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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
1
Review Article
Antiplatelet therapy after gastrointestinal bleeding, decision-making in
a complex situation in clinical practice
Terapia antiagregante posterior a hemorragia gastrointestinal, toma de
decisiones en una situación compleja de la práctica clínica
Thérapie antiplaquettaire après hémorragie gastro-intestinale, prise de
décision en situation complexe en pratique clinique
Authors: Luis Andrés Dulcey-Sarmiento,1 Juan Sebastián Theran-Leon,2 Maria Alejandra Cala3
1Medical Doctor Specialty in Internal Medicine. Universidad Autónoma de Bucaramanga, Colombia. Correo electrónico:
luismedintcol@gmail.com Orcid Code: https://orcid.org/0000-0001-9306-0413
2Medical Doctor. Family Medicine Resident. Universidad de Santander, Colombia. Correo electrónico:
jtheran554@unab.edu.co Orcid Code: https://orcid.org/0000-0002-4742-0403
3Undergraduate Intern in Medicine. Universidad Autónoma de Bucaramanga, Colombia. Correo electrónico:
mcala141@unab.edu.co Orcid Code: https://orcid.org/0000-0002-2406-6763
https://editorial.udv.edu.gt/index.php/RCMV
* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
2
ABSTRACT
Introduction: gastrointestinal bleeding emerges as one of the most frequent complications
associated with the use of antiplatelet therapy due to cardiovascular diseases. Objective: to
analyze the growing evidence related to the management of antiplatelet therapy after
gastrointestinal bleeding. Methods: The methodology used for the elaboration of this article was
through the consultation of databases, such as: Google Scholar, PubMed, Cochrane and SciELO.
The search was performed using the following words: antiplatelet, hemorrhage, gastrointestinal,
basic research, clinical, animal models of human diseases, basic scientific research, clinical
studies, mechanisms, pathophysiology, and translational studies. The search inclusion criteria
were: information from the last 5 years, in Spanish or English, and whether they were review
articles, meta-analyses, or systematic reviews. After that, 300 articles were obtained, of which
those that did not contain valuable and updated information that responded to the objective of
the present review were excluded. After the exclusion, 35 articles that met the proposed
requirements were obtained. Conclusions: gastrointestinal bleeding is a complication of
antiplatelet therapy that can increase the risk of death, so the risk must be estimated in each of
the patients and the continuation must be managed both acutely and after the bleeding, in order
to avoid recurrences and to avoid thrombotic risk.
Keywords: antiplatelet therapy, gastrointestinal bleeding, risk, decision making
RESUMEN
Introducción: la hemorragia gastrointestinal surge como una de las complicaciones más
frecuentes asociadas al uso de la terapia antiagregante debido a enfermedades cardiovasculares.
Objetivo: analizar la creciente evidencia relacionada con el manejo de la terapia antiagregante,
posterior a hemorragia gastrointestinal. Métodos: La metodología utilizada para la elaboración
de este artículo fue por medio de la consulta de bases de datos, tales como lo son: Google
Scholar, PubMed, Cochrane y SciELO. La búsqueda se realizó utilizándose las siguientes palabras:
antiagregante, hemorragia, gastrointestinal, investigación básica, clínica, modelos animales de
enfermedades humanas, investigación científica básica, estudios clínicos, mecanismos,
fisiopatología, estudios traslacionales. Los criterios de inclusión de la búsqueda fueron:
información de los últimos 5 años, en idioma español o inglés y que fueran artículos de revisión,
metaanálisis o revisiones sistemáticas. Posterior a eso, se obtuvieron 300 artículos, de los cuales
se excluyeron aquellos que no contenían información valiosa y actualizada que respondiera al
objetivo de la presente revisión. Posterior a la exclusión, se obtuvieron 35 artículos que cumplen
con los requisitos propuestos. Conclusiones: la hemorragia gastrointestinal es una complicación
de la terapia antiagregante que puede aumentar el riesgo de muerte por lo que debe estimarse
el riesgo en cada uno de los pacientes y se debe manejar la continuación tanto de manera aguda
como posterior al sangrado, con el fin de evitar recurrencias y evitar el riesgo trombótico.
Palabras clave: terapia antiagregante, hemorragia gastrointestinal, riesgo, toma de decisiones
RÉSUMÉ
Introduction: les saignements gastro-intestinaux apparaissent comme l'une des complications
les plus fréquentes associées à l'utilisation d'un traitement antiplaquettaire en raison de maladies
cardiovasculaires. Objectif: analyser les preuves croissantes liées à la prise en charge du
traitement antiplaquettaire après une hémorragie gastro-intestinale. Méthodes: La méthodologie
utilisée pour l'élaboration de cet article est passée par la consultation de bases de données, telles
que: Google Scholar, PubMed, Cochrane et SciELO. La recherche a été effectuée en utilisant les
https://editorial.udv.edu.gt/index.php/RCMV
* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
3
mots suivants: antiplaquettaire, hémorragie, gastro-intestinal, recherche fondamentale, clinique,
modèles animaux de maladies humaines, recherche scientifique fondamentale, études cliniques,
mécanismes, physiopathologie, études translationnelles. Les critères d'inclusion de la recherche
étaient: les informations des 5 dernières années, en espagnol ou en anglais, et s'il s'agissait
d'articles de revue, de méta-analyses ou de revues systématique. Après cela, 300 articles ont été
obtenus, dont ceux qui ne contenaient pas d'informations précieuses et actualisées répondant à
l'objectif de la présente revue ont été exclus. Après l'exclusion, 35 articles répondant aux
exigences proposées ont été obtenus. Conclusions: l'hémorragie gastro-intestinale est une
complication du traitement antiplaquettaire qui peut augmenter le risque de décès, le risque doit
donc être estimé chez chacun des patients et la poursuite doit être gérée à la fois en aigu et après
l'hémorragie, afin d'éviter les récidives et d'éviter le risque thrombotique.
Mots-clés: traitement antiplaquettaire, saignement gastro-intestinal, risque, prise de decisión.
INTRODUCTION
Antiplatelet therapy is currently one of the most important pharmacological measures, both in
primary and secondary prevention of cardiovascular diseases. The benefits in cardiovascular
outcomes are indisputable. However, the use of these antiplatelet agents increases the risk of
bleeding, especially those of gastrointestinal origin. (1)
Randomized clinical trials have shown that the highest risk of bleeding (44.6%) is given in
inhibitors of GP IIa/IIIb compared with a low dose of aspirin (3.6%). On the other hand, studies
have shown that after antiplatelet therapy, the incidence of gastrointestinal bleeding is
approximately 11.9% and this is associated with an increased risk of mortality due to
cardiovascular events. (2)
Despite being a frequent complication, there is no specific evidence to guide us regarding the
mode of intervention for this clinical condition. Hence, the purpose of this study is to analyze the
growing evidence related to antiplatelet management after a gastrointestinal bleeding event.
MÉTODO
The methodology used for the elaboration of this article was through the consultation of
databases, such as: Google Scholar, PubMed, Cochrane and SciELO. The search was carried out
using the following words: "antiplatelet, hemorrhage, gastrointestinal, basic, clinical research,
animal models of human diseases, basic scientific research, clinical studies, mechanisms,
pathophysiology, translational studies". The search inclusion criteria were: information from the
last 5 years, in Spanish or English, and that they were review articles, meta-analyses, or
systematic reviews.
After that, 300 articles were obtained, of which those that did not contain valuable and updated
information that responded to the objective of the present review. After the exclusion, 35 articles
that met the requirements were obtained.
ANALYSIS AND INTEGRATION OF INFORMATION
Assessment of the risk of bleeding associated with antiplatelet therapy
In order to avoid or reduce the probability of gastrointestinal bleeding in patients with antiplatelet
therapy, it is essential to apply tools that allow predicting this outcome. This with the aim of
guiding decision-making regarding the type of therapy, and its duration after a coronary event.
Among the scores currently used, the following stand out.
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
4
CRUSADE (Can Rapid risk stratification of Unstable angina patients suppress ADverse
outcomes with Early implementation of the ACC/AHA Guidelines)
Most useful score in the prediction of intrahospital hemorrhage in the context of patients with
non-ST segment elevation acute myocardial infarction (AMI). But also validated for supra ST
cases. For its application, it takes into account variables such as heart rate, systolic blood
pressure, hematocrit, creatinine clearance, sex, signs of heart failure, and history of arterial
disease or diabetes mellitus. In this way, the score ranges from 1-100 points, considered as very
low risk, scores </= 20; low-risk scores of 21-30; moderate risk scores of 31-40; high-risk scores
of 41-50; and very high-risk scores >50. (3)
PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent
Implantation and Subsequent Dual Antiplatelet Therapy)
Predicts out-of-hospital bleeding risk for patients treated with dual antiplatelet therapy (ASA +
P2Y12 inhibitor) after percutaneous coronary intervention (PCI) with stent implantation. It
includes 5 variables: age, hemoglobin levels, leukocytes, creatinine clearance, and history of
previous bleeding. Based on the result of this, it is possible to compare the ischemic and
hemorrhagic risk of the patients, to determine the duration of the double therapy antiplatelet.
(4,5)
Thus, patients with a PRECISE-DAPT score >25 do not benefit from prolonging antiplatelet
therapy, since this is associated with the same ischemic risk, but with a greater risk of bleeding.
However, it should be borne in mind that patients with a PRECISE-DAPT score <25 and being
managed with short-term dual antiplatelet therapy (6 months) are associated with a higher
ischemic risk and a similar risk of bleeding compared with long-term therapy (12 months). (4)
Endoscopic bleeding risk assessment
Blatchford scale should be applied in order to determine the risk of complications in order to
decide the place of management and consider or not endoscopy. Therefore, if there is a score >2,
the patient should be treated in an intrahospital setting; and if it is >6, it presents a high risk of
complications, which requires endoscopy urgently. (6)
Once the endoscopy has been performed, based on the observed findings, the Forrest scale can
be applied. According to this, the groups at high risk of recurrence are group Ia: jet hemorrhage
with a 90% risk of recurrence; group Ib: drooling hemorrhage with a 10-33% risk of recurrence;
group IIa: visible vessel with a 50% risk of recurrence; group IIb: adhered clot with a 25-30%
risk of recurrence. On the other hand, the groups with a low risk of recurrence are group IIc:
hematin points with a risk of 7-10% of recurrence; group III: lesion with a clean base, 3-5% risk
of recurrence. (7)
However, depending on the risk groups, management can be determined. Thus, low-risk groups
(IIc and III) do not benefit from endoscopic treatment, since it does not impact rebleeding.
Conversely, evidence of recent bleeding seen in groups IA, IB, IIA, and IIB is associated with an
increased 30-day risk of rebleeding. For this reason, they should receive endoscopic therapy
(adrenaline + other mechanical, thermal, or sclerosing therapies) to achieve hemostasis and
prevent rebleeding. It has been shown that these patients must be hospitalized for at least 72
hours, already a great part of the recurrences HE presents in this limit of time. (7,8)
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
5
How to manage patients with gastrointestinal bleeding and antiplatelet therapy?
The type of antiplatelet therapy that the patient receives must be taken into account, since the
risk of bleeding depends on it. As previously mentioned, therapy with GP IIa/IIIb inhibitors is
associated to a greater extent with bleeding compared with aspirin. Likewise, multiple clinical
trials have shown that dual antiplatelet drugs are associated with a bleeding risk of 0.6-4.8%,
compared to 0.6-3.8% with aspirin monotherapy. For this reason, it is necessary to individualize
the type of therapy that the patient receives and the management that he will have both during
active bleeding and after it. (9)
Within the control of bleeding in patients receiving antiplatelet therapy, platelet transfusion has
been considered. However, a study was carried out on patients with gastrointestinal bleeding who
were managed with antiplatelet drugs and without thrombocytopenia-associated platelet
transfusion with a higher risk of mortality without modifying the risk of bleeding. (10)
Management of Gastrointestinal (GI) Bleeding in Patients Using Aspirin (ASA)
Monotherapy
In patients being managed with low doses of ASA, it has been seen that its interruption was
largely associated with higher mortality rates. On the other hand, the continuation of this is
associated with a greater recurrence of bleeding (50%). For this reason, the European Society of
Gastrointestinal Endoscopy recommended that therapy should be continued after endoscopic
evaluation of the source of bleeding, as long as it has a Forrest classification with a low risk of
recurrence (IIc or III). On the contrary, Forrest's classification indicates a high risk of recurrence
(Ia, Ib, IIa, IIb) it is recommended to stop aspirin for 3-7 days, and after that continue it, as long
as the patient is hemodynamically stable. (11)
Management of gastrointestinal bleeding in patients with double antiplatelet therapy
Decisions made regarding the management of bleeding depend on its severity. Thus, it is
recommended to continue dual therapy if Forrest is found to be a low risk on endoscopy. However,
the duration of this should be considered and in cases where the patient receives
ticagrelor/Prasugrel, switch to clopidogrel. (12-14)
When there is moderate bleeding defined as loss of >2 mmol/L of hemoglobin, it is recommended
to discontinue dual antiplatelet therapy and switch to monotherapy; in the context of upper
gastrointestinal bleeding, it should be aspirin or ticagrelor/ prasugrel since it has been seen that
clopidogrel administered together with proton pump inhibitors (PPIs) causes multiple interactions
due to the fact that they share the same metabolism through the cytochrome pathway CYP2C19.
(15-29)
In cases of severe bleeding defined as loss >3 mmol/L of hemoglobin, the same considerations
apply as in moderate bleeding, but with the condition that all antiplatelet therapy be discontinued
if the bleeding persists. In both cases, it is recommended to re-establish dual antiplatelet therapy
at least 3-5 days after the bleeding resolves. (17-21)
The importance of good bleeding control is that the 30-day mortality rate is 20.5% in patients
with bleeding, compared with 2.4% in patients without bleeding. For this reason, the thrombotic
and bleeding risk must be evaluated in patients in whom antiplatelet therapy should be indicated,
in order to make decisions supported by scientific evidence regarding the type of therapy and its
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
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Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
6
duration. In order to achieve the purpose of thrombotic control and decrease cardiovascular
outcomes but without increasing the risk of bleeding. (23-26)
The role of proton pump inhibitors (PPIs)
The use of PPIs in conjunction with antiplatelet therapy is not yet defined. But what is clear is
that these are the number 1 prevention of gastrointestinal bleeding. The reason why PPIs are not
widely used is because they are metabolized by the same pathway as clopidogrel, CYP2C19, so it
is believed that their concomitant use may decrease the antithrombotic action of clopidogrel. (14-
34)
However, in studies such as Clopidogrel with or without omeprazole in coronary artery disease
(COGENT), omeprazole was administered to patients at high cardiovascular risk and this was not
significantly associated with an increase in cardiovascular outcomes but rather decreased the risk
of gastrointestinal bleeding. However, what must be taken into account is the specific population
that would benefit from the administration of PPIs. For this reason, it is essential that bleeding
risk scores be applied when starting antiplatelet therapy. Patients who are at high risk of bleeding
benefit from the administration of PPIs. (14-34)
Another recommendation to take into account is the use of PPIs such as rabeprazole or
pantoprazole that have no effect on CYP2C19 in patients receiving clopidogrel, so as not to run
the risk of diminishing its antithrombotic action. For these reasons, therapy with proton pump
inhibitors would be recommended in patients on antiplatelet therapy who develop gastrointestinal
bleeding and who are at high risk of recurrence; this should be extended for the same time as
antiplatelet therapy. (16-20)
In conclusion, the great importance of antiplatelet therapy in the primary and secondary
prevention of cardiovascular events is undeniable. Even to the point of becoming the fundamental
pillar of management. However, despite their great clinical utility in reducing ischemic events,
they greatly increase the risk of bleeding. To avoid this complication, it is necessary to apply tools
to assess the risk of each of the patients who are managed with antiplatelet therapy, in order to
make the best decisions regarding the appropriate choice of therapy, maintaining a certain
balance between ischemic risk and hemorrhagic.
On the other hand, individualizing the patient regarding the antiplatelet therapy that he should
receive and the duration that it should last, is crucial to reduce the bleeding risk; Considering the
use of proton pump inhibitors in patients with a high risk of bleeding reduces this complication,
which increases mortality in patients.
Even so, there is not enough evidence, and the available evidence has not yet been able to specify
the management of antiplatelet therapy after gastrointestinal bleeding, so research must continue
and clinical practice guidelines should be developed at the national level; so that you can have a
protocol for each of the specific cases of patients, their comorbidities and risk factors for suffering
this complication, which can increase the mortality rate associated with cardiovascular events,
which by itself is already one of the leading causes of death worldwide.
Abbreviations: PPI: proton pump inhibitors, ASA: acetylsalicylic acid, AMI: acute
myocardial infarction.
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
Rev. CMV. 2023;1(1-3):e018 e-ISSN: 2958-9533 - ISSN impresa: 2960-2696
7
THANKS
The authors of this article thank the Revista de Ciencias Médicas y de la Vida for the
opportunity to publicize this review.
FINANCING
No funding was received for the development of this study.
CONFLICTS OF INTEREST
No conflicts of interest are declared.
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
Received: May 2, 2023. Accepted: August 14, 2023.
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* Corresponding author: Luis Andrés Dulcey-Sarmiento. Email: luismedintcol@gmail.com
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Title of the article: Antiplatelet therapy after gastrointestinal bleeding,
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Date: 4/24/2023
Luis Andrés Dulcey
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0002-4742-0403
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6763.
