Introduction

Antiplatelets and anticoagulants significantly increase the risk of upper gastrointestinal bleeding by impairing normal clotting mechanisms. Patients on dual or combined therapy often present with more severe bleeds and poorer endoscopic control. This leads to higher rates of rebleeding, complications, and mortality compared to those not on these therapies.

Aims & Methods

To evaluate the risk and outcomes of non-variceal upper gastrointestinal bleeding (UGIB) in patients on single antiplatelet therapy, dual antiplatelet therapy, and combined antiplatelet-anticoagulant therapy, and to assess associated morbidity, mortality, and rebleeding rates.
A prospective study was conducted involving 150 patients (90 males, 60 females) aged 40–60 years, presenting with upper GI bleeding between 1st January 2023 till 1st January 2025. Patients had co-morbid conditions including hypertension, diabetes mellitus, coronary artery disease, or prior cerebrovascular events, and were on their respective medications for at least 3 months. Patients using NSAIDs, having liver disease, or known bleeding disorders were excluded. Clinical presentations included melena, hematemesis, or both. All patients underwent upper GI endoscopy, with Forrest classification used to characterize ulcers. Laboratory investigations included CBC, LFTs, renal function, PT, and APTT. Bleeding profiles and endoscopic outcomes were analyzed across three medication groups: single antiplatelet (n=60), dual antiplatelet (n=50), and combined antiplatelet-anticoagulant therapy (n=40).

Results

UGIB was reported in 6 (10%) of the single antiplatelet group, 16 (32%) of the dual antiplatelet group, and 14 (35%) of the combined therapy group. Endoscopic findings predominantly revealed Forrest class IIA ulcers. Patients on dual or combined therapy had poorer endoscopic hemostasis. Four patients experienced rebleeding refractory to standard endoscopic measures, requiring angioembolization. One mortality was recorded in the dual antiplatelet group due to massive bleeding and shock.

Conclusion

Dual antiplatelet and combined antiplatelet-anticoagulant therapies significantly increase the risk and severity of non-variceal UGIB, with higher rates of poor endoscopic hemostasis, rebleeding, and mortality. These findings underscore the importance of risk stratification and prophylactic strategies in patients requiring long-term antithrombotic therapy.

References

1. Hao, W., Liu, A., Zhu, H. et al. Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study. BMC Gastroenterol 24, 155 (2024). https://doi.org/10.1186/s12876-024-03238-3
2. Risk of Gastrointestinal Bleeding Increases With Combinations of Antithrombotic Agents and Patient Age Abraham, Neena S. et al. Clinical Gastroenterology and Hepatology, Volume 18, Issue 2, 337 - 346.e19

Introduction

Fecal Microbiota Transplantation (FMT) delivered through capsules is an effective therapy against recurrent Clostrdioides difficile infections (rCDI). Studies suggests that the viral part (mainly represented by bacteriophages) of donor stool plays an important role in FMT treatment effect[1]. Through filtration steps the viral fraction of donor stool can be separated from the bacterial part to produce material that can be capsulized and delivered as fecal virome transplantation (FVT) through capsules[2].
The goal of this study was to compare the effect of FVT capsules against FMT capsules as treatment of rCDI in a randomized controlled pilot trial.

Aims & Methods

In the VISION study treatment with FVT capsules was compared to the standard treatment of FMT capsules in 40 patients with first or second recurrence of C. difficile infection.
Participants were randomized 1:1 to receive either one dose of FMT or FVT capsule treatment preceded by approximately 10 days of Vancomycin 125 mg x 4 daily or Fidaxomycin 200 mg x 2 daily. The same four fecal donors were used to produce FMT and FVT material. The primary endpoint was clinical resolution defined as resolution of diarrhea with ≤ 3 daily bowel movements or persistent diarrhea with a negative C. difficile test result, eight weeks following treatment. Patients receiving antibiotics as treatment of other infections were treated with concurrent Vancomycin and were defined as treatment failures in the Intention-to-treat analysis but were excluded from the per-protocol analysis.

Results

Forty patients were randomized and received FMT or FVT capsule treatment with no significant difference between groups in baseline characteristics (Table 1). The primary outcome was achieved by 70 % (14/20) in the FVT group and 75% (15/20) in the FMT group with no significant difference between groups (p = 1). Three patients were omitted from the per-protocol analysis. Here the primary outcome was achieved by 73.7 % (14/19) in the FVT group and 83.3 % (15/18) in the FMT group with no significant difference between groups (p = 0.69).

Table 1. Baseline characteristics

Conclusion

FVT capsules were effective as treatment of rCDI and were non-inferior to FMT capsules. Larger trials are needed to further explore the efficacy of FVT capsules as treatment of rCDI.

References

[1] Liu Q, Xu Z, Dai M, Su Q, Leung Chan FK, Ng SC. Faecal microbiota transplantations and the role of bacteriophages. Clinical Microbiology and Infection 2023;29:689–94. https://doi.org/10.1016/j.cmi.2022.11.012.
[2] Rasmussen TS, Mao X, Forster S, Larsen SB, Von Münchow A, Tranæs KD, et al. Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments. Microbiome 2024;12:119. https://doi.org/10.1186/s40168-024-01820-1.

Disclosure

Frederik Cold declares support for attending meeting and/or travel from AbbVie and Orion Pharma, Andreas Munk Petersen declares support for attending meeting and/or travel from AbbVie, grants or contracts from Chr. Hansen A/S part of Novonesis and consulting fee from Genfit, Hengameh Chloe Mirsepasi-Lauridsen, Torben Sølbeck Rasmussen, Lars Hestbjerg Hansen, Sofie Ingdam Halkjær, Dennis Sandris Nielsen and Morten Helms declares no conflicts of interest.

Clinical Case Summary

A 29 year old women was diagnosed with Crohn’s disease with ileocolonic involvement and a penetrating behaviour (Montreal classification A2L3B3). After the pre imunosupression workup we proposed the patient to start Infliximab (IFX) with a dosage of 5 mg/kg.
During the first infusion the patient referred sudden visual impairment. There were no visible inflamation of the sclera, conjunctiva or peri orbital area. The patient reported no pain and there were no signs of ophthalmoparesis. We stopped the infusion immediately and asked for an urgent observation by Ophtalmology. Although the fundoscopic examination didn’t detect any abnormalities, there was a significant decrease in the visual acuity of the left eye.
The patient regained full visual acuity the day after the event. We decided to switch the biologic therapy to Ustekinumab. The patient was reevaluated in the outpatient clinic two weeks after discharge, she maintained full visual acuity and showed significant improvement of her symptoms.
IFX is a generally well tolerated drug, participating in the therapeutic approach of a wide variety of autoimmune conditions. Despite its favorable safety profile, IFX is associated with rare paradoxical adverse events that correspond to the development or exacerbation of an inflammatory condition during IFX therapy. Ocular adverse events represent part of this group of complications known as paradoxical adverse events. In the literature we can find reports of: uveitis, optic neuritis, endophthalmitis and orbital apex syndrome.
We report a case of a paradoxical adverse event manifested as a transitory sudden asymmetric loss of visual acuity.
From our research, this is the first report in the literature of transitory visual loss due to IFX. We intend to publish this case to further amplify the medical knowledge regarding the therapy with this drug and better inform both patients and physicians regarding the potential advserse events of IFX.