Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study

Port, Robert J; Molenaar, I. Quintus; Begliomini, B.; Groenland, Theo H. N.; Januszkiewicz, Anna; Lindgren, L.; Palareti, Gualtiero; Hermans, J.; Terpstra, Onno T.

doi:10.1016/s0140-6736(00)02111-5

Cited by 299 publications

(210 citation statements)

References 28 publications

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“…Only 2 of 137 randomized patients developed hepatic artery thrombosis, and these 2 patients were administered placebo. 9 The observed anticoagulant effect of aprotinin is in contrast to effects of recombinant factor VIIa, another prohemostatic drug, recently used in OLT to reduce intraoperative blood loss. 35 Recombinant factor VIIa is a very potent stimulator of the coagulation system, which results in increased generation of thrombin, reflected in vitro by a significant shortening of prothrombin time, APTT, and r on thromboelastography.…”

Section: Discussionmentioning

confidence: 99%

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Molenaar

2001

Liver Transplantation

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Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation ( H emostasis is the overall result of a balance between two proteolytic cascades: the coagulation and fibrinolytic systems. In end-stage liver disease, the delicate balance between coagulation and fibrinolysis is often disturbed. 1,2 One problem encountered in orthotopic liver transplantation (OLT) is the occurrence of hyperfibrinolysis, mainly caused by increased levels of tissue-type plasminogen activator (tPA). 3,4 Especially during the anhepatic and postreperfusion periods, tPA plasma levels are significantly increased, resulting in consumption of its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). 5,6 High tPA activity during OLT stimulates the conversion of plasminogen into plasmin, which causes premature degradation of fibrin clots and subsequent increased blood loss and transfusion requirements. 6 Aprotinin is a serine protease inhibitor derived from bovine lung. 7 It has the ability to inhibit a wide range of proteases that have serine residues at their active site, such as plasmin, kallikrein, and trypsin, by forming reversible stoichiometric enzyme-inhibitor complexes. Inhibition of plasmin and kallikrein results in a strong reduction in fibrinolysis. Neuhaus et al 8 first reported on the blood-sparing effect of aprotinin in OLT. Recently, we completed the European Multicenter Study on the Use of Aprotinin in Liver Transplantation (EMSALT). Results of this randomized, double-blind, placebo-controlled study showed significant reductions in blood loss and transfusion requirements of 50% and 30%, respectively. 9 A potential adverse effect of a prohemostatic drug, such as aprotinin, could be an increased rate of thrombotic complications. Concern has been voiced about the potential risk for this type of complication when aprotinin is administered during OLT. 10 Although the antifibrinolytic activity of aprotinin in OLT has been studied before, data on the specific effects of aprotinin on coagulation and fibrinolysis separately, as well as their interaction in the same

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Section: Discussionmentioning

confidence: 99%

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Molenaar

2001

Liver Transplantation

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“…Although the blood sparing effect of these agents is recognized, 12,13 their systematic use may be hazardous due to adverse effects such as severe allergic reactions and fatal intraoperative thromboembolism. 14,15 On the other hand, the influence of transfusion on outcome and graft survival has been known for several years.…”

Section: Se (%) Sp (%) Ppv (%) Npv (%)mentioning

confidence: 99%

Intraoperative blood losses and transfusion requirements during adult liver transplantation remain difficult to predict

Steib

Freys

Lehmann

et al. 2001

Can J Anesth/J Can Anesth

147

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Purpose: To identify preoperative factors associated with high blood losses during liver transplantation for chronic end-stage liver disease.Methods: Four hundred and ten consecutive patients were included in this retrospective study. Blood losses were calculated, based on transfusion requirements. The population was divided into two groups: the upper quartile was defined as the high blood loss (HBL) group and the lower three quartiles as the low blood loss group. Fourteen preoperative variables were collected. Qualitative variables consisted of the type of hepatopathy, Child-Pugh's classification, sex, the surgical team's experience, previous abdominal surgery and portal hypertension. Quantitative variables were age, hemoglobin concentration Hb, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, fibrin degradation products (FDP) and euglobulin lysis time. Univariate analysis and stepwise multivariate analysis were conducted.Results: Patients in the HBL group required 12 units of red blood cell or more to maintain a Hb $100g·L -1 . HBL was associated with severe liver disease, previous abdominal surgery, use of a venovenous bypass and little surgical experience in orthotopic liver transplantation (OLT). In the HBL group several hemostatic parameters were more disturbed before surgery. The multivariate analysis disclosed three independent variables associated with HBL: Hb and FDP concentrations and previous upper abdominal surgery. When combined, these resulted in a high specificity (98%) but low sensitivity to predict blood loss.Conclusion: Despite our efforts we were unable to identify predictive risk factors of bleeding during OLT even in a homogeneous population. Centres should evaluate their practice individually in an attempt to identify patients at high risk of being transfused.

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“…9 Use of aprotinin in transplant patients significantly lower (60%) blood loss and PRBC transfusion volume when compared with control subjects. 12 …”

Section: Concept Of Passenger Lymphocytes In Organ Transplantsmentioning

confidence: 99%

Transfusion medicine and solid organ transplant – Update and review of some current issues

Sarkar

Philip

Yadav

2013

Medical Journal Armed Forces India

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Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study

Cited by 299 publications

References 28 publications

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Intraoperative blood losses and transfusion requirements during adult liver transplantation remain difficult to predict

Transfusion medicine and solid organ transplant – Update and review of some current issues

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