Estimation of Coagulation Factor XIII Activity Based on the Initial Plasma Fibrinogen Level in Trauma

Coagulation factor XIII (FXIII), a plasma transglutaminase, is known as the final enzyme of the coagulation cascade, responsible for a cross-linking of fibrin to strengthen blood clot. It also minimizes fibrin degradation by its cross-linking it with alfa2-antiplasmin molecules. It has been found that similar to plasma fibrinogen level, FXIII activity can be reduced in the early phase of severe trauma. Therefore, its immediate substitution is of potential therapeutic interest in trauma-induced coagulopathy. However, unlike plasma fibrinogen level evaluation, measurement of the FXIII activity is not routinely available. Therefore, targeted substitution of FXIII is practically impossible. The plasma fibrinogen level is routinely measured in severe trauma patients. Based on pathophysiologic assumptions and a limited number of published data we hypothesize that the FXIII activity correlates with fibrinogen level. In such case, indirect FXIII activity prediction by fibrinogen level measurement would be a convenient approach to enable FXIII targeted substitution. Therefore we decided to perform a prospective observational clinical trial to determine whether the low plasma fibrinogen level in severe trauma correlates with decreased FXIII activity.

Study Overview

• Status: Completed
• Conditions: Coagulation Disorder; Multiple Trauma; Coagulation Defect; Acquired; Coagulation Factor Deficiency
• Intervention / Treatment: Diagnostic test: fibrinogen plasma concentration, coagulation factor XIII activity

Detailed Description

Coagulation factor XIII (FXIII), a plasma transglutaminase, is known as the final enzyme of the coagulation cascade, responsible for a cross-linking of fibrin to strengthen blood clot. It also minimizes fibrin degradation by its cross-linking it with alfa2-antiplasmin molecules. It has been found that similar to plasma fibrinogen level, FXIII activity can be reduced in the early phase of severe trauma. Therefore, its immediate substitution is of potential therapeutic interest in trauma-induced coagulopathy. However, unlike plasma fibrinogen level evaluation, measurement of the FXIII activity is not routinely available. Therefore, targeted substitution of FXIII is practically impossible. The plasma fibrinogen level is routinely measured in severe trauma patients. Based on pathophysiologic assumptions and a limited number of published data we hypothesize that the FXIII activity correlates with fibrinogen level. In such case, indirect FXIII activity prediction by fibrinogen level measurement would be a convenient approach to enable FXIII targeted substitution. Therefore we decided to perform a prospective observational clinical trial to determine whether the low plasma fibrinogen level in severe trauma correlates with decreased FXIII activity.

• Study Type: Observational
• Enrollment (Actual): 357

Contacts and Locations

Study Locations

• Czechia
  • Liberecký Kraj
    • Liberec, Liberecký Kraj, Czechia, 46001
      • Krajska Nemocnice Liberec
  • Plzensky Kraj
    • Plzen, Plzensky Kraj, Czechia, 30100
      • Fakultní nemocnice Plzeň
  • Ústecký Kraj
    • Ústí Nad Labem, Ústecký Kraj, Czechia, 40001
      • Masarykova Nemocnice V Usti Nad Labem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients with presumed severe trauma as assessed by the national trauma triage criteria admitted to a participating centre.

Description

Inclusion Criteria:

• a patient with presumed severe trauma admitted to the participating centre

Exclusion Criteria:

• inflammatory disease
• malignant disease
• pregnancy
• receipt of any fibrinogen / coagulation factor XIII product before blood sampling
• patients on dabigatran

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Multiple Trauma patients	Diagnostic test: fibrinogen plasma concentration, coagulation factor XIII activity; blood sampling for a routine coagulation test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
coagulation factor XIII activity	coagulation factor XIII activity expressed as % of the normal value	1 day

Collaborators and Investigators

• Sponsor: Masaryk Hospital Krajská zdravotní a.s.

Publications and helpful links

General Publications

• Dickneite G, Herwald H, Korte W, Allanore Y, Denton CP, Matucci Cerinic M. Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions. Thromb Haemost. 2015 Apr;113(4):686-97. doi: 10.1160/TH14-07-0625. Epub 2015 Feb 5.
• Theusinger OM, Baulig W, Seifert B, Muller SM, Mariotti S, Spahn DR. Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department. Anesth Analg. 2015 Mar;120(3):627-635. doi: 10.1213/ANE.0000000000000561.
• Sorensen B, Fries D. Emerging treatment strategies for trauma-induced coagulopathy. Br J Surg. 2012 Jan;99 Suppl 1:40-50. doi: 10.1002/bjs.7770.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: July 1, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Estimate): January 4, 2023
• Last Update Submitted That Met QC Criteria: December 31, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Wounds and Injuries; Multiple Trauma
• Other Study ID Numbers: KAPIM-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No