Prothrombin complex concentrate reversal of coagulopathy in emergency general surgery patients

 As such, mortality rates are predicted to be 8 times higher in patients undergoing EGS compared to those undergoing similar elective procedures (Havens et al., 2015). Patients being prescribed anticoagulation treatments are at an increased risk of major bleeding during EGS due to depletion of clotting factors. However, correcting INR pre-operatively can be time consuming and cause delays to surgical interventions. How can anticoagulation be reversed rapidly, while ensuring adverse events are kept to a minimum? In this study, Younis et al. compared reversal agents administered to coagulopathic patients undergoing EGS hoping to uncover a solution to this complex problem.

Traditional forms of reversal come with challenges; vitamin K can take between 4–8 hours to correct INR while fresh frozen plasma (FFP) requires thawing before administration taking 1–2 hours (Chapman et al., 2011). Prothrombin complex concentrate (PCC), however, may offer a more rapid replacement of vitamin K-dependent clotting factors. Currently, PCC is recommended for the reversal of warfarin and to control major bleeding in urgent surgery; a potential solution for rapid coagulopathy reversal prior to EGS (Kozek-Langenecker et al., 2013; National Advisory Committee on Blood and Blood products, 2014).

Measuring the effectiveness of 3-factor PCC in EGS

Investigating the efficacy and safety of PCC, Younis et al. conducted a single institution retrospective analysis of patient records between 2008–2016. The outcomes of EGS in 183 coagulopathic (INR ≥1.5) patients treated with 3-factor PCC (3F-PCC) only, FFP only, or a combination of 3F-PCC and FFP were compared. The treatment decision was at the discretion of the surgeon, and the dose was based on the INR value.

While the demographics between the three groups (3F-PCC only, FFP only, or combination) were similar, it is important to note that patients in the 3F-PCC only group were significantly older than the other groups (p=0.02). In addition, significantly more patients with liver cirrhosis were administered combination therapy (n=8/13) compared to the other groups (p=0.004).

Time to incision

The primary outcome was time from clinical decision of required surgery to time of incision allowing comparison of the speed at which the different reversal agents are administered and reverse coagulopathy.

A significant reduction in the mean time to incision was seen for 3F-PCC compared to FFP only, both in the 3F-PCC only group and the combination group (Figure 1).

Preoperative outcomes

Minimising blood loss prior to surgery is vital to minimise adverse events during surgery and to aid post-operative recovery. Interestingly, the group receiving the most packed red blood cells (PRBC) preoperatively were the combination treatment group (1.1 ± 0.3 combination vs. 0.4 ± 0.2 FFP only vs. 0.1 ± 0.4 3F-PCC only; p=0.0006). The need for PRBCs prior to surgery may have disadvantaged this group when comparing overall surgery success and recovery due to higher rates of blood loss.

The time from reversal agent administration to incision was also significantly greater in the combination group than 3F-PCC only and FFP only groups (8.3 ± 5.9 combination vs. 4.2 ± 3.1 3F-PCC only; p=0.01: 8.3 ± 5.9 vs. 5.6 ± 4.0 FFP only; p=0.01). It is unclear why this difference was seen, but the greater need for PRBCs prior to surgery may have delayed the incision time.

Improvement in INR

The overall change in INR and rate of INR correction are also important indicators or reversal speed and effectiveness. For both the change and rate in INR correction, 3F-PCC only was greater than FFP only. Both the change in INR (3F-PCC only 1.7 [interquartile range [IQR] 1.2–2.8] vs. FFP only 0.7 [IQR 0.4-1.4]; p=0.0005) and rate of INR correction (3F-PCC only 0.22 [IQR 0.17-0.44] vs. FFP only 0.10 [IQR 0.05–0.22]; p=0.001) were significantly different between the 3F-PCC only and FFP only groups. Furthermore, higher rates were also seen in the combination group than the FFP only group (change in INR 1.2 [IQR 0.8–3.2] vs. 0.7 [IQR 0.4–1.4]; p=0.002; rate of INR correction 0.28 [IQR 0.11–0.44] vs. 0.10 [IQR 0.05–0.22]; p=0.0003).

Postoperative outcomes

The key postoperative outcomes were length of hospital stay, occurrence of complications and mortality rates. Interestingly, no significant differences were seen across the three groups for mortality and complications. However, length in ICU stay was greater in the combination group than the FFP only group. The reasons for this are unclear, although the combination group may have been disadvantaged by the higher number of patients with liver cirrhosis or the greater need of preoperative PRBCs.

In this study 3F-PCC either alone or in combination with FFP has demonstrated a reduction in time to incision, increased improvement in INR and greater rates of INR normalisation, with minimal thromboembolic complications when compared to FFP alone. This would suggest that 3F-PCC can provide rapid reversal of coagulopathy prior to EGS with a good safety profile. Further prospective multi-institutional studies are required to evaluate the clinical outcomes of PCC in EGS and validate this practice.