy and safety of reversal strategies for TSOAC-related major bleeding with assessment of clinical outcomes such as bleeding and mortality.

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Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

Cited by 173 publications

References 144 publications

Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis

Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents

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