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Background: Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. Methods: A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. Results: A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). Conclusion: ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.

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PURPOSE: Warfarin shows large inter- and intra-individual variabilities in its pharmacokinetics and pharmacodynamics. Sufficient understanding of factors affecting the response to warfarin is necessary to achieve improved outcomes for warfarin therapy. In this study, we evaluated effects of fasting on the anticoagulant properties of warfarin. METHODS: We conducted a retrospective observational study involving a total of 58 patients, who received cardiovascular surgeries and subsequent warfarin therapy. The effect of dietary intake on the anticoagulant properties with warfarin was assessed by measurement of the international normalized ratio of prothrombin time (PT-INR): the anticoagulant activities of warfarin were expressed as the warfarin sensitivity index (WSI). Additionally, fluctuations in WSI during the study period were obtained as differences between the maximum and minimum WSI. RESULTS: The maximum PT-INR and WSI values were significantly higher for patients who were fasting for different reasons during the postoperative period than those in the group without reduced dietary intake. The differences between maximum and minimum WSI in the fasting group significantly increased compared with those in the groups with moderate or no reduced dietary intake. Meanwhile, effects of other markers of clinical conditions including the baseline Child-Pugh score and Charlson Comorbidity Index on WSI were not significant. CONCLUSIONS: Our results indicate that postoperative fasting was significantly associated with the anticoagulation activity of warfarin. In patients fasting for different reasons during the postoperative period, closer control of PT-INR values and warfarin adjustments may be required to avoid adverse effects such as bleeding in warfarin treatment.

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BACKGROUND: Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain. METHODS: We investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT. RESULTS: Triple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4-87.6%). Kaplan-Meier survival curves showed that warfarin therapy was not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding. CONCLUSIONS: Triple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR.

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