Prothrombin Complex Concentrate Not Superior to Standard Treatment for Massive Bleeding

April 04, 2023

The administration of a four-factor prothrombin complex concentrate (4F-PCC) to trauma patients with major bleeding had no significant effect on blood product usage in the first 24 hours compared with patients who did not receive the treatment, according to the results of a randomized, placebo-controlled superiority trial.

“Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion,” the researchers wrote in the March 21, 2023 issue of JAMA.

Early administration of coagulation factors is known to improve post-traumatic coagulation disorders. 4F-PCC contains the human coagulation factors II, VII, IX and X along with endogenous inhibitor proteins S and C, and is used for the urgent reversal of acquired coagulation factor deficiency in in patients with warfarin- or coumadin-induced acute major bleeding. The researchers hypothesized that the use of 4F-PCC might reduce blood product consumption in the setting of massive bleeding.

However, there was no statistically or clinically significant difference between the groups in terms of median (interquartile range) total 24-hour blood product consumption — 12 units for those who received the treatment compared with 11 units in the placebo group.

The researchers also looked at safety of 4F-PCC in terms of arterial and venous thromboembolic events. Among the patients who received 4F-PCC, 56 patients (35%) presented with at least one thromboembolic event compared with 37 patients (24%) in the placebo group.

The study included 324 patients at the highest trauma level at 12 centers in France; 164 were randomized to receive 4F-PCC. All patients received early ratio-based transfusion (packed red blood cells [RBCs] to fresh frozen plasma [FFP] at a ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.

Acute traumatic coagulopathy (ATC) is common in severe trauma patients (around 25 to 30% of patients with severe trauma) and is associated with increased mortality risk, according to the authors. ATC is associated with fibrinogen and clotting factors deficiencies with management relying on early administration of fibrinogen and blood products in the case of massive transfusion using a 1:1 or 1:2 ratio of FFP to RBC. However, this strategy relies on fast supply of FFP, which is not always possible, they noted.

To overcome delays associated with FFP, the PROCOAG study examined the use of 4F-PCC as alternative to treat coagulation factor deficiency. In addition to fibrinogen treatment, it is thought that PCC can be efficient in ATC management, while reducing risks associated with massive transfusion, according to the authors.