1.
First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion-Further Results of the RETIC Study
Innerhofer N, Treichl B, Rugg C, Fries D, Mittermayr M, Hell T, Oswald E, Innerhofer P, On Behalf Of The Retic Study Group
Journal of clinical medicine. 2021;10(17)
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Abstract
Fibrinogen supplementation is recommended for treatment of severe trauma hemorrhage. However, required dosages and aimed for post-treatment fibrinogen levels remain a matter of discussion. Within the published RETIC study, adult patients suffering trauma-induced coagulopathy were randomly assigned to receive fibrinogen concentrate (FC) as first-line (n = 50) or crossover rescue (n = 20) therapy. Depending on bodyweight, a single dose of 3, 4, 5, or 6 g FC was administered and repeated if necessary (FibA10 < 9 mm). The dose-dependent response (changes in plasma fibrinogen and FibA10) was analyzed. Receiver operating characteristics (ROC) analysis regarding the need for massive transfusion and correlation analyses regarding fibrinogen concentrations and polymerization were performed. Median FC single doses amounted to 62.5 (57 to 66.66) mg.kg(-)(1). One FC single-dose sufficiently corrected fibrinogen and FibA10 (median fibrinogen 213 mg.dL(-1), median FibA10 11 mm) only in patients with baseline fibrinogen above 100 mg.dL(-1) and FibA10 above 5 mm, repeated dosing was required in patients with lower baseline fibrinogen/FibA10. Fibrinogen increased by 83 or 107 mg.dL(-1) and FibA10 by 4 or 4.5 mm after single or double dose of FC, respectively. ROC curve analysis revealed post-treatment fibrinogen levels under 204.5 mg.dL(-)(1) to predict the need for massive transfusion (AUC 0.652; specificity: 0.667; sensitivity: 0.688). Baseline fibrinogen/FibA10 levels should be considered for FC dosing as only sufficiently corrected post-treatment levels limit transfusion requirements.
PICO Summary
Population
Patients with major trauma enrolled in the RETIC study (n= 70).
Intervention
Fibrinogen concentrate (FC) as first line medication (n= 50).
Comparison
FC as crossover rescue medication (n= 20).
Outcome
The dose-dependent response (changes in plasma fibrinogen and FibA10) was analysed. Median FC single doses amounted to 62.5 (57 to 66.66) mg.kg(-)(1). One FC single-dose sufficiently corrected fibrinogen and FibA10 (median fibrinogen 213 mg.dL(-1), median FibA10 11 mm) only in patients with baseline fibrinogen above 100 mg.dL(-1) and FibA10 above 5 mm, repeated dosing was required in patients with lower baseline fibrinogen/FibA10. Fibrinogen increased by 83 or 107 mg.dL(-1) and FibA10 by 4 or 4.5 mm after single or double dose of FC, respectively. Receiver operating characteristics curve analysis revealed post-treatment fibrinogen levels under 204.5 mg.dL(-)(1) to predict the need for massive transfusion (AUC 0.652; specificity: 0.667; sensitivity: 0.688).
2.
Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study
Ziegler B, Bachler M, Haberfellner H, Niederwanger C, Innerhofer P, Hell T, Kaufmann M, Maegele M, Martinowitz U, Nebl C, et al
European journal of anaesthesiology. 2020
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Abstract
BACKGROUND Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients. OBJECTIVE The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed. DESIGN A prospective, randomised, placebo-controlled, double-blinded, international clinical trial. SETTING This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015. PATIENTS A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo. INTERVENTIONS Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre. MAIN OUTCOME MEASURES Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug. RESULTS Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P < 0.0001). Median fibrinogen plasma concentrations in the fibrinogen concentrate Group were kept above the recommended critical threshold of 2.0 g l throughout the observation period. CONCLUSION Early fibrinogen concentrate administration is feasible in the complex and time-sensitive environment of prehospital trauma care. It protects against early fibrinogen depletion, and promotes rapid blood clot initiation and clot stability. TRIAL REGISTRY NUMBERS EudraCT: 2010-022923-31 and ClinicalTrials.gov: NCT01475344.
PICO Summary
Population
Trauma patients with major bleeding and in need of volume therapy (n= 53).
Intervention
Fibrinogen concentrate (FC), prehospital at the scene or during transportation to the study centre (n=28).
Comparison
Placebo (n= 25).
Outcome
Median maximum clot firmness in the FIBTEM assay decreased in patients receiving placebo between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5mm to 11mm, but increased in patients receiving FC from 13mm to 15mm. The median between-group difference in the change in FIBTEM MCF was 5mm.
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Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion-A Sub-Study of the Randomized Controlled RETIC Trial
Tauber H, Innerhofer N, von Langen D, Ströhle M, Fries D, Mittermayr M, Hell T, Oswald E, Innerhofer P
J Clin Med. 2020;9(8)
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Abstract
Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study "Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma" trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 10(9) /L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p =0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome.
PICO Summary
Population
Trauma patients with trauma-induced coagulopathy (TIC) enrolled in the RETIC trial (n= 94).
Intervention
First-line plasma (FFP), (n= 44).
Comparison
Coagulation factor concentrates (CFC), (n= 50).
Outcome
Transfusion rates were significantly higher for FFP 47.7% than CFC 26%. Logistic regression analysis adjusted for the stratification variables injury severity score and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion.