Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol\'s implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

UNASSIGNED: Chronic liver disease (CLD) is one of the important causes of morbidity and mortality in our country, and since the damage to the liver is irreversible, we have to look for many severity markers or predictors for the prognosis of the patient. In this study, we have tried to correlate the level of serum uric acid (UA) with the severity of CLD presented as a Child-Pugh score.
UNASSIGNED: A cross-sectional observational study was conducted at Vijayanagar Institute of Medical Science (VIMS), Ballari, Karnataka, from October 2015 to June 2017 in the Department of General Medicine. Fifty patients diagnosed with CLD, aged between 18 and 65 years, of either gender, were enrolled in the study. Serum UA levels were measured, and liver function and coagulation parameters were assessed. A statistical analysis was performed to evaluate the association between serum UA levels, liver function test, and coagulation parameters.
UNASSIGNED: In our study, the mean serum UA level was 6.52 mg/dl and was raised in patients with CLD in correlation to its severity. Alcoholic liver disease (ALD) was the most common etiology for CLD (80%) followed by hepatitis B (Hep B) virus infection (12%) and hepatitis C (Hep C) virus infection (6%). Serum UA levels increased as the Child-Turcotte-Pugh (CTP) score increased. The mean UA level in CTP class C was 8.29 mg/dl. Various parameters such as serum aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, total bilirubin, international normalized ratio (INR), calcium, and albumin were significantly associated with serum UA levels in CLD patients.
UNASSIGNED: The correlation between rising blood UA levels and the Child-Pugh score shows that UA estimate may be a valid and affordable indicator for assessing the extent of liver cirrhosis in CLD.

This case report presents a 33-year-old woman who presented to the emergency department with abdominal pain and gingival and vaginal bleeding. She admitted to using synthetic cannabinoids, and contamination with brodifacoum was suspected, for which qualitative testing was positive. The patient was discharged with an improved international normalized ratio (INR) seven days later with oral vitamin K. Fourteen days after discharge, she re-presented with widespread ecchymosis, leg swelling, and intermittent gingival and vaginal bleeding. Her INR was again elevated. She was controlled with oral vitamin K therapy, stabilized, and discharged three days later. Twenty-eight days following the second discharge, the patient re-presented with oral swelling, right eye ecchymosis, and vaginal bleeding after abstaining from vitamin K therapy for two weeks. A bedside nasopharyngolaryngoscopy showed the base of the tongue, epiglottis, aryepiglottic (AE) folds, arytenoids, and false vocal folds were all edematous with ecchymosis. Due to the diffuse epiglottic and supraglottic edema, the patient was intubated to avoid further decompensation. After receiving IV and oral vitamin K, she was extubated two days later. Her INR fully normalized, and she was then discharged on day 4. Our case of epiglottitis could demonstrate thermal injury associated with smoking synthetic cannabinoids, but given diffuse ecchymosis and severe coagulopathy, hematoma associated with brodifacoum poisoning was considered the most likely etiology. The patient\'s coagulopathy was rapidly reversed, empiric antibiotic coverage was provided, and she rapidly improved. Brodifacoum exposure has been known to cause increased bleeding, as seen in this case. However, it should also be considered that exposure can lead to epiglottitis. If a similar patient is presented in the future, it is important to consider that coagulopathy may be caused by the adulteration of drugs of abuse, specifically brodifacoum with synthetic cannabinoids.

Patients on long-term anticoagulation therapy require frequent testing of prothrombin time/international normalized ratio (PT/INR) to ensure therapeutic efficacy. Point-of-care (POC) PT tests for at-home monitoring eliminate the burden of visiting the clinic, but realizing a cost-effective and robust at-home POC test for PT has remained elusive. Recent demonstrations of printed PT sensors show promise for addressing the cost concerns; however, the printed sensors have lacked quality control to ensure reliability between tests. In this work, on-chip redundancy is introduced with fully printed impedimetric PT sensors by incorporating simultaneous testing with a single fingerstick volume of blood (8 μL). The influence of electrode dimensions and composition were studied, revealing an optimal electrode spacing of 200 μm and an unexpected dependence on the morphology of the electrodes. Three distinct silver morphologies were studied: aerosol jet printed silver nanoparticles (AgNPs), aerosol jet printed silver nanowires (AgNWs), and evaporated silver (Ag). In general, AgNPs exhibited the best PT sensor performance, due to relatively low conductance and high porosity. Overall, the printed impedimetric PT sensor functionalization was improved by incorporating simultaneous testing and, when combined with a handheld control device, shows promise for leading to a system that overcomes the challenges of commercial PT/INR coagulometers.

OBJECTIVE: We aim to find the time in which a thawed citrate plasma sample that was preserved can be analyzed for routine coagulation testing without losing precision.
METHODS: Whole blood samples from 30 healthy volunteers were collected in 3.2% sodium citrate vacutainer and centrifuged to separate platelet-poor plasma. Each sample was then aliquoted, one aliquot was used immediately for prothrombin time (PT)-international normalized ratio (INR) and activated partial thromboplastin time (APTT), four were stored at -20°C, and four were stored at -80°C for 24 hours. After 24 hours, the aliquots were taken out and thawed at 37°C in water bath and analyzed after 15, 30, 60, and 120 minutes.
METHODS: Data were presented as mean with standard deviation (SD). Repeated measures ANOVA with Tukey post-hoc test was performed for multiple comparisons. All analysis was done using GraphPAD Prism 8.0 software (GraphPad Software, San Diego, California, USA).  Results: In the case of PT and INR, no statistically significant difference was found between the mean values after thawing for 120 minutes when compared with the mean baseline value. However, the APTT showed a statistically significant difference (p = 0.0232) after 30 minutes of thawing when the sample was stored at -20°C. Furthermore, a statistically significance difference (p = 0.0001) was found after 60 minutes of thawing when the samples were stored at -80°C.
CONCLUSIONS: Plasma samples for the PT and INR may be accepted for assessment up to 120 minutes, when stored at -20°C and -80°C for 24 hours. In the case of APTT, the plasma sample can be used for assessment up to 30 minutes after thawing when stored at -20°C and up to 60 minutes when stored at -80°C.

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Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

BACKGROUND: Alectinib, crizotinib, and ceritinib, are anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) that exhibit high protein binding, and their metabolism is associated with the cytochrome P450 (CYP) isoenzymes 2C9 or 3A4. The plasma protein binding rate of warfarin, which is used to prevent and treat venous thromboembolism, is also high. Warfarin is a racemate of S-warfarin and R-warfarin, which are metabolized by CYP2C9 and CYP3A4, respectively. Reports on the drug interactions between each of the above-mentioned ALK-TKIs and warfarin with concurrent use of bucolome are currently lacking.
METHODS: We report a case of a patient receiving warfarin and bucolome, whose international normalized ratio (INR) increased after sequential treatment with alectinib, crizotinib, and ceritinib. The patient was a 61-year-old man with a history of aortic valve regurgitation, who was receiving warfarin treatment following aortic valve replacement. Bucolome, which can enhance the effect of warfarin, was also used simultaneously. The patient was diagnosed with primary lung adenocarcinoma, and ALK rearrangement was detected during second-line chemotherapy. After progression of the disease with chemotherapy, sequential treatment with alectinib, crizotinib, and ceritinib was initiated. Pretreatment INR values were in the therapeutic range (target INR of 2-3) but increased to supratherapeutic levels each time after initiation of alectinib, crizotinib, or ceritinib treatment. Adjustment of warfarin dose or discontinuation of bucolome were necessary to maintain the therapeutic INR range. There were no serious bleeding events or substantial changes in dietary intake. Displacement of plasma protein binding or competitive inhibition of metabolism by alectinib, crizotinib, and ceritinib could increase the plasma concentration of the unbound form of warfarin, resulting in high INR values. In addition, alectinib, crizotinib, and ceritinib might cause displacement of bucolome from plasma proteins, followed by displacement of warfarin or inhibition of warfarin metabolism caused by the unbound form of bucolome.
CONCLUSIONS: Close monitoring of INR and adjustment of warfarin dosage are needed during treatment with alectinib, crizotinib, or ceritinib in patients who receive warfarin with concurrent use of bucolome.

UNASSIGNED: The objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval.
UNASSIGNED: From January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method.
UNASSIGNED: Two hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant.
UNASSIGNED: For patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

Herein, we report two acute ischemic stroke cases that we used prothrombin complex to reverse the effects of warfarin in order to apply intravenous thrombolytic treatment. To the best of our knowledge, there are only limited amount of cases that prothrombin complex concentrates were applied prior to intravenous thrombolytic treatment administration. As one of the biggest acute stroke clinics in our country, we aim to open a discussion for this treatment to be fully researched and understood.