The University of Southampton
University of Southampton Institutional Repository

Efficacy of fibrinogen concentrate in major abdominal surgery – A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei

Efficacy of fibrinogen concentrate in major abdominal surgery – A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei
Efficacy of fibrinogen concentrate in major abdominal surgery – A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. Objectives: To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. Methods: FORMA-05 was an off-label single-center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0-4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4-point scales and adjudicated by an independent committee. Results: One hundred percent of patients receiving HFC (95% confidence interval: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P =.0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P <.0001) and FIBTEM A20 (3.33 vs 0.93 mm; P =.003). Factor XIII, factor VIII, and von Willebrand factor activity were maintained throughout surgery. Only red blood cells were transfused intraoperatively (median units: HFC group, 1.0; cryoprecipitate group, 0.5). Thromboembolic events were detected with cryoprecipitate only. Safety was otherwise comparable between groups. Conclusions: Human fibrinogen concentrate was hemostatically efficacious in patients undergoing major abdominal PMP surgery, with a favorable safety profile. These results are relevant to other surgical settings where bleeding and acquired fibrinogen deficiency occur.

Pseudomyxoma peritonei, cytoreductive surgical procedures, fibrinogen, hemostasis, thrombelastography
1538-7933
352-363
Roy, Ashok
33951307-0af0-4042-932a-173d544964a7
Stanford, Sophia
ea11cec4-d952-4e42-b44c-70e02eb3ec66
Nunn, Sean
d92b61c4-3199-44f8-ba9d-53f64498b239
Alves, Sue
368d5360-a041-4678-9573-bc07de7b7cca
Sargant, Nigel
8dbd451a-b4a5-4e35-a9eb-1cc5c0233a81
Rangarajan, Savita
9a5e4c7e-55ba-4a3a-b5f6-f1e269d927c3
Smith, Emily Arbuthnot
8e0a9af4-47c2-4609-b655-94266e62df3d
Bell, John
b6fd318c-10a1-4b18-90a7-3de345a943bd
Dayal, Sanjeev
b22b44bc-1c90-405c-91d8-effee2546991
Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Tzivanakis, Alexios
3b9dbb38-ed0e-4614-92c9-b1706bea11fc
Kruzhkova, Irina
1fa96a23-4ae6-4879-b88e-3606d57a7a7a
Solomon, Cristina
d63383f9-73b4-41a8-890a-05ef6b971574
Knaub, Sigurd
01e79fc9-fb41-4fb6-8498-534b56e06cb0
Moran, Brendan
76fc3bf0-63a8-4976-8639-dd13f4cb1e43
Mohamed, Faheez
11e760f5-fd56-4f32-9264-22a2e710b365
Roy, Ashok
33951307-0af0-4042-932a-173d544964a7
Stanford, Sophia
ea11cec4-d952-4e42-b44c-70e02eb3ec66
Nunn, Sean
d92b61c4-3199-44f8-ba9d-53f64498b239
Alves, Sue
368d5360-a041-4678-9573-bc07de7b7cca
Sargant, Nigel
8dbd451a-b4a5-4e35-a9eb-1cc5c0233a81
Rangarajan, Savita
9a5e4c7e-55ba-4a3a-b5f6-f1e269d927c3
Smith, Emily Arbuthnot
8e0a9af4-47c2-4609-b655-94266e62df3d
Bell, John
b6fd318c-10a1-4b18-90a7-3de345a943bd
Dayal, Sanjeev
b22b44bc-1c90-405c-91d8-effee2546991
Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Tzivanakis, Alexios
3b9dbb38-ed0e-4614-92c9-b1706bea11fc
Kruzhkova, Irina
1fa96a23-4ae6-4879-b88e-3606d57a7a7a
Solomon, Cristina
d63383f9-73b4-41a8-890a-05ef6b971574
Knaub, Sigurd
01e79fc9-fb41-4fb6-8498-534b56e06cb0
Moran, Brendan
76fc3bf0-63a8-4976-8639-dd13f4cb1e43
Mohamed, Faheez
11e760f5-fd56-4f32-9264-22a2e710b365

Roy, Ashok, Stanford, Sophia, Nunn, Sean, Alves, Sue, Sargant, Nigel, Rangarajan, Savita, Smith, Emily Arbuthnot, Bell, John, Dayal, Sanjeev, Cecil, Tom, Tzivanakis, Alexios, Kruzhkova, Irina, Solomon, Cristina, Knaub, Sigurd, Moran, Brendan and Mohamed, Faheez (2020) Efficacy of fibrinogen concentrate in major abdominal surgery – A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei. Journal of Thrombosis and Haemostasis, 18 (2), 352-363. (doi:10.1111/jth.14665).

Record type: Article

Abstract

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. Objectives: To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. Methods: FORMA-05 was an off-label single-center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0-4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4-point scales and adjudicated by an independent committee. Results: One hundred percent of patients receiving HFC (95% confidence interval: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P =.0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P <.0001) and FIBTEM A20 (3.33 vs 0.93 mm; P =.003). Factor XIII, factor VIII, and von Willebrand factor activity were maintained throughout surgery. Only red blood cells were transfused intraoperatively (median units: HFC group, 1.0; cryoprecipitate group, 0.5). Thromboembolic events were detected with cryoprecipitate only. Safety was otherwise comparable between groups. Conclusions: Human fibrinogen concentrate was hemostatically efficacious in patients undergoing major abdominal PMP surgery, with a favorable safety profile. These results are relevant to other surgical settings where bleeding and acquired fibrinogen deficiency occur.

This record has no associated files available for download.

More information

Accepted/In Press date: 22 October 2019
e-pub ahead of print date: 26 October 2019
Published date: 1 February 2020
Additional Information: Funding Information: The authors thank the study team and patients that participated in this study. This study was sponsored and funded by Octapharma AG. Editorial assistance was provided by Portland Medical Communications Ltd and was funded by Octapharma AG. Funding Information: This study was sponsored and funded by Octapharma AG. A.R. and F.M. have received investigator fees from Octapharma AG. S.S., S.N., S.A., N.S., S.R., E.A.S., J.B., S.D., T.C., A.T., and B.M. have not received support from any organization for the submitted work. I.K., C.S., and S.K. are employees of Octapharma AG. Publisher Copyright: © 2019 Octapharma. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis
Keywords: Pseudomyxoma peritonei, cytoreductive surgical procedures, fibrinogen, hemostasis, thrombelastography

Identifiers

Local EPrints ID: 442754
URI: http://eprints.soton.ac.uk/id/eprint/442754
ISSN: 1538-7933
PURE UUID: 36790370-4478-46d0-8f41-2abc813f317d
ORCID for Savita Rangarajan: ORCID iD orcid.org/0000-0001-7367-133X

Catalogue record

Date deposited: 24 Jul 2020 16:46
Last modified: 17 Mar 2024 04:02

Export record

Altmetrics

Contributors

Author: Ashok Roy
Author: Sophia Stanford
Author: Sean Nunn
Author: Sue Alves
Author: Nigel Sargant
Author: Emily Arbuthnot Smith
Author: John Bell
Author: Sanjeev Dayal
Author: Tom Cecil
Author: Alexios Tzivanakis
Author: Irina Kruzhkova
Author: Cristina Solomon
Author: Sigurd Knaub
Author: Brendan Moran
Author: Faheez Mohamed

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×