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Review

Management of Antithrombotic Therapy in Acute Gastrointestinal Bleeding

by
Konstantinos Papantoniou
1,
Christos Michailides
2,
Dimitrios Velissaris
2 and
Konstantinos Thomopoulos
1,*
1
Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece
2
Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece
*
Author to whom correspondence should be addressed.
Gastroenterol. Insights 2025, 16(4), 41; https://doi.org/10.3390/gastroent16040041
Submission received: 14 August 2025 / Revised: 17 October 2025 / Accepted: 18 October 2025 / Published: 23 October 2025
(This article belongs to the Special Issue Advances in the Management of Gastrointestinal and Liver Diseases)
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Abstract

The management of antithrombotic agents in patients undergoing urgent gastrointestinal (GI) endoscopy presents a common and complex clinical challenge. The use of anticoagulants and antiplatelet therapies, especially in older patients with significant comorbidities, has increased substantially in recent decades due to the rising prevalence of cardiovascular and thromboembolic diseases. Balancing the risk of ongoing hemorrhage against the potentially life-threatening consequences of thrombosis remains a delicate and critical clinical decision. This review provides a practical, evidence-based approach to the periprocedural management of antithrombotic therapy in urgent endoscopy, particularly in the context of acute GI bleeding. We summarize the indications, pharmacokinetics, and reversal strategies for commonly used agents, including warfarin, direct oral anticoagulants (DOACs), low-molecular-weight heparin, aspirin, and P2Y12 inhibitors. Risk stratification is discussed in detail, considering both the urgency and bleeding risk of endoscopic procedures, as well as the thromboembolic risk associated with temporary drug interruption. Special considerations are given to high-risk patients, such as those with recent coronary stents, mechanical heart valves, or atrial fibrillation with elevated stroke risk scores. Close consultation and collaboration with other specialties, including cardiology and hematology, is often essential to optimize patient outcomes. Recommendations based on real-world clinical experience alongside formal guideline directives aim to support safe and timely endoscopic intervention without compromising systemic thrombotic protection, especially in emergent situations.

1. Introduction

The management of antithrombotic therapy in patients undergoing urgent gastrointestinal (GI) endoscopy is a common problem, but it also represents a significant challenge for clinicians. The use of antiplatelets and anticoagulants has increased significantly in recent decades due to aging of the population and the increased prevalence of cardiovascular and thromboembolic comorbidities [1]. These medications are important for the treatment and prevention of diseases such as ischemic cerebrovascular events, myocardial infarction, and venous thromboembolism. On the other hand, they significantly increase the risk of bleeding episodes in different organs, including the GI tract [2].
Many patients who are under antithrombotic treatment often experience bleeding episodes. Urgent GI endoscopy is required either to achieve hemostasis or to exclude active bleeding, and cessation of these agents is usually required to improve the outcomes of the procedure and minimize the risk of rebleeding [3]. However, inappropriate interruption of these agents can expose patients to acute thrombotic episodes that can even prove life-threatening [4]. Therefore, a careful and evidence-based approach is required in these cases.
In this review, we address the pharmacology of commonly used antiplatelets and anticoagulants, patient risk stratification, and practical reversal protocols in everyday practice. Management recommendations for different clinical scenarios are discussed, with emphasis given to high-risk populations and the importance of the cooperation of different medical specialties to achieve optimal results. Through this comprehensive review, we aim to provide a structured, evidence-based approach to the periprocedural management of antithrombotic agents in patients who are in need of urgent GI endoscopy.

2. Materials and Methods

We conducted a literature search of peer-reviewed articles up to August 2025. Studies were identified through electronic databases including PubMed, Scopus, and Google Scholar, using combinations of the following keywords: gastrointestinal bleeding; endoscopy; antithrombotics; antiplatelets; anticoagulants; risk; thrombotic protection. All types of studies were potentially eligible for inclusion in this review. We excluded expert opinions, studies referring to child population, and animal studies. After deduplication, a two-step screening process was conducted independently by three authors (KP, CM, and DV). Original research articles, clinical trials, reviews, and formal guidelines focusing on the management of antithrombotic therapy in the context of urgent GI endoscopy were included in the study. Articles that were not written in English, were conference abstracts, or lacked relevance to antithrombotic medications and GI bleeding were excluded.

3. Classification and Overview of Antithrombotic Agents

Antithrombotic agents are generally classified into antiplatelet drugs and anticoagulants. Understanding the pharmacokinetics, mechanisms of action, and reversal strategies of these medications is essential to plan their management in clinical practice (Table 1).

3.1. Antiplatelet Agents

Aspirin is an agent that has both anti-inflammatory and antiplatelet actions. By reducing the production of prostaglandins, it limits the severity of inflammatory components such as pain, edema, and fever. However, it is the inhibition of cyclooxygenase-1 (COX-1) and the prevention of thromboxane-A2-mediated platelet aggregation that makes aspirin a potent antithrombotic agent [5]. Although aspirin has a short plasma half-life of 10–20 min, its effect on platelets lasts for approximately 10 days, due to reduced production of COX-1 during that period [6].
P2Y12 inhibitors are a class of antiplatelets that inhibit the P2Y12 platelet receptor and stop adenosine diphosphate (ADP)-mediated platelet activation. Clopidogrel, prasugrel, and ticagrelor are the most widely used agents in this class. The first two are thienopyridines that irreversibly inhibit platelet action, while the latter is a triazolopyrimidine with a reversible action. Prasugrel has a rapid onset of action but also a longer washout period compared to clopidogrel [7]. Ticagrelor also has a fast onset of action and reaches its peak concentration in the bloodstream in less than 3 h, while its reversible action allows a faster recovery of platelet action compared to clopidogrel. However, patients must receive ticagrelor twice daily due to its short duration of action [8].
Rapid reversal of antiplatelet action is often required due to bleeding events or for urgent surgical procedures. Platelet transfusion should be considered in patients with active bleeding and recent intake of these agents, but evidence regarding their effect on patient outcomes remains poor. Moreover, clinicians should be aware of possible complications such as volume overload and hemolytic adverse reactions [9]. Other agents such as desmopressin and tranexamic acid have also shown promising results in reversing antiplatelet action; however, their effects are still not adequately studied and their use in clinical practice is not yet established [10]. Bentracimab, a monoclonal antibody with high affinity for ticagrelor and its metabolites, has shown promise as a reversal agent in clinical trials, but has not yet received approval for clinical use [11].

3.2. Anticoagulants

3.2.1. Vitamin K Antagonists

Vitamin K antagonists (VKAs) inhibit the production of vitamin K-dependent clotting factors (II, VII, IX, X) and cause elevation of the international normalized ratio (INR). Warfarin is the most commonly used agent of this class. Close monitoring of INR values is essential to monitor therapeutic effectiveness and reduce adverse events. Warfarin’s long half-life (20–60 h) and narrow therapeutic window make its management in cases of acute bleeding challenging [12].
Exogenous vitamin K is effective at reversing VKA effects through both the oral and intravenous (IV) routes. Moreover, a lack of thromboembolic risk after its administration makes it a safe option for patients with acute events [13]. Prothrombin complexes (PCCs) and fresh frozen plasma (FFP) can also be used as reversal agents. PCCs contain vitamin K-dependent clotting factors in an inactivated or partially activated form, and can achieve rapid reversal of warfarin effects. Therefore, they are preferred when available in cases of major bleeding, because they have a better efficacy and safety profile compared to FFPs [14].

3.2.2. Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs) are newer oral agents that have a more specific mechanism of action. Apixaban, ribaroxaban, and edoxaban inhibit clotting factor Xa, while dabigatran is a direct thrombin inhibitor. These agents have a rapid onset of action (2–4 h) and shorter half-lives (8–14 h with preserved renal function) compared to warfarin. Routine monitoring of coagulation is not required, although specific anti-Xa and thrombin assays can be useful when available [15]. These capabilities have established DOACs as the preferred type of anticoagulants for the treatment and prevention of many types of thromboembolic events [16]. Their use has increased in recent years, especially in older patients with severe comorbidities [17].
In cases of acute bleeding, PCCs can be used to limit the effects of DOACs and rapidly improve coagulation. Active charcoal can also have an effect if the last oral intake was within 2–3 h [18]. However, the use of targeted reversal agents is considered a more effective option. Idarucizumab is a monoclonal antibody that binds dabigatran with high specificity, while Andexanet A is a modified form of human factor Xa protein, which reverses the effects of apixaban and rivaroxaban. Both these antidotes have been approved for use in patients with acute bleeding episodes who require rapid reversal of anticoagulant treatment, but their high cost and limited availability limit their widespread use in clinical practice [19].

3.2.3. Unfractioned Heparin, Low-Molecular-Weight Heparin, and Fondaparinux

Unfractioned heparin (UFH) is a potent anticoagulant that has been used in clinical practice for decades. It basically acts by activating antithrombin and reducing factor Xa activity and thrombin formation, while it also aids downregulation of the exogenous coagulation pathway by activating the tissue factor pathway inhibitor. Despite the rapid onset of UFH action, its short half-life and the need for close monitoring and IV administration led to the development of newer agents. Low-molecular-weight heparins (LMWHs) such as enoxaparin are compounds produced after depolymerization of UFH. They are available as injectable therapy, have longer half-lives, and a better safety profile, while their increased bioavailability also makes them better suited for clinical practice [20]. Moreover, fondaparinux is a synthetic inhibitor of coagulation factor Xa, which is an injectable agent with 100% bioavailability, long half-life, and few adverse events. Its use in different clinical scenarios has been increasing in recent years [21].
Protamine sulfate is an established antidote of UFH, because it reverses its action entirely. However, it does not completely reverse LMWH effects and does not neutralize fondaparinux. In cases of severe acute bleeding, PCCs and recombinant factor VIIa (rFVIIa) can be used to reverse the effects of fondaparinux; however, data supporting their protective effect are limited [10].

4. Risk Stratification in Cases of Urgent Endoscopy

4.1. Procedure-Related Bleeding Risk

Periprocedural management of antithrombotic agents in patients undergoing GI endoscopy relies on a clear understanding of bleeding risk associated with different procedures. The most recent guidelines from the American Society of Gastroenterology [22], British Society of Gastroenterology (BSG)/European Society of Gastroenterology (ESGE) [23], and joint American College of Gastroenterology (ACG)–Canadian Association of Gastroenterology (CAG) [24] classify endoscopic procedures based on their respective bleeding risk into low- and high-risk categories. Low-risk procedures include diagnostic endoscopy with biopsy and GI stenting, while high-risk procedures such as endoscopic submucosal dissection (ESD) and polypectomy are mostly interventional. Urgent GI endoscopy is usually required for patients with suspected or confirmed GI bleeding. Interventions such as clipping and injection therapy are often performed to achieve endoscopic hemostasis. Therefore, these procedures are classified as high risk [22]. Importantly, all major guidelines emphasize that emergency endoscopy should not be delayed for the reversal or cessation of antithrombotic medications in the majority of cases [22,23,24]. The necessity and type of the intervention must therefore be carefully considered in cases of active GI bleeding.

4.2. Patient-Related Thrombotic Risk

Just as procedural bleeding risk guides intervention strategies, thrombotic risk must be carefully considered when deciding whether to interrupt or reverse the effect of antithrombotic therapy. Although the interruption of antiplatelets and anticoagulants in cases of GI bleeding is usually temporary, it can lead to serious and potentially fatal thromboembolic complications. Therefore, a detailed patient history and assessment of indications for antithrombotic therapy can help in risk stratification and guide clinical choices [25]. Key factors that must be taken into account include a history of atrial fibrillation with a CHA2DS2-VASc score higher than 4, venous thromboembolism within the last 3 months, mechanical heart valves especially in the mitral position, coronary stent placement in the last six months, recent cardiac operations such as left ventricular assist device (LVAD) placement and transcatheter aortic valve (TAVI) implantation, and acute coronary syndrome (ACS). In such cases, temporary cessation of antithrombotics must be approached with caution. Close collaboration with other specialties, such as cardiology and hematology, might be required in cases of acute bleeding and very high thrombotic risk [24,26]. A summary of factors associated with high periprocedural thromboembolic risk in patients receiving treatment with anticoagulants is shown in Table 2.

4.3. Pre-Endoscopy Preparation

Multidisciplinary decision-making is required in urgent cases such as those of acute GI bleeding. Procedural bleeding risk and patient thrombotic risk must be taken into account for effective stratification. Factors such as bleeding severity, hemodynamic stability, and the need for hemostatic intervention must be taken into account during initial patient assessment [27]. Furthermore, the antithrombotic regimen and duration of therapy must be identified. The timing of the last dose must be documented, especially for medications with short half-lives such as DOACs. Renal and hepatic function are critical for drug metabolism and clearance, and should therefore be taken into account [23,24].
Moreover, a detailed discussion with patients and their families about the danger of thromboembolic risks associated with stopping therapy as well as the benefits of temporary interruption to reduce bleeding severity is also recommended [23]. A possible need for patient stabilization, transfusions, use of reversal agents, and procedure delay should be considered. Once the decision for the interruption of antithrombotic therapy is made, detailed documentation and planning of the timeline between cessation, possible bridging therapy, and re-initiation of these agents should take place. Examples of such plans that have already been tested in clinical trials can guide clinicians [28]. Consulting with other specialties is important, especially in high-risk cases. An individualized approach and effective risk stratification can guide clinical decision-making and ensure the safest possible patient care in such emergency situations [24].

5. Management in Urgent GI Bleeding

5.1. Initial Assessment

Patients presenting with GI hemorrhage while on antithrombotic agents should be rapidly assessed for hemodynamic stability and need for resuscitation but also for their bleeding and thromboembolic risk (Figure 1). Initial laboratory testing should include a complete blood count, INR, activated partial thromboplastin time (aPTT), urea, creatinine, and liver function tests. These examinations are important to determine drug clearance and the need for transfusions or use of reversal agents [29]. The type and timing of the last dose of the antithrombotic agent should be noted. Consultation with other specialties, including cardiology and hematology, might be required at this stage, especially for high-risk cases such as recent placement of coronary stents, metal heart valves, and atrial fibrillation (AF) with a high CHA2DS2-VASc score [23].

5.2. Interruption and Reversal of Antithrombotic Agents

Management of antithrombotics in cases of acute GI bleeding depends on the severity of bleeding and the danger of thromboembolic complications. Cessation of these agents is often required in cases of severe bleeding with hemodynamic instability, while the use of reversal agents and bridging therapy must be considered. However, continuation of these medications must be sought in patients with less severe bleeding to reduce the risk of thrombotic complications (Table 3).

5.2.1. Antiplatelets

The use of antiplatelets makes patients more susceptible to GI bleeding; however, their abrupt discontinuation might lead to severe adverse events and increase mortality [30]. Aspirin should only be discontinued in patients with acute GI bleeding when it is used for the primary prevention of cardiovascular disease or in cases where bleeding is life-threatening. Platelet transfusion should be considered in cases of severe hemorrhage with platelet counts less than 50 × 109/L, since they do not appear to offer significant benefit in patients without thrombocytopenia [31]. However, in patients receiving aspirin for secondary prevention, cessation of aspirin should be avoided.
Patients with recent placement of coronary stents usually receive dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor for the secondary prevention of cardiovascular disease. Stopping P2Y12 inhibitors must be avoided in patients with coronary stent placement in the last 30 days regardless of stent type [22]. Temporary discontinuation of these agents might be necessary to enable hemostasis in cases of severe bleeding, but a cardiologist should be consulted to determine the best possible approach and possible differences between agents that should be taken into account [23,32].

5.2.2. Warfarin

Warfarin should be stopped immediately in cases of severe GI hemorrhage with hemodynamic instability. Administration of reversal agents is recommended in such scenarios. Endoscopic hemostasis is generally considered safe when the INR value is less than 2.5, so clinicians should aim for INR reduction when it is prolonged. Both ESGE and ACG-CAG guidelines recommend PCC administration instead of FFPs due to its more rapid onset of action and reduced probability of volume overload. Simultaneous IV administration of vitamin K is recommended by ESGE, but not by ACG-CAG [24,33]. Bridging therapy with UFH or LMWH might be needed, and decisions regarding optimal initiation and dosage should be discussed with a cardiologist [34]. However, in cases of less severe bleeding, use of reversal agents is not needed, and they should be avoided as they might result in an increase in thromboembolic risk [35]. Increased INR values alone on bleeding onset have not been shown to be a predictor of negative outcomes in previous studies [36]. Therefore, when warfarin therapy is needed, such as in patients with metal mitral valves, it can be continued with close monitoring by cardiology if there are no signs of instability or stigmata of recent hemorrhage in endoscopy [29].

5.2.3. DOACs

For patients on DOACs, resuscitation and cessation of the antithrombotic agent is usually sufficient for bleeding control. In cases where hemostatic intervention will probably not be required, DOAC treatment should not be interrupted [29]. Reversal strategies should only be implemented in patients with hemodynamic instability who do not respond to initial measures [23,24]. These strategies vary by agent. Idarucizumab can be administered in patients receiving dabigatran if the last dose was received in the last 24 h [37,38]. Due to its renal clearance, hemodialysis can also be used in cases of massive hemorrhage [22]. For inhibitors of factor Xa, Andexanet alfa can be used where available, since its administration has been associated with reduced mortality in hospitalized patients [39]. Active charcoal can be effective if the last dose was received less than a day before bleeding occurrence. Due to the limited availability and high cost of special antidotes, PCCs and FFPs can be considered as alternative options in severe bleeding cases, although their superiority compared to sole cessation of antithrombotic agents has not been confirmed [40,41].

5.2.4. LMWH and Fondaparinux

In patients receiving therapeutic doses of LMWH or fondaparinux, the timing of the last dose is essential due to small half-lives. If the last dose of LMWH was injected less than 12 h before admission with massive bleeding, protamine sulfate can be used for partial reversal of its effects. However, care must be taken to avoid protamine overdosing, because secondary coagulopathies and platelet dysfunction might occur. Further LMWH doses must be withheld until bleeding cessation is achieved [10]. rFVIIa administration should be considered in patients receiving fondaparinux where available, because protamine sulfate does not significantly limit its effect [22].

5.3. Timing of Resumption and Bridging Therapies

5.3.1. Antiplatelet Resumption

Resumption of antithrombotic therapy should generally occur after endoscopic hemostasis has been achieved and the risk of rebleeding is considered low. An individualized re-assessment of the bleeding and thrombotic risk of patients should take place after cessation of bleeding to determine the best timing to restart treatment. In patients where a decision was made to stop aspirin due to severe bleeding, therapy should be restarted early, preferably within 24 h, due to its critical role in the secondary prevention of cardiovascular disease and relatively low bleeding risk [42]. For P2Y12 inhibitors, therapy interruption can be tolerated for a few days, but therapy should be resumed in 3–5 days after bleeding control, especially in patients with coronary stent placement in the last 6 months due to a high risk of stent thrombosis [23,24,43].

5.3.2. Anticoagulants and Bridging Therapies

Anticoagulants should be restarted in patients with clear indications for long-term anticoagulation, as several studies indicate that resuming treatment can reduce thromboembolic events and mortality despite increased rebleeding risk [44]. In patients with low thrombotic risk, restarting these agents can be delayed until a week after hemostasis is achieved. However, in patients with high risk factors, earlier treatment re-initiation, preferably within 48 to 72 h, should be considered to reduce the possibility of adverse events [45]. Bridging therapy, typically with therapeutic doses of LMWH, should be considered for high-risk patients in whom warfarin treatment must be interrupted for a longer period. Patients with mechanical mitral valves or recent thromboembolic events may be appropriate for this kind of treatment, but decisions should be individualized and guided by cardiology or hematology consultation [46]. Routine use of bridging therapy is not recommended, because its use has been associated with increased bleeding recurrence [47].
Data regarding the best timing for DOAC restart are currently lacking. These agents should be restarted as soon as possible, preferably within 3 days in cases of high thrombotic risk [23]. Bridging therapy is not recommended for patients receiving DOACs, because the effects of these agents resume quickly when they are restarted. Moreover, in patients who experience GI bleeding, the choice and dose of DOAC should be reviewed in patients who experience acute GI bleeding, because differences in bleeding episodes between patients receiving different DOACs have been observed. [48]. More specifically, GI bleeding risk appears to be reduced in patients receiving apixaban and low-dose dabigatran compared to warfarin and other DOACs [49,50].

6. Special Populations

Management of antithrombotic agents in the setting of urgent GI endoscopy becomes more complicated in patients with severe comorbidities that increase bleeding and thrombotic risk. In these special groups, individualized approaches and multidisciplinary action are essential.

6.1. High-Risk Cardiac Patients

Patients with acute coronary syndrome and stent placement within 4–6 weeks are considered to be at increased risk of thrombosis. These patients require simultaneous use of several antithrombotic agents, usually oral aspirin and a P2Y12 inhibitor along with parenteral anticoagulation with UFH, LMWH, or fondaparinux [51]. GI bleeding often occurs in patients during hospitalization for acute coronary syndromes (ACSs). These episodes are associated with increased mortality and prolonged hospital stay. Therefore, careful consideration must be given to antiplatelet interruption and the timing of endoscopic intervention. As mentioned above, aspirin is usually continued and P2Y12 inhibitors are stopped to enable hemostasis after cardiology consultation. Successful endoscopic intervention appears to improve outcomes in these patients [52]. However, the continuation of antithrombotic agents should be considered even in cases of severe bleeding, because of the high risk of complications. Successful endoscopic intervention appears to improve outcomes even while continuing these medications, but close monitoring in consultation with cardiology is required to balance bleeding and thrombotic risks. Further studies are required to advance our knowledge regarding optimal management and lead to the development of widely applicable predictive tools for risk stratification in these cases [53].
LVAD and TAVI placement are also associated with increased rates of GI bleeding that lead to frequent hospitalizations, increased health care costs, and often death [54]. The concurrent use of antiplatelets and anticoagulants, severe comorbidities, and increased occurrence of events such as arteriovenous malformations make these patients more susceptible to GI bleeding. In cases of severe bleeding, continuation or more rapid resumption of these agents must be considered in consultation with cardiology to reduce the risk of thrombotic events. Cardiologists and mechanical circular support teams must be consulted in such cases. Antithrombotic medications may be temporarily stopped in patients with severe bleeding, but rapid resumption is required, often with the use of bridging treatment [55].

6.2. Cancer

Patients with malignancies often receive anticoagulation due to their increased susceptibility to thromboembolic events. However, tumor-related GI bleeding is common. LMWH remains the preferred agent in this group due to its short half-life; however, some studies show treatment with DOACs might be associated with reduced GI bleeding events and mortality [56]. In cases of urgent GI endoscopy, anticoagulation treatment should be resumed as soon as possible based on overall patient prognosis, bleeding source, and thrombotic risk [57].

6.3. Liver Cirrhosis

Cirrhosis is characterized by a severe disruption of coagulation pathways that are associated with both thromboembolic and bleeding events. Major vessel thrombosis occurs often in these patients. The presence of portal hypertension and the development of varices along with thrombocytopenia due to splenic enlargement and reduced thrombopoietin levels make these patients more susceptible to bleeding. Decompensation of liver disease and variceal hemorrhage are associated with increased mortality [58]. Therefore, careful selection of antithrombotic treatment is needed. VKAs and LMWH are the preferred agents in these patients, and early initiation of anticoagulation after variceal hemorrhage has been associated with improved liver function and survival in patients with portal thrombosis [59]. Recent studies suggest that the use of DOACs could be associated with better outcomes in patients with compensated liver cirrhosis [60]. However, data regarding the use of DOACs after variceal hemorrhage are lacking, and the use of these agents is generally avoided in patients with Child–Pugh C cirrhosis. Patients must be closely monitored after the re-initiation of anticoagulation treatment, and consulting a hepatologist is advised.

6.4. Chronic Kidney Disease

Patients with chronic kidney disease (CKD) are at increased risk of thromboembolic events compared to the general population, while factors such as platelet dysfunction and thrombocytopenia due to dialysis also make them more susceptible to bleeding episodes [61]. Moreover, many anticoagulants, including DOACs and LMWH, are excreted through the kidney. In patients with chronic renal disease, drug accumulation can lead to increased bleeding risk. GI bleeding is common in these cases, and factors such as renal replacement therapy are associated with increased mortality [62]. Other patient characteristics such as body mass index (BMI) and the presence of severe comorbidities might also impact outcomes after GI bleeding in these cases [63]. Further studies are required to develop specific strategies and provide optimal care in patients with CKD who undergo urgent endoscopy.

7. Future Perspectives and Study Limitations

Although our understanding regarding the optimal management of antithrombotics in cases of urgent GI endoscopy has improved through the increasing number of studies and the development of guidelines focusing on these clinical scenarios, questions still remain. The quality of evidence supporting many recommendations remains low, because much is based on expert opinions and retrospective studies instead of randomized controlled trials. Furthermore, there is a lack of agreement and variation in recommendations from different societies about a variety of subjects, including the use of reversal agents and timing of antithrombotic resumption. Such differences can cause confusion among clinicians and a lack of a structured approach in clinical practice. Future research should aim to address the gaps in evidence, particularly those regarding DOACs, because their use is becoming more frequent even in high-risk groups such as patients with cirrhosis and CKD. Real-world data from multicenter studies can guide changes in current practices. Finally, the development of validated prognostic tools that will incorporate both bleeding and thrombotic risk can assist the development of individualized approaches and improve patient care.
This review has certain limitations. Although we included a wide range of relevant articles, the methodology used was not systematic in nature. We did not keep a detailed log of all studies reviewed, and we did not document specific reasons for excluding articles during the literature search. Additionally, the lack of a formal quality assessment of included studies limits the strength of our conclusions. Future systematic reviews with consistent methodology and well-defined inclusion criteria can provide more definitive, evidence-based guidance on clinical scenarios where patients receiving antithrombotic therapy are required to undergo urgent GI endoscopy. Nevertheless, we believe our review provides valuable information for clinicians. By focusing on recent guidelines and relevant clinical studies, we shed light on critical aspects of antithrombotic treatment before and after urgent GI endoscopy. The description of pharmacology, risk stratification, and optimal management of different antithrombotic medications in the emergency setting can aid the development of a structured approach of these patients in everyday practice, while it also enables the identification of questions that should be addressed in future studies.

8. Conclusions

The periprocedural management of antithrombotic therapy in cases of urgent GI endoscopy remains a challenge for clinicians. A balance between hemorrhagic and thromboembolic risks is essential. As the use of antiplatelets and anticoagulants continues to rise, clinician awareness and evidence-based approaches are essential to optimize patient outcomes. Knowledge of agent pharmacology, detailed documentation of patient history, risk stratification, and cooperation with other specialties such as cardiology and hematology can aid the identification and better management of high-risk cases and reduce adverse events. Current guidelines provide useful guidance and recommendations, but a personalized approach based on individual patient characteristics is currently lacking. Endoscopy must not be delayed in cases of acute bleeding; however, the interruption and timely re-initiation of antithrombotic treatment can significantly improve patient safety without increasing thromboembolic risk. Future trials and real-world data can aid the formation of better-quality evidence and help in the development of individualized approaches to endoscopy in this high-risk population.

Author Contributions

Conceptualization, K.P. and K.T.; methodology, K.P., C.M. and D.V.; software, K.P. and C.M.; validation, K.P. and C.M.; formal analysis, K.P., C.M. and D.V.; investigation, K.P. and C.M.; data curation, K.P. and C.M.; writing—original draft preparation, K.P. and C.M.; writing—review and editing, D.V.; visualization, K.T.; supervision, K.T.; project administration, K.T.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article..

Conflicts of Interest

The authors declare no conflicts of interest.

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Gastroent 16 00041 g001
Figure 1. Proposed management algorithm for acute bleeding in patients receiving antithrombotics.
Figure 1. Proposed management algorithm for acute bleeding in patients receiving antithrombotics.
Gastroent 16 00041 g001
Table 1. Characteristics of antithrombotic agents.
Table 1. Characteristics of antithrombotic agents.
ClassAgentMechanism of
Action		Half-Life with Normal GFR
AntiplateletsAspirinCOX-1 inhibition20 min
ClopidogrelP2Y12 inhibition6–8 h
PrasugrelP2Y12 inhibition2–15 h
TicagrelorP2Y12 inhibition7 h
VKAsWarfarinVitamin K-dependent clotting factors inhibition20–60 h
DOACsDabigatranThrombin inhibition12–17 h
RivaroxabanFactor Xa inhibition5 h
ApixabanFactor Xa inhibition10–14 h
EdoxabanFactor Xa inhibition7 h
HeparinsUFHAntithrombin activation, factor Xa inhibition1–1.5 h
Enoxaparin (LMWH)Antithrombin activation, factor Xa inhibition4.5 h
FondaparinuxFactor Xa inhibition17–21 h
GFR, glomelural filtration rate; COX-1, cyclooxygenase 1; VKAs, vitamin K antagonists; DOACs, direct oral anticoagulants; UFH, unfractioned heparin, LMWH, low-molecular-weight heparin.
Table 2. Patients receiving anticoagulants with high periendoscopic thromboembolic risk.
Table 2. Patients receiving anticoagulants with high periendoscopic thromboembolic risk.
Main Indications for AnticoagulationAssociated High-Risk Factors
Mechanical heart valveProsthetic mitral valve or caged-ball or
tilting-disc aortic valve prosthesis
Stroke or transient ischemic attack in the last 3 months
Atrial fibrillation
Atrial fibrillationStroke or transient ischemic attack in the last 3 months
CHA2DS2VaSc score: >4
Rheumatic valvular heart disease
Prosthetic heart valve
Mitral stenosis
Venous thromboembolismVenous thromboembolism in the last three months
Severe thrombophilia
Table 3. Suggested management of antithrombotics in cases of urgent GI endoscopy.
Table 3. Suggested management of antithrombotics in cases of urgent GI endoscopy.
AgentMain Reversal OptionsTemporary Interruption in High-Risk BleedingTiming of Restart After Bleeding Cessation
AspirinPlatelet transfusionRarePreferably within 24 h
P2Y12 inhibitorsPlatelet transfusionYes3–5 days
WarfarinVitamin K, PCCs, FFPsYesIndividualized, preferably within 3 days in patients with high thrombotic risk
DabigatranIdarucizumab, PCCsYesIndividualized, preferably within 3 days in patients with high thrombotic risk
Apixaban, RivaroxabanAndexanet alfa, PCCsYesIndividualized, preferably within 3 days in patients with high thrombotic risk
LMWHProtamine sulfate (partial)YesIndividualized
FondaparinuxPCCs, rFVIIaYesIndividualized
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Papantoniou, K.; Michailides, C.; Velissaris, D.; Thomopoulos, K. Management of Antithrombotic Therapy in Acute Gastrointestinal Bleeding. Gastroenterol. Insights 2025, 16, 41. https://doi.org/10.3390/gastroent16040041

AMA Style

Papantoniou K, Michailides C, Velissaris D, Thomopoulos K. Management of Antithrombotic Therapy in Acute Gastrointestinal Bleeding. Gastroenterology Insights. 2025; 16(4):41. https://doi.org/10.3390/gastroent16040041

Chicago/Turabian Style

Papantoniou, Konstantinos, Christos Michailides, Dimitrios Velissaris, and Konstantinos Thomopoulos. 2025. "Management of Antithrombotic Therapy in Acute Gastrointestinal Bleeding" Gastroenterology Insights 16, no. 4: 41. https://doi.org/10.3390/gastroent16040041

APA Style

Papantoniou, K., Michailides, C., Velissaris, D., & Thomopoulos, K. (2025). Management of Antithrombotic Therapy in Acute Gastrointestinal Bleeding. Gastroenterology Insights, 16(4), 41. https://doi.org/10.3390/gastroent16040041

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