Elsevier

Injury

Volume 42, Issue 7, July 2011, Pages 697-701
Injury

The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion

https://doi.org/10.1016/j.injury.2010.12.015Get rights and content

Abstract

Introduction

Clinical observations together with recent research highlighted the role of coagulopathy in acute trauma care and early aggressive treatment has been shown to reduce mortality.

Methods

Datasets from severely injured and bleeding patients with established coagulopathy upon emergency room (ER) arrival from two retrospective trauma databases, (i) TR-DGU (Germany) and (ii) Innsbruck Trauma Databank/ITB (Austria), that had received two different strategies of coagulopathy management during initial resuscitation, (i) fresh frozen plasma (FFP) without coagulation factor concentrates, and (ii) coagulation factor concentrates (fibrinogen and/or prothrombin complex concentrates) without FFP, were compared for morbidity, mortality and transfusion requirements using a matched-pair analysis approach.

Results

There were no major differences in basic characteristics and physiological variables upon ER admission between the two cohorts that were matched. ITB patients had received substantially less packed red blood cell (pRBC) concentrates within the first 6 h after admission (median 1.0 (IQR25–75 0–3) vs 7.5 (IQR25–75 4–12) units; p < 0.005) and the first 24 h as compared to TR-DGU patients (median 3 (IQR25–75 0–5) vs 12.5 (8–20) units; p < 0.005). Overall mortality was comparable between both groups whilst the frequency for multi organ failure was significantly lower within the group that had received coagulation factor concentrates exclusively and no FFP during initial resuscitation (n = 3 vs n = 15; p = 0.015). This translated into trends towards reduced days on ventilator whilst on ICU and shorter overall in-hospital length of stays (LOS).

Conclusion

Although there was no difference in overall mortality between both groups, significant differences with regard to morbidity and need for allogenic transfusion provide a signal supporting the management of acute post-traumatic coagulopathy with coagulation factor concentrates rather than with traditional FFP transfusions. Prospective and randomised clinical trials with sufficient patient numbers based upon this strategy are advocated.

Introduction

Uncontrolled haemorrhage is still responsible for more than 50% of all trauma-related deaths within the first 48 h after hospital admission.34 Clinical observations together with recent research highlighted the central role of coagulopathy in acute trauma care4, 5, 17, 22, 23 and early recognition and adequate aggressive management have been shown to substantially reduce mortality and improve outcome in severely injured bleeding patients.3, 24 To date, the use of fresh frozen plasma (FFP) is an integral part of massive transfusion protocols in most trauma centers30, 31 and its early use has been advocated.14 Several retrospective studies have demonstrated a survival benefit for bleeding trauma patients when transfused with an early high red blood cell (RBC):FFP 1:1 ratio both in civilian and military settings.3, 15, 24, 39 However, these results may have been influenced by the fact that quite a few patients died before having had the chance to receive any FFP transfusion, suggesting a considerable bias of results.27 Interestingly, prospectively collected data could not confirm a beneficial effect of aggressively transfused FFP in trauma patients.35 Moreover, there are several well-established risks together with FFP administration in trauma and other critical states of illness, for example transfusion associated cardio-circulatory overload (TACO), acute lung injury (ALI; TRALI), transfusion related immunomodulation (TRIM) and increased susceptibility for infection.7, 33, 39 In the UK, the SHOT (Serious Hazards of Transfusion) database has documented 162 cases of TRALI (Transfusion Related Lung Injury) over the recent 8 years including 36 deaths and 93 cases of major morbidity to identify TRALI as the most prominent cause of transfusion-related morbidity and mortality.38, 40 In addition, the efficacy of FFP in timely correcting coagulation factor deficiency can be questioned.8, 16

Meanwhile, several groups have focused on a more selective approach to correct dilutional coagulopathy as occurring during major surgery and acute coagulopathy of trauma (ACT) by administering specific coagulation factor concentrates according to primary deficiency identified by rotation thromboelastometry (ROTEM®) instead or combined with FFP.26, 37 Fibrinogen and prothrombin complex concentrates (PCC) which are licenced in several European countries for the treatment of congenital and acquired deficiency have previously been given with success to trauma patients and the amount of fibrinogen administered has been correlated with survival after trauma.6, 9, 11, 36, 41 Trauma alters fibrinogen metabolism in several ways: (i) haemorrhage – accelerates fibrinogen breakdown; (ii) hypothermia – inhibits fibrinogen synthesis; and, (iii) acidosis – accelerates fibrinogen breakdown.25, 36 Additionally, intravenous fluids necessary for maintaining normovolaemia further promote a decrease of fibrinogen levels and also interfere with fibrin polymerisation.11, 13, 19, 25

The use of fibrinogen concentrate in trauma patients with coagulation defects may facilitate early correction of ATC by eliminating the time delay associated with cross-matching, thawing and transfusion of FFP, by a known concentration administered and might be beneficial by reducing transfused volumes and thus reducing the potential harmful risks associated with allogeneic blood transfusions.37

In the present study, the datasets from severely injured and bleeding patients with established coagulopathy upon emergency room (ER) arrival derived from two retrospective trauma databases, (i) TraumaRegistry of the Deutsche Gesellschaft für Unfallchirurgie/German Society for Trauma Surgery (TR-DGU/Germany) and (ii) Innsbruck Trauma Databank (ITB/Austria), that had received two different strategies of coagulation management during initial resuscitation, (i) FFP without coagulation factor concentrates, and (ii) coagulation factor concentrates without FFP, were compared with respect to morbidity, mortality and transfusion requirements using a matched-pair analysis approach.

Section snippets

Materials and methods

Two retrospective trauma databases, (i) the TraumaRegistry of the Deutsche Gesellschaft für Unfallchirurgie/German Society for Trauma Surgery (TR-DGU/Germany),32, 42 and (ii) the Innsbruck Trauma Databank (ITB/Austria) were reviewed to identify all primary admitted adult patients (age ≥18 and ≤70 years) from January 1, 2005 to December 31, 2007 who had sustained a severe blunt trauma as reflected by an Injury Severity Score (ISS) ≥16 and a base excess (BE) ≤−2.0 mmol/l upon ER admission. Only

Results

The screening process for age, primary admission, severe blunt trauma to thorax, abdomen and/or extremities (ISS ≥ 16), shock upon ER admission (BE ≤ −2.0 mmol/l) and outcome identified 2147 patients in the TR-DGU and 72 patients in the ITB. For the next step, all criteria for match-code building and all data on coagulation management had to be complete and available leaving 293 patients in the TR-DGU and 18 in the ITB to be finally analysed. All 18 ITB patients could be matched to a corresponding

Discussion

The aim of the present study was to compare two different strategies of coagulopathy management during initial resuscitation, (i) FFP-based treatment, and (ii) coagulation factor concentrate-based treatment, with respect to morbidity, mortality and transfusion requirements using a matched-pair analysis approach on the basis of datasets from two comparable groups of severely injured and bleeding patients with established coagulopathy upon ER arrival derived from two large retrospective trauma

Conclusions

Albeit we did not observe a difference in the overall mortality rate between both groups, significant differences with regard to morbidity and allogenic transfusions provide a strong signal supporting the management of acute post-traumatic coagulopathy with coagulation factor concentrates rather than with traditional FFP transfusions. Prospective and randomised clinical trials with sufficient patient numbers based upon this strategy are strongly advocated.

Conflict of interest statement

In the past 5 years, Petra Innerhofer has received educational grants or honoraria for consulting or lecturing, costs incurring for travel and hotel accommodations and as partial support for conducting studies (without influence on study design, statistics and manuscript preparation) from the following companies: Abbott GmbH (Vienna, Austria), Baxter GmbH (Vienna, Austria), B. Braun Melsungen GmbH (Melsungen, Germany), CSL Behring GmbH (Marburg, Germany), Fresenius Kabi GmbH (Graz, Austria),

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