Mean International Normalized Ratio Research Articles

Incidence of Coagulopathy After Resuscitation at a Role 1 Facility: The Prehospital Trauma Registry Experience.

The development of acute traumatic coagulopathy is associated with increased mortality and morbidity in patients with battlefield traumatic injuries. Currently, the incidence of acute traumatic coagulopathy in the Role 1 setting is unclear. We queried the Prehospital Trauma Registry (PHTR) module of the Department of Defense Trauma Registry (DoDTR) for all encounters from inception through May 2019. The PHTR captures data on Role 1 prehospital care. Data from the PHTR was linked to the DoDTR to analyze laboratory data and patient outcomes using descriptive statistics. We defined coagulopathy as an international normalized ratio (INR) of ≥1.5 or platelet count ≤150×109/L. A total of 595 patients met the inclusion criteria; 36% (212) met our definition for coagulopathy, with 31% (185) carrying low platelet numbers, 11% (68) showing an elevated INR, and 7% (41) with both. The baseline (no coagulopathy) cohort had a mean INR of 1.10 (95% CI 1.09-1.12) versus 1.38 (95% CI 1.33-1.43) in the coagulopathic cohort. The mean platelet count was 218 (95% CI 213-223) ×109/L in the baseline cohort versus 117 (95% CI 110-125) ×109/L in the coagulopathic cohort. Our findings indicate a high incidence of coagulopathy in trauma patients. Approximately one-third of wounded patients had laboratory evidence of coagulopathy upon presentation to a forward medical care facility. Advanced diagnostic facilities are therefore needed to facilitate early diagnosis of acute traumatic coagulopathy. Blood products with a long shelf life can aid in early correction.

Thirty-year outcomes of low-intensity anticoagulation for mechanical aortic valve.

The long-term safety, efficacy, and outcomes of low-intensity anticoagulation for mechanical heart valves remain unclear. This study aimed to evaluate the long-term outcomes of low-intensity anticoagulation therapy after aortic valve replacement (AVR) with a mechanical prosthesis. This retrospective cohort study consulted medical records and conducted a questionnaire to investigate 519 patients who underwent single AVR with the St. Jude Medical bileaflet valve and were in sinus rhythm. All patients were followed up with an international normalized ratio (INR) target of 1.6-2.5, and their INR values were checked throughout the follow-up period. The survival rate, incidence of major adverse cardiac and cerebrovascular events (MACCE), and risk factors for cardiac death and MACCE were investigated. The total follow-up was 9793 patient-years, and the follow-up periods were 19.9 (standard deviation [SD]: 7.9) years. The mean INR was 2.03 (SD: 0.54). Survival rates from cardiac death were 93.6% in 20years and 85.2% in 30years. Advanced age ≥ 70years was the only significant risk factor for cardiac death and MACCE, and the INR < 2.0 was not significant risk factor for MACCE including thromboembolism or bleeding events. Low-intensity anticoagulation with an INR of 1.6-2.5 for patients with sinus rhythm after AVR with a bileaflet mechanical valve is safe and effective, even over 30years.

Time for a Paradigm Shift in Vitamin K Antagonist Reversal - Embracing TGA over INR for Optimal Outcomes?

Introduction: Vitamin K antagonist (VKA) anticoagulation reversal has relied on International Normalized Ratio (INR) as a standard parameter of coagulation status. Reversal of anticoagulation within INR ranges of 2 - 3 is usually achieved by 25 IU/kg of 4-Factor PCC (4F-PCC), resulting in INR &amp;lt;1.5. However, emerging evidence suggests that increases in coagulation factor activities may be more accurately reflected by the thrombin generation assay (TGA), paving the way for a different approach to assessing effectiveness of VKA reversal. To this effect, a Phase I/II clinical study was conducted to assess dose response of 4F-PCC in healthy subjects anticoagulated with a VKA agent. Methods: This was a prospective, randomized, open-label, placebo-controlled study involving healthy subjects aged 18 to 55 years. Participants were pre-treated for 10 days with acenocoumarol to achieve an INR between 2 and 3 (± 10% inclusive). Subsequently, they received a single iv bolus of 4F-PCC at doses of 12.5 IU/kg or 25 IU/kg, or placebo. Blood samples for TGA, INR, and blood clotting factors (FII, FVII, FIX, FX, protein C, and protein S) were assessed at specified intervals from pre-dose VKA (baseline) up to 15 days after 4F-PCC dose. Results: VKA for 10 days decreased plasma activities of blood clotting factors II, VII, IX and X as expected. Thirty minutes after infusion with 4F-PCC, clotting factor levels were increased in a dose-dependent manner, relative to pre-infusion levels. Placebo had no significant effect on any of the clotting factors. 4F-PCC at 12.5 IU/kg, or 25 IU/kg decreased mean INR values within 30 min after dosing from 2.39 to 1.37, and 2.45 to 1.17, respectively. Infusion with 25 IU/kg fully restored peak thrombin generation at 30 min after dosing compared to baseline (mean ratio: 1.08), while 12.5 IU/kg achieved partial restoration (mean ratio: 0.75). Factor II: Doses of 12.5 IU/kg or 25 IU/kg 4F-PCC increased mean FII values at 30 min post-dose from 32% to 65% and 32% to 89%, respectively (Figure 1). The median maximum concentration (Emax 0-12h) was 68% for 12.5 IU/kg, and 92% for 25 IU/kg (Table 1). Factor VII: Doses of 12.5 IU/kg and 25 IU/kg 4F-PCC increased mean FVII values at 30 min from 15% to 30%, and from 14% to 46%, respectively. The median Emax 0-12h was 32% for 12.5 IU/kg, and 46% for 25 IU/kg. Factor IX: Doses of 12.5 IU/kg and 25 IU/kg 4F-PCC increased mean FIX values at 30 min from 29% to 41% and from 29% to 52%, respectively. The median Emax 0-12h was 45% for 12.5 IU/kg, and 56% for 25 IU/kg. Factor X: Doses of 12.5 IU/kg and 25.0 IU/kg 4F-PCC increased mean FX values at 30 min, from 18% to 42% and 18% to 64%, respectively. The median Emax 0-12h was 45% for 12.5 IU/kg, and 66% for 25 IU/kg. Conclusion: After 4F-PCC infusion, clotting factors II, VII, IX and X showed dose-dependent increases at 30 min post-dose. Correspondingly, a dose-dependent TGA response was observed; 4F-PCC resulted in restoration to levels measured before anticoagulation with VKA. The degree of INR normalization appeared to be slightly more pronounced in the higher dosed 4F-PCC group. Factor II was almost normalized after 4F-PCC infusion and is known to be a main driver of the TGA response. Even though the other clotting factors, such as factor VII, remain in the range of approx. 50%, this does not represent a limitation for adequate activation of the coagulation system. Considering 4F-PCC characteristics and the mechanisms underlying either TGA or INR, the choice of TGA rather than INR appears to be more suitable to monitor appropriate restoration of the overall clotting potential after VKA reversal with 4F-PCC.

Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial

BackgroundCurrent guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. MethodsAfter On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. ResultsMean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, −0.07%; 95% CI, −3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. ConclusionsCompared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

Anti-SARS-CoV-2 vaccination does not influence anticoagulation levels in stable long-term warfarin treatment.

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, administration of the currently available vaccines has mostly been recommended for subjects at high risk, including elderly populations on long-term oral anticoagulation therapy (OAT) with warfarin. However, there is no clear evidence of the stability of the International Normalised Ratio (INR) after vaccine administration in those subjects on long-term OAT. The present study aimed to investigate the effects of COVID-19 vaccination on anticoagulation levels in patients on long-term OAT. INR values of patients on long-term OAT who had undergone anti-SARS-CoV-2 vaccination from January to June 2021 were monitored for a total of 90 days follow-up after the first vaccination dose. These were then compared with INR values before vaccination. The second dose, when required, was administered during follow-up. Inclusion criterion was stable long-term INR for at least 6 months before vaccination. Exclusion criteria were recent surgery, intercurrent diseases, or treatment with medication that could compromise findings in the 3 months before vaccination and during follow-up. No differences were observed in the anticoagulation levels before and after COVID-19 vaccination in any of the patients studied: mean INR values were 2.39 (range 2.20-2.63) before vaccination and 2.40 (range 2.16-2.76) after vaccination (p=0.5). There was no difference in anticoagulation levels in relation to age, sex, indication for OAT, or type of vaccine (p>0.5). No bleeding or thrombotic complications were documented during follow-up. These are the first data to be reported on anticoagulation levels in patients on stable OAT after COVID-19 vaccination. No influence on the quality of OAT was detected after the vaccination; no bleeding or thrombotic complications were recorded in the follow-up. No difference between the four available COVID vaccines was found. Dose adjustment was only required in a few cases, thus confirming the stability of anticoagulation levels.

Effect of Fasting in Patients Taking Acenocoumarol

Anticoagulation with acenocoumarol is influenced by dietary changes but the effect of fasting on acenocoumarol therapy is unknown. Objectives: To study changes in international normalized ratio (INR) and the percentage of time within therapeutic range (%TTR) before and during Ramadan. Methods/Patients: In this prospective study, weekly INR readings were taken from participating patients during two study periods: before and during Ramadan. Readings were blinded to patients and their primary physicians except for when pre-set study endpoints were reached. Results: Among 128 participating patients, mean INR increased by 0.25 (P = 0.006) during Ramadan from the pre-Ramadan month. There was no significant difference (P = 0,02) in mean INR between the non-Ramadan months. No bleeding or thrombotic events were recorded. Conclusion: Fasting significantly increases the mean INR of medically stable patients taking acenocoumarol and the likelihood of having an INR above therapeutic targets.

The Effect of Serum Magnesium Level on Stable Anticoagulation in Patients Using Warfarin for Various Cardiac Indications.

Warfarin is a vitamin K antagonist agent that inhibits clotting factors used for long-term anticoagulation. Time in therapeutic range (TTR) in patients using warfarin is one of the primary treatment effectiveness requirements. We aim to investigate the relationship between serum magnesium levels, the international normalized ratio (INR) values, and TTR values in people using warfarin for various indications. Our study is a single-center, cross-sectional, and retrospective study that included 169 patients between 18 and 70 who used warfarin for various indications. Demographic data, biochemical analysis, and coagulation parameters, including TTR calculation, were evaluated for all patients. Those with a TTR value below 60 were defined as labile INR, and those with 60 and above as stable INR group and compared. The mean INR value was higher in the labile INR group than the stable INR group (3.7 ± 2.9, 3.2 ± 0.3, respectively; p = 0.030). The Mg values are significantly lower in the labile INR group than the stable group (1.8 ± 0.2mg/dL, 2.0 ± 0.1mg/dL, respectively; p < 0.001). In binary multivariate logistic regression analysis, magnesium value was the most influential INR stabilization factor (p < 0.001). As a result of our study, it was concluded that magnesium levels are an influential factor in stabilizing INR. We can state that we have contributed to the literature and can be a reference for future studies.

WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement

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Analysis of anticoagulation therapy related complications in patients with prosthetic valves: Our experience

Purpose:The aim of this study is to analyze anticoagulation-related complications in patients following mechanical valve replacement and factors influencing the outcome.Materials and Methods:A total of 250 patients were analyzed during OPD follow-up for anticoagulation-related complications and various factors influencing outcome. Patients received prosthetic valve at mitral and/or aortic or both.Results:Out of 250 patients, 48% were male and 52% were female. The mean age was 41.9 ± 14.4. A total of 139 had mitral valve replacement (MVR), 70 had aortic valve replacement (AVR), 40 had double valve replacement (DVR), and 1 patient had triple valve replacement. Valves implanted were mechanical bileaflet valve. The mean international normalization ratio (INR) in the study was 2.4 ± 0.56. A total of 49 events occurred during follow-up, of which 4.5% per patient years were anticoagulation-related hemorrhagic events and 4.8% per patient years were thromboembolic events. Among thromboembolic events, valve thrombosis occurred in 10 patients and cerebrovascular accidents occurred in 11 patients. Mean INR for thromboembolic events was 1.46 ± 0.25 and anticoagulation-related hemorrhagic events was 4.4 ± 1.03. Mortality rate was 1.6% in AVR, 4% in MVR, and 0.4% in DVR groups; about 34% of patients needed dose modification of Acenocoumarol and reason for derangement of INR was associated with infectious process and poor compliance; 85% of cases showed good compliance for daily anticoagulation therapy.Conclusion:Anticoagulation for mechanical valve replacement can be managed with INR range of 2.0 to 2.5 in MVR and 1.5 to 2.0 in AVR with acceptable hemorrhagic and thromboembolic events. We must educate and counsel the patients during follow-up for better compliance to optimal anticoagulation.

Evaluation of Safety and Efficacy of Combined Low Dose Aspirin and Warfarin Following Mechanical Heart Valve Replacement for Mitral Valve Disease

Introduction: Warfarin is recommended following mechanical valve replacement to prevent thromboembolic complications. A combination of warfarin and aspirin may further reduce thromboembolic events in these patients. This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical mitral valve replacement. Materials and Methods: Purposively selected 99 patients who underwent mechanical mitral valve replacement were divided into two groups. Patients of Group A (n=50) received combined low dose aspirin (75mg) and warfarin. Patients of Group B (n=49) received conventional dose of warfarin alone. International normalized ratio (INR) was targeted 1.8-2.4 for group A Patients and 2.5-3.5 for group B Patients. Post-operatively INR, thromboembolic events, anti-coagulation related haemorrhage and other morbidity and mortality were registered in both groups. Result: Patients were followed up postoperatively for 9 months. The mean dose of warfarin in group A and group B was 4.36 ± 0.31 mg and 5.57±0.52 mg respectively (p&lt;0.001). The overall mean INR of two groups of patients were statistically different (P&lt;0.001) with low INR in group A (2.19±0.13) patients compared to group B (3.03±0.31). The thromboembolic events in group A (0.02/patient year) were lower than those in group B (0.08/Patient year). There was no statistically significant (p=0.362) difference in bleeding episodes between two groups but data indicate proportion of minor bleeding manifestations were higher in patients treated with warfarin plus aspirin group. Conclusion: Following mechanical mitral valve replacement, a combination of aspirin (75mg) and low dose warfarin with an aim to maintain INR between 1.8 and 2.4 (lower than recommended 2.5-3.5) may provide satisfactory outcomes in term of thrombosis, embolism and bleeding without increase in mortality. Bangladesh Heart Journal 2021; 36(1): 24-31

Comparison between 5 mg and 10 mg warfarin loading doses therapy in cardiac care unit patients at Elobied Hospital, Elobied City- Sudan

Background and objectives: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time needed to reach the target international normalized ratio (INR). The right initial dose of warfarin is controversial. This study aimed to determine the best initial dose of warfarin in terms of safety and efficacy. Patients and methods: This is a prospective hospital-based study. Fifty-nine patients who were admitted to the coronary care unit with clinical indication for warfarin were assigned to use the initial dose of warfarin 5 mg or 10 mg with the target INR of 2-3. An ethical clearance was obtained from the state ministry of health. A written consent was taken from each patient. An INR was measured at baseline and then after 72 hours. The data were then collected using a data sheet including age, gender, baseline INR, initial dose of warfarin, INR after 72 hours and whether the patient developed bleeding or not. Patients on Aspirin and other non-steroidal anti-inflammatory drugs were excluded. The data were analyzed using SPSS version 18. Results: A total number of 59 patients were enrolled in the study. In this series, 59% of patients were females. The mean age of patients was 56 years. Five mg loading dose was used in 35 of patients (59%) while 10 mg was used in 24 patients (41%). The mean INR after 72 hours was 2.8 for those with the initial dose of 5 mg. For those with the initial loading dose of 10 mg the mean INR after 72 hours was 3.2. Minor bleeding occurred in three patients, two of them used the initial loading dose of 5mg and only one patient from the group of 10mg. Conclusion: From this study, it seems that 5 mg loading dose of warfarin is reasonable and cost effective; nevertheless, 10mg initial loading dose is not associated with increased risk of bleeding.

English

BACKGROUND Prothrombin time (PT) is routinely used as a test of coagulation. Thromboplastin is the key ingredient in the reagent for this test. Prothrombin time international normalized ratio (INR) readings can vary according to the thromboplastin used in the reagent. The composition of thromboplastin reagents can influence the sensitivity of each batch of reagents. Various thromboplastin reagents having different international sensitivity index (ISI) values are available now. This study was intended to evaluate the effect of different thromboplastins on INR reading for mitral valve replaced patients under stable oral anticoagulant therapy. METHODS The study was conducted on the citrated plasma received from the mitral valve replaced patients having stable international ratio between 2 to 3 for three months. 62 samples were collected from the clinical pathology laboratory, Govt. Medical College, Trivandrum. Each sample was tested with different thromboplastin reagents having international sensitivity index 1.0, 1.1 and 1.6 by measurement of the prothrombin time and conversion into international normalized ratio. The INR obtained from the thromboplastin with international sensitivity index 1.0 was considered as the standard. INR results obtained from samples tested with thromboplastin reagents with ISI 1.1 and 1.6 were compared with the standard by using analysis of variance (ANOVA) and Dunnett’s post hoc tests. RESULTS Sixty-two samples were tested with the thromboplastin reagent having ISI – 1.0, the mean INR is 2.42, for ISI – 1.1 mean INR value is 2.53 and for ISI 1.6, the mean INR value is 3.19. While comparing the mean value of INR for different reagents using ANOVA, the F value was 14.86, which was significant. P value less than 0.01. In the Dunnett post hoc test, the P value of difference between ISI 1.0/1.6 was &lt; 0.01. Between ISI 1.1/1.6 also the P value is &lt; 0.01. Both of these were significant. The P value of difference between the reagents having ISI 1.0 and 1.1 is 0.838 which denotes no significant difference. CONCLUSIONS In conclusion, the thromboplastin reagent with ISI 1.0 or nearest to 1.0 is most desirable for accurate INR report. KEYWORDS Prothrombin Time, International Sensitivity Index, International Normalized Ratio

Enoxaparin Use and Adverse Events in Outpatients With a Continuous Flow Left Ventricular Assist Device at a Single Institution

Background: Patients with left ventricular assist devices (LVADs) are anticoagulated with warfarin and may receive enoxaparin bridging for a subtherapeutic international normalized ratio (INR). There is no guideline regarding enoxaparin bridging in LVAD patients and a dosing strategy to ensure efficacy and safety is uncertain. Objective: The objective was to characterize the use of enoxaparin bridging for subtherapeutic INRs and its impact on thrombotic or major bleeding events (MBE) in patients with an LVAD. Methods: A retrospective review from 6/1/17 to 6/30/18 was performed. Patients with an LVAD were excluded if they had less than 60 days of outpatient anticoagulation or age <18 years old. Patients were divided into 2 cohorts based on enoxaparin exposure. MBE and thrombotic events were classified as related to enoxaparin if events occurred while receiving enoxaparin and up to 7 days or 30 days, respectively, after discontinuation. Results: Seventy-one LVAD patients met inclusion criteria and 50 patients received enoxaparin bridging. Therapeutic-dose enoxaparin was initiated at a mean INR of 1.8 for a mean duration of 2.8 days. In the enoxaparin exposure group, one MBE occurred 6 days after enoxaparin discontinuation, coinciding with an INR increase from 1.8 to 4.7. One thrombotic event occurred 2 days after enoxaparin discontinuation at an INR of 5.0. Conclusion: This institution’s bridging strategy of therapeutic-dose enoxaparin with a short duration has a low rate of bleeding and thrombotic events. Additional prospective studies of anticoagulation bridging based on characteristics such as type of LVAD device are warranted.

Proposal of a prediction model describing the metabolic interaction between warfarin and sorafenib using a population pharmacokinetic approach.

We attempted to examine the applicability of a population pharmacokinetic-pharmacodynamic (PK-PD) model describing the metabolic interaction between warfarin and sorafenib due to CYP2C9 inhibition and to predict the plasma concentrations of sorafenib and S-warfarin, the international normalized ratio (INR), and the optimal maintenance dose of warfarin in the presence of sorafenib in vivo. The sorafenib inhibition constant for S-warfarin metabolism was determined in vitro, and the unbound fraction in the liver was estimated using the published equations. A population PK-PD model describing the interaction between warfarin and sorafenib assuming competitive metabolic inhibition of S-warfarin by sorafenib was developed using NONMEM. The model was evaluated using clinical data and INR collected from the literature. The observed time courses of INR retrieved from Japanese and Caucasian patients given warfarin and sorafenib were mostly within the 90% range of the predicted values. Then, we predicted the plasma sorafenib and S-warfarin concentrations and INR after administration of warfarin (3mg/day) alone and warfarin + sorafenib (800mg/day). The predicted mean plasma S-warfarin concentration and INR at steady state were almost 6 and 2times greater, respectively, in the presence of sorafenib than those for warfarin alone. The predicted S-warfarin concentrations and INR after reduction of the warfarin dose (0.5mg/day) in the presence of sorafenib were comparable to those after 3mg/day warfarin alone. The proposed population PK-PD model has the potential to predict an increase in INR quantitatively after concurrent administration of warfarin and sorafenib.

The effect of warfarin administration on platelet aggregation.

The aim of this study was to assess the effect of anticoagulation treatment on platelet aggregation. The study group consisted of 24 patients on long-term warfarin therapy without any antiaggregation therapy. Platelet aggregation was measured using VerifyNow with arachidonic acid (AA) as an inducer in 23 patients and with light transmission aggregometry (LTA) in 19 patients using four different agonists. All patients had their international normalized ratio (INR) checked regularly. The mean INR value was 2.07 (SD 0.6). The average aggregation measured by VerifyNow was found to be 637.5 (SD 36.6) aspirin reaction units. The values of average aggregability in LTA were 73.3 % (SD 4.5 %), 73.2 % (SD6 %) and 72.1 % (SD 4.8 %) in case of aggregation induced by AA, ADP, and collagen, respectively. Epinephrine‑induced aggregability was 65.3 % (SD 14.7 %). Regression analysis between INR and values of collagen- or epinephrine‑induced aggregability (r = 0.654 and 0.575) was found statistically significant (p = 0.004 and 0.016); every increase in INR by 0,1 brings about an increase in collagen- and epinephrine‑induced aggregation values by 1.5 and 4, respectively. Administration of warfarin does not produce a significant reduction in platelet aggregation. On the contrary, prolonged INR evokes a mild increase in aggregation induced by collagen or epinephrine (Tab. 2, Fig. 3, Ref. 32). Text in PDF www.elis.sk Keywords: platelet aggregation, anticoagulation, warfarin, platelet function tests, chronic ischemic heart disease.

Impact of different anticoagulation management strategies on outcomes in atrial fibrillation: Dutch and Belgian results from the GARFIELD‐AF registry

BackgroundThe uptake rate of non–vitamin K oral anticoagulants (NOAC) for the treatment of non‐valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5. ObjectivesTo explore the effect of these differences on thromboembolism (TE) and bleeding. MethodsData from the GARFIELD‐AF registry was used. Patients with new‐onset AF and ≥1 investigator‐determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow‐up were used. ResultsIn NL and BE, 1186 and 1705 patients were included, respectively. Female sex (42.3% vs 42.2%), mean age (70.7 vs 71.3 years), CHA2DS2‐VASc (3.1 vs 3.1), and HAS‐BLED score (1.4 vs 1.5) were comparable between NL and BE. At diagnosis in NL vs BE, 72.1% vs 14.6% received vitamin K antagonists (VKA) and 17.8% vs 65.5% NOACs, varying greatly across cohorts. Mean INR was 2.9 (±1.0) and 2.4 (±1.0) in NL and BE, respectively. Event rates per 100 patient‐years in NL and BE, respectively, of all‐cause mortality (3.38 vs 3.90; hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65‐1.15), ischemic stroke/TE (0.82 vs 0.72; HR 1.14, 95% CI 0.62‐2.11), and major bleeding (2.06 vs 1.54; HR 1.33, 95% CI 0.89‐1.99) did not differ significantly. ConclusionsIn GARFIELD‐AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

Antimycotic Treatment of Oral Candidiasis in Warfarin Users

PurposeAzole antimycotics and nystatin oral solution are used to treat oral candidiasis. Azoles inhibit cytochrome (CYP) P450-dependent metabolism of warfarin, which could increase the anticoagulant effect of warfarin. Nystatin is not expected to interfere with warfarin metabolism, but current data are conflicting. With this study, we aimed to explore the potential drug-drug interactions between warfarin and azole antimycotics used in the treatment of oral candidiasis, that is, systemic fluconazole, miconazole oral gel, and nystatin oral solution. MethodsBy linking clinical data on international normalized ratio (INR) measurements with administrative data on filled prescriptions of warfarin and antimycotics during 2000-2015, we explored INR changes in warfarin users relative to initiation of systemic fluconazole (n = 413), miconazole oral gel (n = 330), and nystatin oral solution (n = 399). ResultsWe found a significant increase in mean INR of 0.83 (95% confidence interval [CI] 0.61-1.04) and 1.27 (95% CI 0.94-1.59) following initiation of systemic fluconazole and miconazole oral gel, respectively. Also, the proportion of patients experiencing an INR-value above 5 was increased after initiation of fluconazole (from 4.3% to 15.3%) and miconazole (from 5.5% to 30.1%). INR was unaffected by initiation of nystatin oral solution (mean change 0.08; 95% CI -0.10 to 0.25). ConclusionInitiation of systemic fluconazole and miconazole oral gel was associated with increased INR in warfarin users. A similar association was not found for nystatin oral solution, which thus appears to be the safest alternative when treating oral candidiasis in warfarin users.

Fibrinolysis in left-sided mechanical prosthetic valve thrombosis with high INR.

A significant number of patients with prosthetic valve thrombosis have a prothrombin time international normalised ratio in the therapeutic range at presentation. Surgery may not be possible in many patients and traditionally a high international normalised ratio is considered a relative contraindication for fibrinolysis. We conducted an observational study in patients with left-sided obstructive prosthetic valve thrombosis with international normalised ratio at or above the therapeutic range at presentation who received fibrinolysis. The fibrinolytic regimens, timing of initiation, success of fibrinolysis, risk of major and minor bleeding and ischaemic stroke were evaluated in the study. Of 30 patients included in the study 70% received immediate fibrinolysis and in 30% it was delayed. The majority of patients (90%) presented with New York Heart Association class III/IV symptoms. The mean international normalised ratio at fibrinolysis was 3.04 ± 0.70 in the immediate group and 2.42 ± 0.89 in the delayed group. Haemodynamically stable patients who had delayed initiation of fibrinolysis had a trend towards less bleeding without an increase in mortality. The rates of intracranial haemorrhage (0% vs. 7.7%), minor bleeding (12.5% vs. 25.1%) and ischaemic stroke (0% vs. 30.7%) were lower in patients who received low dose infusion compared to a conventional dose. Fibrinolysis can be considered in patients with prosthetic valve thrombosis with high international normalised ratio at presentation. For haemodynamically stable patients, delayed initiation of fibrinolysis is associated with a marginally lower bleeding risk without an increase in mortality. Low dose infusion may be considered over a conventional dose as it is associated with a lower incidence of ischaemic stroke and a good rate of valve function restoration with a trend towards less bleeding.

International normalised ratio as an independent predictor of mortality in limb necrotising fasciitis with sepsis.

Necrotising fasciitis with sepsis is a life threatening disease. The aim of this study was to analyse the association between international normalised ratio (INR) and mortality in sepsis patients with necrotising fasciitis. A retrospective review was undertaken of 106 patients suffering from necrotising fasciitis with sepsis between November 2007 and December 2016. Data on comorbidities, clinical manifestations, laboratory findings, causative microbiological organisms, APACHE II (Acute Physiology and Chronic Health Evaluation II) score and outcomes were extracted. Logistic regression was carried out to examine the factors affecting mortality. Forty patients (37.7%) died. There was no significant difference in the white blood count (WBC) for the survivor and non-survivor groups. Non-survivors had a lower mean oxygenation index (OI) (288.7mmHg vs 329.4mmHg, p=0.032) and platelet count (PC) (139.5 vs 214.8 x 109/l, p=0.028), and a higher mean INR (1.9 vs 1.3, p=0.000), activated partial thromboplastin time (APTT) (54.6 vs 44.2 seconds, p=0.005) and serum creatinine (2.3mg/dl vs 1.4mg/dl, p=0.007). Mortality in patients with INR >1.5 was significantly higher than in those with INR <1.5 when all risk factors (WBC, PC, OI, INR, APTT, creatinine) were considered (odds ratio: 4.414, 95% confidence interval: 1.263-15.428, p=0.020). Even after adjusting for age, sex, bacteraemia, diabetes and hepatic disorders, the data still exhibited elevated mortality for patients with INR >1.5 (odds ratio: 5.600, 95% confidence interval: 1.415-22.166, p=0.014). INR is a significant independent predictor of mortality in sepsis patients diagnosed with necrotising fasciitis.

Anticoagulation related nephropathy

Background :Anticoagulation related nephropathy (ARN) is an under diagnosed complication of anticoagulation that is associated with increased renal morbidity and mortality.While warfarin has been in use since 1954, its harmful effects on the kidneys have only recently been fully recognized. ARN is clinically defined as acute kidney injury (AKI) without obvious aetiology in the setting of over anticoagulation .When it is caused by warfarin, it is often associated with supra therapeutic International Normalized Ratio (INR) (more than 3.0) .AIM: this work aimed to early detection of ARN and how to manage it. Patients and methods: This study was carried out in internal medicine department of Benha University Hospitals, where 50 patients on oral anticoagulation suffered from acute kidney injury were selected and subjected to careful history , clinical examination and laboratory investigation after taking their written consents from march 2019 to march 2020. Results: From the 50 patients ARN was observed in 30% of patients (15 patients) .80% of patients were on warfarin and 20%of patients were on dapigatran. 34% of patients were hypertensive, 56% of patients were chronic kidney disease (CKD) and 40% of patients were diabetic .At the start of the study serum creatinine was 1.5± o.5 mg/dl and mean INR was 2.4±0.6 and after starting oral anticoagulants (OACs) mean INR increased to 6.3±1.8 and serum creatinine increased to 2.6±o.8 mg/dl at the first month of follow up then by controlling INR to 2.8±0.4 at the second month serum creatinine decreased to 2± 0.6 mg/dl. Conclusion: ANR should be suspected in any patients with over anticoagulation and increased serum creatinine and this need rapid intervention to reverse renal injury.