Recombinant factor VIIa and major liver surgery: seeking for labelled indications
andrea de gasperi, Niguarda Ca Granda Hospital- Milan - Italy
22 February 2006
Sirs, into our opinion in spite of the two large and well conducted randomized studies (1,2), the definite conclusions on the use of rFVIIa during OLT have yet to be drawn and , probably, they should not be as positive as proposed in your review (Critical Care 2005, 9: 560). 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. According to the data reported by Hendriks et al (4), we found improvements in the thromboelastographic parameters. The safety profile was excellent and we did not find out any early or late thrombotic complication.
Into our opinion the problem of bleeding during OLT, or generally speaking in major liver surgery, as quoted by Porte and Caldwell (5) in the editorial accompanying the articles by Planinsic (1) and Lodge (2), is substantial: however, surprisingly, it seems that further work has still to be done to find the best way to properly intervene in this specific setting (5). As we suggested, commenting the same item in a letter to "Liver Transplantation" (in press, 2006), we are strongly convinced (and in this hypothesis we are now heavily supported by the definitive data by Planinsic and Lodge) that rFVIIa should not be recommended “ per se” as a universal prophylaxis to reduce transfusion requirements during OLT or during major liver resection: this is particularly true in settings in which good surgical technique and expertise in the perioperative management and pharmacological manipulation of coagulation are available. Cost effectiveness of rFVIIA into our opinion has to be challenged against the result reported in the recent Lodge’s and Planinsic’s studies in liver transplantation. As a matter of fact, in spite of the high dose used in the Lodge study, the only significant result was that 7 to 10% of the treated patients were able to avoid RBC transfusion: however, not different were FFP or other blood products needs, when compared to the transfusion needs in the controls. We think the “surgical” use of rFVIIa should be redefined in a randomized fashion, in very selected subgroups of OLT candidates at known risk of surgical or non- surgical bleeding (Split Liver Transplants, retransplantation procedures performed years after the first procedure, liver transplantation in candidates with previous major abdominal surgery, frequent spontaneous bacterial peritonitis or with renal failure) or in patients admitted to major liver resection with well defined bleeding risks . In such a setting, rFVIIa could be administered as a sort of preemptive therapy in a subset of patients not yet bleeding, but at substantial risk because of specific factors: this approach substantially differs from administering a useless and expensive prophylaxis “just because” a patient is undergoing a “possible” risky procedure. This could be a chance to redefine at least some of the many “off label” indications proposed for rFVIIA, eventually helping in finding possible recognised “surgical” indications
Andrea De Gasperi, MD – Anesthesia / CCM – Ospedale Niguarda Ca Granda – Milan - Italy
Luciano De Carlis, MD – Liver Transplant Surgery - Ospedale Niguarda Ca Granda – Milan - Italy
Bibliography
1. Planinsic RM, van der Meer J, TestaG et al. Safety and efficacy of a single bolus administration of rFVIIa in liver transplantation. Liver Transpl, 2005; 11: 895 – 900
2. Lodge JP, Jonas S, Jones RM et al. Efficacy and safety of repeated perioperative doses of r FVIIa in in liver transplantation. Liver Transpl, 2005; 11: 973-9
3. De Gasperi A, Baudo F, De Carlis L. Recombinant FVII in orthotopic liver transplantation (OLT) : a preliminary single center experience. Intensive Care Med, 2005; 31: 315-6 (letter)
4. Hendriks HGD, Mejer K, De Wolf JT, Klompaker IJ, Porte R, et al Reduced transfusion requirements by recombinant Factor VII a in orthotopic liver transplantation. Transplantation, 2001; 71: 402 - 5
5. Porte RJ, Caldwell SH. The role of recombinant factor VIIa in liver transplantation. Liver Transpl, 2005; 11: 872-4
Critical Care
Recombinant factor VIIa and major liver surgery: seeking for labelled indications
22 February 2006
Sirs, into our opinion in spite of the two large and well conducted randomized studies (1,2), the definite conclusions on the use of rFVIIa during OLT have yet to be drawn and , probably, they should not be as positive as proposed in your review (Critical Care 2005, 9: 560). 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. According to the data reported by Hendriks et al (4), we found improvements in the thromboelastographic parameters. The safety profile was excellent and we did not find out any early or late thrombotic complication.
Into our opinion the problem of bleeding during OLT, or generally speaking in major liver surgery, as quoted by Porte and Caldwell (5) in the editorial accompanying the articles by Planinsic (1) and Lodge (2), is substantial: however, surprisingly, it seems that further work has still to be done to find the best way to properly intervene in this specific setting (5). As we suggested, commenting the same item in a letter to "Liver Transplantation" (in press, 2006), we are strongly convinced (and in this hypothesis we are now heavily supported by the definitive data by Planinsic and Lodge) that rFVIIa should not be recommended “ per se” as a universal prophylaxis to reduce transfusion requirements during OLT or during major liver resection: this is particularly true in settings in which good surgical technique and expertise in the perioperative management and pharmacological manipulation of coagulation are available. Cost effectiveness of rFVIIA into our opinion has to be challenged against the result reported in the recent Lodge’s and Planinsic’s studies in liver transplantation. As a matter of fact, in spite of the high dose used in the Lodge study, the only significant result was that 7 to 10% of the treated patients were able to avoid RBC transfusion: however, not different were FFP or other blood products needs, when compared to the transfusion needs in the controls. We think the “surgical” use of rFVIIa should be redefined in a randomized fashion, in very selected subgroups of OLT candidates at known risk of surgical or non- surgical bleeding (Split Liver Transplants, retransplantation procedures performed years after the first procedure, liver transplantation in candidates with previous major abdominal surgery, frequent spontaneous bacterial peritonitis or with renal failure) or in patients admitted to major liver resection with well defined bleeding risks . In such a setting, rFVIIa could be administered as a sort of preemptive therapy in a subset of patients not yet bleeding, but at substantial risk because of specific factors: this approach substantially differs from administering a useless and expensive prophylaxis “just because” a patient is undergoing a “possible” risky procedure. This could be a chance to redefine at least some of the many “off label” indications proposed for rFVIIA, eventually helping in finding possible recognised “surgical” indications
Andrea De Gasperi, MD – Anesthesia / CCM – Ospedale Niguarda Ca Granda – Milan - Italy
Luciano De Carlis, MD – Liver Transplant Surgery - Ospedale Niguarda Ca Granda – Milan - Italy
Bibliography
1. Planinsic RM, van der Meer J, TestaG et al. Safety and efficacy of a single bolus administration of rFVIIa in liver transplantation. Liver Transpl, 2005; 11: 895 – 900
2. Lodge JP, Jonas S, Jones RM et al. Efficacy and safety of repeated perioperative doses of r FVIIa in in liver transplantation. Liver Transpl, 2005; 11: 973-9
3. De Gasperi A, Baudo F, De Carlis L. Recombinant FVII in orthotopic liver transplantation (OLT) : a preliminary single center experience. Intensive Care Med, 2005; 31: 315-6 (letter)
4. Hendriks HGD, Mejer K, De Wolf JT, Klompaker IJ, Porte R, et al Reduced transfusion requirements by recombinant Factor VII a in orthotopic liver transplantation. Transplantation, 2001; 71: 402 - 5
5. Porte RJ, Caldwell SH. The role of recombinant factor VIIa in liver transplantation. Liver Transpl, 2005; 11: 872-4
Competing interests
none