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


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
02 2020
Historique:
received: 23 08 2019
revised: 18 10 2019
accepted: 22 10 2019
pubmed: 28 10 2019
medline: 15 5 2021
entrez: 27 10 2019
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 31654548
doi: 10.1111/jth.14665
pmc: PMC7027898
pii: S1538-7836(22)01502-1
doi:

Substances chimiques

Hemostatics 0
Fibrinogen 9001-32-5

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

352-363

Informations de copyright

© 2019 Octapharma. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Références

J Thorac Cardiovasc Surg. 2009 Sep;138(3):694-702
pubmed: 19698858
Surg Oncol Clin N Am. 2003 Jul;12(3):585-603
pubmed: 14567019
Dis Colon Rectum. 1987 Oct;30(10):772-9
pubmed: 2820671
J Thorac Cardiovasc Surg. 2014 Oct;148(4):1647-55
pubmed: 24951020
Can J Surg. 1989 May;32(3):164-70
pubmed: 2713770
Transfus Med. 2016 Apr;26(2):118-22
pubmed: 27030339
Biologicals. 2018 Mar;52:72-77
pubmed: 29336864
Br J Surg. 1998 Oct;85(10):1332-9
pubmed: 9782010
Crit Care. 2019 Mar 27;23(1):98
pubmed: 30917843
J Cardiothorac Vasc Anesth. 2015;29(3):694-702
pubmed: 25836953
Br J Anaesth. 2014 Dec;113(6):922-34
pubmed: 24972790
Eur J Anaesthesiol. 2017 Jun;34(6):332-395
pubmed: 28459785
Int J Surg Oncol. 2011;2011:468698
pubmed: 22312509
J Am Heart Assoc. 2015 Jun 02;4(6):e002066
pubmed: 26037084
Transfus Apher Sci. 2012 Apr;46(2):159-62
pubmed: 22227402
Vox Sang. 2018 Feb;113(2):120-127
pubmed: 29238971
Transfus Med. 2012 Oct;22(5):344-9
pubmed: 22994449
Br J Anaesth. 2010 May;104(5):555-62
pubmed: 20348140
Eur J Surg Oncol. 2008 Feb;34(2):196-201
pubmed: 17524597
Ann Surg. 1995 Jan;221(1):29-42
pubmed: 7826158
Gastroenterol Res Pract. 2012;2012:635314
pubmed: 22927838
Anesthesiology. 2013 Jan;118(1):40-50
pubmed: 23249928
Singapore Med J. 2017 Aug;58(8):488-496
pubmed: 27121920
PLoS One. 2018 Jun 21;13(6):e0193657
pubmed: 29927924
Acta Anaesthesiol Scand. 2016 Sep;60(8):1033-42
pubmed: 27109179
Crit Care. 2011;15(2):R83
pubmed: 21375741
Br J Anaesth. 2016 Jul;117(1):41-51
pubmed: 27317703
J Thromb Haemost. 2020 Feb;18(2):352-363
pubmed: 31654548
Br J Haematol. 2010 Jun;149(6):834-43
pubmed: 20456356
Crit Care. 2010;14(2):R55
pubmed: 20374650
Br J Anaesth. 2009 Jun;102(6):785-92
pubmed: 19411671
Cancer. 2008 Jul 15;113(2):315-25
pubmed: 18473354
Transfusion. 2013 Jan;53 Suppl 1:91S-95S
pubmed: 23301979
Crit Care. 2015 Mar 12;19:83
pubmed: 25880548
Br J Anaesth. 2008 Dec;101(6):769-73
pubmed: 18818192
Transfusion. 2014 May;54(5):1379-87
pubmed: 24192484

Auteurs

Ashok Roy (A)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Sophia Stanford (S)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Sean Nunn (S)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Sue Alves (S)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Nigel Sargant (N)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Savita Rangarajan (S)

University Hospital Southampton NHS Foundation Trust, UK.
KJ Somaiya Ayurvihar, Mumbai, India.

Emily Arbuthnot Smith (EA)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

John Bell (J)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Sanjeev Dayal (S)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Tom Cecil (T)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Alexios Tzivanakis (A)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Irina Kruzhkova (I)

Octapharma AG, Lachen, Switzerland.

Cristina Solomon (C)

Octapharma AG, Lachen, Switzerland.

Sigurd Knaub (S)

Octapharma AG, Lachen, Switzerland.

Brendan Moran (B)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Faheez Mohamed (F)

Basingstoke and North Hampshire Hospital, Basingstoke, UK.

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Classifications MeSH