[Clinical characteristics and literature review of ectopic gastric mucosa in the small intestine].

The study aims to summarize the clinical characteristics of patients with ectopic gastric mucosa in the small intestine, comparing clinical presentation differences between domestic and foreign patients through literature review. The clinical characteristics of cases diagnosed with ectopic gastric mucosa in the small intestine at Peking Union Medical College Hospital from January 2000 to January 2024 were retrospectively analyzed. By searching databanks, such as PubMed, EMBASE, the Cochrane Library, Wanfang, VIP, CNKI, and etc (the inclusion period was from the establishment of the database to January 1, 2024). The literature review was conducted on ectopic gastric mucosa in the small intestine. A total of 10 cases were included, all male, age [M (Q1, Q3)] was 27 (13-69) years old. Gastrointestinal bleeding was the first manifestation in most cases, with severe cases leading to hemorrhagic shock. Abdominal CT indicated local intestinal wall thickening and luminal narrowing in 3 cases. Four cases lesions were located at the beginning of the jejunum and 6 lesions were located in the end segment of ileum. All cases underwent local lesion resection, with postoperative pathology confirming ectopic gastric mucosa. Symptoms disappeared postoperatively, with a follow-up period of 0.5-3.0 years. Literature review indicates that the main clinical manifestation of gastric mucosa ectopia in the small intestine in China is gastrointestinal bleeding, while foreign patients are often complicated with intestinal duplication and intussusception, with abdominal pain and vomiting as the primary and main symptoms. The occurrence rate of intestinal obstruction in female patients, both domestically and abroad, is higher than that in male patients. The occurrence rate of ileal lesions with intestinal obstruction and small intestinal duplication is higher than that of duodenal lesions in both domestic and foreign patients. Local small intestine resection is an effective treatment method with generally good prognosis. Ectopic small intestinal mucosa is relatively rare, with symptoms of gastrointestinal bleeding and intestinal obstruction being common presentations, which can serve as one of the differential diagnoses for unexplained gastrointestinal bleeding.

Application of small bowel capsule endoscopy in children with Meckel's diverticulum.

BACKGROUND: Meckel diverticulum (MD) is an important cause of gastrointestinal bleeding in children. Small bowel capsule endoscopy (SBCE) is a first-line examination method applied to patients with obscure gastrointestinal bleeding, but there are few studies on its application in children with MD. This article aims to provide evidence in favor of the auxiliary diagnosis of MD in children by analyzing its characteristics using SBCE. METHODS: We retrospectively collected the clinical data of patients with suspected MD. RESULTS: A total of 58 children were included in this study. All 58 children presented overt gastrointestinal bleeding (bloody stool or melena). Capsule endoscopy identified protruding lesions in 2 cases, double-lumen changes in 30 cases (all considered as MD), vascular lesions in 7 cases, intestinal mucosal inflammatory lesions in 3 cases, ulcers or erosion in 3 cases, and no obvious abnormalities in SBCE in 12 cases. Both SBCE and technetium-99 scans were performed for 24 cases, 22 of which were diagnosed MD by their combined results, giving a diagnostic coincidence rate of 91.7%. Eight cases were highly suspected as MD but were negative for the technetium-99 scan and positive for SBCE. CONCLUSION: SBCE has high accuracy in the diagnosis of MD in children, especially when performed in combination with a technetium-99 scan, which can greatly improve the diagnostic rate of MD in children.

Characterization of early-stage lesions and investigation on the role of mucosal trauma in hemorrhagic bowel syndrome in cattle.

Hemorrhagic bowel syndrome (HBS) is characterized by a dissecting intramucosal hematoma at the small bowel, causing obstruction and severe hemorrhage in dairy cattle. Recent investigation revealed the presence of early-stage lesions in cows affected by HBS. These are presumed to be the initial stage of the hematoma, as both share unique dissection of the lamina muscularis mucosae (LMM) as histological hallmark. Early-stage lesions of HBS have not been characterized in greater detail, and neither has the hypothesis of mucosal abrasion as etiology been explored. Therefore, the first objective of the present study was to characterize the morphology of early-stage lesions, by gross examination, histochemistry, immunohistochemistry and transmission electron microscopy. The second objective was to determine the effect of mucosal abrasion to the small intestine in an ex vivo model. A total of 86 early-stage lesions from 10 cows with HBS were characterized. No underlying alterations at the LMM were evident which could explain their occurrence. However, degeneration at the ultrastructural level of the LMM smooth muscle cells was present in 3 of 4 lesions, it is however unclear whether this is primary or secondary. Bacteriological examination did not reveal any association with a specific bacterium. Experimental-induced and early-stage lesions were gross and histologically evaluated and scored in three cows with HBS and seven controls. Experimentally induced lesions in both affected cows and controls, were histologically very similar to the naturally occurring early-stage lesions. Altogether, the results are suggestive for mucosal trauma to play a role in the pathogenesis of HBS.

Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Patients.

BACKGROUND Severe anemia caused by hemorrhoidal hematochezia is typically treated preoperatively with reference to severe anemia treatment strategies from other etiologies. This retrospective cohort study included 128 patients with hemorrhoidal severe anemia admitted to 3 hospitals from September 1, 2018, to August 1, 2023, and aimed to evaluate preoperative blood transfusion requirements. MATERIAL AND METHODS Of 5120 patients with hemorrhoids, 128 (2.25%; male/female: 72/56) experienced hemorrhoidal severe anemia, transfusion, and Milligan-Morgan surgery. Patients were categorized into 2 groups based on their preoperative hemoglobin (PHB) levels after transfusion: PHB ≥70 g/L as the liberal-transfusion group (LG), and PHB <70 as the restrictive-threshold group (RG). The general condition, bleeding duration, hemoglobin level on admission, transfusion volume, length of stay, immune transfusion reaction, surgical duration, and hospitalization cost were compared between the 2 groups. RESULTS Patients with severe anemia (age: 41.07±14.76) tended to be younger than those with common hemorrhoids (age: 49.431±15.59 years). The LG had a significantly higher transfusion volume (4.77±2.22 units), frequency of immune transfusion reactions (1.22±0.58), and hospitalization costs (16.69±3.31 thousand yuan) than the RG, which had a transfusion volume of 3.77±2.09 units, frequency of immune transfusion reactions of 0.44±0.51, and hospitalization costs of 15.00±3.06 thousand yuan. Surgical duration in the LG (25.69±14.71 min) was significantly lower than that of the RG (35.24±18.72 min). CONCLUSIONS Patients with hemorrhoids with severe anemia might require a lower preoperative transfusion threshold than the currently recognized threshold, with an undifferentiated treatment effect and additional benefits.

Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.

Gastrointestinal bleeding in patients with COVID-19: an integrative review.

INTRODUCTION: In 2020, the world suffered a major impact from the COVID-19 pandemic, especially due to the high transmissibility of the virus. It is a disease that predominates with respiratory manifestations, but there is involvement of the gastrointestinal tract, causing symptoms ranging from mild to more severe. Highlighting gastrointestinal bleeding, it is a symptom resulting from the involvement of the SARS-CoV-2 virus described by several reports and case series. METHODS: through an integrative literature review, of a qualitative nature, works that corresponded to the eligibility criteria were selected, totaling 16 articles included in this review. RESULTS: of the patients who manifested gastrointestinal symptoms associated with the disease, common comorbidities and clinical manifestations were identified, in addition to therapies used to treat the infection, which were predisposing factors for the development of gastrointestinal bleeding. CONCLUSION: The presence of gastrointestinal bleeding in patients with COVID-19 is established in the literature, since the pathophysiological mechanisms of the disease directly affect the GIT. Early recognition of symptoms and suspicion of gastrointestinal involvement allows better management of patients and complications.

Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

Guideline versus clinician recommended duration of dual antiplatelet therapy following acute coronary syndrome (ANZACS-QI 78).

AIM: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) for patients without atrial fibrillation varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. Patients on DAPT with a high risk of gastrointestinal bleeding are also recommended to receive a proton pump inhibitor (PPI). Our aim was to audit current practice against the 2020 European Society of Cardiology (ESC) guideline recommendations. METHODS: One hundred consecutive ACS patients treated with percutaneous coronary intervention discharged from Middlemore Hospital and without atrial fibrillation in the first quarter of 2023 were studied. ANZACS-QI ischaemic (I) and bleeding (B) risk scores were calculated, with patients categorised in four groups based on ESC recommendations-low I/low B risk, low I/high B, high I/low B and high I/high B. Guideline and clinician recommended duration of DAPT and prescription of PPI were compared. RESULTS: All patients were planned for DAPT at discharge and 91% a PPI. Up to four out of five ACS patients could have been planned for shorter DAPT durations based on the ESC guideline recommendations. Over half of included patients (53%) had a high bleeding risk, yet 85% of these patients received 12 months of DAPT despite ESC recommendations of 1-3 months. CONCLUSIONS: There was a divergence between clinical practice and the recommendations of the 2020 ESC guidelines. We discuss these results in relation to the updated August 2023 ESC guidelines, which have reaffirmed a 12-month duration of DAPT as the default position.

Endoscopic management of intraprocedural bleeding during endoscopic interventions.

Endoscopic resection techniques have evolved over time, allowing effective and safe resection of the majority of pre-malignant and early cancerous lesions in the gastrointestinal tract. Bleeding is one of the most commonly encountered complications during endoscopic resection, which can interfere with the procedure and result in serious adverse events. Intraprocedural bleeding is relatively common during endoscopic resection and, in most cases, is a mild and self-limiting event. However, it can interfere with the completion of the resection and may result in negative patient-related outcomes in severe cases, including the need for hospitalization and blood transfusion as well as the requirement for radiological or surgical interventions. Appropriate management of intraprocedural bleeding can improve the safety and efficacy of endoscopic resection, and it can be readily achieved with the use of several endoscopic hemostatic tools. In this review, we discuss the recent advances in the approach to intraprocedural bleeding complicating endoscopic resection, with a focus on the various endoscopic hemostatic tools available to manage such events safely and effectively.

Prevention of delayed bleeding after resection of large colonic polyps.

A significant problem encountered in the resection of large, complex colonic polyps is delayed bleeding. This can occur up to two weeks after the procedure and is a significant source of comorbidity. Untreated it can prove life threatening. It is therefore a priority of modern endoscopy to develop and employ techniques to minimaize this. In this article we will review and discuss the evidence base and controversies in this field, with cold EMR technique, Post-EMR clip closure, and topical haemostatic agents.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

Double balloon enteroscopy versus single balloon enteroscopy: A comparative study.

Device assisted enteroscopy (DAE) like the double balloon enteroscopy (DBE) and single balloon enteroscopy (SBE) are postulated to ease small bowel examination and performance of therapy. However, studies comparing the effectiveness of these 2 modalities have yielded varying results. The aim of this study is to compare the efficacy and safety of SBE and DBE. We retrospectively reviewed records of patients who underwent DBE (n = 82) or SBE (n = 45) for small bowel exam in our unit from January 2014 to January 2022. Our primary outcomes were to compare the technical success and diagnostic success rates between DBE and SBE. Our secondary outcomes were to compare the therapeutic success, and complication rates. The main indications were suspected GI bleeding (DBE 41.5% vs SBE 48.9%), iron deficiency anemia (DBE 9.8% vs SBE 4.4%) and small bowel lesions (DBE 28.0% vs SBE 44.4%) detected either from prior capsule endoscopy or radiological imaging. Majority of the enteroscopy exam was by antegrade approach (DBE 67.1% vs SBE 77.8%). We found no significant difference in the technical success (DBE 95.1% vs SBE 97.8%, P = .46), diagnostic success (DBE 69.5% vs SBE 77.8%, P = .36) and the therapeutic success rate (DBE 63.2% vs SBE 54.3%, P = .09) between the groups. Complications occurred in 1 case from each group (mucosal tear). None of the complications were major. In patients who underwent enteroscopy, the diagnostic and therapeutic performance of SBE is similar to DBE. Both procedures were safe with low complication rates.

Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.