Supratherapeutic INR Research Articles

Factors contributing to poor outcome in patients on warfarin receiving 4-factor prothrombin complex concentrate in critically ill.

Aim:To compare the demographical profile, indications, efficacy, and contributors to adverse outcome following administration of 4F-PCC in patients on warfarin with supratherapeutic INR.Methodology:Retrospective cross-sectional study was performed in a community-based teaching hospital. All patients 18 years and older on warfarin with supratherapeutic INR, who had received 4F-PCC between January 2014 and December 2018 were eligible and included in the study.Results:44 patients were included in the analysis. The mean age of the patients was 79.5 years. The male to female ratio was 1:1. Patients were on warfarin for atrial fibrillation, thromboembolism in 79.5% (N-35), and 20.5% (N-9) respectively. Indications for use of 4F-PCC were active bleeding in 93% (N-41) of patients. The common sites of bleeding were gastrointestinal, intracranial, and musculoskeletal which were seen in 54.5% (N-24), 29.5% (N-13) and 6.8% (N-3) respectively. The median number of doses of 4F-PCC administered was 1 per patient. The mean dose administered was 2,883u. Clinical improvement was documented in 84% (N-37) of patients. Mortality was seen in 16% (N-7) of patients. BMI greater than 30, anemia, hypotension, presence of intracranial bleed, the requirement of blood products, and mechanical ventilation were associated with higher odds for mortality. Hypotension and requirement of mechanical ventilation were statistically significant.Conclusion:4F-PCC continues to be an effective agent in the rapid reversal of warfarin therapy in patients with supratherapeutic INR presenting with major bleeding events. Most patients have clinical improvement with a single, weight-adjusted dose.

S2119 Upper Gastrointestinal Bleeding Caused by Iron Pill-Induced Gastric Ulcers

INTRODUCTION: The WHO reports that iron deficiency anemia (IDA) affects approximately 25% of the world's population. Iron supplementation via oral ferrous sulfate tablet is the most commonly prescribed treatment for IDA. It is known that high doses of oral iron can cause GI tract injury. However, it is not a common association at therapeutic doses of iron. CASE DESCRIPTION/METHODS: 75-year-old-male with PMH of afib on warfarin, CAD, CHF with preserved EF, aortic stenosis status post TAVR, and AV block status post pacemaker presented to ED with several days of epistaxis. Epistaxis ceased shortly after nasal packing. However, his hospital course was complicated by supratherapeutic INR and melena. Despite warfarin being held for a week, melena continued with down trending HgB, prompting EGD and colonoscopy. Initial endoscopy was unremarkable, and initial colonoscopy was poorly prepared revealing only copious blood and clots throughout. Even though bidirectional endoscopy was negative for active source, the patient continued to have dropping hemoglobin requiring 14 units of packed RBC. After 10 days the patient underwent repeat endoscopy, revealing multiple actively bleeding gastric fundus ulcers that were clipped. Fundic ulcers biopsies revealed features of iron pill-induced gastritis on iron staining. Patient's HbG stabilized status post EGD with clipping. DISCUSSION: Treatment for IDA is with oral iron supplements due to cost and efficacy. However, adverse outcomes, i.e. gastritis, can result due to iron oxidation. The level of gastritis seen here, is not seen at therapeutic dosages; making it easily missed in geriatric populations who have impaired gastric motility. Biopsy is the mainstay of diagnosis, and shows extracellular deposits of brown material. Liquid form of iron supplementation is much less toxic to the gastric mucosa and does not result in the injury to epithelium seen with iron tablets. This is thought to be because the liquid formulation cannot concentrate as easily into one site. Encouraging patients on iron pills to drink enough water with pill ingestion and avoid taking it at bedtime might reduce the risk of this problem. In conclusion, we recommend more studies in elderly populations with risk factors of impaired gastric motility for more conclusive results. In the meantime, it would be safer to prescribe these populations liquid iron supplementation.Figure 1.: Gastric mucosa biopsy with iron staining.

S2146 Rare Presentation of a Bleeding Arteriovenous Malformation Within a Periampullary Duodenal Diverticulum

INTRODUCTION: The incidence of duodenal diverticula (DD) is reported between 0.16% and 23% in the literature, depending on the method of diagnosis, with more than 60% arising in the second part of the duodenum. Though typically asymptomatic, various complications including pancreatitis, diverticulitis, duodenal obstruction, and bleeding have rarely been reported in the literature. We present a case of melena that was initially thought to be due to epistaxis in the setting of a supra-therapeutic INR, and was later found to be secondary to an arteriovenous malformation (AVM) within a periampullary DD. CASE DESCRIPTION/METHODS: A 72-year-old male with a history of metastatic renal cell carcinoma status-post nephrectomy, aortic stenosis, end-stage renal disease on peritoneal dialysis, and atrial fibrillation on Coumadin presented with subacute epistaxis and melena. Abdominal exam was unremarkable, and labs were notable for a hemoglobin 7.1 g/dL, platelet 76 k/uL, sodium 121 mmol/L, and INR 4.5. Given a history of epistaxis requiring otolaryngology intervention on admission that could explain his melena, a gastroenterology consult was not at first pursued. However, 12 days into the hospitalization, he continued to have melena with blood transfusion requirements, despite no evidence of recurrent epistaxis. An EGD was then done and showed a 4-mm non-bleeding ulcer in the duodenal bulb, a bleeding 5-mm AVM in a large DD treated with argon plasma coagulation (APC) and clipping, and a bleeding AVM in the posterior duodenal bulb. Ongoing melena and persistent anemia later prompted an additional push enteroscopy, colonoscopy and capsule endoscopy, which showed no evidence of ongoing bleeding at the previously treated sites or new lesions with bleeding. To reduce the risk of rebleeding, the patient's medications were adjusted (Coumadin switched to Apixaban and his VEGF inhibitor was discontinued). DISCUSSION: Definitive treatment for bleeding arising from DD traditionally involves surgical removal, though there have been increasing reports of successful endoscopic therapy. In this case, we showed that APC and clipping of a bleeding AVM within a periampullary DD was a safe and effective approach. We also highlight the need to avoid the premature assumption that persistent melena in the setting of recent recurrent epistaxis precludes coexistent gastrointestinal bleeding.Figure 1.: Bleeding AVM within duodenal diverticulum, prior to treatment.Figure 2.: AVM within duodenal diverticulum after treatment with APC and clip.Figure 3.: A CT of the abdomen/pelvis demonstrating an air-filled diverticulum of the second portion of the duodenum.

ANTICOAGULANT-RELATED NEPHROPATHY COMPLICATED BY HEPATORENAL SYNDROME FROM LUPOID HEPATITIS

Anticoagulant related nephropathy (ARN) is a newly recognized phenomenon. ARN is defined as over anticoagulation mostly associated with supratherapeutic INRs from warfarin leading to bleeding into the glomeruli. The diagnosis is confirmed with a kidney biopsy, which will show renal tubules filled

International Survey for Strategies Used for Oral Anticoagulation Reversal in Children

Background: Vitamin K antagonists (VKA) have been the main stay of oral anticoagulation (OAC) in pediatrics. However, VKA have multiple challenges. The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. The off-label use of DOACs is however on the rise within the pediatric population. The increasingly broad and varied use of DOACs, lack of published clinical guidance, and limited data on reversal strategies have created the imperative to identify strategies for OAC reversal in pediatrics. We conducted an online survey for strategies used for oral anticoagulants reversal in pediatrics. Study Design: Institutional review board approval was obtained and an online survey was developed using the RedCap. The survey was electronically distributed by International Society of Hemostasis and Thrombosis (ISTH) to its Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee group members. The survey questions asked approach to common hypothetical clinical scenarios for OAC reversal.The data were analysed descriptively. Results: There were 76 respondents, majority from academic free-standing Children'sHospitals. Seventy-two percent reported having a hemostasis-thrombosis/anticoagulation service but only 29 % have a dedicated anticoagulation pharmacist. Approximately 40% do not have a formal protocol in place for VKA reversal. For a supra-therapeutic INR (INR > 5) in a non-bleeding patient, 95% opted to manage by omitting the next dose of VKA while 18 % opted to give oral vitamin K alone or comitantly. For clinically relevant non-major bleeding, majority indicated using Vitamin K; oral (51%) or IV (37). For major bleeding on VKA, majority use either a combination of 4F-PCC and IV Vitamin K or plasma and IV Vitamin K (44/76 and 26/76 respectively). The presence of bleeding seemed to be the major driver for the choice of route (enteral versus parenteral) for Vitamin K for VKA reversal. Thirty-six of the 76 respondents indicated using DOACs; 94% used FXa inhibitors and 1/3 use dabigatran in their clinical practice. For non-urgent DOAC reversal, 97% indicated omitting the next dose. For non-major bleeding on DOAC, majority (29/36) indicated omitting the next dose/doses, some chose 4F-PCC (8/36) and only a few indicated use of specific reversal agents (3/36 and 1/36 for Dabigatran and Andexanet respectively). For major bleeding while on DOACs, the use of specific reversal agents (11/35, 6/35 for Andexanet and idarucizumab respectively) followed by 4F-PCC (9/35) was the major intervention indicated. Dilute thrombin time and partial thromboplastin time were the most commonly utilized tests to measure residual dabigatran activity. For Factor Xa inhibitors routine heparin assay rather than DOAC calibrated anti-Xa activity is utilized by most of the responders to assess presence of the plasma drug activity. Conclusion: Practices for oral anticoagulants reversal vary substantially in the pediatric population. Plasma is still used for urgent VKA reversal in many pediatric centers. The off-label use of DOACs in children is on the rise. Our results highlight the need for further studies to standardize OAC reversal in children. Disclosures Gupta: Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Research Funding; Novartis: Honoraria, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sarode:Portola: Honoraria; Octaphrarma: Consultancy; CSL Behring: Consultancy; Siemens: Research Funding. OffLabel Disclosure: The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. They are currently not approved in children. The off-label use of DOACs is however on the rise within the pediatric population.

Initiation of a fixed-dose four-factor prothrombin complex concentrate protocol.

Patients who require urgent warfarin reversal often receive four-factor prothrombin complex concentrate (4F-PCC), which is traditionally dosed according to weight and initial INR. Our institution implemented a fixed-dose 4F-PCC strategy, using an initial dose of 1500 units. We evaluated the frequency with which the initial fixed dose 4F-PCC was inadequate, as defined by need for supplemental dosing. As part of the protocol, if the initial fixed-dose 4F-PCC is administered and does not achieve INR goal, then the remainder of the standard weight- and INR-based dosing can be given. During the study period, 63 patients on warfarin received 4F-PCC using the fixed-dose protocol. Based on the INR following 4F-PCC administration, 11 patients (17%) were eligible to receive a supplemental dose based on failure to achieve their specified INR goal. Two of the 11 patients eligible for supplemental 4F-PCC dosing received the second dose, both with initial supratherapeutic INRs > 3.5. We found that most patients given an initial fixed-dose 4F-PCC achieved their INR goals, and of those who did not, most did not receive supplemental dosing, suggesting that clinical providers felt that adequate hemostasis had been achieved. In addition, fixed-dose 4F-PCC was able to be given rapidly, with few dosing errors, suggesting that this is a reasonable option for 4F-PCC delivery.

586 Investigation of Gastrointestinal Bleeding Among Left Ventricular Assist Device Recipients

INTRODUCTION: Left ventricular assist device (LVAD) therapy is a form of mechanical support for patients with advanced heart failure as either a bridge to heart transplant or destination therapy. The association between gastrointestinal bleeding (GIB) and LVAD recipients is well established. There has been reported literature comparing demographics and clinical associations between patients with and without GIB. The aim of this study was to further investigate these characteristics, identify associations with GIB, and further understand endoscopic management of GIB among LVAD recipients. METHODS: This was a single-center retrospective study analyzing randomly selected patients from a population of 425 Heartmate (HMII) and 193 Heartware recipients from 2007 to 2018. Chart review was performed and data pertaining to demographics, LVAD therapy intention and settings, endoscopic reports, home medications, and echocardiogram reports was collected. Univariate analysis was performed. RESULTS: A total of 188 HMII and 134 Heartware patients were included in this study. Patients that developed GIB tended to be older (56.4 vs. 61.7 years; P = 0.0002). No differences were found in race and gender. Patients that developed a GIB had a higher baseline Cr (1.2 vs. 1.4; P = 0.0284) and lower baseline Hg (10 vs. 11; <0.001). A supratherapeutic INR was associated with GIB (14.7% vs. 26.7%; P = 0.0075). Patients prescribed angiotensin II receptor blockers had less occurrence of GIB (Table 1). Melena was the most common presenting sign. Bleeding lesions were most frequent in the small bowel (42.6%). Of all bleeding lesions identified, 73% were found with EGD and 80.4% were found with push enteroscopy. Arteriovenous malformations were the predominant etiology (Table 2). CONCLUSION: This is one of the largest single-center studies of GIB among patients with LVADs. Small bowel gastric arteriovenous malformations were the most common etiology. The majority of upper GI bleeds were within reach of a push enteroscope (proximal small bowel), which had an incremental diagnostic yield over EGD. There was a protective association with reduced occurrence of GIB among patients taking angiotensin II receptor blockers. The use of proton pump inhibitors showed no association in GIB occurrence and may be overused in this population. Further development of the association between angiotensin II receptor blockers and GIB effect in LVADs are warranted. Multivariate analyses to validate these associations are in progress.

2181 Gallbladder Irrigation via Cholecystostomy Tube as a Novel Technique for Improving EUS-Guidance During Placement of Lumen-Apposing Metal Stent (LAMS) for Cholecystoduodenostomy

INTRODUCTION: Cholecystectomy is the preferred treatment of acute cholecystitis, but it may be relatively contraindicated in patients with medical comorbidities or advanced age. Non-surgical approaches include percutaneous transhepatic cholecystostomy tube and endosonographic stent placement. Adequate endosonographic imaging of the gallbladder is essential for correct stent deployment. CASE DESCRIPTION/METHODS: A 55-year-old male was admitted for endoscopic cholecystoduodenostomy for palliation of chronic cholecystitis. He had prior admissions for cholecystitis and choledocholithiasis with cholangitis with prior ERCPs requiring sphincterotomy, sphincteroplasty, stone removal and common bile duct stent placement. He was a poor candidate for cholecystectomy due to multiple medical comorbidities and chronic anticoagulation and was referred for endoscopic therapy. The patient was brought to the endoscopy suite and placed under general anesthesia. The Olympus linear echoendoscope was passed to the second portion of the duodenum. The gallbladder was collapsed due to prior patent sphincterotomy and sphincteroplasty. With IR assistance, the gallbladder was irrigated with normal saline boluses of to a volume of 600 mL. Due to the patent sphincterotomy, the gallbladder would collapse requiring additional irrigation. Maximal size of the gallbladder 30 mm in the long axis and 20 mm in the short axis. The duodenal wall and the gallbladder were punctured under endosonographic guidance using the hot AXIOS electrocautery-enhanced delivery system. A stoma was created and a 15 × 10 mm AXIOS stent was placed with flanges in close approximation to the gallbladder and duodenal wall through the cholecystoduodenostomy. The echoendoscope was then withdrawn. Next, a solution of normal saline and methylene blue was injected through the percutaneous cholecystostomy tube and this solution was seen to flow from the duodenal portion of the AXIOS stent on endoscopic views, confirming adequate location of the AXIOS stent in the gallbladder and duodenum. DISCUSSION: The patient did well in the immediate post-procedural period. Six days post-procedure, he was noted to have melena in the setting of supratherapeutic INR and aPTT. Repeat upper endoscopy showed no evidence of bleeding. The AXIOS stent appeared normal on endoscopic views. Due to the difficulty of stent placement and palliative intent, we left the AXIOS stent in situ. The patient is currently asymptomatic and was referred to IR for removal of percutaneous cholecystostomy tube.

1867 A Case of Mistaken Identities: Impact of Kayexalate on the Colon

INTRODUCTION: End stage renal disease (ESRD) affects nearly 750,000 Americans each year. Kayexalate (sodium polystyrene sulfonate) is commonly used to manage hyperkalemia in ESRD. Kayexalate is a nonspecific cation exchange resin that acts in the large intestine to allow for the exchange of sodium for any cation (potassium, calcium or magnesium). Kayexalate has an inherent lattice structure. Addition of calcium ions can lead to crystal formation that appears basophilic, rhomboid/triangular with a fish-scale appearance on Hematoxylin and Eosin (H&E) stain. Studies show that the combination of kayexalate and sorbitol, an osmotic laxative, may lead to osmotic shifts and ischemic damage. However, the impact of kayexalate alone in gastrointestinal tract is less established. We present a case of kayexlate crystal deposition appearing as a pseudo-polyp in the appendiceal orifice. CASE DESCRIPTION/METHODS: A 51-year-old woman with a past medical history significant for systemic lupus erythematosus, radical nephrectomy for renal mass complicated by dialysis dependent ESRD, mitral and aortic valve replacement on Coumadin, presented to the hospital for hyperkalemia requiring emergent dialysis. The patient developed melena in the setting of supratherapeutic INR. Colonoscopy revealed a non-obstructing 10mm yellow mass protruding from, and tethered to, the appendiceal orifice. The pseudo-polyp appeared to be on a stalk. Resection was performed using a biopsy forceps at the base. Pathology revealed foreign crystalline material that was suggestive of kayexalate deposition. The source of gastrointestinal bleeding was later identified as a jejunal arteriovenous malformation. DISCUSSION: Reports of kayexalate effects on the gastrointestinal tract are somewhat limited, but include findings of acute inflammatory tissue injury in as early as 24 hours, potentially with colonic ulceration. Kayexalate can also cause mechanical obstruction secondary to the development of crystalline structures in the colon. Prolonged uses of this medication can likewise lead to reversible crystal deposition within the esophagus, stomach and duodenum. This case highlights the potential for crystal resin deposition to appear as a pseudopolyp. Gastroenterologists should carefully review medication history when approaching a patient with a mechanical obstruction or colon ulceration in the setting of ESRD.

Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous-flow left ventricular assist devices.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

THE IMPACT OF TEMPORARY INTERRUPTIONS OF WARFARIN ON DOWNSTREAM TIME IN THERAPEUTIC RANGE IN PATIENTS WITH ATRIAL FIBRILLATION: RESULTS FROM ORBIT AF

Temporary interruption (TI) of warfarin in atrial fibrillation (AF) may be associated with subsequent sub- or supra-therapeutic INR. Our objective was to study time in therapeutic range (TTR) before and after a TI. AF patients on warfarin who had a TI followed by resumption in the Outcomes Registry

Emergency management of patients with Supratherapeutic INRs on Warfarin: a multidisciplinary education study

Objective: Supratherapeutic INRs exceeding 4.5 are associated with increased risk of haemorrhage. The aim of this study was to evaluate the efficacy of an educational program focused at improving emergency clinician compliance with the Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) guidelines. Design: A pre and post-intervention study was undertaken. Retrospective data from 1 July 2014 to 30 June 2015 andprospective data 1 January 2016 to 31 December 2016 were collected. Setting: This study was conducted in a large tertiary care hospital in Melbourne, Victoria, Australia. Subjects: Included were all consecutive patients in the study periods that presented to the emergency department with an initial INR result of >4.5 on warfarin only. Interventions: Development and delivery of an educational program in accordance with the current THANZ guidelines was implemented. Main outcome measures: To improve education regarding the correct management of emergency patients on warfarin with a supratherapeutic INR. Results: Data on 158 patients with an INR >4.5 were collected. Data on 46 patients were excluded. Management in 31patients did not follow recommended guidelines. There was no difference detected between groups with 17 compliant with guidelines pre-intervention and 14 post intervention; p=0.87.

Investigation on Dabigatran Etexilate and Worsening of Renal Function in Patients with Atrial fibrillation: The IDEA Study.

Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function. One hundred and seven patients treated long term with dabigatran etexilate for non-valvular atrial fibrillation (NVAF) were followed upfor 90days. DPC, serum creatinine (SCr) and serum cystatin C were prospectively measured.Ninety five patients had complete follow-up data and were evaluable for primary endpoint. Eleven patients had supratherapeutic DPC, defined as DPC higher than 200 ng/ml at study enrolment, but at the end of follow-up no patient showed a persistent increase in SCr. No patients experienced acute kidney injury. Our study shows that no persistent renal detrimental effect is associated with dabigatran treatment. An increase in SCr during dabigatran treatment is reversible and it seems to be unrelated to dabigatran itself.

Rates of Gastrointestinal Bleeding in Cirrhotics Treated With Warfarin

Introduction: It is well accepted that there is an increased risk of bleeding for patients prescribed anticoagulants like warfarin. Moreover, cirrhosis, particularly when associated with portal hypertension, also increases the risk of gastrointestinal bleeding (GIB). However, while there is data on outcomes for cirrhotics treated with anticoagulants for portal vein thrombosis, there is a paucity of data on the risk of GIB in cirrhotics who are treated with anticoagulants like warfarin for other indications. Methods: Retrospective review comparing patients at our local VA prescribed warfarin between 2009 and 2016 who had cirrhosis (cases) or did not have cirrhosis (controls). Patients were enrolled when anticoagulation was begun or when cirrhosis was diagnosed if already on anticoagulation. Controls were required to have a fib-4 score < 1.45. Primary outcome was the rate of GIB at 30 days, 90 days, 1 year, and 2 years. Results: 82 cases and 62 controls were identified. Etiology of cirrhosis for the cases included hepatitis C 49%, alcohol 39%, non-alcoholic steatohepatitis 22%, hepatitis B 2%, and others 17%. 14 (17%) had a history of esophageal varices. >80% of cases and controls were on warfarin for atrial fibrillation or venous thromboembolism (VTE). Charlson comorbidity index and HAS-BLED scores were higher in cases as compared to controls. There were no differences in use of antiplatelet agents, proton pump inhibitors, H2 receptor blockers, or statins. Cases were treated more often with beta-blockers (71% vs 37%, p60% of both cases and controls who experienced GIB presented with supratherapeutic INRs. Rates of GIB trended towards occurring significantly more often for cases (see table). Of the cirrhotics who experienced GIB on warfarin, 5 (25%) were due to portal hypertensive causes. All cause mortality rates were higher for cases as compared to controls, but the difference was not significant. Conclusion: Not unexpectedly, patients with cirrhosis treated with warfarin for common indications like atrial fibrillation or VTE have high rates of GIB with over 10% of patients experiencing GIB after 1 year of therapy. Interestingly, 75% of cirrhotics on warfarin bled from causes other than portal hypertension. This is important information to share with patients when discussing risks and benefits of anticoagulant therapy.556 Figure 1. Baseline demographics and results

Utility of Screening EGD in High Risk Patients Undergoing Transesophageal Echocardiography

Introduction: Transesophageal echocardiography (TEE) probes are introduced and advanced into the distal esophagus blindly. Concern for esophageal injury often prompts gastroenterology consultations for screening esophagogastroduodenoscopies (EGDs), especially in patients who are at high risk for esophageal lesions. There is insufficient data in the current literature on the utility of screening EGDs prior to TEE. Methods: This is a retrospective study at a tertiary referral center. We reviewed charts of all patients who underwent a TEE between August 2015 and November 2016. We included all adult patients (≥18 years old), who underwent and EGD within a month of TEE. Results: 3,130 TEEs were performed during the study period and only 4 (0.13%) potential complications were identified. 213 patients underwent 226 EGDs within one month of the TEE. 89 (39.4%) EGDs were preformed prior to TEE and 137 (60.6%) after. Average time between procedures was 9 days. 106 patients were considered high risk. EGD indications are summarized in TABLE 1. No TEE complications were reported in patients without active symptoms, including those who were defined as high risk patients for esophageal lesion such as cirrhotics and those with prior history of upper GI bleed. We identified only 4 patients with potential TEE complications; one patient developed melena and acute drop in hemoglobin one day after TEE, EGD revealed a small false esophageal lumen with active oozing from the site, attributed to blunt trauma. Another patient developed melena one week after a TEE, which started in the setting of supratherapeutic INR. EGD demonstrated a visible esophageal vessel vs clot in upper third of the esophagus and an ischemic appearing necrotic mucosa in middle esophagus. The two other patients reported GI bleeding prior to TEE: hematemesis and hematochezia. EGDs in both cases were performed the within 24 hours after TEEs and showed Mallory Weiss tear in the distal esophagus in the former and diffuse severe esophagitis with small oozing ulcerations in upper and lower esophagus in the latter. In the latter two cases other associated interventions and lesions could explain the findings and symptoms. Conclusion: Our results demonstrate the low rate of esophageal complications related to TEE, including in high risk patients. In asymptomatic high risk patients screening EGD may not be beneficial or change management. On the other hand, high risk patients with active bleeding symptoms may benefit from EGDs prior to TEEs.361_A Figure 1 No Caption available.361_B Figure 2 No Caption available.

Abdominal Pain, Hypotension With Rectal Bleeding: A Unique Presentation of Emphysematous Cholecystitis From Squamous Cell Carcinoma of Gallbladder (GB)

Carcinoma of GB is a rare tumor which presents significant diagnostic challenges. We present a case of an elderly woman who presented with abdominal pain and hematochezia was found to have septic shock from emphysematous cholecystitis in the setting of squamous cell carcinoma of the gallbladder. A 70 year old woman with past medical history of hypertension, anemia, CKD Stage III and DVT on warfarin presented with diffuse abdominal pain and bright red rectal bleeding. Her initial blood pressure was 74/38 mm hg with significant epigastric tenderness on exam. Rectal exam revealed hematochezia. Labs revealed hemoglobin of 9.7 g/dL. Initially believed to have lower GI bleed in the setting of supratherapeutic INR (3.1) she was transfused fresh frozen plasma and packed red blood cells. In view of significant epigastric tenderness CT scan of abdomen was done which revealed a markedly distended stone-containing GB with wall thickening, fat stranding and gas anteriorly dependent within the GB concerning for emphysematous cholecystitis. She was treated with IV antibiotics with emergent cholecystectomy. Pathology of the GB was significant for poorly-differentiated squamous cell carcinoma with positive cystic duct lymph node and acute cholecystitis with cholelithiasis. Cancer of the GB is an uncommon malignancy comprising just 0.6% of all new cancer diagnoses, and just 3.7% of all new digestive system cancer diagnoses in 20161. Histologic subtypes include adenocarcinoma, and squamous/adenosquamous carcinoma with an incidence of 90% and 1.7-12% respectively. Occurring primarily in the elderly with a 3:1 predominance in women3,4, GB carcinoma is a highly aggressive disease entity. Due to the lack of typical presenting symptoms GB cancer is usually diagnosed in advanced stages. In certain instances, patients may present with complaints of abdominal pain, nausea and vomiting and are eventually diagnosed with cholecystitis as the tumor obstructs outflow of bile. Aim of treatment is surgical resection when possible. Our case was clinically challenging as the initial presentation was consistent with massive lower GI bleeding but the CT scan of the abdomen helped us reach to the correct diagnosis and treatment. It is important for physicians to think of a broad differential diagnosis as sometimes the disease presentation is not straight forward like in our case where in the presenting complaint of rectal bleeding eventually led to a diagnosis of squamous cell cancer of GB.1241_A.tif Figure 1: Axial view of emphysematous gallbladder with foci of anteriorly dependent air.1241_B.tif Figure 2: Coronal view of markedly distended gallbladder with multiple stones, irregularly thickened wall and pericholecystic fluid.

Abstract 178: A Shocking Inefficiency: Unexpected Cancellations of Elective Cardioversions at a High Volume Electrophysiology Lab

Background: Despite advances in pharmacologic therapies and ablation techniques, elective cardioversions (CV) remain integral to the care of patients with atrial fibrillation (AF). These outpatient procedures require appropriate patient preparation to maintain patient safety and maximize success rates. These preparations include confirming adequate anticoagulation and pre-CV heart rhythm recording. Despite these preparations, unexpected cancellations of CV occur and lead to patient dissatisfaction and lost productivity. The objective of this study was to examine the frequency and cause of unexpected CV cancellations in a large volume center and to assess how novel technologies may improve efficiency in the future. Methods: Patients with AF who presented for scheduled elective CV were screened consecutively for enrollment. All patients were contacted the day before CV to confirm adequate anticoagulation and to provide instructions regarding fasting and the use of medications the morning of the planned CV. Information regarding the patients’ anticoagulation strategies and history were recorded at the time of enrollment. INR levels were obtained using routine serum and point of care testing. Statistical analysis was performed to evaluate trends in cancelled CV, potential impacts on the EP lab and to assess the ability of mobile technology to improve the CV process. Results: Two hundred patients were enrolled (Age 68 ± 12). Anticoagulation strategies varied in this group and included apixaban (N=90), warfarin (N=73), rivaroxaban (N=35) and dabigatran (N=2). Three patients required unplanned transesophageal echocardiogram. Thirty-two patients presented for CV but had their procedure cancelled due to a subtherapeutic INR (N=5), supratherapeutic INR (N=2), being in normal sinus rhythm (N=14), thrombus present on TEE (N=5) and intolerance of the TEE (N=2). CV was successful in 96% of patients (N=192). Point of care testing (POCT) and standard serum measurements were strongly correlated (r=0.961, p&lt;0.001) although POCT INR testing results were, on average, 0.2 higher than standard serum measurements (95% CI [0.15-0.25]). Conclusions: A shocking percentage of CV are cancelled unexpectedly highlighting an opportunity to improve efficiency and productivity in the EP lab. The cancellations appear to be driven by inadequate anticoagulation and patients unexpectedly arriving in normal sinus rhythm. Technology providing remote assessment of both of these clinical variables is already commercially available. This remote monitoring of heart rhythm and INR may provide opportunities to reduce cancellations, improve patient satisfaction and boost EP lab productivity.

Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population.

We aimed to study potential variables involved in interindividual variability to acenocoumarol (AC) response in order to establish a pharmacogenetic algorithm (PA) that includes clinical and genetic factors to predict adequate AC dose to stabilize anticoagulation in a cohort of Tunisian patients. Genotyping of the CYP2C9, VKORC1, CYP4F2, and CALU polymorphisms was conducted on 246 patients using PCR-RFLP technique. AC normalized maintenance dose (NMD):((mean maintenance dose/international normalized ratio (INR)) equilibrium) was calculated. The statistical study was carried out with SPSS V20. A significant correlation was found between age, BMI, and daily AC dose (r = - 0.397; p < 0.001 and r = 0.215; p = 0.001, respectively). The carriers of mutated alleles CYP2C9*2or CYP2C9*3 or VKORC1 haplotypes (H1 and H7) were associated with AC hyper-sensibility. After adjustment to potential covariates, these patients presented supra-therapeutic INR during treatment period and needed low AC dose (ORs* = 0.28 [0.06-0.60], p = 0.004; ORs* = 0.12 [0.04-0.05], p < 0.001; ORs* = 0.45 [0.24-0.84], p = 0.01; and ORs* = 0.28 [0.06-0.98], p = 0.049, respectively). However, carriers of VKORC1 haplotypes (H3 and H12) or mutated alleles CYP4F2 (rs2108622) or CALU (rs1043550) tend to resist to treatment, hence long period of therapy initiation, and must be treated with high AC dose (ORs* = 2.67 [81.12-5.91], p = 0.013; ORs* = 8.76 [1.07-76.26], p = 0.019; ORs* = 3.12 [1.01-9.63], p = 0.047; and ORs* = 3.96 [1.41-11.09], p = 0.009, respectively). A final multivariate regression model explained 48.1% of the global interindividual variability in AC dose requirement. The PA demonstrated that VKORC1 and CYP2C9 polymorphisms contribution was more important than clinical factors. Applying the PA would allow dose adjustment to treat patients in a personalized manner.

The Anticoagulation Champion: Efficacy of Warfarin Anticoagulation in a Resident-Based Primary Care Clinic

SESSION TITLE: Quality Improvement 2 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Warfarin is still anticoagulant of choice for many patients. Therapeutic time in range (TTR) is used to assess quality of warfarin anticoagulation. A TTR of above approximately 60% has been show to improve mortality and reduce risk of complications.Our hypothesis was the creation of a resident Anticoagulation Champion (AC) would be more efficacious than individual provider driven anticoagulation in a primary care resident clinic. METHODS: To be the AC residents were given a lecture on warfarin anticoagulation and assigned to the AC role for 2 week intervals. Duties included monitoring the anticoagulation book, calling patient’s for appointment reminders, education, following up INR’s and prescribing. There were a total of 56 patient charts which were reviewed from April 2014- March 2016. Three were excluded for not having INR values recorded during the time period. Of the 53 patients included, 5 patients had INR goals of 2.5-3.5 and 48 patients INR goal was 2-3. When calculating TTR, this range was extended to 1.95-3.04 and 2.45-3.54 as dosage would not be adjusted at these values. Patients were classified as not therapeutic with sub therapeutic and supra therapeutic INR’s. Data was then split into 2 time periods: pre-resident based (April 2014-March 2015) and with AC (April 2015-March 2016). We calculated TTR using the traditional method. We compared TTR by month, age and sex. Comparisons were analyzed with a t-test. RESULTS: Of the subjects included, 57% were male. Mean and Median ages of patients were 60.94 and 60.5 respectively with range from 31 to 90 years old. Twenty patients were >65 years. The highest and lowest INR’s in this study were 6.22 and 0.92 respectively. A total of 415 INR values were recorded. Pre- AC there was 37 values and with AC 378 values. TTR for males was 56% and females 49%. Average TTR by age was 53.47% for those <65yo and 57.25% for >65 years old. 11 patients had data before and with AC. The TTR pre-AC was 49.52% and with AC was 55.83%. The p value was 0.37. TTR by month ranged from 37-74%. CONCLUSIONS: There was a dramatic improvement in frequency of INR monitoring with the initiation of AC as shown by an increase of INR values during this time period. There was also a trend of improvement in the TTR with AC, however it was not statistically significant likely secondary to the low sample size. CLINICAL IMPLICATIONS: This suggests warfarin anticoagulation could be more efficacious with implementation of an Anticoagulation Champion in resident based primary care clinics. DISCLOSURE: The following authors have nothing to disclose: Janine Harewood, Gina Cook, Jini Veith, Blanca Sckell No Product/Research Disclosure Information

Encountered a Black Swan During ERCP: A Rare Case of IVC Filter Migration to Ampulla

Inferior Vena Cava (IVC) filter penetration of the vessel wall into surrounding gastrointestinal (GI) structures is a possible but rare complication. Few cases of IVC filter migration into the duodenum have been reported. We present a case of Greenfield IVC filter penetrating in the ampulla, visualized only during ERCP. To the best of our knowledge, IVC filter migration to ampulla has not been reported in the literature. An 87-year-old female presented to the hospital with melena, and abdominal pain. Her past medical history was significant for Atrial Fibrillation and recurrent DVTs for which she takes coumadin. The patient had a Greenfield IVC filter placed around 20 years ago for her recurrent DVTs as she had contraindication to anticoagulation at that time. She did not follow-up and the filter was not removed. On examination upper abdomen was tender. Lab studies revealed anemia (Hemoglobin 7.5 mg/dl), supratherapeutic INR and abnormal liver function test suggestive of cholestasis. MRCP showed dilated bile ducts and choledocholithiasis. Upper GI endoscopy was performed but did not reveal any source of bleeding. GI bleeding resolved spontaneously with reversal of anticoagulation and supportive care. ERCP was then performed for management of choledocholithiasis which incidentally revealed a protruding piece of hardware which was consistent with Greenfield filter prawn (Image 1). The protruding prawn was grasped with the biopsy forceps and fluoroscopic images were taken (Image 2). Images confirmed it to be a part of IVC filter while the rest of body was extraluminal, likely in the IVC. It was left undisturbed while choledocholithiasis was treated with sphincterotomy. Patient's abdominal pain resolved.Considering patient's age, comorbidities and her being asymptomatic, it was decided to manage the perforating filter conservatively. Long standing IVC filter can perforate the duodenal wall and can result in obscure GI bleeding. Generally, filters migrating to the duodenal wall can be seen on endoscopy with forward view scopes. We believe the migrated IVC filter caused GI bleeding in our patient which was missed on EGD. IVC filter strut at the ampulla was visualized only during an ERCP. One of the implications of this rare finding is that if there is high suspicion for IVC filter perforation, then inspection of the ampulla with a duodenoscope should be considered as well. Our case also highlights the importance of timely removal of IVC filters.Figure: Leg of IVC filter seen perforating at Ampulla during ERCP.Figure: Fluoroscopic image showing IVC filter.