Impact of Dietary Vitamin K Intake on Anticoagulation Therapy in Patients With Left Ventricular Assist Device During the 2018 Osaka Earthquake.

Background: The 2018 Osaka earthquake caused severe damage to the National Cerebral and Cardiovascular Center, and the interruption to the delivery of hospital food in particular had a significant effect on patients with left ventricular assist devices (LVAD). Methods and Results: We retrospectively assessed 10 patients who had been provided with emergency rations on the day of earthquake and the next day for breakfast. Catered foods were provided thereafter. Vitamin K content was largely reduced due to emergency rations; the prothrombin time-international normalized ratio (PT-INR) on day 2 was significantly higher than on day 1. Conclusions: Close monitoring of PT-INR and assessing vitamin K content may be important for preventing complications in patients with a LVAD during a disaster.

Kinetic-pharmacodynamic model of warfarin for prothrombin time-international normalized ratio in Japanese patients.

AIMS: Genotype-guided dosing algorithms can explain about half of the interindividual variability in prothrombin time-international normalized ratio (PT-INR) under warfarin treatment. This study aimed to refine a published kinetic-pharmacodynamic model and guide warfarin dosage for an optimal PT-INR based on renal function. METHODS: Using a retrospective cohort of adult patients (>20 years) who were administered warfarin and underwent PT-INR measurements, we refined the kinetic-pharmacodynamic model with age and the genotypes of cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 using the PRIOR subroutine in the nonlinear-mixed-effect modelling programme. We searched the significant covariates for parameters, such as the dose rate for 50% inhibition of coagulation (EDR50 ), using a stepwise forward and backward method. Monte Carlo simulation determined a required daily dose of warfarin with a target range of PT-INR (2.0-3.0 or 1.6-2.6) based on the significant covariates. RESULTS: A total of 350 patients with 2762 PT-INR measurements were enrolled (estimated glomerular filtration rate [eGFR]: 47.5 [range: 2.6-199.0] mL/min/1.73 m2 ). The final kinetic-pharmacodynamic model showed that the EDR50 changed power functionally with body surface area, serum albumin level and eGFR. Monte Carlo simulation revealed that a lower daily dose of warfarin was required to attain the target PT-INR range as eGFR decreased. CONCLUSIONS: Model-informed precision dosing of warfarin is a valuable approach for estimating its dosage in patients with renal impairment.

Factors influencing postoperative bleeding after dental extraction in older adult patients receiving anticoagulation therapy.

OBJECTIVES: To investigate factors influencing postoperative bleeding occurrence after dental extraction in older patients receiving anticoagulation therapy. MATERIALS AND METHODS: This retrospective study included patients aged ≥ 65 years receiving one of the following anticoagulants: apixaban, edoxaban, rivaroxaban, and warfarin. Patients who underwent one to multiple tooth extractions in the geriatric dentistry clinic at Tokyo Medical and Dental University Hospital between August 1, 2016, and November 30, 2020, were included. The outcome variable was postoperative bleeding occurrence. Logistic regression analysis was performed with the following ten factors as explanatory variables: age, sex, maximum systolic blood pressure during the extraction, type of local anesthesia, vertical incision, osteotomy, usage of surgical splints, the mesiodistal width of the extracted tooth on a radiograph, use of antiplatelet agents, and history of diabetes requiring medication. RESULTS: Among 395 participants (mean age, 82.3 ± 6.5 years) included in this study, 75 patients experienced postoperative bleeding after tooth extraction. Logistic regression analysis revealed that the odds ratios for the vertical incision (18.400, p < 0.001), osteotomy (3.630, p = 0.00558), usage of surgical splints (1.860, p = 0.0395), and the mesiodistal width of the extracted tooth on a radiograph (1.060, p = 0.0261) were statistically significant. CONCLUSIONS: For dental extraction in older patients receiving anticoagulants, postoperative bleeding is more likely to occur in patients with vertical incision, osteotomy, and posterior or multiple tooth extractions. CLINICAL RELEVANCE: Dentists should consider suturing and adjunctive hemostatic procedures for patients undergoing vertical incision, osteotomy, and multiple tooth extractions while receiving anticoagulation therapy to minimize the risk of postoperative bleeding.

Predictive Value of the Prothrombin Time-International Normalized Ratio to Albumin Ratio in the Prognosis of Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Background: Acute-on-chronic liver failure is a common clinical syndrome with high short-term mortality, and early assessment of its mortality risk is crucial, but the search for valid and accurate prognostic biomarkers is a challenging endeavor. The purpose of this study was to investigate the predictive value of the prothrombin time-international normalized ratio to albumin ratio (PTAR) for mortality in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Patients and methods: A total of 354 patients with HBV-ACLF were included in the retrospective study. Patients were divided into survival and non-survival groups based on 90-day follow-up. Cox regression analysis was used to explore the relationship between PTAR and 90-day mortality in patients with HBV-ACLF. The area under the receiver operating characteristic curve was used to evaluate the effectiveness of PTAR in predicting mortality. Results: PTAR was significantly higher in non-survivors than in survivors. The results of multivariate analysis showed that PTAR was a valid independent predictor of mortality in patients with HBV-ACLF. Its predictive ability for mortality was similar to that of the Child-Turcotte-Pugh score, the end-stage liver disease model (MELD) score, and the MELD-sodium score. Conclusion: PTAR may be a simple and effective tool for predicting the prognosis of patients with HBV-ACLF.

Frequency of prothrombin time-international normalized ratio monitoring and the long-term prognosis in patients with mechanical valve replacement.

BACKGROUND: The study aimed to assess the correlation between the monitoring frequency of PT-INR and the long-term prognosis in patients with mechanical heart valve (MHV) replacement after discharge. METHODS: This single-center, observational study enrolled patients who underwent MHV replacement and discharged from June 2015 to May 2018. Patients or their corresponding family members were followed with a telephone questionnaire survey in July-October 2020. Based on monitoring intervals, patients were divided into frequent monitoring (FM) group (≤ 1 month) and less frequent monitoring (LFM) group (> 1 month). The primary endpoint was the composite of thromboembolic event, major bleeding or all-cause death. The secondary endpoints were thromboembolic event, major bleeding or all-cause death, respectively. RESULTS: A total of 188 patients were included in the final analysis. The median follow-up duration was 3.6 years (Interquartile range: 2.6 to 4.4 years). 104 (55.3%) patients and 84 (44.7%) patients were classified into the FM group and the LFM group, respectively. The FM group had a significantly lower incidence of the primary endpoint than the LFM group (3.74 vs. 1.16 per 100 patient-years, adjusted HR: 3.31 [95% CI 1.05-10.42, P = 0.041]). Secondary analysis revealed that the risk of thromboembolic events and all-cause death were also reduced in the FM group. CONCLUSIONS: The management of warfarin treatment in patients after MHV replacement remains challenging. Patients with less frequent monitoring of PT-INR might have worse clinical prognosis than those with frequent PT-INR monitoring.

Effect of hepatic artery reconstruction techniques on prognosis of liver transplantation / 器官移植

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

External Evaluation of a Bayesian Warfarin Dose Optimization Based on a Kinetic-Pharmacodynamic Model.

Warfarin is a representative anticoagulant with large interindividual variability. The published kinetic-pharmacodynamic (K-PD) model allows the prediction of warfarin dose requirement in Swedish patients; however, its applicability in Japanese patients is not known. We evaluated the model's predictive performance in Japanese patients with various backgrounds and relationships using Bayesian parameter estimation and sampling times. A single-center retrospective observational study was conducted at Tokyo Women's Medical University, Medical Center East. The study population consisted of adult patients aged >20 years who commenced warfarin with a prothrombin time-international normalized ratio (PT-INR) from June 2015 to June 2019. The published K-PD model modified by Wright and Duffull was assessed using prediction-corrected visual predictive checks, focusing on clinical characteristics, including age, renal function, and individual prediction error. The external dataset included 232 patients who received an initial warfarin daily dose of 3.2 ± 1.28 mg with 2278 PT-INR points (median [range] follow-up period of 23 d [7-28]). Prediction-corrected visual predictive checks carried a propensity for underprediction. Additionally, age >60 years, body mass index ≤25 kg/m2, and estimated glomerular filtration rate ≤60 mL/min/1.73 m2 had a pronounced tendency to underpredict PT-INR. However, Bayesian prediction using four prior observations reduced underprediction. To improve the prediction performance of these special populations, further studies are required to construct a model to predict warfarin dose requirements in Japanese patients.

Pharmacist-physician collaborative care for outpatients with left ventricular assist devices using a cloud-based home medical management information-sharing system: a case report.

BACKGROUND: The standard anticoagulation therapy for patients implanted with left ventricular assist devices (LVADs) includes warfarin therapy. We developed a cloud-based home medical management information-sharing system named as LVAD@home. The LVAD@home system is an application designed to be used on iPad tablet computers. This system enables the sharing of daily information between a patient and care providers in real time. In this study, we reported cases of outpatients with LVADs using this system to manage anticoagulation therapy. CASE PRESENTATION: The patient, a man in his 40s with end-stage heart failure owing to non-ischemic dilated cardiomyopathy, underwent LVAD implantation and warfarin was started on postoperative day 1. He started to use LVAD@home to manage warfarin therapy after discharge (postoperative day 47). He sent his data to care providers daily. By using this system, the pharmacist observed his signs of reduced dietary intake 179 days after discharge, and after consulting the physician, told the patient to change the timing of the next measurement earlier than usual. On the next day, the prothrombin time-international normalized ratio increased from 2.0 to 3.0, and thus the dose was decreased by 0.5 mg. Four patients used this system to monitor warfarin therapy from October 2015 to March 2018. In these patients, the time in therapeutic range was 90.1 ± 1.3, which was higher than that observed in previous studies. Additionally, there were no thromboembolic events or bleeding events. CONCLUSIONS: The cloud-based home management system can be applied to share real-time patient information of factors, including dietary intake that interact with warfarin. It can help to improve long-term anticoagulation outcomes in patients implanted with LVAD.

The prognostic value of routine coagulation tests for patients with heat stroke.

OBJECTIVE: To evaluate the prognostic value of routine coagulation tests for patients with heat stroke. METHODS: This was a multi-center retrospective study. Patients who arrived at the hospital <24 h after the onset of Heat Stroke (HS) were included. The routine coagulation variables were detected within 24 h after the onset, including the lowest platelet count (PLC). RESULTS: 60-day mortality rate was 20.9%. The median Prothrombin Time-International Normalized Ratio (PT-INR) of the non-surviving patients was significantly higher than that of the survivors (P < 0.01). The median Activated Partial Thromboplastin Time (APTT) in non-surviving patients was significantly higher than in the surviving patients (P < 0.01). A Cox regression analysis revealed that 60-day mortality was associated with PT-INR (P = 0.032) and APTT (P = 0.004). The optimal PT-INR point for predicting 60-day mortality rate was 1.7. The optimal APTT point for predicting 60-day mortality was 51.45. Patients with increased PT-INR (≥1.7) levels had, overall, a significantly reduced survival time (P < 0.01). Patients with elevated APTT (≥51.45) also had a decrease in survival time (P < 0.01). The prognostic scoring, with increased PT-INR (≥1.7) and prolonged APTT (≥51.45) at one point each, was also demonstrated to be useful in predicting 60-day mortality. Patients whose temperature fell to 38.9 °C within 30 min had significantly lower levels of PT-INR and APTT within 24 h than those who took longer to cool down. CONCLUSIONS: A prolonged APTT and elevated PT-INR within 24 h are independent prognostic factors of 60-day mortality in HS.

Monitoring of anticoagulation in thrombotic antiphospholipid syndrome.

Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin or an alternative vitamin K antagonist. The role of direct oral anticoagulants for thrombotic APS is not established due to the lack of definitive evidence and has recently been addressed in international guidance. Other anticoagulant options include low molecular weight heparin, unfractionated heparin, and fondaparinux. In APS patients, lupus anticoagulant can affect phospholipid-dependent coagulation monitoring tests, so that they may not reflect true anticoagulation intensity. Accurate assessment of anticoagulation intensity is essential, to optimize anticoagulant dosing and facilitate thrombus resolution; minimize the risk of recurrent thrombosis or bleeding; inform assessment of whether recurrent thrombosis is related to breakthrough thrombosis while on therapeutic anticoagulation, subtherapeutic anticoagulation, non-adherence, or spurious results; and guide the management of bleeding. Knowledge of anticoagulant intensity also informs assessment and comparison of anticoagulation regimens in clinical studies. Considerations regarding anticoagulation dosing and/or monitoring of thrombotic APS patients underpin appropriate management in special situations, notably APS-related severe renal impairment, which can occur in APS or APS/systemic lupus erythematosus-related nephropathy or catastrophic APS; and APS-related thrombocytopenia. Anticoagulant dosing and monitoring in thrombotic APS patients also require consideration in anticoagulant-refractory APS and during pregnancy. In this review, we summarize the tests generally used in monitoring anticoagulant therapy, use of the main anticoagulants considered for thrombotic APS, lupus anticoagulant effects on anticoagulation monitoring tests, and strategies for appropriate anticoagulant monitoring in thrombotic APS.

Factors influencing the effectiveness of recombinant human soluble thrombomodulin on disseminated intravascular coagulation: a retrospective study.

BACKGROUND: Although recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status. METHODS: This retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p <  0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates. RESULTS: Univariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p <  0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451-3.433, p <  0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009-2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065-2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment. CONCLUSION: rTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.

Association of marked prolongation of prothrombin time-international normalized ratio with warfarin and endoscopic nasobiliary drainage for biliary fistula after left hemihepatectomy.

WHAT IS KNOWN AND OBJECTIVE: Vitamin K deficiency is known to cause impaired coagulation. We report a case of marked prolongation of the prothrombin time-international normalized ratio (PT-INR) associated with warfarin and vitamin K deficiency caused by endoscopic nasobiliary drainage (ENBD). CASE PRESENTATION: Oral administration of warfarin was initiated in a 67-year-old man after left hemihepatectomy. He developed a biliary fistula after surgery that was treated by ENBD, which resulted in significant prolongation of the PT-INR. WHAT IS NEW AND CONCLUSION: The effect of warfarin was enhanced in this patient due to reduced absorption of vitamin K as a result of external biliary drainage.

Research on clinical efficacy of liver transplantation for severe liver disease / 器官移植

@#Objective To explore the clinical efficacy of liver transplantation for severe liver disease. Methods The clinical data of 51 patients who underwent liver transplantation for severe liver disease were retrospectively analyzed. The general intraoperative conditions were observed, including operation duration, warm ischemia time, cold ischemia time, anhepatic phase, bleeding volume, blood transfusion volume, plasma transfusion volume and so on. The changes in indexes such as total bilirubin (TB), prothrombin time activity (PTA), and prothrombin time international normalized ratio (PT-INR) were observed before operation and at 3 d, 1 week and 2 weeks after operation. The postoperative survival and occurrence of complications were analyzed. The indexes that might affect the prognosis of patients with severe liver disease were analyzed by Cox regression analysis. Results For the 51 patients, operation duration, warm ischemia time and cold ischemia time was 8 (7, 9) h, 3 (2, 3) min and 6 (5, 8) h respectively, intraoperative anhepatic phase was 80 (70, 100) min, intraoperative bleeding volume was 1 000 (550, 1 500) mL, and intraoperative blood transfusion volume was 1 200 (200, 1 600) mL. Postoperative TB, PTA, PT-INR and other indexes improved significantly compared to those preoperatively. Among the 51 patients, 10 cases died, with the death causes of multiple organ failure and severe infection(7 cases), renal insufficiency (2 cases), and cardiovascular complications (1 case). Survival rates at 1 month and 1 year post-transplantation for patients with severe liver disease were 82% and 80%, respectively. Cox regression analysis suggested that abnormal preoperative PTA and PT-INR were the risk factors for post-transplantation death in patients with severe liver disease. Conclusions Liver transplantation significantly improves the survival rate for patients with severe liver disease, perioperative infection prevention and treatment as well as multiple organ function management play key roles in improving post-transplantation survival rate in patients with severe liver disease.

Investigation of the Safety of Injection Laryngoplasty under Antithrombotic Therapy.

BACKGROUND: Glottic insufficiency negatively affects phonation and swallowing function. Injection laryngoplasty is a convenient and minimally invasive treatment for glottic insufficiency. This study assessed whether injection laryngoplasty is safe under continued administration of antithrombotic drugs, and aimed to establish measurable laboratory values under which such a procedure can be safely performed. METHOD: This retrospective medical record review covered the period from November 2012 to June 2018. We examined 17 patients who underwent injection laryngoplasty (47 injections) under continued administration of antithrombotic drugs at the University of Tokyo Hospital. We analyzed clinical and demographic profiles, complications, and blood test values. Statistical analyses were performed regarding the risks of complications due to injection side, route of administration, and number of antithrombotic drugs. RESULTS: No patients exhibited airway narrowing or dyspnea; however, bleeding after injection laryngoplasty was observed in 3 patients. All patients exhibited values within the optimal treatment range. There were no significant differences regarding the risks of complications due to injection side, route of administration, or number of antithrombotic drugs. CONCLUSIONS: When the platelet count, prothrombin time-international normalized ratio, and activated partial thromboplastin time were within the optimal range prior to treatment, injection laryngoplasty could safely be performed, regardless of the administration of antithrombotic drugs.

Double-crescent sign as a predictor of chronic subdural hematoma recurrence following burr-hole surgery.

OBJECTIVE: Subdural hygroma has been reported as a causative factor in the development of a chronic subdural hematoma (CSDH) following a head trauma and/or neurosurgical procedure. In some CSDH cases, the presence of a 2-layered space delineated by the same or similar density of CSF surrounded by a superficial, residual hematoma is seen on CT imaging after evacuation of the hematoma. The aims of the present study were to test the hypothesis that the double-crescent sign (DCS), a unique imaging finding described here, is associated with the postoperative recurrence of CSDH, and to investigate other factors that are related to CSDH recurrence. METHODS: The authors retrospectively analyzed data from 278 consecutive patients who underwent single burr-hole surgery for CSDH between April 2012 and March 2017. The DCS was defined as a postoperative CT finding, characterized by the following 2 layers: a superficial layer demonstrating residual hematoma after evacuation of the CSDH, and a deep layer between the brain's surface and the residual hematoma, depicted as a low-density space. Correlation of the recurrence of CSDH with the DCS was evaluated by multivariate logistic regression modeling. The authors also investigated other classic predictive factors including age, sex, past history of head injury, hematoma laterality, anticoagulant and antiplatelet therapy administration, preoperative hematoma volume, postoperative residual hematoma volume, and postoperative brain reexpansion rate. RESULTS: A total of 277 patients (320 hemispheres) were reviewed. Fifty (18.1%) of the 277 patients experienced recurrence of CSDH within 3 months of surgery. CSDH recurred within 3 months of surgery in 32 of the 104 hemispheres with a positive DCS. Multivariate logistic analyses revealed that the presence of the DCS (OR 3.36, 95% CI 1.72-6.57, p < 0.001), large postoperative residual hematoma volume (OR 2.88, 95% CI 1.24-6.71, p = 0.014), anticoagulant therapy (OR 3.03, 95% CI 1.02-9.01, p = 0.046), and bilateral hematoma (OR 3.57, 95% CI 1.79-7.13, p < 0.001) were significant, independent predictors of CSDH recurrence. CONCLUSIONS: In this study, the authors report that detection of the DCS within 7 days of surgery is an independent predictive factor for CSDH recurrence. They therefore advocate that clinicians should carefully monitor patients for postoperative DCS and subsequent CSDH recurrence.

Coagulation in chronic liver disease and the use of prothrombin complex concentrate for an emergent procedure: a case report and review of literature.

Synthetic dysfunction observed in cirrhosis results in altered production of procoagulants and anticoagulants that can lead to both bleeding and thrombotic events, respectively. In patients with decompensated cirrhosis, frequent hospital visits often require bedside procedures such as diagnostic paracenteses, thoracenteses and endoscopy. It can be difficult to determine at what coagulation threshold procedures can safely be performed. Currently, the most common therapies given pre-procedurally include fresh frozen plasma (FFP) and vitamin K. The effectiveness of these treatments is estimated by international normalized ratio (INR), an imprecise measure of coagulation in the setting of cirrhosis. Transfusion with FFP may lead to detrimental side effects, including worsening volume overload and increased portal hypertension. We present a case of a 60-year-old patient intubated for acute hypoxic respiratory failure secondary to volume overload who subsequently developed bilateral pneumothoraces, requiring immediate chest tube placement. In this case, the patient had ongoing hepatic decompensation with volume overload and acute worsening of coagulopathy with an INR of 4.2. In this setting, 4-Factor Prothrombin Complex Concentrate (4F-PCC) was chosen to correct coagulation parameters with a low infusion volume. One hour following administration, INR was 1.5. Chest tubes were placed bilaterally and oxygenation improved without bleeding complications. While the data is still lacking, 4F-PCC may be considered for urgent and emergency situations in cirrhotic patients.

A Comparative Study of Point-of-Care Prothrombin Time in Cardiopulmonary Bypass Surgery.

OBJECTIVE: Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available. DESIGN: Prospective, observational study. SETTING: University hospital, single center. PARTICIPANTS: Healthy volunteers and warfarin-treated and cardiac surgical patients. MEASUREMENT AND MAIN RESULTS: In WB samples obtained from 6 healthy volunteers, PT-INR results of DRI PT-S were not affected by an in vitro addition of heparin <6.0 U/mL. In warfarin-treated samples (n = 88, PT/INR 0.98-3.87), PT-INR with DRI PT-S showed acceptable correlation with the laboratory method (r2 = 0.85, p < 0.001). In blood samples obtained from cardiac surgical patients (n = 72), heparin prolonged the PT/INR with the laboratory assay, dry-hematology method with non heparin neutralization technology (DRI PT), Coaguchek XS (Roche Diagnostics, Basel, Switzerland), and Hemochron Jr. (Accriva Diagnostics, Edison, NJ), but DRI PT-S was not affected by heparin anticoagulation. In nonheparinized samples, different methods between DRI PT-S and the laboratory method yielded acceptable correlations (r2 = 0.76, p < 0.0001). There was a moderate correlation between factor levels and the PT-INR with DRI PT-S (factor [F]II: r2 = 0.63, FVII: r2 = 0.47, FX: r2 = 0.67; p < 0.0001). CONCLUSIONS: This study demonstrated that PT/INR can be accurately assessed using the dry-hematology method in WB under therapeutic heparin levels. Currently available other POC PT/INR tests are affected by heparin, and thus they are not recommended for coagulation monitoring during cardiopulmonary bypass.

Prothrombin time-international normalized ratio is a useful marker for edoxaban efficacy in preventing venous thromboembolism after total knee arthroplasty.

BACKGROUND: Deep vein thrombosis (DVT) is one of the main complications following total knee arthroplasty (TKA). In this study, oral administration of 15 mg edoxaban (a factor Xa inhibitor) once daily for 14 days efficiently prevented the incidence of DVT. Our hypothesis was that prothrombin time-international normalized ratio (PT-INR) on the third postoperative day could predict the incidence of DVT following TKA. METHODS: In this study, 286 subjects were enrolled and divided into two groups according to the presence or absence of DVT. Several variables [age, body mass index, postoperative D-dimer level, PT-INR, and functional recovery findings (standing)] were analysed to determine the predictors of DVT, and for DVT diagnosis, ultrasonography was performed for seven days after surgery. RESULTS: The PT-INR levels were significantly higher in the group that did not develop DVT (p = 0.01). Further analysis with logistic regression analysis and receiver operating characteristic curve was performed. The PT-INR on the third postoperative day was an independent factor of the incidence of DVT (odds ratio 0.210; p = 0.035). The cut-off PT-INR was calculated to be 1.425. CONCLUSION: PT-INR level is a useful marker in determining whether 15 mg edoxaban administration can prevent DVT after TKA. It is suggested that increment of edoxaban to control PT-INR over the cut-off point might prevent the incidence of DVT.

Performance Evaluation and Local International Sensitivity Index Verification Using Automated Coagulation Analyzer Coapresta 2000

BACKGROUND: The Coapresta 2000 (CP2000; Seikisui, Japan) system is a fully-automated random-access multiparameter coagulation analyzer equipped with a photo-optical clot detection unit. It can perform clotting time assays as well as colorimetric assays. METHODS: We evaluated the analytical performance of CP2000 for several coagulation test parameters and compared its performance with that of the CA-7000 (Sysmex, Japan) system. Fresh and frozen plasma samples were used to evaluate the performance of CP2000 with respect to four routine coagulation test parameters: prothrombin time (PT), activated partial thromboplastin time, fibrinogen, and D-dimer. On-board stability of the liquid reagents was confirmed. Additionally, local international sensitivity index (ISI) verification was performed with four levels of calibrants and direct PT/international normalized ratio (INR) line. RESULTS: The intra- and inter-assay coefficients of variation were below 5% for every parameter in both normal and pathological ranges. Carryover was not detected. The results obtained using CP2000 showed good correlation (r 2 over 0.95) with those obtained by the CA-7000 analyzer. On-board stability in open-vial state, which was expected to be much longer than that of other reagents, was confirmed. Local verification of ISI showed an acceptable bias range of INR, compared with the values using calibrants. CONCLUSIONS: The high-throughput, CP2000 analyzer is a fast, user-friendly system with long on-board reagent stability. Its results were concordant with the CA-7000 analyzer, for analysis of the routine coagulation test parameters. Furthermore, this system would add greater confidence to the reporting of INR data.

A Drug Interaction between Crizotinib and Warfarin in Non-Small-Cell Lung Cancer: A Case Report.

We report a case of increased prothrombin time-international normalized ratio (PT-INR) when crizotinib and warfarin were co-administered. A 74-year-old Japanese woman presented to the hospital with dyspnea, and was diagnosed with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). Three years after surgical resection of the tumor, the patient started crizotinib because of the recurrence of NSCLC. She received 2 mg/day warfarin due to a medical history of cerebral infarction and chronic atrial fibrillation. Before crizotinib initiation, the patient's PT-INR was 2.60. After 7 days of daily doses of crizotinib, the patient's PT-INR increased to 3.65. This case report provides the first evidence of a drug interaction between crizotinib and warfarin.