REDUCED TRANSFUSION REQUIREMENTS BY RECOMBINANT FACTOR VIIa IN ORTHOTOPIC LIVER TRANSPLANTATION

Hendriks, H. G. D.; Wolf, Jtm de; Klompmaker, I. J.; Porte, R. J.; Kam, PJ de; Hagenaars, Ajm; Melsen, Tina; Slooff, Mjh; Meer, Jan van der

doi:10.1097/00007890-200102150-00011

Cited by 240 publications

(150 citation statements)

References 22 publications

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“…In a small single-center experience we published last February in Intensive Care Medicine, 3 at variance with the first preliminary study published by Hendriks et al, 4 we were not able to find any difference in blood loss and transfusion requirements whether or not the drug was administered. We used rFVIIa (20 /kg at the start of operation plus 20 /kg 30-40 minutes after reperfusion in case of significant bleeding) in 6 patients with end-stage liver disease (Child-Turcotte-Pugh, 9 Ϯ 2.5; range, 9-11) who underwent OLT in February 2003.…”

contrasting

confidence: 68%

“…Blood loss and transfusion requirements did not statistically differ in the treated group (blood loss, 3,500 Ϯ 1,300 mL; range, 1,600-5,000 mL; packed red cells, 9 Ϯ 4 units; range, 4-11 units) mL and in controls (blood loss, 1,800 Ϯ 1,200 mL; range, 500-4,000 mL; packed red cells, 7 Ϯ 2.5; range, 4-10. 3 On the contrary, according to the data reported by Hendriks et al, 4 we found improvements in the following thromboelastographic parameters: r (reduced, P Ͻ 0.05), alpha angle (increased, P Ͻ 0.05), maximum amplitude (tendency toward larger maximum amplitude, not statistically significant). All the patients were discharged in good conditions and are alive (follow-up 16 months).…”

contrasting

confidence: 39%

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Use of recombinant factor VIIa during orthotopic liver transplantation

Gasperi¹,

Baudo²

2006

Liver Transpl

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contrasting

confidence: 68%

contrasting

confidence: 39%

Use of recombinant factor VIIa during orthotopic liver transplantation

Gasperi¹,

Baudo²

2006

Liver Transpl

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“…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. 36 Aprotinin does not have these effects: it does not stimulate the coagulation cascade and has no intrinsic procoagulant effect.…”

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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“…One study has demonstrated that a single dose of rFVlIa (80 mcg/kg) could reduce transfusion requirements in cirrhotic patients undergoing orthotopic liver transplant [15]. Controlled trials have shown rFVIIa to be of no benefit in reducing transfusion in liver resection or transplantation.…”

Section: Perioperative Blood Lossmentioning

confidence: 99%

Rational Use of Recombinant Factor VIIa in Clinical Practice

Dutta

Verma

2013

Indian J Hematol Blood Transfus

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In the United States, the FDA-approved indications for recombinant factor VIIa is for bypassing inhibitors to factors VIII and IX in patients with hemophilia A and B respectively and for treatment of congenital factor VII deficiency. In European countries, rFVIIa is licensed for the above indications as well as for Glanzmann's thrombasthenia. In absence of high-quality data favoring off-label use of this agent and laboratory test to predict response to this agent, and in view of high cost of rFVIIa, off-label use of recombinant factor VIIa should be restricted to only when hemorrhage has not responded to transfusion or other conventional therapy. It appears, two such conditions where recombinant factor VIIa may be beneficial are traumatic and postpartum hemorrhages.

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REDUCED TRANSFUSION REQUIREMENTS BY RECOMBINANT FACTOR VIIa IN ORTHOTOPIC LIVER TRANSPLANTATION

Abstract: A single dose of 80 microg/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.

Cited by 240 publications

References 22 publications

Use of recombinant factor VIIa during orthotopic liver transplantation

Use of recombinant factor VIIa during orthotopic liver transplantation

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

Rational Use of Recombinant Factor VIIa in Clinical Practice

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