Assessing the efficacy of prothrombin complex concentrate in multiply injured patients with high-energy pelvic and extremity fractures

Coagulopathy of trauma (COT) has been demonstrated to increase mortality after major trauma. It is a common issue, with up to 25% of serious trauma patients exhibiting clinically-significant coagulopathy. The condition arises as a result of tissue trauma, hypoperfusion, haemodilution and inflammation. Recent developments in trauma care have suggested a damage control resuscitation approach – comprising liberal administration of blood products, replacement of clotting factors and minimising crystalloid fluid. Used for both volume and clotting factor replacement, FFP has been a standard treatment in this setting for some time, but studies demonstrating a faster coagulation correction with recombinant factor VIIa, and the less expensive alternative, PCC, have gained increased recognition. The use of these treatments has not been reported in the setting of multiply injured lower limb and pelvic fracture patients – a recognition which provoked this study.

The authors analysed a prospectively-maintained database, selecting all patient cases with a high-energy fracture of the femur, tibia or pelvic ring who had presented with an INR of ≥1.5 that was not explained by other causes. They separated the data into two populations (those who initially received PCC or FFP), and carried out propensity matching on a 1:2 ratio to control for demographic, injury and clinical factors which may have influenced the data. Primary outcomes were: whether INR was corrected (defined as <1.5), time to INR correction, thromboembolic complications and blood products used.

There were 81 patients included in the final analysis; 27 patients received PCC, 54 received FFP. The mean age of the patients was 49, with blunt injury the most common mechanism, while motorcycle accident was the most frequent mode of injury. The time to initiation of therapy and overall correction of INR was similar between the treatment groups. The patients receiving PCC had a significantly faster correction of INR compared to the FFP group (mean 285 versus 490 mins; p=0.0001), less time to surgical fixation (mean 324 versus 702 mins; p=0.0002) and fewer blood products administered (mean packed red cells: 3.2 versus 5.4 units; p=0.009; mean overall FFP: 5.1 versus 7.8 units; p=0.005). There was no significant difference in rate of development of thromboembolic complications. The cost of therapy was higher for the PCC group, but given the additional transfusion costs, overall hospital costs and patient charges for the FFP group, the total costs were not significantly different.

In their discussion, the authors remark on the recognition in the literature that correction of COT is an important aspect of management, and that this study demonstrates a promising role for PCC. Early operative fixation is linked with shorter stays and fewer complications – reduced mortality, fewer thromboembolic complications and less cases of malunion. There is potential for the required ABO matching and thawing of FFP to delay that process – although the time to administration was not shown to be significantly longer. Consistent with the current literature was the finding that patients receiving PCC needed fewer blood products overall, and did not have a higher incidence of thromboembolic complications.

This study was limited by its retrospective, non-randomised nature, allowing for potential biases to influence results. The population studied was also small, and as the authors acknowledge, there was no universal protocol for coagulation testing.

Due to the potential volume of haemorrhage in long bone and pelvic fractures, the question of how best to correct both organ perfusion and coagulopathy is one that is less straightforward than it may initially appear. This study, alongside a similar investigation led by the same author (Joseph B et al., 2014), are beginning to establish relevant evidence to shape protocols for these treatment areas.