PROCOAG RCT – Early PCC for Trauma Patients at Risk of Massive Transfusion

April 25, 2023

Written by Seth Walsh-Blackmore

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This well-designed RCT finds early administration of 4-factor prothrombin complex concentrate (PCC) to patients at risk of receiving massive transfusion protocol (MTP) did not reduce 24-hour blood product consumption or mortality but did increase thrombotic events.

Why does this matter?
Observational studies suggest that early administration of PCC reduces blood product consumption and improves survival vs. FFP alone^1,2. A higher level of evidence for this effect could be practice-changing, and now we have it.

Don’t close your blood bank account just yet
This was a double-blind RCT of 12 French level 1 adult trauma centers in patients at risk of MTP. At risk was defined as at least 1 unit packed red blood cells (PRBC) prehospital or within 1 hour of arrival and Assessment of Blood Consumption Score ≥2 or physician clinical assessment.

Patients were randomized within 1 hour of arrival to receive 1mL/kg of PCC or normal saline (NS = placebo). The transfusion protocol was PRBC and fresh-frozen-plasma (FFP) in a 1:1 or 2:1 ratio with platelet concentrate targeting > 50 x 10⁹/L. Fibrinogen was given based on viscoelastic or serum testing. TXA was given prehospital in a majority of patients.

Three-hundred and twenty-four (164 PCC, 160 NS) patients were analyzed, achieving the estimated sample to detect a 25% difference in total units of blood products (PRBC, FFP, platelets) consumed within the first 24 hours. A median of 12U (IQR 5-19) and 11U (6-19) were consumed in the PCC and NS groups, respectively, with an absolute difference of 0.2% (95%CI -2.99% to 3.33%, p=0.72). There was an absolute difference of 11% more thrombotic events at 28 days in the PCC group (95%CI 1% to 21%), RR 1.48 (1.04 to 2.10). No significant differences occurred in 24-hour and 28-day mortality or other secondary outcomes.

Though baselines and protocols were overall well balanced, 10% more placebo patients received prehospital TXA. This is unlikely to have wholly offset PCC benefit, nor would it explain increased thrombotic events with PCC.  They excluded patients known to be anticoagulated, an important group for further study of preemptive PCC administration.

Source
Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial. JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.4080. Online ahead of print.

Works Cited

1. Zeeshan, Muhammad, et al. Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: a nationwide propensity-matched analysis. Journal of Trauma and Acute Care Surgery 87.2 (2019): 274-281.
2. Schöchl, Herbert, et al. Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Critical Care 15.2 (2011): 1-9.