Prothrombin complex concentrate versus fresh-frozen plasma for reversal of coagulopathy of trauma: is there a difference?

Acute coagulopathy of trauma develops following severe injury and blood loss, occurring primarily as a result of hypoperfusion – also contributed to by consumption and dilution of clotting factors. It is commonly reversed by FFP administration, which provides volume support and replaces clotting factors. Evidence has shown that administration of refined clotting factors, such as recombinant factor VIIa, provide a more rapid correction of coagulopathy. In this role, PCC is a cost-effective alternative to refined clotting factors, although it does not provide volume support. The authors suggest that combination FFP + PCC should provide volume replacement as well as more rapid correction of deranged coagulation.

The authors analysed a database retrospectively. They defined coagulopathy as a patient presenting with an INR of 1.5 or greater in trauma, in the absence of other reasons for the derangement. Propensity matching was carried out to couple the 63 patients in the FFP + PCC group with corresponding patients in the FFP cohort in a 1:3 ratio. Primary outcomes were:

• Correction of INR (to < 1.5)
• Time to correction
• Thromboembolic complications
• Blood product utilisation
• Cost of therapy (FFP or FFP + PCC only)
• Cost of transfusion (therapy cost plus additional blood products administered)

The secondary outcome was any difference in mortality. Statistical analysis was carried out on the results.

The most common cause of injury was blunt trauma. Following the matching process, there were no significant clinical or demographic differences between the two cohorts. There was no significant difference in attaining INR correction, although the mean time to INR correction was significantly faster with FFP + PCC; 394 mins (± 311 [all figures quoted as mean ± 1 SD]) vs. 1,050 mins (± 1,126) (p = 0.001). The overall number of units of packed red cells and FFP required were also significantly less in the FFP + PCC group:

• 6.6 units ± 4.1 [FFP + PCC] vs. 10 units ± 8.3 [FFP] for packed red cells (p = 0.001)
• 2.8 units ± 1.8 [FFP + PCC] vs. 3.9 units ± 1.3 [FFP] for FFP (p = 0.01).

This contributed to a significantly lower overall cost of transfusion, despite a higher therapy cost for PCC + FFP. There were no significant differences in number of thromboembolic events between groups. There was a significantly lower overall mortality rate in the FFP + PCC group (23% [FFP + PCC] vs. 28% [FFP]; p = 0.04). There were no significant differences in hospital or ITU (intensive treatment unit) length of stay, or overall hospital costs between the two groups.

In their discussion, the authors describe the conundrum that currently faces clinicians – tissue hypoperfusion is the main driver of trauma-related coagulopathy, but crystalloid infusion to correct the perfusion exacerbates the coagulopathy. The optimal way of replacing both volume and coagulation factors is yet to be discerned. Recent studies have demonstrated a faster correction of coagulopathy with PCC, while others have shown a survival benefit relating to more rapid coagulopathy correction. This is upheld in the current findings. Remarking on their outcomes, the authors note that the small sample size is a limiting factor and larger-scale studies are needed to demonstrate a clear mortality benefit. They also acknowledge that there was no established clinical PCC-related protocol, and that the retrospective nature may have allowed confounders and bias to have an effect. Timing of the INR serial measurements was irregular and determined by clinician preference – also limiting the potential utility of their findings.

This study fits with current findings of the improved efficacy of coagulation correction conferred by PCC, and seeks to establish a therapeutic combination that is safe and efficacious. A subsequent study by Joseph et al. (2016), has also demonstrated that PCC is safe and effective at reversing coagulopathy of trauma – specifically in patients with lower limb or pelvic fractures.