Elevated International Normalized Ratio Research Articles

Evaluation of the Effect of Apixaban on INR in the Inpatient Population.

Direct oral anticoagulants (DOACs), particularly direct factor Xa inhibitors, have been associated with prolongation of the prothrombin time and the international normalized ratio (INR). Although DOACs do not require monitoring, elevations in the INR have been reported in in vitro and observational studies. The literature surrounding the extent of elevation and the clinical significance is limited. The objective of this study was to quantify the degree of INR elevation in hospitalized patients receiving apixaban. This was a single-center, retrospective, observational analysis of adult patients who received at least 1 dose of apixaban during their hospital admission and had at least 1 INR sample collected prior to and following administration. The major end point of this study was to characterize the effect of apixaban on the INR by determining the percentage of patients with an INR higher than our laboratory defined normal (defined as INR > 1.1). Minor end point outcomes included the incidence of an INR increase >0.3 from baseline INR and additional patient-specific factors that may influence INR elevation. Seventy-nine patients were included in the analysis. On day 1 of therapy, the median (interquartile range, IQR) INR was 1.4 (1.3:1.6) with 84.5% of patients having an elevated INR. The median (IQR) INR increased to 1.5 (1.4:1.6) and 1.7 (1.5:1.9) on day 4 and day 7, respectively. Of patients whose INR increased by more than 0.3, the median (IQR) change in INR from baseline was 0.5 (0.4:0.6). Apixaban is associated with a notable increase in INR in hospitalized patients, although it is not clear the clinical impact of the increase. Although literature does not support monitoring INR as a marker of apixaban activity, it is important for clinicians to understand the association apixaban has on the INR to avoid inappropriate interpretation of routine coagulation assays.

Why are acute ischemic stroke patients not receiving thrombolysis in a telestroke network?

Objective The purpose of this study was to determine reasons for not giving intravenous tissue plasminogen activator to eligible patients with acute ischemic stroke in a telestroke network. Methods We performed a retrospective analysis of prospectively collected data of patients who were seen as a telestroke consultation during 2015 and 2016 with the Arkansas Stroke Assistance through Virtual Emergency Support programme for possible acute ischemic stroke. Results Total consultations seen were 809 in 2015 and 744 in 2016, out of which 238 patients in 2015 and 247 patients in 2016 received intravenous tissue plasminogen activator. In 2015 and 2016, out of the remaining 571 and 497 patients, 294 and 200 patients respectively were thought to be cases of acute stroke based on clinical evaluation. The most common reasons for not being treated in 2015 and 2016, respectively, were; (a) minimal deficits in 42.17% and 49.5% cases, (b) falling out of the 4.5-hour time window in 22.44% and 22% cases, (c) patient/next of kin refusal in 18.02% and 16.5% cases. Less common reasons included limited functional status, abnormal labs (thrombocytopenia, elevated international normalised ratio (INR)/prothrombin time (PT)/partial thromboplastin time (PTT), hypo or hyperglycemia etc), recent surgery and symptoms being too severe etc. Conclusion ‘Minimal deficits’ and ‘out of time window’ continue to be the major causes for not receiving thrombolysis during acute ischemic stroke in both traditional and telestroke systems. Patient/next of kin refusal was high in our telestroke system when compared to traditional practices. Considering the increasing utility of telestroke this needs to be further looked into, along with the ways to address it.

Periaortic abscess forming pulsatile sac around graft in a patient with prosthetic valve endocarditis after bentall operation

A 62-year-old man with high fever, general fatigue, and history of transient ischemic attack was transferred to our cardiology clinic with high clinic suspicious of endocarditis. He had a history of mitral ring annuloplasty and coronary artery bypass grafting operation before many years ago and reoperation for aortic dissection as Bentall procedure about 3 months ago. Blood tests showed leukocytosis with massive elevation of C-reactive protein, modest elevation of troponin, marked elevation of International Normalized Ratio, mild anemia, and hypoalbuminemia. Transesophageal echocardiogram (TEE) revealed a 4-mm × 15-mm round mobile mass originating from the anterior part of the mitral annular ring. In addition, there were a sac surrounding aortic graft and surrounding aneurismal aorta suggests a separation of graft because of possible aortic perivalvular abscess. There was blood flow into the sac and extensive thrombus with mobile component was seen in it. Blood cultures were positive for Streptococcus pneumoniae . Vancomycin, gentamicin, and rifampicin were chosen as antibiotic regimen. Early surgery planned for endocarditis and drained abscess cavity. However, the patient was persistently refused the third heart surgery operation. Repeat TEE showed the absence of vegetation on mitral valve and evident shrinkage of thrombus. Chest X-ray showed large left pleural effusion. Computed tomography with contrast enhancement confirmed this finding and revealed that contrast leak to the periaortic area and spreading a path under pulmonary artery to adjacent of the anterior wall of left ventricle. Thoracentesis was performed. Fistula to left pleura was suspected but not clearly confirmed. At 6 weeks of hospitalization, he clinically deteriorated. Due to confusional state, informed consent was obtained from attending relatives. The patient was transferred to the operating room. Cardiopulmonary resuscitation was initiated and thoracotomy was performed. Dehiscence of the aortic valve was seen. Infected tissues were extracted and repair with new prosthesis aortic valve was performed. Despite all resuscitation efforts, the patient died.

A Very Rare Case of Ibuprofen—Induced Acute Liver Failure

iDILI due to ibuprofen is quite rare, occurring in approximately 1 per 100,000 patients. The patient will typically have a hypersensitivity reaction as well, such as toxic epidermal necrolysis or Stevens Johnson syndrome. While chronic ibuprofen use may cause transaminitis, it is typically no more than the low 100s. Ibuprofen overdose (greater than 5—10 grams) is typically associated with altered mental status, respiratory depression, coma and lactic acidosis, which may prove fatal. Most cases have not been associated with liver injury. A 29yo F was admitted for altered mental status. She was lethargic and not answering questions. Per her mother, she had taken around 300 tabs of 200mg ibuprofen. Medical history included depression, asthma, alcohol abuse and past drug abuse. She was tachycardic and hypotensive. Initial CBC and BMP were normal. She was intubated and dialyzed for ibuprofen overdose. Mental status returned to normal and she was extubated. She developed transaminitis and elevation of INR, so GI was consulted. Differentials included ischemic liver from her initial hypotension and ibuprofen toxicity. Her transaminitis worsened, but transplant hepatology stated she was not a candidate for emergent transplant. With supportive care, her transaminitis began to downtrend. She still required intermittent dialysis due to acute renal failure. She was discharged to the psych unit for further monitoring, where her transaminitis eventually resolved. In this patient, the initial thought process revolved around ischemic shock liver, while ibuprofen toxicity was a secondary differential. However, once her LFTs did not begin to downtrend as expected, ibuprofen toxicity quickly became the leading differential. While it is exceedingly rare in general, it is even more rare in this case because it was not accompanied by any systemic signs or symptoms. Overall, when it comes to acute liver failure, iDILI ranks second to acetaminophen toxicity (11% compared to 46%). Only about 10% of those with iDILI will progress to acute liver failure, but about 60% of those will require liver transplant. The severity of the liver injury is typically unpredictable and the main therapies are withdrawal of the suspected agent along with supportive care. Of note, corticosteroids have not been shown to play a major role in therapy. N—acetyl cysteine may be administered, but the most important prognostic factors are not only early detection but timely evaluation for liver transplant.3046_A.tif Figure 1: Trend of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and platelets.3046_B.tif Figure 2: Trend of international normalized ratio (INR), total bilirubin, and albumin.

Elevated International Normalized Ratio Is Associated With Ruptured Aneurysms.

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Elevated International Normalized Ratio Is Not Associated With Increased Perioperative Morbidity in Podiatric Limb Salvage Surgery: A Retrospective Analysis

The risk of hemorrhage always exists in anticoagulated patients with an elevated international normalized ratio (INR), a risk that must be measured against the necessity for surgical procedures. The objective of the present retrospective medical record study was to assess the safety with which limb salvage procedures can be conducted in patients with an INR >1.4. The medical records of 231 patients who had undergone limb salvage procedures by 1 surgeon at the Yale New Haven Health System from November 2008 through July 2014 were reviewed. All patients were administered foot blocks with monitored intravenous sedation. The patients' demographic data, comorbidities, preoperative anticoagulant use, coagulation profile, intraoperative analgesic administration, estimated blood loss, total operating room time, total postanesthesia care unit time, intraoperative ankle tourniquet use, and postoperative complications within the initial 72 hours were reviewed. We found no differences in intraoperative bleeding, total intraoperative time, or recovery time between the INR <1.4 group (n = 212) and the INR >1.4 group (n = 19). None of the patients experienced any postoperative complications, defined as any cardiac or pulmonary event, the need for invasive monitoring, or admission to the intensive care unit within the initial 72-hour period. Our findings suggest that patients are suitable for undergoing peripheral procedures with foot blocks and monitored intravenous sedation even in the presence of an elevated INR.

PP-59 - An Unusual Case of Asymptomatic Diffuse Alveolar Hemorrhage Related to Amiodarone Induced INR Elevation

Abstract: Pulmonary adverse effects of amiodarone is an important cause of morbidity. Despite pulmonary toxicity occurs as pneumonitis, rarely, it may also occur as diffuse alveolar hemorrhage. Another important amiodarone-induced adverse effect is hepatotoxicity. Hepatotoxicity mostly presents as asymptomatic elevation of liver enzymes. To the best of our knowledge, in amiodarone-induced hepatotoxicity AST, ALT elevation is well known, however, there is no clear data about high International normalized ratio (INR) level in this condition. In this case report, a patient was presented under management of chronic low-dose amiodarone who admitted to emergency department for hematoma on his tongue. During the assessment for bleeding diathesis, INR was found to be 8.59. All other causes were excluded for high INR level in this case and amiodarone was related to high INR level. Since there were diffuse infiltrations on chest X-ray, the patient underwent thorax tomography. Asymptomatic diffuse alveolar hemorrhage secondary to INR elevation was considered. This patient is the first case who had amiodarone-induced INR elevation, and as a consequence, developed asymptomatic diffuse alveolar hemorrhage.

Safety and Outcomes of Transradial Access in Patients with International Normalized Ratio 1.5 or above

PurposeTo examine the safety and outcomes for patients undergoing transradial noncoronary interventions with international normalized ratio (INR) ≥1.5. Materials and MethodsA retrospective review of 2,271 transradial access (TRA) cases performed from July 2012 to July 2016 was conducted. Criteria for inclusion were moderate bleeding risk cases with preprocedure INR ≥1.5. Within the study period, there were 176 moderate bleeding risk procedures (transarterial chemoembolization: 70/176 [39.8%]; Barbeau B: 121/176 [68.8%]; 5-F sheath: 157/176 [89.2%]) performed on 122 patients (age 61.6 ± 12.1 years, 68.9% male, body mass index 28.0 kg/m2) with INR ≥1.5. ResultsTechnical success was achieved in 98.9% of cases. Grade 1/2 hematomas developed in 10 cases (5.7%). Age ≥65 years (P = .042) and female sex (P = .046) were predictive of access site bleeding complications. Fresh frozen plasma (FFP) transfusion was administered in 11.4% of cases (n = 20). Baseline INR and creatinine were significantly different between transfused and nontransfused cases (P values .006 and .028, respectively). Minor access site bleeding occurred in 3/20 cases (15%) receiving prior FFP transfusion and 7/156 nontransfused cases (4.5%), with no significant difference between these 2 groups (P = .072). ConclusionsTRA in patients with elevated INR appears to be safe in our experience. Age ≥65 years and female sex were associated with increased incidence of access site bleeding. Although INR correction was not standardized in this cohort, preprocedure FFP transfusion did not decrease bleeding complications.

Abstract WMP66: Infection and Coagulopathy in Left Ventricular Assist Device (LVAD)-Associated Intracranial Hemorrhage: A Case-Crossover Study

Introduction: Left ventricular assist device (LVAD)-associated intracranial hemorrhage carries a high morbidity and mortality rate. Despite the common occurrence, the etiology of intracranial hemorrhage is uncertain. We aim to explore the impact of infection and coagulopathy on intracranial hemorrhage in a case-crossover study. Methods: We reviewed consecutive patients with intracranial hemorrhage in a prospectively collected data of LVAD patients from a single, tertiary center from October 2004 to December 2016. Information on infection and international normalized ratio (INR) values were collected at the time of hemorrhage and 1 month prior to the ictus as controls. Cerebral angiogram studies were reviewed to investigate the presence of infectious intracranial aneurysm (IIA). Results: Of 477 persons with LVAD, 47 (10%) developed intracranial hemorrhage (27 intracerebral, 14 subarachnoid, and 6 subdural hemorrhages). Of 47 (median age 58 [interquartile range 47-67]; 39 male), 27 (54%) persons had active infection at the time of intracranial hemorrhage, and 7 (15%) at 1 month prior to the ictus. The relative risk of intracranial hemorrhage due to active infection compared to the infections at 1-month was 2.4 (95% CI 1.6-3.5; p&lt;0.0001). Using a paired t-test, the mean INRs at the time of intracranial hemorrhage were also significantly higher at the time of hemorrhage compared to those at 1-month (2.6±1.9 vs. 1.8±0.8; p=0.01). Thirteen persons underwent cerebral angiogram (7 subarachnoid hemorrhage, 6 intracerebral hemorrhage). Four (57%) IIAs were identified only in SAH patients who also had acute bloodstream infections. In contrast, none of intracerebral hemorrhages had IIAs. Conclusions: Active infection and elevated INR increase the risk of LVAD-associated intracranial hemorrhage. Bloodstream infection and subarachnoid hemorrhage are associated with the presence of IIA in LVAD.

The Effect of Time to International Normalized Ratio Reversal on Intracranial Hemorrhage Evolution in Patients With Traumatic Brain Injury.

The incidence of geriatric traumatic brain injury (TBI) is increasing throughout the United States, with many of these patients taking anticoagulation (AC) medication. The purpose of this investigation was to determine the effect of time to international normalized ratio (INR) reversal on intracranial hemorrhage evolution in TBI patients taking prehospital AC medication. We hypothesized that rapid reversal of INR improves outcomes of head-injured patients taking AC medication. Admissions to a Level II trauma center between February 2011 and December 2013 were reviewed. Patients presenting with an initial INR of 2.0 or more, computed tomographic scan positive for intracranial hemorrhage, and INR reversal to less than 1.5 in hospital were included. Patients with nontraumatic intracranial hemorrhage were excluded. Reversal of INR was achieved using some combination of fresh frozen plasma, prothrombin complex concentrate, and vitamin K. A binary logistic regression model assessed the adjusted impact of rapid INR reversal on intracranial hemorrhage evolution. Significance was defined as p < .05. One hundred subjects were included. Four patients with nontraumatic intracranial hemorrhage were excluded, resulting in a final study population of 96 patients. The most common intracranial hemorrhage in the study population was subarachnoid hemorrhage (71.9%), followed by subdural hemorrhage (35.4%). Reversal of INR of less than 5 hr was not associated with intracranial hemorrhage evolution; however, reversal of less than 10 hr was found to be associated with a decreased odds ratio for intracranial hemorrhage evolution (p = .043). Rapid reversal of elevated INR levels (<10 hr) may decrease intracranial hemorrhage evolution in TBI patients taking prehospital AC medication.

Role of Initial Albumin Levels Among Other Liver Tests and Prognostic Scores in Predicting In-Hospital Mortality and Illness Severity in Critically Ill Septic Patients

SESSION TITLE: Severe Sepsis & Septic Shock SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Liver test abnormalities are common in critically ill patients with sepsis, but their prognostic significance is not well defined. In this study, we aim to describe the role of initial liver test evaluation in critically ill septic patients in regards to in-hospital mortality and illness severity and compare how Albumin levels, among other markers, predict these outcomes in conjunction with other severity-of-disease scores. METHODS: We conducted a retrospective cohort study via chart review, in a single-center Intensive Care Unit (ICU) in the United States, which included all consecutive patients admitted with severe sepsis/septic shock from November 2011 to October 2013. Liver tests collected within 24 hours of admission were analyzed to determine their prognostic significance in inpatient mortality and illness severity. Univariate, followed by multivariate logistic regression and Cox regression analysis were used to estimate disease severity and mortality, respectively. RESULTS: The study included 304 severe sepsis/septic shock patients without pre-existing liver disease or coagulopathy admitted directly from the Emergency Department to the ICU. The mean APACHE-II score was 22.42 ± 7.13 and mean SAPS-II 43.53 ± 14.97. Multivariable Cox Regression Analysis showed that hypoalbuminemia (p=0.003) and elevated INR (International Normalized Ratio; p<0.0001) were independent predictors of mortality in septic patients without pre-existing liver disease. Albumin levels and in-hospital mortality were inversely exponentially correlated, with an albumin level of 1g/dL associated with 32% mortality and 4g/dL with 9% mortality. Elevated transaminases and INR were associated with higher illness severity and were independent predictors of higher APACHE-II (transaminases coefficient 1.11, p=0.007; INR coefficient 1.92, p=0.009) and SAPS-II scores (transaminases coefficient 2.59, p=0.003; INR coefficient 3.59, p=0.023). Hypoabluminemia was an independent predictor of mechanical ventilation (p=0.011), vasopressor use (p<0.001) and higher APACHE-II score (p=0.002). Albumin levels were independent predictors of mortality even after adjusting for APACHE-II or SAPS-II scores (Albumin HR 0.64 p=0.027; HR 0.62 p=0.009, respectively). CONCLUSIONS: Liver tests have important prognostic significance in critically ill septic patients. Low Albumin, elevated INR, and transaminase levels are associated with higher illness severity. Low Albumin levels on admission predict higher in-hospital mortality in critically ill patients, regardless of their APACHE-II or SAPS-II scores. CLINICAL IMPLICATIONS: Albumin levels on admission can be a simple and readily available adjunct marker to clinicians for assessing hospitalization prognosis in critically ill patients. DISCLOSURE: The following authors have nothing to disclose: Paris Charilaou, Vaia Florou, Damodar Penigalapati, Haris Rana, Capecomorin S Pitchumoni, Gregoris Komodikis No Product/Research Disclosure Information

Low-dose Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Hemorrhage with INR Less Than 2.0.

Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1.6-1.9) in the setting of both traumatic and spontaneous intracranial bleeding. A total of 21/134 (15.7%) patients with either spontaneous or traumatic intracranial hemorrhage presented with an INR value of 1.6-1.9. Nine patients (43%) presented with traumatic bleeding and 12 (57%) with spontaneous bleeding. The median (IQR) presenting INR was 1.8 (1.7, 1.9) which decreased to 1.3 (1.2, 1.3) following the administration of low-dose 4F-PCC (median dose=1062 units; 15.2 units/kg). A total of 19/20 (95%) patients achieved a goal INR value of ≤1.5 on the first check following dosing and 17/20 (85%) achieved an INR value ≤1.3. One patient did not have follow-up INR testing due to withdrawal of life support. No patient experienced hematoma expansion within 48h of 4F-PCC, and there were no thromboembolic events within 72h of administration. The administration of low dose (15 units/kg) of 4F-PCC for urgent warfarin reversal in the setting of CNS hemorrhage was effective in correcting the INR in patients presenting with INR values of 1.6-1.9. Further assessment of low-dose PCC for urgent reversal of modest INR elevation is warranted.

Use of four-factor prothrombin complex concentrate in the reversal of warfarin-induced and nonvitamin K antagonist-related coagulopathy.

: To evaluate the efficacy of international normalized ratio (INR) reversal using four-factor prothrombin complex concentrate (4F-PCC) in nonmedication-induced coagulopathy. We performed a single-site, retrospective cohort study of patients receiving off-label use of 4F-PCC. Cohorts included liver dysfunction if they had acute liver decompensation or cirrhosis without other causative factors of liver failure such as sepsis, coagulopathy of acute sepsis (CAS) if they had documentation of sepsis and no underlying liver disorder, known factor deficiencies, or medication-induced coagulopathy, or warfarin if they were taking warfarin. Patients with unknown medication or direct oral anticoagulant usage were excluded. 4F-PCC was administered 32 times in 26 patients for nonvitamin-K antagonist related coagulopathy (11 CAS and 21 liver dysfunction) and 47 administrations were in warfarin patients. Liver dysfunction patients had a mean model for end-stage liver disease score of 28 ± 10. CAS and warfarin patients had significant INR reductions (ΔINR 1.9, P < 0.01; ΔINR 3.9, P < 0.01, respectively). Liver dysfunction patients mean change in INR trended toward significance (ΔINR 0.7, P = 0.09). Patients who received 4F-PCC based upon previously established dosing guidelines for moderate elevations in INR (20-30 IU/kg) doing demonstrated similar reductions in INR between CAS and warfarin patients (ΔINR 1.3, P = 0.03, ΔINR 1.0 P < 0.01, respectively). 4F-PCC significantly reduces the INR in CAS patients and trended toward significant reductions in liver dysfunction patients. Adequately powered, prospective trials are needed to demonstrate 4F-PCC efficacy in reversal of these coagulopathies.

Characterization of distinct coagulopathic phenotypes in injury: Pathway-specific drivers and implications for individualized treatment.

International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation. Plasma samples were prospectively collected from 1,262 critically injured patients at a single Level I trauma center. Standard coagulation measures and an extensive panel of procoagulant and anticoagulant factors were assayed and analyzed with demographic and outcome data. Fourteen percent of patients were coagulopathic on admission. Among these, 48% had abnormal INR and PTT (BOTH), 43% had isolated prolonged PTT (PTT-CONTACT), and 9% had isolated elevated INR (INR-TF). PTT-CONTACT and BOTH had lower Glasgow Coma Scale score than INR-TF (p < 0.001). INR-TF had decreased factor VII activity compared with PTT-CONTACT, whereas PTT-CONTACT had decreased factor VIII activity compared with INR-TF. All coagulopathic patients had factor V deficits, but activity was lowest in BOTH, suggesting an additive downstream effect of disordered activation pathways. Patients with PTT-CONTACT received half as much packed red blood cell and fresh frozen plasma as did the other groups (p < 0.001). Despite resuscitation, mortality was higher for coagulopathic patients; mortality was highest in BOTH and higher in PTT-CONTACT than in INR-TF (71%, 60%, 41%; p = 0.04). Discordant phenotypes demonstrate differential factor deficiencies consistent with dysfunction of contact versus tissue factor pathways with additive effects from common pathway dysfunction. Recognition and treatment of pathway-specific factor deficiencies driving different coagulopathic phenotypes in injured patients may individualize resuscitation and improve outcomes. Prognostic/epidemiological study, level II.

The Use of 3- and 4-Factor Prothrombin Complex Concentrate in Patients With Elevated INR

Background: PCC (Kcentra®) is an Food and Drug Administration (FDA)–approved 4-factor PCC used for the treatment of warfarin-related coagulopathy (WRC), but it has also been used off-label to treat non-WRC. Three-factor PCC in the form of coagulation factor IX human (Bebulin®) has also been used for WRC and off-label to treat non-WRC. It is unclear whether the use of 3- or 4-factor PCCs is effective for the treatment of non-WRC,. Objective: Our aim is to characterize the use of 3- and 4-factor PCCs for patients identified with a non-WRC. Methods: A retrospective analysis of patients who received PCCs for both WRC and non-WRC between January 2012 and July 2015 was conducted. Results: A total of 187 patients with elevated international normalized ratio (INR) who received PCCs were analyzed; 53.9% of patients in the WRC group and 27.7% in the non-WRC group corrected to an INR of 1.3 or less after 3- or 4-factor PCC administration. In those patients with non-WRC and who had underlying liver disease, 3- and 4-factor PCCs reduced mean INR by 0.98 and 1.43, respectively. Conclusion: Three and 4-factor PCCs can reduce INR in patients with WRC and in those with non-WRC secondary to liver disease.

International Normalized Ratio Is Significantly Elevated With Rivaroxaban and Apixaban Drug Therapies: A Retrospective Study

PurposeDirect factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. MethodsThe data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions. FindingsNo statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001). ImplicationsBoth of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.

Pneumatosis Intestinalis Predictive Evaluation Study

Our group has previously published a retrospective review defining variables predictive of transmural bowel ischemia in the setting of pneumatosis intestinalis (PI). We hypothesize this prospective study will confirm the findings of the retrospective review, enhancing legitimacy to the predictive factors for pathologic PI previously highlighted.Data were collected using the Research Electronic Data Capture. Forward logistic regression was utilized to identify independent predictors for pathologic PI. Statistical significance was defined as p ≤ 0.05.During the 3-year study period, 127 patients with PI were identified. Of these, 79 had benign disease, and 49 pathologic PI defined by the presence of transmural ischemia during surgical exploration or autopsy. Laboratory values such as elevated international normalized ratio (INR), decreased hemoglobin, and a lactate value of greater than 2.0 mmol/L were predictive of pathologic PI, as well as clinical factors including adynamic ileus, peritoneal signs on physical examination, sepsis, and hypotension. The location was also a significant factor, as patients with small bowel PI had a higher incidence of transmural ischemia than colonic PI. On multiple logistic regression, lactate value of greater than 2.0 mmol/L (odds ratio, 5.1, 1.3-19.5; p = 0.018), elevated INR (odds ratio, 3.2, 1.1-9.6; p = 0.031), peritonitis (15.0, 2.9-78; p = 0.001), and decreased hemoglobin (0.70, 0.50-0.97, 0.031) remained significant predictors of transmural ischemia (area under the curve, 0.90; 0.83-0.97). A lactate value of 2.0 mmol/L or greater and peritonitis are common factors between the retrospective review and this prospective study.We recommend surgical exploration to be strongly considered for those PI patients presenting also with a lactate greater than 2 mmol/L and/or peritonitis. We suggest strong suspicion for necrosis in those patient with PI and small bowel involvement, ascites on computed tomography scan, adynamic ileus, anemia, and a high INR.Prognostic study, level II; therapeutic study, level II.

The relation between international normalized ratio and mortality in acute pulmonary embolism: A retrospective study.

Acute pulmonary embolism (PE) is a serious clinical disease characterized by a high mortality rate. The aim of this study was to assess the prognostic value of international normalized ratio (INR) in acute PE patients not on anticoagulant therapy. The study included 244 hospitalized acute PE patients who were not receiving previous anticoagulant therapy. Based on their 30-day mortality, patients were categorized as survivors or non-survivors. INR was measured during the patients' admission, on the same day as the diagnosis of PE but before anticoagulation started. Thirty-day mortality occurred in 39 patients (16%). INR was higher in non-survivors than in survivors (1.3±0.4 vs 1.1±0.3, P=.003). In multivariate analysis, INR (HR: 3.303, 95% CI: 1.210-9.016, P=.020) was independently associated with 30-day mortality from PE. Inclusion of INR in a model with simplified pulmonary embolism severity index (sPESI) score improved the area under the receiver operating characteristics (ROC) curve from 0.736 (95% CI: 0.659-0.814) to 0.775 (95% CI: 0.701-0.849) (P=.028). Also, the addition of INR to sPESI score enhanced the net reclassification improvement (NRI=8.8%, P<.001) and integrated discrimination improvement (IDI=0.043, P=.027). Elevated INR may have prognostic value for 30-day mortality in acute PE patients not on anticoagulation. Combining INR with sPESI score improved the predictive value for all-cause mortality. However, further large-scale studies are needed to confirm it's prognostic role.

Outcomes of Salvage Percutaneous Biliary Drainage after Occlusion of Endoscopic Stents

PurposeTo describe outcomes of patients with malignant biliary obstruction who undergo salvage percutaneous biliary drainage after occlusion of endoscopic biliary stents. Materials and MethodsA single-center retrospective review was performed of 47 patients (25 men, 22 women) who underwent percutaneous biliary drainage for recurrent obstruction after endoscopic stent placement between 2005 and 2015. Primary malignancies were bile duct (n = 13), colorectal (n = 11), gallbladder (n = 7), pancreas (n = 5), hepatocellular (n = 4), and other (n = 7). Indication for salvage drain placement was infection (n = 19) and jaundice or need to decrease bilirubin (n = 28). Kaplan-Meier and Cox regression methods were used for survival analysis. Logistic and multivariate regressions were employed to identify factors associated with survival. ResultsMedian survival after salvage biliary drain placement was 1.8 months (95% confidence interval [CI], 1.3–2.7). Elevated international normalized ratio (INR) ≥ 1.5 before drainage was associated with poorer survival after drainage (median survival 0.7 months vs 2.4 months, P < .01). Median survival was shorter in 28 patients (64%) with bilirubin ≤ 2 mg/dL (34.2 µmol/L) after drainage (1.2 months vs 5.4 months, P < .001). Left-sided drain placement, elevated bilirubin, and elevated INR correlated with decreased likelihood of achieving bilirubin ≤ 2 mg/dL (34.2 µmol/L) (odds ratio [OR] 0.13, 95% CI, 0.02–0.71, P = .02; OR 0.18, 95% CI, 0.05–0.69, P = .01; OR 0.10, 95% CI, 0.01–0.90, P = .04). ConclusionsSurvival is limited for most patients who undergo salvage percutaneous biliary drainage. Elevated bilirubin and INR before drainage portend a poor prognosis.

Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort.

Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort. We retrospectively studied PSC patients attending two tertiary referral hospitals over 20years. Diagnosis of PSC was made according to international guidelines by positive cholangiography and/or liver biopsy (for small duct PSC) with supporting clinical and laboratory evidence. Of 208 PSC patients (61% male) were studied (2271patient-years follow-up). The median age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40years vs 42years, P=.35). All 33 deaths occurred in PSC-IBD patients while there were no deaths in PSC-only patients (21% vs 0%, P<.01). However, there were no significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P=.45) and transplant-free survival between PSC-only and PSC-IBD patients (P=.43). On multivariate Cox regression, only elevated international normalized ratio (INR) was associated with a greater risk of death or liver transplant (HR 2.0, 95% CI 1.1-3.6, P=.02). Development of gastrointestinal malignancy was higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P<.01). Australian PSC patients have similar characteristics compared to European and North American cohorts. IBD is a significant predictor of gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall transplant-free survival remained similar in PSC-IBD and PSC-only groups. An elevated INR was an independent predictor of death or liver transplantation.