Which is the most effective strategy: early detection of coagulopathy with thromboelastometry or use of hemostatic factors or both?

In an article in the previous issue of Critical Care, Schochl and colleagues suggested that, in trauma patients, a hemostatic strategy combining the use of fi brino gen concentrates or prothrombin complex concen trates (PCCs) (or both) guided by thromboelastometry resulted in a reduction of exposure to allogeneic blood products when compared with a strategy using fresh frozen plasma (FFP) guided by standard coagulation assays [1]. Th e primary concern with this analysis is the comparison of a series of patients treated at a single center with a highly protocolized approach to transfusion against a registry-based cohort of patients from multiple centers with no standardized protocol. Also, several very specifi c biases introduced into the analysis are of concern. First, the time required to obtain a hemostatic result varied greatly between groups, ranging from less than 15 minutes with the rotation thrombelastography (ROTEM) to usually more than 45 to 60 minutes in the standard group [2]. Th e timing of coagulation component replacement must be factored into this analysis. Th e second bias centers around the concentration of fi brinogen delivered: 3 g of fi brinogen (median of 6 units of FFP) in the FFP group versus a median of 6 g in the fi brinogenPCC group. Previous reports have demonstrated a close relationship between blood loss and fi brinogen level [3,4].

In an article in the previous issue of Critical Care, Schöchl and colleagues suggested that, in trauma patients, a hemostatic strategy combining the use of fi brino gen concentrates or prothrombin complex concen trates (PCCs) (or both) guided by thromboelastometry resulted in a reduction of exposure to allogeneic blood products when compared with a strategy using fresh frozen plasma (FFP) guided by standard coagulation assays [1]. Th e primary concern with this analysis is the comparison of a series of patients treated at a single center with a highly protocolized approach to transfusion against a registry-based cohort of patients from multiple centers with no standardized protocol. Also, several very specifi c biases introduced into the analysis are of concern. First, the time required to obtain a hemostatic result varied greatly between groups, ranging from less than 15 minutes with the rotation thrombelastography (ROTEM) to usually more than 45 to 60 minutes in the standard group [2]. Th e timing of coagulation component replacement must be factored into this analysis. Th e second bias centers around the concentration of fi brinogen delivered: 3 g of fi brinogen (median of 6 units of FFP) in the FFP group versus a median of 6 g in the fi brinogen-PCC group. Previous reports have demonstrated a close relationship between blood loss and fi brinogen level [3,4].
Finally, it should be noted that thromboelastometry is not mandatory for the use of PCC and fi brinogen [5]. Although the use of thromboelastometry and a hemostatic strategy combining fi brinogen and PCC is very attractive, further controlled studies will have to determine which part of this strategy is really eff ective: early detection of coagulopathy or a combination of hemostatic factors or both?

Herbert Schöchl and Cristina Solomon
We thank David and colleagues for their comments. We acknowledged in our paper that there are limitations to the comparison of patients treated in one center according to a protocol with those from multiple centers with no standardized protocol. Th us, our results are not as robust as those from randomized controlled trials but do represent the only published controlled study of combined fi brinogen concentrate and PCC in trauma.
David and colleagues described two biases, which relate to diff erences in time taken to obtain hemostatic results and fi brinogen dose. However, these are not biases. Instead, they represent inherent diff erences between the two treatment approaches and their inclusion ensures that the study is applicable to clinical practice. Th e point regarding fi brinogen dose is interesting as the dose of FFP required to increase the fi brinogen level by a certain amount is dependent on the starting point. Much higher volumes are needed to increase the fi brinogen level from 1 to 1.5 g/L compared with 0.5 to 1.0 g/L. Th e dose-response curve for fi brinogen administered via FFP is not linear, and the required dose increases exponentially as the target level approaches 2 g/L, which is the mean concentration in FFP [6]. David and colleagues comment that use of thromboelastometry is not mandatory. Although this is true, the risk-benefi t profi le of coagulation factor concentrates can almost certainly be improved by thromboelastometry. In thromboelastometry (in contrast to fi xed-dose therapy), assessment of the patient's coagulation status before treatment and monitoring of the post-treatment response (feedback loop) allow under-or over-treatment to be avoided.
Th e improvements reported in our study are attributable to changes in both therapy and diagnostics. We agree that it would be interesting to prospectively assess the relative contributions of these two aspects.

Competing interests
This study was performed without external funding. HS, CS, and MM have received honoraria as speakers and research support from CSL Behring (King of Prussia, PA, USA) (manufacturer of fi brinogen concentrate and PCC) and Tem International GmbH (Munich, Germany) (manufacturer of the TEM device). AH has received honoraria as speaker and research support from CSL Behring. GH is an employee of CSL Behring. All other authors declare that they have no competing interests. Editorial assistance was provided by Ken Sutor, of Fishawack Communications Ltd (Knutsford, UK), during late-stage development of this manuscript. Financial support for this assistance was provided by CSL Behring GmbH.