Several reviews and systematic analyses explore the use of prothrombin complex concentrates (PCC) in a variety of settings.
Chronic liver disease:
A 2023 review summarizes current evidence on the use of PCC in chronic liver disease (CLD), emphasizing that cirrhosis produces a fragile but “rebalanced” hemostatic state in which conventional tests such as international normalized ratio (INR) poorly reflect bleeding risk. In vitro studies consistently show that PCC markedly increases thrombin generation in cirrhotic plasma—more so than fresh frozen plasma (FFP)—and this effect becomes stronger with worsening liver disease, indicating potential utility but also raising concern for thrombotic complications. Clinical data remain limited and are largely retrospective, heterogeneous, and underpowered. Across studies of prophylactic use before procedures (e.g., TIPS, paracentesis, hepatobiliary interventions, or liver transplantation) PCC reliably improves INR but has inconsistent impact on transfusion requirements or clinical bleeding, and most investigations lack a control arm. Evidence for treating active bleeding is similarly inconsistent: PCC may correct laboratory parameters but has not been clearly shown to improve hemostasis, and bleeding in cirrhosis is often driven by portal hypertension rather than coagulopathy. The thromboembolic risk associated with PCC in CLD appears modest (approximately 3–6%), although cases of disseminated intravascular coagulation have been described, particularly in decompensated cirrhosis or with higher doses. Overall, PCC cannot be routinely recommended for CLD, but may be considered in carefully selected patients with significant bleeding when other measures fail, or when low-volume correction is essential. Robust randomized trials—currently lacking—are needed to define safety, efficacy, and appropriate dosing in this population. [1]
A 2025 systematic review and meta-analysis described the use of PCC in liver transplant based on data from 8 studies; 7 explicitly reported PCC exposure, encompassing 392 of 1,901 patients (21%), while 1 study grouped PCC with fibrinogen concentrate, yielding 576 of 939 patients (61%) receiving factor concentrates including PCC. The results demonstrated no statistically significant pooled effect of PCC on any major transfusion or clinical outcome in liver transplantation. Across all pooled outcomes, confidence intervals (CI) crossed the null, indicating no clear benefit or harm at the meta-analytic level. The pooled analysis demonstrated that PCC had no statistically significant effect on transfusion requirements or major clinical outcomes in liver transplantation when data were aggregated across studies. For intraoperative blood product use, pooled mean differences showed no meaningful reduction in units transfused: red blood cells (MD −0.05 units, 95% CI −1.63 to +1.53), fresh frozen plasma (MD −0.18 units, 95% CI −3.09 to +2.73), platelets (MD −0.09 units, 95% CI −1.45 to +1.27), and cryoprecipitate (MD −0.12 units, 95% CI −0.80 to +0.56) all crossed the line of no effect. Clinical endpoints were similarly neutral. The pooled odds ratio for any thromboembolic event was 1.12 (95% CI 0.42–2.98), indicating no increase in risk. Acute kidney injury was not more common with PCC (OR 0.94, 95% CI 0.52–1.69), and mortality remained unchanged (OR 1.05, 95% CI 0.64–1.72). Additional pooled outcomes—including reoperation for bleeding (OR 0.91, 95% CI 0.44–1.87) and ICU length of stay (MD −0.2 days, 95% CI −1.1 to +0.7)—also showed no significant differences. Overall, the pooled evidence indicates that PCC neither reduces transfusion burden nor increases adverse events at the meta-analytic level, with all effect estimates crossing the null and substantial heterogeneity limiting precision. [2]
A 2021 review discussed the use of PCC in the setting of liver failure. Patients with end-stage liver disease (ESLD) are in a fragile state of rebalance where reduced procoagulant function is counterbalanced by reducing the anticoagulant activity. This balance can be easily disrupted, leading to bleeding or thromboembolism (TE). Four-factor PCC (4F-PCC) have been utilized in scenarios where patients have a high model for end-stage liver disease (MELD) score as an alternative to frozen plasma (FP) for correcting the hypercoagulation state. The primary argument for utilizing 4F-PCC is to reduce the risk of consequences related to FP including FP-associated immunomodulation, transfusion-related acute lung injury, or transfusion-associated circulatory overload (TACO). However, the concern for thromboembolism has prevented the widespread use of 4F-PCC in patients with liver disease. The use of 4F-PCC is mainly observed as prophylaxis prior to surgery or for active bleeding and are typically used in combination with other blood products. 4F-PCC is sometimes used to correct elevated INR with a target INR of <1.5 commonly utilized, but an optimal hemostatic endpoint has not been established in liver failure. The authors conclude that the evidence seems promising but requires further study to determine optimal dosing and thrombotic potential, especially with repeat dosing. [3]
A 2020 abstract poster reported the outcomes of patients with liver disease who received 4F-PCC (Kcentra) for management of major/life-threatening hemorrhage or need for emergent surgery that failed to respond to blood products or cannot tolerate FFP. From a total of 52 patients receiving 72 doses of Kcentra, 67% of patients presented with liver failure secondary to cirrhosis, and 28% had acute liver failure. Kcentra was mostly used for gastrointestinal bleeding followed by use prior to surgery. Hemostasis was achieved in 27.6% of patients. Adverse events within 30 days include venous thromboemboli (7.8%), line-related thrombosis (3.1%), myocardial infarction (1.6%), and other (3.1%). At discharge, 53.1% of patients perished and 4.6% went to hospice while the rest were discharged. The authors noted the rate of adverse events reported in their study was higher than the rate reported in the package insert (7-8%) while only helping a quarter of hepatic impaired patients achieve hemostasis. [4]
Trauma-induced coagulopathy:
A 2023 meta-analysis explored the use of PCC for managing trauma-induced coagulopathy (TIC) in adult patients. The analysis included 9 observational studies and 1 randomized controlled trial (RCT), comprising a total of 1,150 patients treated with PCC. The primary outcomes assessed were incidence of in-hospital mortality and venous thromboembolism (VTE). Among the observational studies, 8 reported on mortality with a pooled odds ratio (OR) of 0.97 (95% CI 0.56 to 1.69), and 5 reported on deep venous thrombosis (DVT) with a pooled OR of 0.83 (95% CI 0.44 to 1.57). When the observational studies were combined with the RCT data, the OR for mortality was 0.94 (95% CI 0.60 to 1.45), and for DVT, OR 1.00 (95% CI 0.64 to 1.55). These findings highlighted that PCCs did not significantly reduce mortality rates in TIC patients, nor did they increase the risk of VTE, although potential thrombotic risks remain a concern. The authors underscored the inconsistency in outcome reporting across studies and the lack of standardized protocols for PCC administration. Most studies involved 4-factor PCCs given at doses between 20 to 30 IU/kg, with various co-interventions like whole blood, fibrinogen concentrate, or fresh frozen plasma. Given the high risk of bias in many of the observational studies and the lack of effect observed in the only RCT, the current evidence does not robustly support the efficacy of PCC for reducing mortality in TIC. The authors called for ongoing and future RCTs to address the efficacy and safety concerns related to PCC use in trauma settings. [5]
A 2020 meta-analysis evaluated the effectiveness of PCC for the treatment of bleeding in patients not taking anticoagulants. Seventeen observational studies involving 3,060 patients were included across trauma, cardiac surgery, liver surgery, and mixed bleeding populations. Across all patient groups combined, PCC administration was not associated with a reduction in mortality compared with non-PCC strategies (OR 0.83; 95% CI 0.66 to 1.06; p= 0.13; I²= 0%). In subgroup analyses, PCC use in trauma patients, primarily as an adjunct to FFP, was associated with reduced mortality (OR 0.64; 95% CI 0.46 to 0.88; p= 0.007; I²= 0%), whereas no mortality difference was observed in cardiac surgery populations. Blood loss outcomes were reported exclusively in cardiac surgery patients. PCC administration was associated with lower postoperative blood loss compared with control strategies (MD −293 mL; 95% CI −546 to −41; p= 0.02), although heterogeneity was high (I²= 86%). Red blood cell (RBC) transfusion requirements were lower in PCC-treated patients overall (MD −1.61 units; 95% CI −3.00 to −0.22; p= 0.02; I²= 93%), with reductions observed in trauma (MD −2.99 units; 95% CI −4.06 to −1.91; p<0.00001; I²= 68%) and cardiac surgery (MD −2.01 units; 95% CI −3.35 to −0.67; p= 0.003; I²= 81%) subgroups, with increased RBC use reported in liver surgery patients (MD 2.06 units; 95% CI 1.27 to 2.84; p<0.00001; I²= 0%). Thromboembolic events were reported in 15 studies and occurred at similar rates in PCC and non-PCC groups. Overall, PCC use was not associated with increased thromboembolic risk (OR 1.11; 95% CI 0.82 to 1.50; p= 0.49; I²= 0%). The authors concluded that, in bleeding patients not on anticoagulants, PCC was not associated with reduced mortality overall but was associated with lower mortality in trauma patients, reduced RBC transfusion needs across most settings, reduced blood loss in cardiac surgery, and no increase in thromboembolic events.[6]
Cardiac surgery:
A 2019 meta-analysis evaluated the safety and efficacy of PCC as first-line treatment for coagulopathy in adult patients undergoing cardiac surgery. The analysis included 4 studies (N= 861) comparing those who received perioperative PCC (n= 423) with those who received FFP (n= 438). No randomized studies were identified, indicating a reliance on observational data and a quality assessment showed that all the included studies were at significant risk of bias. Additionally, the PCC dose varied among the studies, with a reported range between 15 and 25 IU/kg. Pooled results demonstrated that patients receiving PCC had a significantly reduced risk of RBC transfusion (OR 2.22; 95% CI 1.45 to 3.40) and fewer units of RBCs received (OR 1.34; 95% CI 0.78 to 1.90). The analysis, however, found no significant differences between PCC and FFP groups concerning rates of re-exploration for bleeding (OR 1.09; 95% CI 0.66 to 1.82), chest drain output at 24 hours (OR 66.36; 95% CI –82.40 to 216.11), hospital mortality (OR 0.94; 95% CI 0.59 to 1.49), stroke (OR 0.80; 95% CI 0.41 to 1.56), and acute kidney injury (OR, 0.80; 95% CI 0.58 to 1.12). Despite these findings, a trend towards an increased risk of renal replacement therapy in the PCC group was noted, though not statistically significant (OR 0.41; 95% CI 0.16 to 1.02). Despite the potential benefits illustrated in the reduction of perioperative blood transfusions, the authors emphasized the need for randomized controlled trials to definitively establish the safety profile of PCC in cardiac surgery settings. [7]
A 2025 meta-analysis evaluated the efficacy and safety of PCC versus FFP for hemorrhage management in cardiac surgery. Four randomized controlled trials including 671 adult patients were analyzed, of whom 343 (51.1%) received PCC and 328 (48.9%) received FFP. All patients underwent cardiac surgery with cardiopulmonary bypass. The primary outcome, postintervention hemoglobin concentration, was significantly higher in patients treated with PCC compared with FFP (MD 1.17 g/dL; 95% CI 0.93 to 1.41; p<0.01; I²= 17.4%). Sensitivity analyses excluding individual trials did not alter this finding. Postintervention international normalized ratio (INR) values also favored PCC over FFP. Secondary outcomes showed no statistically significant differences between PCC and FFP in 30-day mortality, overall adverse events, or reoperation rates for bleeding. However, patients in the PCC group required fewer red blood cell transfusions within the first 24 hours after surgery, and fewer patients required transfusion during this period. This reduction in transfusion exposure was not sustained at 7 days. Use of recombinant factor VII was higher in patients receiving FFP compared with PCC. Overall, the analysis revealed that, in bleeding cardiac surgery patients, PCC was associated with higher postintervention hemoglobin levels, improved correction of coagulation parameters, and reduced early transfusion requirements compared with FFP, without an increase in adverse events, supporting its role as a hemostatic option when rapid and effective correction is needed. [8]
A 2024 meta-analysis investigated the efficacy and safety of prothrombin complex concentrate (PCC) in managing massive bleeding for patients undergoing cardiac surgery. The review included an analysis of 12 studies sourced from databases such as PubMed, Embase, and the Cochrane Library, focusing on publications prior to September 10, 2022. The analysis revealed that PCC use was not linked to increased mortality (risk ratio [RR] 1.18; 95% CI 0.86 to 1.60), shorter hospital stay (MD -2.17 days), reduced total thoracic drainage (MD -67.94 mL; 95% CI -239.52 to 103.65), thromboembolíc events (RR 1.10; 95% CI 0.74 to 1.65), increase ín atríal fibríllatíon events (RR 0.73; 95% CI 0.52 to 1.05), and myocardial infarction (RR 1.10; 95% CI 0.80 to 1.51) compared with non-PCC approaches. However, notable improvements were documented in reduced ICU length of stay (MD -0.81 days) and decreased bleeding (MD -248.67 mL) when PCC was utilized. Additionally, PCC use demonstrated a reduction in intra-aortic balloon pump/extracorporeal membrane oxygenation (ECMO) events (RR 0.65). The research highlights the potential advantages of PCC in managing bleeding and post-operative ICU requirements without increasing the risk of mortality or thromboembolic complications, thereby supporting its use as a viable alternative to fresh frozen plasma in managing coagulopathy during cardiac surgery. [9]