Effect of Early Administration of Coagulation Factor XIII on Fistula After Pancreatic Surgery: the FIPS Randomized Controlled Trial

Overview

Journal Langenbecks Arch Surg

Specialty General Surgery

Date 2018 Dec 4

PMID 30506109

Citations 2

Authors

Yoshinori Takeda

Yoshihiro Mise

Naoki Ishizuka

Sohei Harada

Brian Hayama

Yosuke Inoue

Takeaki Ishizawa

Hiromichi Ito

Yu Takahashi

Akio Saiura

Affiliations

Soon will be listed here.

Abstract

Purpose: The administration of exogenous factor XIII (FXIII) is reportedly effective for fistula closure in patients with a low plasma FXIII level. This study was performed to analyze the effect of early administration of exogenous FXIII on postoperative pancreatic fistula (POPF).

Methods: A single-center randomized controlled, open-label, parallel group, superiority trial was conducted from October 2015 to August 2016 in Japan. Patients with POPF and a plasma FXIII level of ≤ 70% on postoperative day 7 were randomly assigned to an early replacement (ER) group or control group in a 1:1 ratio by an independent coordinator using a computer-generated random number table. The ER group received FXIII concentrate the day after randomization, and the control group received no FXIII concentrate within 2 weeks. The primary endpoint was the duration of drain placement from randomization (DDPR).

Results: Fifty patients were randomized (ER group, 24; control group, 26), and all were analyzed with an intention-to-treat approach. There was no significant difference in the DDPR between the two groups (18 vs. 16 days; hazard ratio, 1.45; 95% confidence interval, 0.813-2.583). No serious harm was reported in either group.

Conclusion: Early administration of exogenous FXIII does not facilitate the healing of POPF.

Trial Registration: University Hospital Medical Information Network (UMIN) Center (UMIN000019480, http://www.umin.ac.jp ).

Citing Articles

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Kleber C, Sablotzki A, Casu S, Olivieri M, Thoms K, Horter J Crit Care. 2022; 26(1):69.

PMID: 35331308 PMC: 8943792. DOI: 10.1186/s13054-022-03940-2.

Effectiveness and failure factors of manual aspiration using a small needle for large pneumothorax in stable patients.

Homma T, Ojima T, Shimada Y, Tanabe K, Yamamoto Y, Akemoto Y J Thorac Dis. 2022; 14(2):321-332.

PMID: 35280475 PMC: 8902101. DOI: 10.21037/jtd-21-1587.

References

Herouy Y, Hellstern M, Vanscheidt W, Schopf E, Norgauer J . Factor XIII-mediated inhibition of fibrinolysis and venous leg ulcers. Lancet. 2000; 355(9219):1970-1. DOI: 10.1016/S0140-6736(00)02333-3. View

Dindo D, Demartines N, Clavien P . Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004; 240(2):205-13. PMC: 1360123. DOI: 10.1097/01.sla.0000133083.54934.ae. View

Inbal A, Lubetsky A, Krapp T, Castel D, Shaish A, Dickneitte G . Impaired wound healing in factor XIII deficient mice. Thromb Haemost. 2005; 94(2):432-7. DOI: 10.1160/TH05-04-0291. View

Fujita I, Kiyama T, Mizutani T, Okuda T, Yoshiyuki T, Tokunaga A . Factor XIII therapy of anastomotic leak, and circulating growth factors. J Nippon Med Sch. 2006; 73(1):18-23. DOI: 10.1272/jnms.73.18. View

Yoshioka R, Saiura A, Koga R, Seki M, Kishi Y, Morimura R . Risk factors for clinical pancreatic fistula after distal pancreatectomy: analysis of consecutive 100 patients. World J Surg. 2009; 34(1):121-5. DOI: 10.1007/s00268-009-0300-3. View

Saeki H, Masuda T, Okada S, Ando K, Sugiyama M, Yoshinaga K . Impact of perioperative peripheral blood values on postoperative complications after esophageal surgery. Surg Today. 2010; 40(7):626-31. DOI: 10.1007/s00595-009-4135-1. View

Kanda M, Fujii T, Kodera Y, NAGAI S, Takeda S, Nakao A . Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2010; 98(2):268-74. DOI: 10.1002/bjs.7305. View

Saigusa S, Yamamura T, Tanaka K, Ohi M, Kawamoto A, Kobayashi M . Efficacy of administration of coagulation factor XIII with definitive surgery for multiple intractable enterocutaneous fistulae in a patient with decreased factor XIII activity. BMJ Case Rep. 2012; 2011. PMC: 3063276. DOI: 10.1136/bcr.09.2010.3342. View

Levy J, Greenberg C . Biology of Factor XIII and clinical manifestations of Factor XIII deficiency. Transfusion. 2012; 53(5):1120-31. DOI: 10.1111/j.1537-2995.2012.03865.x. View

10.

Callery M, Pratt W, Kent T, Chaikof E, Vollmer Jr C . A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2012; 216(1):1-14. DOI: 10.1016/j.jamcollsurg.2012.09.002. View

11.

Soendergaard C, Kvist P, Seidelin J, Nielsen O . Tissue-regenerating functions of coagulation factor XIII. J Thromb Haemost. 2013; 11(5):806-16. DOI: 10.1111/jth.12169. View

12.

Melloul E, Raptis D, Clavien P, Lesurtel M . Poor level of agreement on the management of postoperative pancreatic fistula: results of an international survey. HPB (Oxford). 2013; 15(4):307-14. PMC: 3608986. DOI: 10.1111/j.1477-2574.2012.00599.x. View

13.

Schroeder V, Kohler H . Factor XIII deficiency: an update. Semin Thromb Hemost. 2013; 39(6):632-41. DOI: 10.1055/s-0033-1353392. View

14.

Nishino H, Kojima K, Oshima H, Nakagawa K, Fumura M, Kikuchi N . [A case of pancreatic and duodenal fistula after total gastrectomy successfully treated with coagulation factor XIII]. Gan To Kagaku Ryoho. 2014; 40(12):2304-6. View

15.

Valle J, Palmer D, Jackson R, Cox T, Neoptolemos J, Ghaneh P . Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014; 32(6):504-12. DOI: 10.1200/JCO.2013.50.7657. View

16.

Bassi C, Buchler M, Fingerhut A, Sarr M . Predictive factors for postoperative pancreatic fistula. Ann Surg. 2014; 261(4):e99. DOI: 10.1097/SLA.0000000000000577. View

17.

Allen P, Gonen M, Brennan M, Bucknor A, Robinson L, Pappas M . Pasireotide for postoperative pancreatic fistula. N Engl J Med. 2014; 370(21):2014-22. DOI: 10.1056/NEJMoa1313688. View

18.

Inoue H, Nishiyama N, Mizuguchi S, Nagano K, Izumi N, Komatsu H . Clinical value of exogenous factor XIII for prolonged air leak following pulmonary lobectomy: a case control study. BMC Surg. 2014; 14:109. PMC: 4274675. DOI: 10.1186/1471-2482-14-109. View

19.

Inoue Y, Saiura A, Yoshioka R, Ono Y, Takahashi M, Arita J . Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic Anterior Artery-first Approach. Ann Surg. 2015; 262(6):1092-101. DOI: 10.1097/SLA.0000000000001065. View

20.

Probst P, Knebel P, Grummich K, Tenckhoff S, Ulrich A, Buchler M . Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study. Ann Surg. 2015; 264(1):87-92. DOI: 10.1097/SLA.0000000000001372. View