The present study compared TEM-guided haemostatic therapy using fibrinogen concentrate and PCC, with standard FFP-based therapy, in trauma patients. RBC transfusion was avoided in 29% of patients in the fibrinogen-PCC group, and these patients received no transfusion of any allogeneic blood products. In contrast, RBC transfusion was avoided in only 3% of patients in the FFP group. Transfusion of platelet concentrate was avoided in 91% of patients in the fibrinogen-PCC group, compared with 56% in the FFP group. In our trauma centre, TEM-guided haemostatic therapy with fibrinogen concentrate and PCC has been associated with a continuing decrease in the use of all types of allogeneic blood products.
Minimising or avoiding exposure to allogeneic blood products is clearly desirable. The reasons for developing alternative treatments include intermittent supply shortages and public concern regarding the safety of allogeneic blood products [20, 21]. Transfusion of FFP, for instance, carries the risk of transfusion-related lung injury, transfusion-associated circulatory overload, acute respiratory distress syndrome, transfusion-related immunomodulation and pathogen transmission [22–24]. Attempts to reduce FFP transfusion are complicated by the fact that small quantities of FFP are not effective in correcting coagulopathy [25, 26]. Therefore, administration of FFP in larger amounts should be recommended, but high doses may have a dilutional effect on haematocrit, leading to an increase in RBC transfusion. In contrast, our study showed a reduction in RBC and platelet concentrate transfusion among patients treated with fibrinogen concentrate and PCCs. High levels of fibrinogen increase maximum clot firmness even in patients with a low platelet count, suggesting possible compensation for reduced platelet levels (it is hypothesised that an increased number of fibrin molecules binding a smaller number of platelets may be feasible without compromising clot integrity) [13, 14]. The explanation for reduced RBC transfusion is more uncertain, but coagulation factor concentrates may provide faster cessation of bleeding and reduced haemodilution compared with allogeneic blood products. Due to their low volume of administration, coagulation factor concentrates are also likely to have a smaller effect on haematocrit. The use of TEM to diagnose coagulopathy may additionally help reduce RBC and platelet concentrate transfusion. There is increasing evidence of the usefulness of viscoelastic methods for diagnosing trauma-induced coagulopathy [12, 27–29], and several reports have described a reduction in transfusion requirements following its introduction to treatment algorithms [30–32].
Our approach to managing coagulopathy in trauma patients focuses on the use of fibrinogen concentrate and PCC, which are quicker to administer than allogeneic blood products. Several groups have suggested that reducing the time to administer haemostatic therapy may improve patient outcomes [8–10]. Our group recently described an algorithm of goal-directed coagulation therapy with fibrinogen and PCC in major trauma patients , and in that study 52% of patients received the first dose of fibrinogen concentrate within the first hour, most of them within 30 minutes. In contrast, in a study published by Snyder et al., the first unit of FFP was typically administered at a median of 93 minutes after arrival at the ER . Such delay may be related to the need for blood group matching, thawing and warming of FFP before administration (thawing and warming usually take about 30 minutes). It may be possible to address this delay, for example by storing thawed plasma for immediate application . The use of pre-defined transfusion packages has also been described . Most trauma centres use defined transfusion packages containing cooled RBC and frozen or thawed FFP. Unfortunately, thawing FFP in advance may have negative consequences, because unused thawed units must be discarded. To reduce apparent wastage, physicians may be tempted to overuse FFP. This tendency must be considered in the context of today's economic and administrative pressures, because the costs of blood products are high and often underestimated . The time to infuse medication is another consideration. In general, it is recommended that one unit of FFP is administered over a period of about 30 minutes. In contrast, typical doses of fibrinogen concentrate and PCC may be administered in less than 10 minutes [16, 36], and plasma levels of the coagulation factors administered rise rapidly after infusion.
This study was not designed to establish whether TEM-guided haemostatic therapy with fibrinogen concentrate and PCC improves mortality. Large numbers of patients would be required to provide statistically robust evidence on mortality . We nevertheless report an encouraging trend towards lower mortality in the fibrinogen-PCC group compared with the FFP group: 7.5% versus 10.0% (P = 0.69). One factor likely to affect survival is the speed of administration of haemostatic therapy - as discussed above, TEM-guided haemostatic therapy with fibrinogen concentrate and PCC may be advantageous from that point of view. The quantity of fibrinogen administered may also affect mortality rates. Stinger et al. reported correlations between the amount of fibrinogen administered and blood loss and survival in severely bleeding patients from the Iraq war . Successful haemostatic therapy with fibrinogen concentrate has been described in other settings involving extensive surgery and blood loss (e.g., cardiovascular surgery) [39–41]. Successful use of PCC to treat acquired coagulopathy in the perioperative setting has previously been reported, albeit in limited numbers of patients [11, 12, 42, 43]. Animal experiments have suggested that PCC may be more effective than FFP in the trauma setting , whereas Austrian guidelines recommend PCC administration in bleeding patients if clotting time measured by thrombelastography (TEG)/TEM is prolonged . In the present study, PCC was administered to treat bleeding when clotting time in the EXTEM assay was prolonged.
The study inclusion criteria aimed at minimise between-group differences in patient characteristics. The choice of 1 g fibrinogen/500 U PCC as inclusion criteria was based on practical therapy. The minimum amount of fibrinogen concentrate administered in clinical practice is 1 g, and patients from the STC were eligible for inclusion in the study once they had received this dose. Similarly, the minimum dose of PCC was 500 U. We chose 2 units of FFP as the criterion for the comparator group because this dose should contain approximately 1 g of fibrinogen , thus enabling comparison with the fibrinogen-PCC group.
The data analysis revealed some between-group differences in patient characteristics, and these are worthy of consideration. Although ISS, TRISS, RISC and AIS for abdomen and extremity were not significantly different, there was a significant trend towards more severe head and chest trauma in the FFP-group. Surprisingly, however, the score predicting massive transfusion (TASH) was higher in the fibrinogen-PCC group. Furthermore, it is difficult to estimate whether trauma-induced coagulopathy related to hypoperfusion was more pronounced in either of these two groups. On the one hand, blood pressure was significantly lower in the fibrinogen-PCC group, and base deficit was non-significantly lower in this group. On the other hand, both PT (expressed as a percentage) and platelet count were higher in the FFP group (P not significant for platelet count). Had hypoperfusion been more pronounced in the fibrinogen-PCC group, the significantly lower transfusion rates would appear even more encouraging.
The present study has several limitations. Data for the fibrinogen-PCC group were collected retrospectively from only one centre. TR-DGU data are collected via standardised forms from trauma centres throughout central Europe. Although only the main parameters of trauma management and patient outcome are reported and the collection of data was carefully checked, there may be some reporting bias. Furthermore, for some patients included in the study, the data were incomplete - particularly regarding platelet concentrate transfusion. It cannot be ruled out that some centres providing data to the TR-DGU may be using TEM sporadically. As there are currently no publications on the use of TEM in these centres, the impact on our results is difficult to estimate. The present study did not evaluate any safety aspects, such as thromboembolic or infectious complications. The important difference observed in LOS in the hospital between the two groups, although encouraging, may be influenced by local patient management protocols. A prospective study would be needed to confirm which therapeutic approach offers the more favourable outcome.