**Background:** Management of coagulopathy in chronic liver disease (CLD) is challenging due to the complex, rebalanced haemostatic state that can shift toward bleeding or thrombosis. Prothrombinex®-VF, an Australian four-factor prothrombin complex concentrate (4F-PCC), offers rapid onset and low-volume administration but is contraindicated in disseminated intravascular coagulation (DIC). Evidence for its use in CLD is limited, with case reports of acute intravascular coagulation and fibrinolysis (AICF)/DIC following administration. This study aimed to evaluate the efficacy and safety of Prothrombinex®-VF in CLD patients.
**Methods:** This was a retrospective, multi-centre, observational study conducted across Metro South and West Moreton Health Services (11 hospitals) in Queensland, Australia, from January 2018 to December 2020. All adult patients with CLD who received Prothrombinex®-VF were included; those on therapeutic anticoagulation or with congenital/acquired coagulation factor deficiencies were excluded. Patients were subclassified into acute-on-chronic liver failure (ACLF; n=15), acute decompensated cirrhosis (ADC; n=11), and compensated cirrhosis (CC; n=4) using EASL criteria. The primary endpoint was reversal of coagulopathy within 72 hours, defined as INR <1.5, PT <20 s, APTT <59 s (1.5× upper limit normal), and fibrinogen >1 g/L. Secondary endpoints included markers of AICF/DIC (elevated D-dimer, ≥15% worsening of hypofibrinogenaemia, thrombocytopaenia, PT, APTT, fibrinogen discordance ≥0.3, red cell fragmentation), venous or arterial thromboembolic events within 30 days, and overall survival. Data were analysed using descriptive statistics; sample size precluded inferential analysis.
**Key Results:** Of 959 adults receiving Prothrombinex®-VF during the study period, only 30 (3%) had CLD. The cohort had advanced liver disease: median MELD 23 (range 16–40), median Child-Pugh 10 (range 7–13), median CLIF-C ACLF 53 (range 43–81). Alcohol-related liver disease was the most common aetiology (56%). Acute bleeding was the indication in 60% of cases (gastrointestinal bleeding 37%). The median Prothrombinex®-VF dose was 25 IU/kg (range 6–63). Most patients had disturbed coagulation markers at baseline and failed to achieve reversal after administration. Among ACLF patients, 53% had clinical bleeding from mucosae or intravascular lines, 60% had worsening hypofibrinogenaemia (<1 g/L), 60% had worsening thrombocytopaenia (<100×10⁹/L), and 60% had fibrinogen discordance ≥0.3. Only six patients (all with ACLF) had D-dimer testing, all elevated. ADC and CC subgroups were relatively unaffected by AICF/DIC markers. Venous thromboembolism occurred in 2 patients (6%) within 5 days. All-cause in-hospital mortality was 43% overall and 60% in the ACLF subgroup. In ACLF, 6 of 9 deaths were due to multiorgan failure; the remainder from uncontrolled haemorrhage, sepsis, and end-stage liver disease. ADC mortality was 18% (2 deaths).
**Clinical Implications:** This study demonstrates that Prothrombinex®-VF did not lead to meaningful reversal of coagulopathy in CLD patients and was associated with progression to an AICF/DIC-like state in a significant proportion of ACLF patients. The findings highlight the importance of recognising that conventional laboratory tests (particularly INR) do not accurately reflect bleeding risk in CLD, and that hypofibrinogenaemia and thrombocytopaenia are better indicators. The authors suggest that correction of hypofibrinogenaemia (target fibrinogen >1 g/L) and optimisation of coagulation with other haemostatic products prior to Prothrombinex®-VF administration may improve safety, though this requires prospective validation. The study is limited by its retrospective design, small sample size (n=30), and inability to perform inferential statistics. The high mortality (43% overall, 60% in ACLF) reflects the severity of underlying liver disease. The authors conclude that Prothrombinex®-VF should be used with caution in CLD and is contraindicated in DIC, which may go unrecognised in advanced cirrhosis. Further prospective studies are urgently needed to establish evidence-based guidelines for haemostatic management in this population.