The study has demonstrated an excellent consistency of agreement of ROTEM FIBTEM A5 and A10, with an ICC (95% CI) of 0.972 (0.969–0.975) across a large cohort of trauma patients. This level of consistency of agreement was maintained within all subgroups analysed and importantly in the groups of major trauma (ISS ≥ 12) and massive transfusion (≥ 10 units PRCs in 24 hr). These sub-groups who are critically unwell are most likely to derive a treatment benefit from quicker identification and treatment of hypofibrinogenaemia during resuscitation and in which demonstrating reliability of FIBTEM A5 as a surrogate for A10 is most useful. Based on ROTEM results, locally published data demonstrate that teams can expect to deliver fibrinogen concentrate to such patients within 30 minutes or cryoprecipitate within 60 minutes (20, 21). Early ROTEM values (by virtue of being point-of-care) have shorter turnaround times than urgent laboratory coagulation studies; FIBTEM A5 has been measured to have a turnaround time of 12 minutes versus 37 minutes for Clauss fibrinogen (15). The authors of this study are not aware of a study directly measuring turnaround time of A5 versus A10 results, but theoretically a five-minute difference would be expected. In severely bleeding patients, this potentially allows for identification and correction of coagulopathy earlier. It should be noted that multiple assays are often performed over the course of a resuscitation and this time benefit could be present at each stage. This study further supports the use of FIBTEM A5 over A10 as a rapid decision-making tool for targeted resuscitation of coagulopathy in trauma.
To the authors’ knowledge the consistency of agreement and magnitude of differences between FIBTEM A5 and A10 has not been reported previously in the field of trauma. Strong correlations (albeit inappropriate Pearson or Spearman correlation (22)) have been demonstrated in elective surgery (cardiac and non-cardiac) studies (13–15). Similarly, strong correlations have been observed in trauma between other related ROTEM values: FIBTEM A5 and MCF; A10 and MCF (23) and EXTEM A5 and A10 and MCF (16). The intra-class correlation was used in this study (versus Pearson correlation) as it validly provides a more robust measure of consistency of agreement for the comparison of two diagnostic tests measuring the same clinical concept (24, 25).
The findings demonstrate FIBTEM A10 had a bias of 1.49 mm from A5 (A10 result was on average 1.49 mm greater than its corresponding A5 result). This was in line with our hypothesis: a positive difference is to be expected as the blood clot has had five more minutes to strengthen between the A5 and A10 result. This bias was used to modify our existing fibrinogen replacement threshold with cautious success. Our institution’s protocol for fibrinogen replacement in trauma haemorrhage has two criteria: 1) clinical suspicion of significant ongoing haemorrhage and 2) ROTEM FIBTEM A5 < 11 mm (Appendix 1). The protocol was initially constructed as A10 < 11 mm as this was felt to better represent hypofibrinogenaemia at the time. Over time this was approximated to A5 < 11 mm to give a time-saving benefit.
Our analyses identified that 27.8% patients (424 of 1525) met the current ROTEM threshold (A5 < 11 mm) for fibrinogen replacement. Use of the original threshold (A10 < 11 mm) would have resulted in 19.3% (295 of 1525) meeting criteria. Use of the A5 value with the original threshold for replacement therefore qualified an additional 129 patients (8.5%): this is a relative increase of 43.7%. Only a small minority of these extra patients (six) received fibrinogen replacement. The most likely reason for this is that for the majority there was no clinical suspicion of bleeding. Nonetheless, use of the current A5-based criterion might predispose to increased replacement of fibrinogen. Unnecessary replacement of fibrinogen with fibrinogen concentrate, cryoprecipitate or fresh frozen plasma is undesirable. There is a relatively unknown degree of risk of iatrogenic harm from the products themselves (26, 27); misinterpretation of a ‘step-wise’ algorithm could lead to failure to correct other abnormal variables; and all methods of replacement are financially costly (28).
Our modification of the A5 threshold resulted in 19.28% meeting the replacement criterion. This is noted to be almost exactly the same proportion as using the original threshold of A10 < 11 mm. In similar cohorts of trauma patients, Rourke et al (9) and Baksaas Aasen et al (12) found that FIBTEM A5 thresholds of 9.5 mm and 10 mm respectively were optimal for detecting laboratory Clauss hypofibrinogenaemia of < 1.5 g/l and < 2.0 g/l with sensitivities (specificities) of 78% (70%) and 70% (76%). The current study did not include receiver operating curve analysis comparing FIBTEM A5 to Clauss fibrinogen and so we cannot provide direct validity to these thresholds. These studies demonstrate that there is no consensus as to what level of hypofibrinogenaemia should trigger transfusion. However, it is likely that our threshold of FIBTEM A5 < 10 mm corresponds to Clauss hypofibrinogenaemia < 1.5–2.0 g/l. Further work is required to develop a consensus ROTEM FIBTEM threshold for replacement of fibrinogen in the context of trauma(11).
The authors acknowledge several limitations to the current study. Whilst it includes every patient who had a ROTEM on admission, not all trauma patients had a ROTEM. However, the likely bias in the study in this case would be towards including more severe trauma and this is the cohort of most clinical relevance. The particular viscoelastic haemostatic device used was ROTEM Delta. This is a multi-step, partially manual assay that was performed by clinicians in an emergency trauma setting. Whilst all users had training there are multiple stages where errors could occur. The fully automated ROTEM Sigma assay was not studied. Finally, the analyses of numbers of patients meeting different FIBTEM criteria for fibrinogen replacement were retrospective and theoretical: throughout the study period the clinical criterion used was the ‘current’ threshold of A5 < 11 mm.