Prothrombin Time-international Normalized Ratio Research Articles

Optimum INR intensity and therapeutic INR control in patients with mechanical heart valve prosthesis on warfarin oral anticoagulation at Dr George Mukhari academic hospital: a three-year retrospective study

Background: Available evidence suggest that the optimum prothrombin time-international normalised ratio (PT-INR) intensities recommended for anticoagulation of patients with mechanical heart valve ...

A clinical study of sepsis-related coagulation disorder.

Objective To study in the correlation of the laboratory markers of coagulation, fibrinolysis and thrombosis in patients with sepsis and SOFA score, the procalcitonin (PCT) concentration and seven-day survival rate. Methods From February 2017 to March 2018, 119 patients with sepsis admitted in ICU and another 119 patients with non-sepsis undergoing selective surgery were enrolled as control in this study. APTT (activated partial thromboplastin time), PT-INR (prothrombin time - international normalized ratio), FIB (fibrinogen), AT-Ⅲ (antithrombinⅢ), D-Dimer, FDP (fibrinogen degradation products), sTM (soluble thrombomodulin), TAT (thrombin antithrombin complex), PIC (plasmin-a2 plasminogen inhibitor complex) and t-PAI-C (tissue plasminogen activator and its inhibitor complex), were simultaneously monitored at admission. The correlation between the given laboratory markers mentioned and SOFA score, the PCT concentration and seven-day survival rate were analyzed with the Spearman correlation analysis. Results ① In the patients with sepsis, a positive correlation between SOFA score and sTM, t-PAI-C, TAT respectively was found, and a negative correlation between SOFA score and PLT (platelet count) was observed, and no correlation between SOFA score and PIC was noticed. ② A positive correlation between PCT and sTM, t-PAI-C respectively was significant, a negative correlation between PCT and PLT was marked, and no correlation between PCT and AT-Ⅲ, TAT, PIC respectively was found. ③ A negative correlation between seven-day survival rate and sTM, t-PAI-C and TAT respectively was obvious, a positive correlation between seven-day survival rate and AT-Ⅲ, PLT respectively was occurred, and no correlation between seven-day survival rate and PIC was determined. Conclusions Soluble thrombomodulin (sTM), thrombin-antithrombin (TAT) , antithrombin Ⅲ (AT-Ⅲ) and tissue plasminogen activator inhibitor complex (t-PAI-c) were good clinical monitoring indicators of coagulation disorder in patients with sepsis, which were the representative of the endothelial cell damage with highly activated coagulation, relatively insufficient anti-coagulation function and poor fibrin degradation ability. These were good adjuvants to PLT, INR and APTT for core diagnostic criteria of coagulation disorder in sepsis. Key words: Sepsis; Coagulation; Prognosis; Soluble thrombomodulin; AntithrombinⅢ; Thrombin-antithrombin

Alterations of serum vitamin K levels and prothrombin time-international normalized ratio during tooth extractions among patients receiving warfarin

ObjectiveThe British guideline described that antibiotic treatment during tooth extraction kills bacteria in the intestine, which reduces their production of vitamin K and leads to an increased prothrombin time-international normalized ratio (PT-INR). In this study, we attempted to clarify the influence of antibiotics on serum vitamin K levels and alteration of PT-INR in patients receiving warfarin. MethodsWe measured PT-INR and serum vitamin K levels (K1 from diet and K2 from intestinal bacteria) among 11 patients receiving warfarin during tooth extractions (on days 0, 1, 3, and 5) at Dokkyo Medical University Hospital, Sano Kosei General Hospital and Kamma Memorial Hospital from 2008 to 2018. All patients received 5 days of oral antibiotic treatment after the tooth extractions. ResultsThere were no significant changes in PT-INR between days 0 and 5. Serum vitamin K1 levels on day 0 were varied. Most patients had decreased serum vitamin K1 levels on days 1 and 3. Mean serum vitamin K1 levels on day 3 were significantly lower than those on day 0 (p = 0.04) in patients who were admitted to Dokkyo Medical University Hospital. Most patients still had low serum vitamin K1 levels between days 3 and 5. Serum vitamin K2 levels in most patients examined were below the detection limit (0.05 ng/ml) except two patients (0.24 ng/ml, 0.06 ng/ml at day 0). ConclusionIt appears that antibiotic treatment during tooth extractions might not affect PT-INR among patients receiving warfarin through the alteration of serum vitamin K2 production by intestinal bacteria.

Portable coagulometer for vitamin K-antagonist monitoring: the patients’ point of view

PurposeThe aim of this study was to know the patients’ point of view on the monitoring of vitamin K-antagonist (VKA) therapy by means of a point of care testing (POCT), ie, using a portable coagulometer by self-testing at home. At first, patients had prothrombin time (PT) international normalized ratio (INR) monitoring at a thrombosis center; afterward, they were shifted to self-testing at home. An interview was done to evaluate the patients’ point of view on the two monitoring periods.Patients and methodsA total of 92 oral anticoagulated patients were enrolled. The questionnaire contained nine questions that elicited a maximum of five closer answers that were arranged in increasing levels of satisfaction: very little, little, enough, much and completely. Percentage of time in therapeutic range (TTR) and adverse events were compared during the two periods of conventional monitoring and self-testing.ResultsThe period of conventional monitoring was shorter than that of self-testing (p<0.0001), and the median TTR was satisfactory but lower than that of self-testing (p<0.0001). A total of 85% of the patients were satisfied with self-testing at home. In all, 83% and 73% (p=0.06) of patients felt comfortable about side effects while measuring the PT INR at both home and the thrombosis center, respectively. During the self-testing period, quality of life was improved in 87% of the patients. The cost of test strips was medium–high for 89% of the patients, and 75% of them stated that it was worth improving their quality of life. A switch from VKA to a direct oral anticoagulant (DOAC) was proposed to 24% of the patients, but 68% of them declined because they felt more comfortable monitoring their oral anticoagulant therapy by POCT.ConclusionVKA monitoring using POCT at home may play a role in improving the patients’ quality of life and may be considered as an alternative to the use of DOAC at least in certain settings of patients.

Enhancement of Warfarin Anticoagulant Reaction in Patients with Repeated Oral Tolvaptan Administration.

The pharmacokinetics and pharmacodynamics of warfarin remained unaffected by tolvaptan during clinical trials. However, tolvaptan prolonged the prothrombin time-international normalized ratio (PT-INR) level of patients with cardiovascular disease taking warfarin. Tolvaptan was prescribed to 576 patients from December 2010 to December 2015. Of these patients, 37 underwent anticoagulant therapy. We investigated PT-INR fluctuation immediately before tolvaptan therapy was initiated. PT-INR remained unchanged in the control group and in groups administered with less than 7.5 mg/d tolvaptan, whereas it was significantly increased (p=0.03) in the group administered with more than 7.5 mg/d tolvaptan. This result indicates the possibility that tolvaptan affects the pharmacodynamics of warfarin in vivo. However, further research is necessary to clarify the mechanism of this phenomenon.

Interaction between warfarin and short-term intravenous amiodarone in intensive care unit patients after cardiac surgery

BackgroundAmiodarone and warfarin are sometimes administered immediately after cardiac surgery. Although the interaction between long-term oral amiodarone and warfarin has been reported, the interaction between warfarin and short-term intravenous amiodarone has not been reported. In this study, we investigated the effect of short-term intravenous amiodarone on the anticoagulant effect of warfarin in patients who underwent cardiac surgery.MethodsWe retrospectively reviewed the medical records of 11 patients who received oral warfarin before and after cardiac surgery, and loading doses of 125–150 mg or a 750 mg continuous infusion of amiodarone, or both in the intensive care unit (ICU) within 5 days after the surgery between July 2011 and January 2017. The prothrombin time-international normalized ratio (PT-INR)/daily warfarin dose (PT-INR/dose) was used as an indicator of anticoagulant effect. The values before surgery were considered as the baseline.ResultsThe PT-INR and PT-INR/dose values were elevated in 7 and 10 patients, respectively, after amiodarone administration. The mean PT-INR values were not significantly different before and after amiodarone administration (2.13 ± 0.58 vs 2.29 ± 0.50, respectively, p = 0.643). In contrast, the mean PT-INR/dose values were significantly elevated after the administration of amiodarone (0.93 ± 0.46 vs 1.54 ± 0.63, respectively, p = 0.002).ConclusionsShort-term intravenous amiodarone enhanced the anticoagulant effect of warfarin in patients admitted to the ICU after cardiac surgery. We suggest that the dose of warfarin should be carefully adjusted for a few days after cardiac surgery if intravenous amiodarone is coadministered.

Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD).

This study aimed to investigate relationships between times in therapeutic range (TTR) or warfarin sensitivity indexes (WSI) and VKORC1-1639G>A and CYP2C9 polymorphisms in patients with left ventricular assist devices (LVAD). Severe heart failure patients who received LVAD from January 1, 2013 to October 31, 2017 were recruited. Relationships between TTR or WSI and VKORC1-1639G>A and CYP2C9 gene polymorphisms were investigated immediately after LVAD implantation (period 1) and immediately prior to hospital discharge (period 2). Among 54 patients, 31 (72.1%) had VKORC1-1639AA and CYP2C9*1/*1 (AA group) polymorphisms and 12 (27.9%) had VKORC1-1639GA and CYP2C9*1/*1 (GA group) polymorphisms. During period 1, mean prothrombin time-international normalized ratio (PT-INR) values were significantly higher in the AA group than in the GA group (2.21 vs. 2.05, p< 0.0001). Mean WSI values were 1.68-fold greater in the AA group than in the GA group (1.14 vs. 0.68, p< 0.0001). In addition, times below the therapeutic range (TBTR) in the GA group were significantly greater than in the AA group during period 1 (39.8 vs. 28.3%, p= 0.032), and insufficient PT-INR was more frequent in the GA group than in the AA group. However, mean PT-INR values during period 2 did not differ and no significant differences in TTR, TATR, and TBTR values were identified. In subsequent multivariable logistic regression analyses, the VKORC1-1639GA allele was significantly associated with insufficient anticoagulation. Patients with the VKORC1-1639GA and CYP2C9*1/*1 alleles may receive insufficient anticoagulation therapy during the early stages after implantation of LVAD, and VKORC1-1639G>A and CYP2C9 genotyping may contribute to more appropriate anticoagulant therapy after implantation of LVAD.

Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women.

During pregnancy, interpretation of results from coagulation parameters can be difficult as the physiological changes that occur may affect the biochemical parameters. The aim of this study was to describe the normal course of five coagulation parameters in healthy pregnancies, and to estimate the within-subject biological variation (CVI). Blood samples were obtained every 4th week during pregnancy and three samples after delivery in 20 healthy women and every 4th week during a 40-week period in 19 healthy non-pregnant women. Activated partial thromboplastin time (APTT), prothrombin time (PT), PT International Normalized Ratio (INR), fibrinogen, factor VIII clot (FVIII:C) and von Willebrand factor antigen (vWF:Ag) were analyzed. The physiological changes during pregnancy were compensated by transformation into multiples of the median (MoM) and it is natural logarithm (lnMoM) in order to establish a kind of steady state, and CVI was calculated from the standard deviation. During pregnancy, APTT, PT and INR remained unchanged or decreased, depending upon the reagent used, while fibrinogen, FVIII:C and vWF:Ag increased gradually until delivery. The CVI in pregnancy were 2.2 and 3.0% for APTT, 2.3 and 2.6% for PT, 2.2 and 2.3% for INR, 7.2% for fibrinogen, 12.2% for FVIII:C and 11.3% for vWF:Ag, and corresponded with the CVI in non-pregnant women. Transformation of coagulation parameters in healthy pregnancies to MoM is a tool to establish a kind of steady state. Although there is a physiological change in these coagulation parameters during pregnancy, the CVI after lnMoM transformation was comparable with the CVI of non-pregnant women.

Coexistence of Bilirubin ≥10 mg/dL and Prothrombin Time-International Normalized Ratio ≥1.6 on Day 7: A Strong Predictor of Early Graft Loss After Living Donor Liver Transplantation.

Early allograft dysfunction (EAD) defined by serum total bilirubin (TB) of 10 mg/dL or greater or prothrombin time-international normalized ratio (PT-INR) of 1.6 or greater on postoperative day 7 (POD 7) or aminotransferase greater than 2000 IU/L within the first week, is associated with early graft loss after deceased-donor liver transplantation. We aimed to determine the prognostic impact of the EAD definition in living-donor liver transplantation (LDLT). We analyzed the validity of the EAD definition and its impact on early graft survival in 260 adult recipients who underwent primary LDLT. Eighty-four (32.3%) patients met the EAD criteria; 59 (22.7%) and 46 (17.7%) patients had TB of 10 mg/dL or greater and PT-INR of 1.6 or greater on POD 7, respectively, and 22 (8.5%) patients satisfied both criteria. Graft survival differed significantly when stratified according to TB of 10 mg/dL or greater and PT-INR of 1.6 or greater (P < 0.0001). PT-INR of 1.6 or greater resulted in higher graft mortality (risk ratio [RR], 3.87; P < 0.0001 at 90 days; RR, 2.97; P < 0.0001 at 180 days), as did TB of 10 mg/dL or greater (RR, 1.89; P = 0.027 at 90 days; RR, 1.91; P = 0.006 at 180 days). Coexistence of TB of 10 mg/dL or greater and PT-INR of 1.6 or greater was strongly associated with early graft loss (59.1%, RR, 6.97 at 90 days; 68.2%; RR, 5.75 at 180 days). In Cox regression analysis, PT-INR of 1.6 or greater and TB of 10 mg/dL or greater on POD 7 were significant risk factors for early graft loss (hazard ratio, 4.10; 95% confidence interval, 2.35-7.18; P < 0.0001, and hazard ratio, 2.43; 95% confidence interval, 1.39-4.24; P = 0.0018, respectively). TB of 10 mg/dL or greater and/or PT-INR of 1.6 or greater on POD 7 predicted early graft loss after LDLT, and their coexistence worsened patient outcomes.

Simple method for removing DOACs from plasma samples

AimTo evaluate a simple method using an adsorbent product (DOAC Stop) for extracting direct oral anti-coagulants (DOACs) from plasmas. MethodDOAC Stop was tested on normal and a range of abnormal plasmas initially using activated partial thromboplastin time (APTT) tests and a more DOAC-sensitive Russells viper venom-based clotting test (DOAC Test). Further tests for prothrombin time/International Normalized Ratio (PT/INR), lupus anticoagulants, activated protein C (APC) resistance, antithrombin, plasminogen, protein C and S were carried out on various patient samples. ResultsDOAC Stop was found to remove all types of DOACs including dabigatran, apixaban, rivaroxaban and edoxaban from test plasmas with minimal effect on any of the (mainly clotting) tests considered in this study. SummaryDOAC Stop can be used to identify plasmas containing DOAcs using simple clotting tests. It reduces the false positivity for lupus anticoagulants observed in dilute Russells viper venom time (dRVVT) tests on DOAC-containing plasmas and could be useful for eliminating unwanted effects of DOACs on routine coagulation testing.

Preventive effects of low molecular weight heparin on formation of deep vein thrombosis by reducing D dimer values in patients undergoing spinal surgery.

Deep vein thrombosis (DVT) is one of the most common complications for patients undergoing spinal surgery. This study aims to investigate preventive effects of low-molecular-weight heparin (LMWH) on the formation of DVT. This study involved 37 patients who underwent spinal surgery between April 2016 and April 2017. Patients were divided into LMWH group and Control group. Clinical parameters, including operation time, intra-operative blood loss, incision length, post-operative visual analogue scale (VAS), exercise-time leaving bed and post-operative extubation time, were collected. Blood routine analysis, including platelet count (PLT), red blood cell count (RBC), white blood cell count (WBC) and hemoglobin (HGB) were also conducted. Coagulation parameters, including prothrombin time-international normalized ratio (PT-INR), fibrinogen (FIB), activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time 1 (PT-1) and D-dimer (DD), were evaluated. The drainage fluid was collected. LMWH treatment significantly decreased operative time, blood loss and incision length compared to Control group at 1st, 3rd and 7th day post-operation (all p<0.05). LMWH treatment significantly increased WBC levels compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). LMWH treatment significantly decreased DD levels in the post-operative patients compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). However, LMWH treatment doesn't affect drainage amounts of patients. DD levels were positively correlated with WBC counts for the LMWH treated patients. Low molecular weight heparin effectively prevents the formation of DVT by reducing DD values in patients undergoing spinal surgery.

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

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. Prospective, observational study. University hospital, single center. Healthy volunteers and warfarin-treated and cardiac surgical patients. 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). 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.

Periprocedural Bleeding Risk Assessment in Chronic Liver Disease

AbstractInvasive procedures are common in the management of cirrhosis-related chronic liver disease (CLD). Assessing bleeding risk prior to these procedures is challenging because of commonly seen laboratory abnormalities among traditional testing used to evaluate bleeding risk in patients with advanced liver disease. However, this ‘coagulopathy’ seen in advanced liver disease is not a true bleeding or clotting disorder. The prothrombin time/international normalized ratio (PT/INR) test is frequently elevated in CLD patients, but has been shown to poorly correlate with bleeding risk in this population. A traditional interpretation of this laboratory test can lead to unnecessary transfusion of blood product, procedure delay, or even potential harm to the patient. An understanding of the ‘coagulopathy’ of advanced liver disease and alternative methods, to more accurately assess bleeding risk, allows clinicians to treat safely CLD patients.

The risk factors associated with postoperative hemorrhage after tooth extraction: a multi-center retrospective study of patients receiving oral antithrombotic therapy.

The purpose of this study was to retrospectively investigate the multivariate relationships between specific risk factors and postoperative hemorrhage after tooth extraction in patients who were prescribed oral antithrombotic therapy. Risk factors for postoperative hemorrhage after tooth extraction were evaluated using univariate and multivariate analyses. Patient characteristics such as age and gender; the presence or absence of known comorbidities such as diabetes mellitus, hypertension, cerebral infarction, and alcohol consumption; and perioperative diarrhea were assessed. The drug used for antithrombotic therapy, preoperative blood test results, the presence or absence of preoperative antibiotics or nonsteroidal anti-inflammatory drug (NSAID) administration, the total number of extracted teeth, and the type of surgical procedures were also evaluated. We found that the preoperative administration of antibiotics (odds ratio (OR)=2.52), an increased prothrombin time international normalized ratio (PT-INR) value (OR=1.94), and the extraction of multiple teeth (OR=2.10) were significantly associated with postoperative hemorrhage. There was no significant association between postoperative hemorrhage and any other demographic factors or comorbidities, including concomitant alcohol use. We demonstrated the multivariate relationship between the risk factors and postoperative hemorrhage after tooth extraction in patients receiving oral antithrombotic therapy. Surgeons should be aware of these risks and monitor the PT-INR of anticoagulated patients.

The effects of dry ice exposure on plasma pH and coagulation analyses.

We recently observed that exposure to dry ice lowered sample pH and increased clotting times in lupus anticoagulant analyses, and that such changes could be prevented by placing samples at -80°C after dry ice exposure. In the current study, we sought to evaluate the effects of dry ice exposure on pH and various commonly used coagulation analyses. Citrated plasma from 30 healthy blood donors was allocated to four preanalytical regimes: (1) immediate analysis of fresh plasma or (2) storage at -20°C; (3) storage at -20°C followed by dry ice exposure for 24 h or (4) storage at -20°C followed by dry ice exposure for 24 h and storage at -80°C for 24 h before analysis. Analyses of pH, prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), antithrombin, fibrinogen, protein C and protein S was performed. Samples exposed to dry ice had significantly lower pH, prolonged clotting times in PT-INR, APTT and fibrinogen analyses as well as lower levels of protein C, than samples not exposed to dry ice. These changes in coagulation analyses were not present if samples were stored at -80°C for 24 h after dry ice exposure. Antithrombin and protein S were not significantly affected by dry ice exposure. Dry ice exposure lowered sample pH and affected various coagulation analyses. These effects were avoided by storing samples at -80°C for 24 h after dry ice exposure.

Association Between Hypercoagulability and Severe Obstructive Sleep Apnea

ImportanceObstructive sleep apnea (OSA) is related to the increased risk of cardiovascular disease. Although the pathogenesis of this association remains unclear, an alteration in coagulability is suspected as a link.ObjectiveTo investigate the association between the severity of OSA and blood coagulability.Design, Setting, and ParticipantsA retrospective cohort study conducted at a tertiary care university hospital evaluated 146 patients with OSA from January 1, 2009, to July 31, 2015. The participants were divided into 4 groups according to the severity of OSA: control, mild, moderate, and severe. Main Outcomes and MeasuresAssociation between the severity of OSA and coagulation test results, including platelet count, bleeding time, prothrombin time (PT) in seconds and as international normalized ratio (INR), and activated partial thromboplastin time.ResultsOf the 146 patients, 135 (92.5%) were men; mean (SD) age was 34.8 (11.1) years. The control group included 41 (28.1%) patients; mild OSA, 32 (21.9%); moderate OSA, 30 (20.5%); and severe OSA, 43 (29.5%). Significant correlations were found between the apnea-hypopnea index and the PT seconds (Spearman r coefficient, −0.30; 95% CI, −0.44 to −0.14) and PT INR (Spearman r coefficient, −0.30; 95% CI, −0.44 to −0.14). There were significant differences between the OSA severity groups for PT seconds for the control group (mean, 11.26 [0.78] seconds) vs the moderate OSA group (10.74 [0.62] seconds; mean difference [MD], 0.52; 95% CI, 0.27 to 1.01) and the severe OSA group (10.67 [0.77] seconds; MD, 0.59; 95% CI, 0.14 to 1.03). Significant differences were also noted in PT INR between the control group (1.00 [0.07]) vs the moderate OSA group (0.95 [0.05]; MD, 0.04; 95% CI, 0.01 to 0.07) and the severe OSA group (0.94 [0.07]; MD, 0.05; 95% CI, 0.02 to 0.08). However, there was no significant difference between the control and mild OSA groups in PT seconds.Conclusions and RelevanceThese results suggest that patients with moderate to severe OSA have elevated blood coagulability markers compared with healthy individuals, which may contribute to the occurrence of cardiovascular complications.

A retrospective study on the risk factors for bleeding events in warfarin therapy, focusing on renal function

The anticoagulant effect of warfarin used to treat stroke has been shown to vary with the concomitant use of medications and comorbidity. Concomitant use of antithrombotic drugs and underlying chronic kidney disease (CKD) represent risk factors for bleeding events. We conducted a comprehensive investigation of the background characteristics and concomitant use of drugs to identify the risk factors for warfarin-related bleeding, focusing on renal function. The study population consisted of patients prescribed warfarin at the Tokyo Women's Medical University Hospital. A retrospective review of the patient data, including bleeding events, bleeding sites, the patient's background, concomitant use of drugs, and laboratory data was carried out, and the incidence of bleeding events was compared in patient groups stratified according to CKD stage and antithrombotic drug use. Multivariate logistic regression analysis was performed to determine the risk factors for warfarin-related bleeding. Of the 3,831 patients included in the study, the incidence of warfarin-related bleeding was 3.0 events per 100 patient-years. The multivariate logistic regression analysis identified age>65years, body mass index (BMI), alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, prothrombin time-international normalized ratio (PT-INR), and concomitant use of antithrombotic drugs as risk factors for warfarin-related bleeding. The present analyses identified age>65years, BMI, ALT, eGFR <30mL/min/1.73m2, PT-INR, and concomitant use of antithrombotic drugs as independent risk factors for warfarin-related bleeding. We should pay attention to the risk factors associated with warfarin-related bleeding when prescribing warfarin in patients with renal impairment.

Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.

Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

Real-Life Management of Venous Thromboembolism With Rivaroxaban: Results From EXperience VTE, an Italian Epidemiological Survey.

Two large randomized controlled trials examined the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE). The aim of this epidemiological study was to analyze a cohort of Italian patients affected by VTE who were treated with rivaroxaban in clinical practice. The data were collected by physicians using an online electronic questionnaire. The study was performed during a 6-month period from January to June 2014. We analyzed the clinical characteristics, risk factors for VTE, comorbidities, diagnostic techniques, and treatments in the whole population and in the subgroups with deep vein thrombosis (DVT) only, pulmonary embolism (PE) only, and DVT+PE. Overall, 75.9% of patients were affected by DVT; 20% of patients had DVT and PE; and 4.8% of patients had only PE. Approximately 90% of patients were symptomatic upon diagnosis, and 46.3% of patients required hospitalization. More than half of the patients switched to rivaroxaban after receiving another anticoagulant therapy. The main reasons for changing treatment included difficulties in managing vitamin K antagonists, patient choice, and prothrombin time-international normalized ratio (PT-INR) instability. The switch to rivaroxaban occurred after a mean of 1.8 PT-INR measurements. Clinical characteristic were overall similar to those of patients enrolled in prior clinical trials evaluating the safety and efficacy of rivaroxaban.

Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study.

Low platelet count on admission to an intensive care unit (ICU) is associated with increased mortality and is thus included in some severity scoring systems such as the simplified acute physiologic score 3 (SAPS 3); however it is unclear whether other routine coagulation tests also predict mortality. The purpose of this retrospective single-centre study was to investigate whether activated partial thromboplastin time (APTT) or prothrombin time - international normalized ratio (PT-INR) measured on admission to the ICU in patients with severe sepsis or septic shock may be associated with mortality independent of SAPS 3 score. All patients admitted to a tertiary general ICU from 2007 to 2014 diagnosed with severe sepsis or septic shock were eligible. Results from APTT and PT-INR within 1.5h of admission as well as SAPS 3 were used as independent variables in a Cox regression. Of total 5485 ICU admissions during the study period we identified 647 unique patients with severe sepsis or septic shock. APTT and PT-INR were found to correlate significantly with mortality with a hazard ratio (HR) of 1.014 [95% confidence interval of HR (1.006-1.023)] for APTT and 1.422 (1.117-1.811) for PT-INR. HR for SAPS 3 was 1.036 (1.028-1.044). Activated partial thromboplastin time prolongation and raised PT-INR on ICU admission in patients with severe sepsis or septic shock is associated with increased mortality independent of SAPS 3 score. This indicates that APTT prolongation and PT-INR increase represents morbidity that is not accounted for in SAPS 3.