Cefoperazone/sulbactam is commonly prescribed for the treatment of infected patients with cirrhosis.

To investigate the effect of cefoperazone/sulbactam on coagulation in cirrhotic patients and assess the effectiveness of vitamin K1 supplementation in preventing cefoperazone/sulbactam-induced coagulation disorders.

This retrospective cohort study compared coagulation function in 217 cirrhotic patients who received cefoperazone/sulbactam with and without vitamin K1 supplementation (vitamin K1 group, n = 108; non-vitamin K1 group, n = 109). Propensity score matching (PSM) was used to to reduce confounders’ influence, the SHapley additive exPlanations (SHAP) model to explore the importance of each variable in coagulation disorders.

In the non-vitamin K1 group, the post-treatment prothrombin time (PT) was 16.5 ± 6.5 s and the activated partial thromboplastin time (aPTT) was 34.8 ± 9.4 s. These were significantly higher than pre-treatment values (PT: 14.6 ± 2.4 s, p = 0.005; aPTT: 30.4 ± 5.9 s, p < 0.001). In the vitamin K1 group, no differences were observed in PT, thrombin time, or platelet count, except for a slightly elevated post-treatment aPTT (37.0 ± 10.4 s) compared to that of pre-treatment (34.4 ± 7.2 s, p = 0.033). The vitamin K1 group exhibited a lower risk of PT prolongation (OR: 0.211, 95% CI: 0.047–0.678) and coagulation disorders (OR: 0.257, 95% CI: 0.126–0.499) compared to that of the non-vitamin K1 group. Propensity score matching analysis confirmed a reduced risk in the vitamin K1 group for prolonged PT (OR: 0.128, 95% CI: 0.007–0.754) and coagulation disorders (OR: 0.222, 95% CI: 0.076–0.575). Additionally, the vitamin K1 group exhibited lower incidences of PT prolongation, aPTT prolongation, bleeding, and coagulation dysfunction compared to the non-vitamin K1 group.

Cefoperazone/sulbactam use may be linked to a higher risk of PT prolongation and coagulation disorders in cirrhotic patients. Prophylactic use of vitamin K1 can effectively reduce the risk.