A 19-year-old man is admitted to your trauma center after a gunshot wound to the chest. He is in hemorrhagic shock, and you are considering 4-factor prothrombin complex concentrate (4-PCC) in addition to blood transfusion. According to a recent study that compared 4-PCC with placebo for traumatically injured patients at risk of massive transfusion, which of the following is MOST likely if he receives 4-PCC?

  • □ (A) Similar 24-hour total blood product consumption
  • □ (B) Shorter time to hemorrhage control
  • □ (C) More ventilator-free days

Trauma-induced coagulopathy is one of the main causes of mortality in a trauma patient. Severe tissue damage and hemorrhagic shock managed with transfusion can lead to the inability to form and maintain a clot, resulting in the lethal triad of trauma: acidosis, coagulopathy, and hypothermia. High fixed-ratio blood product transfusion, viscoelastic testing-guided transfusion, or a combination of the two are approaches used to mitigate trauma-induced coagulopathy. One key principle used in these strategies is early transfusion of coagulation factors. The combination of 4-PCC, a concentrate with factors II, VII, IX, and X, and fresh frozen plasma (FFP) has been shown in observational studies to reduce blood product consumption by increasing thrombin generation. However, the risk of thromboembolic events is still a concern. The goal of a recent double-blind, placebo-controlled study from France was to determine the efficacy and safety of the addition of 4-PCC during possible massive transfusion events.

The study included 324 patients with the highest trauma level activation. After randomization, 164 patients received 1 mL/kg of 4-PCC and 160 patients received 1 mL/kg of 0.9% normal saline. Team members and data handlers were blinded to the assignment. Patients were treated with tranexamic acid (TXA) and early transfusion with a packed red blood cell to FFP ratio between 1:1 and 2:1. Coagulopathy was defined by measuring the prothrombin time ratio (a measure similar to the international normalized ratio). A prothrombin time ratio greater than 1.2 was deemed acute traumatic coagulopathy, while a ratio greater than 1.5 was considered severe. Although comorbidities between the groups were similar, more patients in the placebo group received TXA and a higher dose of fibrinogen than those in the 4-PCC group.

The primary outcome of the trial was total number of blood products within 24 hours of arrival. Secondary outcomes included time to prothrombin time ratio less than 1.5, individual blood components transfused within 24 hours of arrival, time to hemorrhage control, number of intensive care unit-free days, ventilator-free days, hospital-free days through day 28, and mortality at 24 hours and 28 days. Safety was determined by the occurrence of thromboembolic events, such as pulmonary embolism, venous thrombosis, stroke, mesenteric and extremity ischemia, and myocardial infarction.

The investigators found no difference in 24-hour total blood product consumption between the 4-PCC group and the placebo group (median [IQR], 12 U [5 to 19] vs. 11 U [6 to 19]; absolute difference, 0.2; 95% CI, –2.99 to 3.33). They also found no difference in any of the secondary outcomes, including time to hemorrhage control and ventilator-free days. Fifty-six patients in the 4-PCC group had at least one thromboembolic event compared to 37 patients in the placebo group (relative risk, 1.48; 95% CI, 1.04 to 2.10). The 4-PCC group had a total of 63 thromboembolic events compared to a total of 46 in the placebo group. A posthoc analysis revealed that patients with a prothrombin time ratio greater than 1.2 who received 4-PCC had a higher rate of thromboembolic events than those who received placebo (31 of 90 [34%] vs. 19 of 87 [22%]). However, in patients with a prothrombin time ratio less than 1.2, the rate of thromboembolic events was the same between those who received 4-PCC versus placebo (6 of 49 [33%] vs. 13 of 40 [33%]).

In conclusion, no difference was found in 24-hour total blood consumption or time to correction of laboratory values when 4-PCC was added during a massive transfusion event. However, there was an increase in thromboembolic events, even in the setting of more TXA and fibrinogen administration in the placebo group.

Answer: A