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

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More information

Accepted/In Press date: 22 October 2019
e-pub ahead of print date: 26 October 2019
Published date: 1 February 2020
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

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Date deposited: 24 Jul 2020 16:46
Last modified: 28 Apr 2022 02:30

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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

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