Four-factor prothrombin complex concentrate (PCC) may be more effective than frozen plasma in managing excessive bleeding due to coagulation factor deficiency in patients undergoing cardiopulmonary bypass surgery, according to new findings from the Factor Replacement in Surgery (FARES) research program. The study, published March 29 in
JAMA, found that PCC was associated with non-inferior and superior hemostatic efficacy. Patients treated with PCC experienced significantly fewer bleeding events compared with those treated with frozen plasma.
In the unblinded FARES-II trial, investigators at 12 hospitals in Canada and the United States randomized adult patients with bleeding related to coagulation factor deficiency after cardiopulmonary bypass to receive either PCC or thawed frozen plasma. A second dose of PCC was given if ordered within 24 hours, with additional doses in both groups consisting of frozen plasma. The primary endpoint was hemostatic response (defined as the absence of further interventions for bleeding) within 24 hours.
Among 420 patients, 77.9% of those receiving PCC achieved hemostatic effectiveness compared to 60.4% in the frozen plasma group. PCC recipients also required fewer red blood cell transfusions, with 45.5% receiving transfusions within 24 hours, compared with 63.8% in the frozen plasma group. Despite the improved hemostatic response, mortality rates, ICU and hospital length of stay and thromboembolic event rates were similar between groups.
Investigators noted that PCC’s concentrated procoagulant factors likely contributed to its effectiveness in restoring thrombin generation after surgery. They also highlighted the potential for PCC to reduce overall frozen plasma use, alleviating supply pressures for plasma-derived medicinal products, and lowering overall transfusion requirements.
“The superior hemostatic efficacy of PCC will benefit patients and the health care system by reducing major bleeding, red blood cell and platelet transfusions and use of other hemostatic therapies such as recombinant activated factor VII, all of which have been linked to increased adverse outcomes and overuse of health care resources,” the researchers wrote.
In an
accompanying editorial, Ryan Wang, MD, and Elliott Bennett-Guerrero, MD, further discussed the implications of the FARES-II trial and explored the potential benefits and limitations of PCCs in cardiac surgery. They noted that PCC’s smaller volume (typically 80 mL for a standard dose) allowed for faster administration. In FARES-II, the first dose of PCC was administered 19 minutes faster than thawed frozen plasma (7 minutes versus 26 minutes). However, they pointed out that the higher cost of PCC compared to frozen plasma may limit its widespread adoption, though PCC’s ability to reduce the need for additional blood products may offset its higher upfront cost.
The editorial also addressed a strength and potential limitation of FARES-II, the requirement for point-of-care INR testing, which they noted may not be widely available. “Testing the safety and efficacy of PCC in the FARES-II trial using a protocolized approach likely ensured that only patients most likely to benefit from PCC were randomized and included in the analysis,” they wrote. “However, requiring point-of-care INR testing to determine the need for factor replacement may limit the generalizability of this study.”
Finally, Wang and Bennett-Guerrero discussed thromboembolic risk, noting that the trial excluded high-risk patients with a recent history of thromboembolism, which may have reduced the thromboembolic risk of administering PCC to patients without factor deficiency.
They concluded that while the trial provides substantial evidence that PCC, when used with a structured algorithm and point-of-care INR testing, is more effective than thawed frozen plasma in treating bleeding, the modest differences in blood product administration and the lack of impact on mortality, ICU or hospital length-of-stay suggest it may not provide a major clinical benefit for most patients.
