Increase In International Normalized Ratio Research Articles

Association of initial assessment variables and mortality in severe pediatric traumatic brain injury

BackgroundPredictive scales have been used to prognosticate long-term outcomes of traumatic brain injury (TBI), but gaps remain in predicting mortality using initial trauma resuscitation data. We sought to evaluate the...

Elevated International Normalized Ratio and Mortality in Hospitalized Patients Treated with Direct Oral Anticoagulants

BackgroundDirect oral anticoagulants (DOACs) are associated with a prolongation of the prothrombin time and an increased international normalized ratio (INR). The clinical significance of these changes is unclear. This study aimed to examine the association between an elevated INR on admission and in-hospital death and long-term survival in patients treated with DOACs. MethodsData were retrospectively retrieved from records of hospitalized patients at the Sheba Medical Center between November 2008 and July 2023. Patients were selected based on DOAC treatment, coagulation profile, and INR test done within 48 hours of hospitalization. The outcomes were in-hospital mortality and mortality in the year following hospitalization. ResultsThe study included 11,399 hospitalized patients treated with DOACs. Patients with elevated INR had a 180% higher risk of in-hospital mortality (adjusted odds ratio 2.80; 95% confidence interval, 2.30-3.39) and a 57% increased risk of death during the following year (adjusted hazard ratio 1.57; 95% confidence interval, 1.44-1.71). Similar results were observed in subgroup analyses for each DOAC. ConclusionsAn elevated INR on admission is associated with a higher risk for in-hospital death and increased risk for mortality during the first year following hospitalization in hospitalized patients treated with DOACs. This highlights that elevated INR levels in patients on DOACs should not be dismissed as laboratory variations due to DOAC treatment, as they may serve as a prognostic marker.

Analysis of acenocoumarol and levofloxacin interaction in elderly institutionalized patients

ObjectiveTo analyze the interaction between acenocoumarol and levofloxacin in the elderly. We also assessed how hypoalbuminemia affects international normalized ratio variation. MethodRetrospective study carried on elderly institutionalized patients who were prescribed levofloxacin concomitantly with acenocoumarol. International normalized ratio variation during levofloxacin treatment was analyzed with the t-Student test. Correlation between albuminemia and international normalized ratio variation was calculated using Pearson's correlation coefficient. ResultsThe mean international normalized ratio previous to treatment with levofloxacin was 2.5 (standard deviation: 0.6) and during treatment it was 4.7 (standard deviation: 1.9) (p < 0.05). In 54.3% of the cases, the international normalized ratio value was equal to or greater than 4.5. Not linear association between albuminemia and international normalized ratio increase was found using Pearson's test (R = –0.16). ConclusionsIn more than half of the occasions international normalized ratio raised to clinically rellevant values (≥ 4.5). No influence of hypoalbuminemia in the increase in international normalized ratio was shown.

The association between warfarin usage and international normalized ratio increase: systematic analysis of FDA Adverse Event Reporting System (FAERS).

Elevated international normalized ratio (INR) has been commonly reported as an adverse drug event (ADE) for patients taking warfarin for anticoagulant therapy. The purpose of this study was to determine the association between increased INR and the usage of warfarin by using the pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS). The ADEs in patients who took warfarin (N = 77,010) were analyzed using FAERS data. Association rule mining was applied to identify warfarin-related ADEs that were most associated with elevated INR (n = 15,091) as well as possible drug-drug interactions (DDIs) associated with increased INR. Lift values were used to identify ADEs that were most commonly reported alongside elevated INR based on the correlation between both item sets. In addition, this study sought to determine if the increased INR risk was influenced by sex, age, temporal distribution, and geographic distribution and were reported as reporting odds ratios (RORs). The top 5 ADEs most associated with increased INR in patients taking warfarin were decreased hemoglobin (lift = 2.31), drug interactions (lift = 1.88), hematuria (lift = 1.58), asthenia (lift = 1.44), and fall (lift = 1.32). INR risk increased as age increased, with individuals older than 80 having a 63% greater likelihood of elevated INR compared to those younger than 50. Males were 9% more likely to report increased INR as an ADE compared to females. Individuals taking warfarin concomitantly with at least one other drug were 43% more likely to report increased INR. The top 5 most frequently identified DDIs in patients taking warfarin and presenting with elevated INR were acetaminophen (lift = 1.81), ramipril (lift = 1.71), furosemide (lift = 1.64), bisoprolol (lift = 1.58), and simvastatin (lift = 1.58). The risk of elevated INR increased as patient age increased, particularly among those older than 80. Elevated INR frequently co-presented with decreased hemoglobin, drug interactions, hematuria, asthenia, and fall in patients taking warfarin. This effect may be less pronounced in women due to the procoagulatory effects of estrogen signaling. Multiple possible DDIs were identified, including acetaminophen, ramipril, and furosemide.

Healing effect of warfarin in the course of cerulein-induced acute pancreatitis in rats.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Fish Oil-Induced Elevated International Normalized Ratio in Patients Taking Warfarin: A Case Report and Literature Review

Warfarin is an oral anticoagulant commonly used to prevent thromboembolism. Its pharmacodynamics can be affected by interactions with other drugs and dietary supplements, although there is only limited information available on these interactions. One dietary supplement that has been associated with increased international normalized ratio (INR) levels, potentially leading to supratherapeutic levels, is fish oil. However, the data available on this interaction are not extensive. This case study focused on a sixty-nine years old Thai female who was prescribed warfarin at a weekly dose of 30 milligrams (maintaining an INR range of 2.5-3.5) to prevent thromboembolism resulting from atrial fibrillation (AF) following a mechanical valve replacement at the mitral position. The patient began taking fish oil supplements for a period of 2 months. After initiating the fish oil supplement in addition to the warfarin, the patient’s INR had increased from 2.94 to 4.13, although no bleeding symptoms were observed. When combining fish oil with warfarin, it is important for medical professionals to exercise caution and to monitor the INR levels in all cases to ensure safety and optimize efficacy. KEYWORDS warfarin, fish oil, dietary supplement

Elevated INR in a COVID-19 patient after concomitant administration of azvudine and anticoagulants.

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

Potential Association of Holidays on Internationalized Normalized Ratio in Warfarin-Users at a Multidisciplinary Clinic.

Warfarin is approved by the United States Food and Drug Administration for numerous clinical indications. The effectiveness of warfarin is highly dependent on the time-in-therapeutic range based on the international normalized ratio (INR) goal, which may be altered by changes in diet, alcohol intake, concomitant drugs, and travel, all of which are prevalent during the holidays. At this time, there are no published studies assessing the impact of holidays on INR in warfarin-users. A retrospective chart review was conducted on all adult patients taking warfarin and managed at a multidisciplinary clinic. Patients were included if they were taking warfarin at home regardless of indication for anticoagulation. The INR pre- and post-holiday was assessed. Of a total of 92 patients, the mean age was 71.5 ± 14.3 years, and most patients were on warfarin with an INR goal of 2 - 3 (89%). There were significant differences in INR before and after Independence Day (2.55 vs. 2.81, P = 0.043) and Columbus Day (2.39 vs. 2.82, P < 0.001). The remaining holidays showed no significant differences in INR before and after each respective holiday. There may be factors related to Independence and Columbus Day that are increasing the level of anticoagulation in warfarin-users. Although the mean post-holiday INR values, in essence, maintained within the typical target of 2 - 3, our study underscores the specialized care that is warranted in higher risk patients to prevent a continued increase in INR and subsequent toxicities. We hope our results would be hypothesis-generating and aid in the development of larger, prospective evaluations to validate the findings of our present study.

Clinically relevant increases in the international normalized ratio and model of end-stage liver disease score by therapeutic doses of direct oral anticoagulants in patients with cirrhosis

BackgroundPatients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC–induced increases in the INR may thus lead to artificial inflation of the MELD score. ObjectiveWe studied the effect of DOACs on INR prolongation in patients with cirrhosis. MethodsWe spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes. ResultsIn controls and patients, the INR increased by an ex vivo addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points. ConclusionsTaken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted.

Risk Factor–Guided Early Discharge and Potential Resource Allocation Benefits in Patients with Traumatic Subarachnoid Hemorrhage

We sought to develop screening criteria predicting the lack of poor neurologic outcomes in patients presenting with traumatic subarachnoid hemorrhage (tSAH) and to evaluate their potential to improve resource allocation in these cases. We retrospectively reviewed patients presenting with tSAH to the emergency department (ED) of a tertiary-care institution from 2016 to 2018. We defined good neurologic outcomes as patients with stable/improving neurologic status, who did not require neurosurgical intervention, had no expanding bleed, and needed no hospital readmission. Univariate and multivariate models were generated to predict risk factors inversely associated with good neurologic outcome. A total of 167 patients presented with tSAH from 2016 to 2018. The presence of depressed skull fracture, concomitant spinal fracture, low Glasgow Coma Scale (GCS) score, cranial nerve palsies, disorientation, concomitant hemorrhages, midline shift, increased international normalized ratio (INR), and emergent medical intervention were inversely correlated with likelihood of good neurologic outcome on univariate analysis. Multivariate regression showed that midline shift (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.89; P= 0.04), GCS score <13 (OR, 0.22; 95% CI, 0.05-0.99; P= 0.05), increased INR (OR, 0.18; 95% CI, 0.03-0.85; P= 0.04), and emergent medical intervention (OR, 0.18; 95% CI, 0.04-0.63; P= 0.01) were independently associated with lower likelihood of good neurologic outcome. Forty-six patients without any factors had good outcomes but were held in the ED or admitted to the hospital. These patients (if instead discharged directly) meant a potential cost savings of $179,172. In our study, we found multiple risk factors inversely associated with good neurologic outcome, namely low GCS score, midline shift, emergent medical intervention, and INR ≥1.4. Our findings may aid clinicians in determining which tSAH patients are candidates for safe early discharge.

Post-thrombolytic coagulopathy and complications in patients with pulmonary embolism treated with fixed-dose systemic alteplase

Alteplase treatment can cause a systemic coagulopathy although the incidence and contributory factors are unknown in pulmonary embolism (PE). Fixed-dosing of alteplase for PE may lead to interpatient variability in drug exposure and influence post-thrombolytic coagulopathy (PTC). While changes in fibrinogen and INR have been used to describe PTC, no universal PTC definition is available. Evaluate the incidence of PTC after alteplase treatment for PE, the effect of patient weight and blood/plasma volume and the association with bleeding complications. We conducted a retrospective cohort study of patients treated with alteplase for massive or high-risk submassive PE. Demographics, alteplase dosing, laboratory assessment of coagulopathy, and bleeding events were collected. The primary endpoint was incidence of PTC defined as an international normalized ratio (INR) > 1.5 or fibrinogen < 170mg/dL. Secondary outcomes included correlation between coagulopathies and alteplase dose normalized to actual body weight (ABW), ideal body weight (IBW), plasma volume (PV), and estimated blood volume (EBV). Bleeding events in patients with and without PTC were compared. 125 patients met criteria for inclusion in the study. PTC occurred in 35.3% of patients, with INR >1.5 in 21.8% and fibrinogen <170mg/dL in 26%. Alteplase dose >50mg was associated with increased odds of PTC (OR 6.5, CI 2.1-19.9). Dose normalized to ABW and EBV correlated weakly with absolute increase in post-alteplase INR (r =0.20, p =0.06 and r =0.21, p =0.057 respectively) and to percent change in INR (r =0.20, p = 0.058 and r =0.21, p =0.048 respectively). Dose/ABW, dose/PV, and dose/EBV each correlated moderately with absolute decrease in fibrinogen (r =-0.53, -0.49, and -0.47 respectively, p <0.001 for each) and percent change in fibrinogen (r = -0.55, -0.49, and -0.49 respectively, p < 0.001 for each). Dose/IBW correlated weakly with absolute and percent decrease in fibrinogen (r = -0.32, p =0.013 and r =-0.33, p =0.011). Patients with bleeding were more likely to have PTC (58.3% vs. 28.6%, p= 0.05) and a bleeding event was predictive of PTC (OR 5.33, 1.32-23.99). PTC is prevalent in patients with PE. PTC is influenced by alteplase dose and exposure parameters (ABW, IBW, PV, EBV) and may contribute to the bleeding risk.

AVK overdose in Covid-19 infected patients.

During the Covid-19 pandemic, four patients were admitted to a healthcare centre. They were treated with vitamin K antagonists (AVK). We observed a substantial increase in their International Normalised Ratio (INR). The mean age of these patients was 90 (± 8 years). All had different usual long-term therapy treatments but had fixed doses of AVK to reach a stable INR. No changes to the background regimen were implemented. One patient presented a cough whereas the three others were asymptomatic. In the context of the pandemic, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was carried out for each patient. The results of the RT-PCR rests were all positive and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 which increased to 5.93 the day after RT-PCR positivity. AVK treatment was stopped but the INR one day after was 7.89. Ms J. presented INR values between 1.96 and 4.58, 10 days later. a PCR test was conducted and AVK treatment was stopped, but the INR still increased to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24 hours after a positive PCR result. Ms F. presented a gradual increase in INR from 1.5 to 3.36, 72 hours after a positive PCR result and three days after discontinuation of AVK. This study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a haemorrhagic risk as the INR increases. There could be a risk of overdose when patients are treated with AVK and are positive for Covid-19. This raises the question of discontinuing AVK and substituting it with another anticoagulant, or performing INR checks more frequently in the context of Covid-19. Moreover, an unexpected increase in INR should indicate the need to conduct a Covid-19 RT-PCR test in the context of this pandemic context.

VKA overdose in Covid-19 infected patients

During the Covid-19 pandemic, four patients were admitted in a healthcare center. They were treated by vitamin K antagonists (VKA). We observed a substantially increased of their International Normalized Ratio (INR) The mean age of patients was 90 (± 8). All had different usual long-term therapy treatments but had fixed doses of VKA to reach a stable INR. No change of background treatment were realized. One patient presented cough whereas the three others were asymptomatic. In the pandemic context, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was realized for each patients. RT-PCR were all positives and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 and it increased to 5.93 the day after RT-PCR positivity. The VKA treatment was stopped but the INR one day after was 7.89. Mrs J. presented INR value from 1.96 to 4.58, 10 days later. PCR have been realized and VKA treatment was stopped: INR still increased up to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24h after positive PCR results. Mrs F. presented a gradually increase of INR from 1.5 to 3.36, 72h after PCR results three days after VKA discontinuation. Finally, this study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a hemorrhagic risk with the elevation of the INR. It could have a risk of overdose when patients treated with VKA and positive to Covid-19. This raises the question of discontinuing VKA and substituting them with another anticoagulant, or performing INR controls more frequently in the context of Covid-19. Moreover, an unexpected increase of INR could lead to realize a Covid-19 RT-PCR in this pandemic context.

OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic

BackgroundEarly in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing....

In vitro analysis of n-acetylcysteine (NAC) interference with the international normalized ratio (INR)

Background Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro. Methods Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman’s test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC). Results Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 − 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p = .0008, Stago p < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p = .02 and p = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07–1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p < .0001, Stago p < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p < .05). Conclusion Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

Outcomes of variceal upper gastrointestinal bleeding: A prospective, multicenter, population-based study from West Hungary

Acute variceal gastrointestinal bleeding is associated with significant morbidity and mortality. Our aim was to evaluate the characteristics and prognostic factors in the management of acute upper gastrointestinal bleeding in a large multi-center study from Hungary. This prospective one-year study (between January 1, 2016 and December 31, 2016) involved six community hospitals in Western Hungary. Data collection included demographic characteristics, vital signs at admission, comorbidities, medications, time to hospital admission and endoscopy, laboratory results, endoscopic management, risk assessment using Glasgow-Blatchford Score (GBS), Rockall Score (RS) and the American Society of Anesthesiologists (ASA) Physical Status Score, transfusion requirements, length of hospital stay and mortality. 108 cases (male: 69.4%) of acute variceal gastrointestinal bleeding were registered during the 1-year period. Endoscopic therapeutic intervention was performed in 57.4%. On initial endoscopy, 39.8% of the patients were treated with sclerotherapy and 18.5% had ligation. 76.9% of the patients required blood transfusion. The overall mortality (including in-hospital bleedings) was 24.1%. The GBS predicted transfusions (AUC: 0.793; cut-off: GBS >8 points). The ASA Score was associated with transfusion (OR 7.6 [CI 95% 2.7-21.6]; p<0.001), endoscopic intervention (OR 12.6 [CI 95% 3.4-46.5]; p = 0.033), and showed similar trend with mortality (OR 3.6 [0.8-16.7]; p = 0.095). The increased international normalized ratio (INR) and creatinine levels were associated with mortality (p = 0.001 and p = 0.002). Incidence rates of acute variceal gastrointestinal bleeding in Western Hungary are high. The ASA Score, GBS predicted outcomes and transfusion requirements. The observed high mortality rates, coupled with relatively low rates of endoscopic ligation, warrant optimization of management strategies in acute variceal gastrointestinal bleeding. Orv Hetil. 2021; 162(31): 1252-1259.

Role of leucocytosis, hyperbilirubineamia, decreased mean platelet volume and increased international normalized ratio in prediction of complicated appendicitis

Background: A diagnostic approach for complicated appendicitis is still controversial. We analyzed the preoperative laboratory markers that may predict complicated appendicitis.Methods: To study the role of leukocytosis, hyperbilirubinemia, decreased mean platelet volume (MPV) and increased international normalized ratio (INR) in the prediction of complicated appendicitis. Total 60 patients were enrolled and divided them into 2 groups, un-complicated (AUA) and complicated (ACA) acute appendicitis, each having 30 cases.Results: Total leucocyte count (TLC) &gt;10000 mm³ was found in 70% of AUA cases and 80% of ACA cases serum bilirubin &gt;1 mg/dl was found in 66.67% of AUA cases and 80 % of ACA cases. MPV&lt;7.6 fL was found in 60% of AUA and 80% of ACA cases INR &gt;1.2 was found in 20 % of AUA and 40% of ACA cases. TLC &gt;10000/mm³, serum bilirubin &gt;1 mg/dl and MPV &lt;7.6 fL was found in 46.67% of AUA cases and 70 % of ACA cases.Conclusions: Total leucocyte count, serum bilirubin and mean platelet volume have a predictive potential for the diagnosis of complicated appendicitis.

Independent Risk Factors for Transfusion in Contemporary Revision Total Hip Arthroplasty

BackgroundThe incidence of transfusion in contemporary revision total hip arthroplasty (THA) remains high despite recent advances in blood management, including the use of tranexamic acid. The purpose of this prospective investigation was to determine independent risk factors for transfusion in revision THA. MethodsSix centers prospectively collected data on 175 revision THAs. A multivariable logistic analysis was performed to determine independent risk factors for transfusion. Revisions were categorized into subgroups for analysis, including femur-only, acetabulum-only, both-component, explantation with spacer, and second-stage reimplantation. Patients undergoing an isolated modular exchange were excluded. ResultsTwenty-nine patients required at least one unit of blood (16.6%). In the logistic model, significant risk factors for transfusion were lower preoperative hemoglobin, higher preoperative international normalized ratio (INR), and longer operative time (P < .01, P = .04, P = .05, respectively). For each preoperative 1g/dL decrease in hemoglobin, the chance of transfusion increased by 79%. For each 0.1-unit increase in the preoperative INR, transfusion chance increased by 158%. For each additional operative hour, the chance of transfusion increased by 74%. There were no differences in transfusion rates among categories of revision hip surgery (P = .23). No differences in demographic or surgical variables were found between revision types. ConclusionDespite the use of tranexamic acid, transfusions are commonly required in revision THA. Preoperative hemoglobin and INR optimization are recommended when medically feasible. Efforts should also be made to decrease operative time when technically possible.

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.