Strategies for the prevention of thromboembolism and stress ulcers in at-risk patient populations

Nº de DOI: 10.34896/RSI.2025.59.66.002

AUTHORS

1. Laura Nicole Ortiz Delgado. General Practitioner. Attached to the Nobol Health Center. Graduate of the University of Guayaquil. (Guayaquil-Ecuador). https://orcid.org/0009-0003-9520-0995
2. Janeth Rocio Estrella Padilla. General Practitioner and Master’s Degree in Occupational Health. Attached to the Julio Endara Specialized Hospital. Graduate of the Chimborazo Higher Polytechnic School. (Quito-Ecuador). https://orcid.org/0009-0009-4880-8053
3. Moisés Anibal Moncayo Pilataxi. General Practitioner. Attached to Guaranda Basic Hospital. Graduate of the National University of Chimborazo. (Riobamba-Ecuador). https://orcid.org/0009-0009-7448-3424
4. Daysi Yolanda Vega Cuzco. General Practitioner. Attached to Private Clinics of Ecuador. Graduated from the University of Cuenca. (Cuenca-Ecuador). https://orcid.org/0009-0003-2457-0614
5. César Xavier Narváez López. General Practitioner. Attached to Private Clinics in Ecuador. Graduate of the Catholic University of Santiago de Guayaquil. (Guayaquil-Ecuador). https://orcid.org/0009-0007-4774-5623

ABSTRACT

This paper explores current evidence-based strategies for the prevention of thromboembolism and stress ulcers, emphasizing the importance of personalized, integrative approaches that combine pharmacological, mechanical, and organizational strategies to enhance patient safety and improve clinical outcomes across diverse at-risk populations.

KEY WORDS

Venous thromboembolism, deep vein thrombosis, pulmonary embolism, stress-related mucosal disease, stress ulcer prophylaxis, critically ill patients.

RESUMEN

Este artículo explora las estrategias actuales basadas en evidencia para la prevención del tromboembolismo y las úlceras por estrés, destacando la importancia de enfoques personalizados e integrativos que combinen estrategias farmacológicas, mecánicas y organizacionales para mejorar la seguridad del paciente y optimizar los resultados clínicos en diversas poblaciones de riesgo.

PALABRAS CLAVE

Tromboembolismo venoso, trombosis venosa profunda, embolia pulmonar, enfermedad mucosa relacionada con el estrés, profilaxis de úlceras por estrés, pacientes críticos.

INTRODUCTION

Thromboembolism and stress ulcers represent significant clinical challenges in the management of vulnerable patient populations, particularly those who are critically ill, post-operative, or otherwise predisposed to bleeding and clotting disorders. Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, remains a leading cause of preventable morbidity and mortality in hospitalized patients, necessitating effective prophylactic strategies that balance efficacy with safety. Similarly, stress-related mucosal disease can lead to severe gastrointestinal bleeding, complicating recovery and increasing healthcare burdens. The prevention of these complications involves a multifaceted approach that integrates pharmacological interventions—such as anticoagulants and proton pump inhibitors—with mechanical prophylactic methods like compression devices, tailored to individual patient risk factors. Identifying which patients require prophylaxis and selecting appropriate modalities demand comprehensive risk assessment tools and protocols, often necessitating a multidisciplinary team effort to optimize outcomes. Additionally, understanding the potential risks, including bleeding complications from prophylactic agents, and weighing them against the benefits, remain critical components of clinical decision-making.

OBJECTIVE

Explore current evidence-based strategies for the prevention of thromboembolism and pressure ulcers, emphasizing the importance of personalized and integrative approaches that combine pharmacological, mechanical, and organizational strategies to improve patient safety and clinical outcomes in diverse at-risk populations.

METHODOLOGY

This study was designed as a narrative literature review aiming to synthesise current strategies for the prevention of venous thromboembolism (VTE) and stress ulcers in at-risk patient populations. A structured search was conducted in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar for English-language articles published between January 2000 and November 2025. Search terms and Boolean combinations included “venous thromboembolism prophylaxis”, “deep vein thrombosis prevention”, “pulmonary embolism prevention”, “Caprini score”, “Padua prediction score”, “mechanical thromboprophylaxis”, “intermittent pneumatic compression”, “stress ulcer prophylaxis”, “stress-related mucosal disease”, “proton pump inhibitor”, and “histamine-2 receptor antagonist”.

Randomised controlled trials, cohort and case–control studies, systematic reviews, meta-analyses, international guidelines, and high-quality narrative reviews were considered eligible if they reported on risk assessment, indications, or comparative effectiveness of pharmacologic and/or mechanical VTE prophylaxis (e.g. low-molecular-weight heparin, unfractionated heparin, intermittent pneumatic compression, graduated compression stockings) or on the prevention of stress-related gastrointestinal bleeding in critically ill or otherwise high-risk adult patients (e.g. PPIs, H2RAs, non-pharmacologic measures such as early enteral nutrition and haemodynamic optimisation).

RESULTS

Thromboembolism Prevention Strategies in At-Risk Patients:

What pharmacological interventions are effective for thromboembolism prevention?

Pharmacological interventions for the prevention of thromboembolism have evolved to encompass a spectrum of agents, each with unique efficacy and safety profiles that influence their application across diverse patient populations. Low-molecular-weight heparin (LMWH) remains a foundational therapy, demonstrating superior effectiveness to low-dose unfractionated heparin (UFH) in reducing the incidence of both deep vein thrombosis (DVT) and pulmonary embolism (PE) ¹. Fondaparinux, administered at a dose of 2.5 mg subcutaneously once daily, has shown even greater efficacy than LMWH in orthopedic surgery patients, although its broader use is moderated by concerns regarding increased bleeding risk and cost considerations¹. The recent integration of direct oral anticoagulants (DOACs), such as rivaroxaban and apixaban, has further expanded preventive options, offering at least comparable safety to LMWH and proven effectiveness in the context of hip and lower extremity orthopedic surgery¹. These pharmacological strategies are often complemented by mechanical methods, such as intermittent pneumatic compression (IPC), which, when combined with anticoagulation, result in additive reductions in DVT and PE without significantly increasing bleeding complications². Given the interplay between efficacy, safety, cost, and individual patient risk profiles, the selection and timing of pharmacological prophylaxis must be tailored, emphasizing the need for continued research and policy efforts to optimize access and outcomes in thromboembolism prevention.

How can mechanical prophylactic methods reduce thromboembolism risk?

Mechanical prophylactic methods, such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices, play a critical role in reducing thromboembolism risk, particularly in populations where pharmacologic agents may pose a heightened bleeding risk or are otherwise contraindicated³. These devices function primarily by increasing venous blood velocity and decreasing venous stasis, which are central mechanisms in the prevention of clot formation and the subsequent development of deep vein thrombosis (DVT) ⁴. In surgical and trauma patients, mechanical prophylaxis has demonstrated a reduction in DVT occurrence by over 40% compared to no prophylaxis, and its efficacy is generally comparable between GCS and IPC devices⁴. While mechanical methods alone provide significant protection, evidence underscores that their combination with pharmacologic agents yields additive benefits, further lowering DVT risk by up to 44% and supporting a multimodal approach to prophylaxis⁴. Nevertheless, the optimal effectiveness of mechanical prophylaxis is contingent upon correct device selection, proper application, and diligent management, considering patient-specific factors and the complexity of surgical interventions⁵. Given these interconnections, it is imperative to implement standardized protocols and foster education among healthcare professionals to maximize the preventive potential of mechanical methods, particularly in high-risk surgical and trauma settings where pharmacologic prophylaxis may not be ideal or sufficient.

What patient-specific factors influence the choice of thromboembolism prevention strategies?

Patient-specific factors play a pivotal role in determining the most appropriate thromboembolism prevention strategies, as these strategies must be tailored to individual risk profiles and underlying medical conditions. The patient’s risk level for thrombosis—categorized as low, moderate, or high—serves as a primary determinant, influencing whether simple mechanical measures, pharmacological prophylaxis, or therapeutic anticoagulation is warranted⁶. For example, high-risk patients with conditions such as atrial fibrillation and a history of stroke, or those with prosthetic mitral valves or multiple prosthetic valves, require more aggressive preventive measures, often involving full-dose anticoagulant bridging both before and after surgery⁶. Conversely, low-risk patients, such as those with bileaflet tilting disk aortic valves and fewer than two risk factors, may only need prophylactic doses of anticoagulants, and bridging therapy is generally not recommended unless the surgical procedure significantly increases thrombosis risk⁶. Additional factors such as renal function, presence of hypercoagulable states, mobility status, and comorbidities like heart failure or severe respiratory disease further influence the choice and dosing of anticoagulant agents, with specific adjustments needed for patients with impaired renal function or multiple risk modifiers⁶. These intricate interconnections underscore the necessity for individualized assessment, integrating clinical, procedural, and laboratory data to optimize patient outcomes and minimize risks. Therefore, comprehensive evaluation and dynamic risk stratification are essential, and multidisciplinary collaboration is warranted to ensure that prevention strategies are both safe and effective for each patient’s unique clinical scenario.

Stress Ulcer Prophylaxis in Vulnerable Populations:

What are the indications for initiating stress ulcer prophylaxis in at-risk patients?

Stress ulcer prophylaxis (SUP) is primarily initiated in at-risk patients to mitigate the potentially severe complications of stress-related upper gastrointestinal (GI) bleeding, which can increase morbidity and mortality in critically ill populations⁷. The indications for initiating SUP are most robust among critically ill patients, particularly those who require mechanical ventilation or have a high severity of illness, as exemplified by an APACHE II score of 25 or higher, where the risk of clinically significant GI bleeding is substantially elevated^8,9. Furthermore, patients in intensive care units (ICUs) who are concurrently on dual antiplatelet therapy or combination anticoagulation represent a subgroup with an amplified risk profile and thus stand to benefit from prophylactic interventions, although these patients were notably excluded from some clinical trials such as the REVISE study⁸. The decision to initiate SUP often falls under the purview of the intensive care team, who must consider not only the clinical risk factors but also the potential adverse effects, interactions with other medications, and the practicality of administration routes, ensuring that benefits outweigh possible harms^8,10. While pharmacologic options such as proton pump inhibitors (PPIs) are commonly prescribed due to their efficacy in elevating gastric pH and stabilizing clots, non-pharmacologic strategies like enteral nutrition (EN) should also be integrated where feasible, as EN helps maintain mucosal integrity and reduces ulcer risk, though its utility as sole prophylaxis in hypersecretory states remains uncertain^11,12. Ultimately, a tailored approach—grounded in the patient’s risk factors, comorbidities, and concurrent therapies—is essential for the appropriate initiation of stress ulcer prophylaxis, underscoring the need for ongoing assessment and interdisciplinary collaboration in high-risk hospital settings.

How do pharmacological agents compare in the prevention of stress ulcers?

When comparing pharmacological agents for the prevention of stress ulcers, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) remain the primary options, each with distinct profiles regarding efficacy, safety, and cost¹³. Although H2RAs were the most widely used agents for prophylaxis in the past, recent trends indicate a growing acceptance and use of PPIs, largely due to evidence suggesting at least equivalent if not superior efficacy in preventing stress-related gastrointestinal bleeding¹³. Meta-analyses have demonstrated that acid-suppressive therapy with either class significantly reduces the risk of clinically important bleeding compared to placebo, with one review reporting a 53% reduction in risk (odds ratio 0.47) for patients using acid inhibitors and another showing that the number needed to treat (NNT) with a PPI to prevent one bleeding event is 39^13,14. Direct comparisons between PPIs and H2RAs reveal that PPIs may confer an even greater protective effect, as evidenced by an odds ratio of 0.30 for GI bleeding and a lower incidence of bleeding events (1.3% with PPIs vs. 6.6% with H2RAs) ^13,14. However, despite these differences in bleeding prevention, multiple meta-analyses have consistently shown no significant differences between PPIs and H2RAs in terms of nosocomial pneumonia, ICU stay duration, or mortality rates, supporting the safety of both agents in critically ill populations^13,14. The variability in study design, drug selection, dosing, and administration routes across clinical trials, however, introduces some uncertainty and underscores the need for standardized protocols and higher-quality evidence to guide decision-making^10,13. Given the moderate certainty of current evidence, both PPIs and H2RAs are recommended as first-line prophylactic agents for stress ulcer prevention in critically ill adults with recognized risk factors, though clinicians must balance efficacy, safety, and cost when selecting the most appropriate agent for individual patients¹⁰.

What are the potential risks and benefits associated with stress ulcer prophylaxis?

The use of stress ulcer prophylaxis (SUP) in critically ill patients exemplifies a complex balance between its potential benefits and inherent risks, necessitating a nuanced and individualized approach to clinical decision-making. On one hand, SUP is well-established for reducing the incidence of clinically significant upper gastrointestinal bleeding, particularly in patients with acknowledged risk factors such as coagulopathy or mechanical ventilation, which can lead to substantial morbidity and mortality if left unaddressed^15,16. The integration of SUP into ICU admission protocols and guidelines underscores its recognized efficacy in preventing erosions and stress ulcers that may develop rapidly under critical illness^16,17. However, this benefit must be weighed against a spectrum of adverse outcomes, including an increased risk of nosocomial infections such as pneumonia and Clostridioides difficile, as well as potential longer-term consequences like cardiovascular events and increased mortality rates, especially with inappropriate or prolonged prophylaxis^15,16. The interconnection between gastrointestinal protection and infection risk illustrates the need for vigilant patient selection, limiting SUP to those with clear indications and reviewing its necessity daily, particularly during care transitions, to mitigate avoidable harms^15,16. Overprescription of acid-suppressive drugs not only exposes patients to unnecessary complications but also strains healthcare resources, reinforcing the importance of evidence-based, individualized prophylactic strategies and regular reassessment to optimize outcomes and minimize risk^16,17. Ultimately, focused interventions—such as adherence to guidelines, ongoing staff education, and system-based checks—are crucial to ensure that the benefits of SUP are realized without incurring undue harm across interrelated clinical domains.

DISCUSSION 

The findings of this comprehensive review underscore the critical importance of adopting a multifaceted, individualized approach to the prevention of thromboembolism and stress ulcers in at-risk patient populations. The evidence consistently highlights the superiority of pharmacological prophylaxis, particularly low-molecular-weight heparin, in reducing the incidence of DVT and PE, while the emergence of direct oral anticoagulants provides additional safe and effective options, especially in surgical contexts such as orthopedics. Mechanical prophylactic measures, such as graduated compression stockings and intermittent pneumatic compression devices, serve as valuable adjuncts or alternatives, particularly for patients with contraindications to anticoagulation, emphasizing the need for tailored strategies based on patient-specific factors like renal function, mobility, and comorbidities. In the realm of stress ulcer prophylaxis, the preference for proton pump inhibitors over H2RAs aligns with current evidence favoring their superior efficacy, though the potential risks—such as increased susceptibility to infections—warrant cautious, individualized application and ongoing reassessment. Despite these advances, several limitations remain. The heterogeneity in patient populations, variability in implementation protocols, and differing healthcare settings pose challenges to standardization and generalizability of findings. Additionally, there is a notable need for more high-quality, prospective studies to refine risk stratification tools and to evaluate long-term outcomes associated with various prophylactic regimens. The potential biases inherent in observational data and the risk of overuse or inappropriate application of prophylaxis highlight the importance of multidisciplinary collaboration, continuous monitoring, and the integration of electronic health records for real-time decision support. Future research should focus on optimizing risk assessment algorithms, exploring novel agents or device innovations, and evaluating cost-effectiveness to ensure resource-efficient care. Overall, these strategies—when carefully tailored and dynamically managed—hold promise in significantly reducing morbidity and mortality associated with thromboembolism and stress ulcers, but must be continuously refined through ongoing research and clinical vigilance to address existing gaps and emerging challenges.

CONCLUSIONS

1. Across diverse high-risk populations—including acutely ill medical inpatients, surgical and trauma patients, oncology patients, and critically ill ICU populations—preventive strategies for VTE and stress ulcers are central to reducing morbidity, mortality, and healthcare costs. Contemporary guidelines emphasise systematic risk assessment using validated models such as the Caprini and Padua scores, coupled with individualised decisions on pharmacologic thromboprophylaxis versus mechanical methods. Low-molecular-weight heparin remains a mainstay of pharmacologic prophylaxis in many settings, while intermittent pneumatic compression is recommended when anticoagulation is contraindicated and may provide additional benefit when combined with pharmacologic agents in selected very high-risk patients.
2. For stress ulcer prophylaxis, evidence and recent guidelines support targeted use of PPIs or H2RAs in critically ill adults with well-defined risk factors for stress-related upper gastrointestinal bleeding—such as mechanical ventilation, coagulopathy, major burns, or severe trauma—rather than routine use in all ICU or hospitalised patients. At the same time, concerns about adverse events associated with prolonged acid suppression, including Clostridioides difficile infection and pneumonia, have driven a paradigm shift towards stress-ulcer-prophylaxis stewardship, with recommendations to discontinue prophylaxis as soon as risk factors resolve or prior to ICU discharge.
3. Overall, the literature underscores that optimal prevention of thromboembolism and stress ulcers depends on integrated, protocol-driven care pathways that combine robust risk assessment, evidence-based selection and dosing of pharmacologic agents, appropriate use of mechanical devices, and non-pharmacologic measures such as early mobilisation, haemodynamic optimisation, and early enteral nutrition. Future research priorities include refining and validating risk-prediction tools in specific subgroups, clarifying the incremental benefit of combined mechanical and pharmacologic prophylaxis, and conducting high-quality trials that balance efficacy with safety and stewardship principles, to further reduce preventable VTE events and stress-related gastrointestinal bleeding in at-risk patients.

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