History Of Gastrointestinal Bleeding Research Articles

Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.

: Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin. : Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users. : The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049). : In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.

Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study

ObjectiveEvidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with ‘underlying’ chronic kidney disease (CKD) remains scarce, although PPI use is generally associated...

Clinical significance of gastrointestinal bleeding history in patients who undergo left atrial appendage closure.

Anticoagulant users with nonvalvular atrial fibrillation (NVAF) sometimes suffer from gastrointestinal bleeding (GIB) and have difficulty continuing the medication. Left atrial appendage closure (LAAC) has been developed for such situations. We aimed to clarify the clinical significance of a history of GIB in comparison to other factors in patients who had undergone LAAC. From October 2019 to September 2023, patients with NVAF who underwent LAAC at our hospital were enrolled. We investigated the percentage of patients with a history of GIB who underwent LAAC and compared the incidence of post-LAAC bleeding in these patients compared to those with other factors. A total of 45 patients were included. There were 19 patients (42%) with a history of GIB who underwent LAAC. In a Kaplan-Meier analysis, the cumulative incidence of bleeding complications after LAAC was significantly higher in patients with a history of GIB in comparison to patients with other factors. There were eight cases of post-LAAC bleeding in total, and seven cases had GIB. We need to recognize that GIB is a significant complication in patients who undergo LAAC. The management of GIB by gastroenterologists is essential to the success of LAAC.

Construction of a prediction model for predicting rebleeding in patients with obscure gastrointestinal bleeding after capsule endoscopy

Objective: To explore the risk factors of rebleeding in patients with obscure gastrointestinal bleeding (OGIB) after capsule endoscopy (CE), and construct a model to predict rebleeding. Methods: The data of patients with OGIB who underwent CE in Zhongda Hospital Affiliated to Southeast University from July 2018 to September 2021 were retrospectively analyzed. Follow-up data were obtained via electronic medical records or telephone interviews. Univariate and multivariate Cox regression models were performed to figure out the risk factors of rebleeding in OGIB patients. Then the optimal prediction model was determined and presented as a nomogram. The model was evaluated by C statistic, calibration curve and decision curve analysis. Results: One hundred and thirty patients with OGIB were included, including 64 females and 66 males, aged (55.8±17.2) years (18-87 years), and 39 (30.0%) cases developed rebleeding during follow-up. Univariate and multivariate Cox regression model analysis showed the duration of more than 2 weeks OGIB (HR=3.70, 95%CI: 1.85-7.42, P<0.001), a history of previous gastrointestinal bleeding (HR=5.25, 95%CI: 2.00-13.81, P<0.001), positive CE findings (HR=3.72, 95%CI: 1.66-8.33, P=0.001), and the lowest hemoglobin level before CE<80 g/L (HR=2.00, 95%CI: 1.02-3.84, P=0.044) were risk factors for rebleeding, while specific treatment (HR=0.25, 95%CI: 0.11-0.54, P<0.001) was a protective factor. The corresponding scores of the above five predictive factors were: OGIB duration>2 weeks: 79 points; Previous history of gastrointestinal bleeding: 100 points; The result of CE was positive: 79 points; Specific treatment:-85 points; Minimum hemoglobin before CE<80 g/L: 41 points. The prediction model constructed from the above five variables had good discriminative capability (concordance index=0.798, 95%CI: 0.732-0.865). The calibration curves showed high consistency between nomogram-predicted probabilities and actual observations. The decision curves showed that when the threshold probability was above 0.04, the use of the nomogram to predict rebleeding provided a greater net benefit than the assumption of "all patients rebleeding or no patients rebleeding". Conclusion: The prediction model established in this study has a good ability to predic rebleeding in patients with OGIB after CE examination.

Assessment of adherence to the national stress ulcer prophylaxis guidelines: A cross-sectional analysis

BackgroundClinical guidelines support the use of stress ulcer prophylaxis (SUP) in patients at risk of gastrointestinal (GI) bleeding such as those with coagulopathy, renal replacement therapy, and mechanical ventilation. Despite the observed benefits of SUP, its overuse has been highly associated with serious adverse effects. ObjectiveTo assess the adherence to the national SUP guidelines in a tertiary hospital in Saudi Arabia. MethodsA cross-sectional study was conducted using electronic health records at King Fahad Specialist Hospital (KFSH), Buraydah, Saudi Arabia. We collected the data from January 1st to December 31st, 2020. Adult patients aged 18 and older who received SUP prescriptions were included. Descriptive analysis was performed to assess the adherence to the guidelines and to explore the factors associated with SUP use in a hospital-based setting. ResultsA total of 424 patients were enrolled in this study. The median age of patients was 55.2 years old. Only 54% of patients were candidates for SUP. Internal medicine and surgery wards ranked the highest in prescribing SUP at 34.2% and 30.4%, respectively. The most common major criterion to start SUP was the concomitant use of two or more of these medications (anticoagulants, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and antidepressants) followed by using NSAIDs or corticosteroids by older adult patients aged (≥65 years) or have GI bleeding history at 43.2% and 21.5%, respectively. ConclusionThe observed overuse of anti-ulcer drugs (AUD) indicates a need for greater adherence to SUP guidelines. Areas of improvement can be implemented to ensure appropriate adherence to SUP guidelines to control the costs and avoid unnecessary anti-ulcer-related adverse effects.

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL)

BackgroundIt is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. ObjectivesPrimary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. MethodsRetrospective multicenter study in French national HHT Registry patients exposed to AT. ResultsWe included 126 patients with 180 courses of AT. Median follow-up was 24 [11–52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). ConclusionTolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.

Principles for the use of non-steroidal anti-inflammatory drugs with proton pump inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in numerous areas of medicine. By inhibiting the prostaglandin synthesis pathway, they contribute to the development of injuries to the mucous membranes within the gastrointestinal tract, possibly leading to gastrointestinal bleeding. Proton pump inhibitors (PPIs) are used to prevent such events in high-risk groups. The bleeding risk is highest in patients above the age of 65, patients with a history of gastrointestinal bleeding, and patients with a history of peptic ulcer disease. The efficacy of bleeding prevention could not be proven in other groups. Notably, PPIs are associated with serious side effects, including acute kidney injury, malabsorption syndrome, and osteoporosis. Therefore, recommending the use of PPIs within the framework of prevention should be approached with caution. The widespread belief that IPP should be automatically prescribed together with NSAIDs is false and harmful to patients.

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma.

In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication. We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events. There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20-50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT. The intake of ASA until thrombocytopenia with a platelet count of 20-50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.

Clinical outcomes of left atrial appendage occlusion in patients with previous intracranial or gastrointestinal bleeding: Insights from the LOGIC (Left atrial appendage Occlusion in patients with Gastrointestinal or IntraCranial bleeding) International Multicenter Registry.

To compare outcomes of patients who underwent left atrial appendage occlusion (LAAO) for nonvalvular atrial fibrillation (NVAF) and contraindication to anticoagulants due to history of either gastrointestinal (GI) or intracranial (IC) bleeding. Patients with NVAF that underwent LAAO for GI or IC bleeding from seven centers were included in this observational study. Baseline characteristics, procedural features, and follow-up data were collected, and compared between the two groups. The primary outcomes were incidence of ischemic and hemorrhagic events at 12-month. Six hundred twenty-eight patients were included, 57% with previous GI-bleeding, and 43% with previous IC-bleeding. Median CHA 2 DS 2-VASc score was 4 (interquartile range[IQRs]: 3-5) for both GI-bleeding and IC-bleeding patients, while GI-bleeding patients had a higher HAS-BLED score (4 [IQRs: 3-4] vs. 3 [IQRs]: 2-3]; p = 0.001). At 12-month follow-up, relative risk reduction for stroke was similar between the two groups. The GI-bleeding group had more hemorrhagic events compared to IC-bleeding group (any bleeding 8.4% vs. 3.2%; p = 0.012; major bleeding BARC 3-5: 4.3% vs. 1.8; p = 0.010). At multivariate analysis history of GI bleeding was an independent predictor of hemorrhagic events (adjusted HR: 2.39, 95% confidence interval:1.02-5.63; p = 0.047). Outcomes after LAAO may be affected by the different indications for the procedure. In our study,GI-bleeding and IC-bleeding as indication to LAAO differ in their baseline characteristics. LAAO confirms its efficacy in ischemic risk reduction in both groups, while GI bleeding seems to be an independent predictor of bleeding recurrence at 12 months behind the antithrombotic regimen.

Successful aspiration of an iatrogenic clot in transit secondary to a failed mechanical thrombectomy in pulmonary embolism.

A 68-year-old female presented with an intermediate-high-risk bilateral pulmonary embolism (PE) (Panel A) with a severely dilated right ventricle (Panel B). Ultrasound of both femoral veins was normal. Thrombolysis was not performed owing to recent history of gastrointestinal bleeding. The PE team decided to perform a percutaneous mechanical thrombectomy (MT) using the FlowTriever (FT) system (Inari Medical, Irvine, CA, USA). After the first procedure, a large thrombus was obtained from the right pulmonary artery (Panels C–E and Supplementary Video 1); however, we failed to extract any thrombus from the left pulmonary artery (LPA) with both the 24 and 16 Fr catheters, due to tortuosity and poor wire support, with non-sustained ventricular tachycardia. A transthoracic echocardiogram (TTE) and a subsequent transoesophageal echocardiography revealed the presence of a massive clot attached to the tricuspid valve, with severe tricuspid regurgitation (Panels F and G and Supplementary Video 2) that was not present in baseline TTE. Considering it was an iatrogenic event due to a ‘lollipop thrombus’, and the risk of re-embolization, a further MT procedure was performed, with TTE guidance, with the successful retrieval of the clot in transit (Panels H and I), and the remaining LPA thrombi (Panels J–L, Supplementary Video 3).

Characterization of Novel &lt;i&gt;F5&lt;/i&gt; Intronic Variant Associated with Aberrant Splicing and Severe Factor V Deficiency

Congenital factor V deficiency is a rare autosomal recessive bleeding disorder, caused by defects in F5 gene and associated with bleeding manifestations of variable severity. In this study we report molecular and functional characterization of a novel F5 variant which causes aberrant splicing and significantly reduces protein expression in a patient with severe FV deficiency. We performed F5 mutation screening and functional study in a proband (FV:C 0.4%) with a history of gastrointestinal bleeding, post-traumatic bleeding, hematomas, ecchymoses, and discomfort in ankle joints since infancy. Sequencing revealed a novel homozygous F5 gene variant NC_000001.10:169519985GC (or NM_000130.5:c.1297 –8CG). Bioinformatics sequence analysis predicted that this variant would lead to the acceptor site loss of the intron 8/exon 9 junction. However mRN-A analysis identified, that it also activated the aberrant splice site located 7 nucleotides upstream of the normal one and was associated with the production of an anomalous F5 transcript with retention of seven nucleotides of intron 8 resulting in a premature stop codon. We revealed no traces of normal transcript in the patient. Our findings confirm that not only changes in canonical splicing dinucleotides could significantly disrupt the splicing sites and impair pre-mRNA processing.

Development and external validation of prognostic scoring models for portal vein thrombosis: a multicenter retrospective study

BackgroundPortal vein thrombosis is a common complication of liver cirrhosis and hepatocellular carcinoma; however, few studies have reported its long-term clinical prognosis. This study aimed to establish and validate easy-to-use nomograms for predicting gastrointestinal bleeding, portal vein thrombosis resolution, and mortality of patients with portal vein thrombosis.MethodsThis multicenter retrospective cohort study included 425 patients with portal vein thrombosis who were divided into training (n = 334) and validation (n = 91) sets. Prediction models were developed using multivariate Cox regression analysis and evaluated using the consistency index and calibration plots.ResultsPredictors of gastrointestinal bleeding included a history of gastrointestinal bleeding, superior mesenteric vein thrombosis, red color sign observed during endoscopy, and hepatic encephalopathy. Meanwhile, predictors of resolution of portal vein thrombosis included a history of abdominal infection, C-reactive protein and hemoglobin levels, and intake of thrombolytics. Predictors of death included abdominal infection, abdominal surgery, aspartate aminotransferase level, hepatic encephalopathy, and ascites. All models had good discriminatory power and consistency. Anticoagulation therapy significantly increased the probability of thrombotic resolution without increasing the risk of bleeding or death.ConclusionsWe successfully developed and validated three prediction models that can aid in the early evaluation and treatment of portal vein thrombosis.

Thrombosis in hereditary hemorrhagic telangiectasia

Thrombosis in hereditary hemorrhagic telangiectasia

Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia

BackgroundAntithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed in patients with hereditary hemorrhagic telangiectasia (HHT); however, data describing and guiding its use are very limited. ObjectivesTo investigate the safety, tolerability, and effectiveness of antithrombotic therapy in HHT in a cohort large enough to compare agents, evaluate for baseline predictors of premature discontinuation, and evaluate hematologic support requirements and healthcare utilization before and after antithrombitc therapy initiation. MethodsWe performed a multicenter observational cohort study characterizing the outcomes of antithrombic therapy in adults with HHT. ResultsA total of 119 patients with HHT with 187 discrete antithrombotic therapy episodes were included. Of these, 59 patients (50%) dose-reduced and/or prematurely discontinued therapy (including 52 patients [44%] who discontinued) due to worsened bleeding complications. Initiation at reduced dose intensity had a similar premature discontinuation rate (49%) as initiation at standard dose intensity (43%). In a multivariable logistic model, a history of gastrointestinal bleeding was associated with 3.25-fold odds of discontinuation (p = .001). Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, p < .001), and the need for hematologic support (intravenous iron and/or red blood cell transfusion) was significantly higher (29 patients vs 12 patients, p = .004) in the 3 months after antithrombotic therapy initiation vs the 3 months before; emergency department visits and hospital admissions due to bleeding also increased. The rates of dose-reduction and/or premature discontinuation were similar regardless of the anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulants, 44%) or with multiple simultaneous agents (44%) but were slightly lower with single-agent antiplatelet therapy (37%). Thromboembolism despite receiving antithrombotic therapy was common (18 patients, 15%) with varying outcomes. ConclusionAntithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and health care utilization from worsened bleeding. Discontinuation rates approached 50% regardless of the dose intensity at initiation or type of antithrombotic agent used and were higher in patients with a gastrointestinal bleeding history.

АССОЦИАЦИЯ ВАРИКОЗНО РАСШИРЕННЫХ ВЕН ПИЩЕВОДА И ЖЕЛУДКА С ДРУГИМИ ФЕНОТИПИЧЕСКИМИ СТИГМАМИ ЦИРРОЗА ПЕЧЕНИ

Background. Portal hypertension resulted from the increased pressure in the portal system is one of the leading syndromes of liver cirrhosis. A frequent and often fatal manifestation of portal hypertension is upper gastrointestinal bleeding mainly due to varicose veins of the esophagus and the stomach. Objective. To study the prevalence of esophageal and gastric varices and their association with other phenotypic stigmas of cirrhosis. Material and methods. A total of 108 patients with cirrhosis, including 46 (42.59%) men and 62 (57.41%) women, were included in the study. Results. Varicose veins were detected in 77 (71,3%) of 108 examined patients. All varices were localized in the esophagus. Of all patients examined, 36 patients (33.33%) were Child-Pugh class A, 58 patients (53.70%) were class B, and 14 patients (12.96%) were class C. Among Class A patients, 9 patients (11.7%) had grade I varicose veins, 9 patients (11.7%) had grade II, 8 patients (10.4%) had grade III, while 13 patients (16.9%), 24 patients (31.2%) and 3 patients (3.9%) had grade B varicose veins, respectively. All patients classified as class C had large varicose veins. The size of varices was associated with the severity of liver cirrhosis (τ=0.2, 95% CI: p˂0.05). Grade II-III varices were seen in 55 patients (50.9%), 9 of whom (16.4%) had a history of gastrointestinal bleeding. Such complication was not observed in any patient with class A cirrhosis, but occurred in all patients with Child-Pugh class C cirrhosis. Conclusions. Patients with liver cirrhosis should undergo follow-up upper GI endoscopy for early detection of varices and, if necessary, for prescription of prophylactic therapy to reduce the risk of bleeding and associated high mortality.

Deprescription of aspirin for primary prevention is uncommon at discharge in hospitalised patients with gastrointestinal bleeding.

Guidelines recommend against aspirin for primary prevention of cardiovascular events in individuals with a history of gastrointestinal bleeding (GIB). It is unknown how often patients on primary prevention aspirin hospitalised with GIB have aspirin discontinued at discharge. To determine the rate of aspirin deprescription and explore long-term outcomes in patients taking aspirin for primary prevention of cardiovascular events. We evaluated all patients hospitalised at Yale-New Haven Hospital between January 2014 and October 2021 with GIB who were on aspirin for primary prevention. Our primary endpoint was the frequency of aspirin deprescription at discharge. Our secondary endpoints were post-discharge hospitalisations for major adverse cardiovascular events (MACE) or GIB. Time-to-event analysis was performed using Kaplan-Meier curves and the log-rank test. We identified 320 patients with GIB on aspirin for primary prevention: median age was 72 (interquartile range [IQR] 61-81) years and 297 (92.8%) were on aspirin 81 mg daily. Only 25 (9.0%) patients surviving their hospitalisation were deprescribed aspirin at discharge. Among 260 patients with follow-up (median 1103 days; IQR 367-1670), MACE developed post-discharge in 2/25 (8.0%) with aspirin deprescription versus 37/235 (15.7%) with aspirin continuation (log-rank p=0.28). 0/25 patients with aspirin deprescription had subsequent hospitalisation for GIB versus 17/235 (7.2%) who continued aspirin (log-rank p=0.13). Aspirin for primary cardiovascular prevention was rarely deprescribed at discharge in patients hospitalised with GIB. Processes designed to ensure appropriate deprescription of aspirin are crucial to improve adherence to guidelines, thereby improving the risk-benefit ratio in patients at high risk of subsequent GIB hospitalisations with minimal increased risk of MACE.

A Multicenter Study of Safety, Tolerability, and Effectiveness of Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia

Introduction: With a prevalence of 1 in 5000 persons, hereditary hemorrhagic telangiectasia (HHT) is the second-most common hereditary bleeding disorder in the world. As HHT is a bleeding disorder with a concomitant elevated thrombotic risk, antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed, but data describing its use is extremely limited. Antithrombotic therapy recommendations in the recently published Second International HHT Guidelines are based on this very limited data (largest prior cohort study including 28 patients) or expert opinion alone. Methods: We evaluated outcomes in a 5-hospital observational cohort study of adults with HHT receiving antithrombotic therapy over a 26-year period. Patients were identified via electronic database query, and eligibility was confirmed and data collection performed via manual chart review. Multivariable logistic modeling was used to assess for predictors of premature antithrombotic therapy discontinuation and hematologic characteristics and healthcare utilization before and after initiation of antithrombotic therapy were evaluated using paired t-tests (continuous data) and chi-square tests (categorical data). Results:Patients and Episodes: 119 HHT patients with 187 discrete antithrombotic therapy episodes were included. Median (range) age was 70 (27-92) years and 69 patients (58%) were female. Most common antithrombotic indications were venous thromboembolism (61 episodes), coronary artery disease (29 episodes), and atrial fibrillation (29 episodes). Most common antithrombotic agents used (by number of episodes) were aspirin (57), warfarin (35), low molecular weight heparin (26), apixaban (15), rivaroxaban (8), and multiple simultaneous medications (41). Tolerability and Effectiveness Overall and by Antithrombotic Therapy Class: 59 patients (50%) prematurely discontinued and/or dose-reduced therapy (including 52 patients [44%] who discontinued) due to worsening bleeding. Initiation at reduced dose-intensity had a similar premature discontinuation rate (49%) as initiation at standard dose-intensity (43%). Difficulty receiving indicated therapy may have resulted in increased thromboembolic recurrence (20 patients, 17%). Rates of dose-reduction and/or premature discontinuation were similar regardless of anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulant [DOAC], 44%) or with multiple simultaneous agents (44%) but slightly lower with single-agent antiplatelet therapy (37%). Predictors of Therapy Discontinuation: In a multivariable logistic model, a history of GI bleeding was associated with 3.25-fold odds of discontinuation (P=0.001, Figure). Adverse Events Associated with Antithrombotic Therapy: Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, P<0.001), and need for intravenous iron and RBC transfusion significantly higher (29 patients vs 12 patients, P=0.004), in the 3 months after antithrombotic therapy initiation versus the 3 months before (Table); number of patients requiring ED visits and/or hospital admissions due to bleeding also increased. 75 patients (63%) developed worsened epistaxis (of whom 33% dose-reduced or discontinued antithrombotic therapy due to epistaxis) and 44 patients (37%) developed newly-diagnosed or worsened gastrointestinal bleeding (of whom 59%, dose-reduced or discontinued antithrombotic therapy due to GI bleeding). Conclusions: Successful administration of antithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and healthcare utilization from worsened bleeding. Discontinuation rates approached 50% regardless of dose-intensity at initiation or type of antithrombotic agent used and were higher in patients with a history of gastrointestinal bleeding. These findings, from the largest and most comprehensive evaluation of antithrombotic therapy in HHT to date, challenge at least two recommendations made based on limited prior data or expert opinion alone in the Second International HHT Guidelines: the recommendation for use of warfarin or heparin-based therapy over DOACs and the avoidance of multiple simultaneous agents even when otherwise indicated due to concern for higher bleeding risk. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure.

Transcatheter left atrial appendage closure (LAAC) is performed in patients unsuitable for long-term anticoagulation, predominantly due to prior bleeding events. The study aimed to investigate the incidence and predictors of clinically significant bleeding (CSB) post-LAAC. Consecutive patients after LAAC with an Amplatzer or WATCHMAN device were analyzed (05.2014-11.2019). Bleeding was classified as CSB when associated with at least one of the following: death, ≥2 g/dL hemoglobin drop, ≥2 blood units transfusion, critical anatomic site, or hospitalization/invasive procedure. Among 195 patients (age 74 (68-80), 43.1% females, HAS-BLED score 2.0 (2.0-3.0)), during median follow-up of 370 (IQR, 358-392) days, there were 15 nonprocedural CSBs in 14 (7.2%) patients. Of those, 9 (60.0%) occurred during postprocedural dual antiplatelet therapy (DAPT) (median 46 (IQR: 16-60) days post-LAAC) vs. 6 (40%) after DAPT discontinuation (median 124 (81-210) days post-LAAC), translating into annualized CSB rates of 14.0% (per patient-year on DAPT) vs. 4.6% (per patient-year without DAPT). In 92.9% (13/14) of patients, the post-LAAC nonprocedural CSB was a recurrence from the same site as bleeding pre-LAAC. In the multivariable model, admission systolic blood pressure (SBP) > 127 mmHg (HR = 10.73, 1.37-84.26, p = 0.024), epistaxis history (HR = 5.84, 1.32-25.89, p = 0.020), permanent atrial fibrillation (AF) (HR = 4.55, 1.20-17.20, p = 0.025), and prior gastrointestinal bleeding (HR = 3.35, 1.01-11.08, p = 0.048) predicted post-LAAC CSB. Nonprocedural CSBs after LAAC, with a similar origin as the pre-LAAC bleedings, were observed predominantly during postprocedural DAPT and predicted by elevated admission SBP, prior epistaxis, permanent AF, and gastrointestinal bleeding history. Whether a more reserved post-LAAC antiplatelet regimen and stringent blood pressure control may improve LAAC outcomes remains to be studied.

Clinical Case 26—Is it possible to live with thrombosed left ventricular assist device (LVAD)?

Abstract LVAD HeartWare was implanted in a 63-year-old patient with end-stage dilated cardiomyopathy. The postoperative course was complicated by massive gastrointestinal (GI) bleeding that required surgical exploration of the GI tract. For the next 1.5 years, the patient has significantly improved functional capacity with proper LVAD function. A month before the incident, an alarm indicating a pump malfunction was recorded. The patient presents with congestive symptoms and an altered sound of LVAD. Laboratory indicates seven times elevated LDH values, low HGB and INR 3.03. Thrombophilia tests were negative. Echo examination does not indicate pump thrombosis, but the pump parameters show increased energy consumption (&amp;gt;6 W) and increased flow (&amp;gt;7 L/min). A diagnosis of LVAD thrombosis was made. Fibrinolytic therapy was contraindicated because of a history of GI bleeding, so a continuous infusion of heparin was started. Despite this, the patient's clinical condition deteriorates, and a decision was made to discontinue the LVAD, to prevent further hemolysis that led to acute kidney injury (AKI). The procedure was performed without endangering the patient. Massive hemolysis, however, leads to the progressive development of AKI requiring CVVHDF. Global respiratory insufficiency develops and mechanical ventilation was started. After six days of intensive treatment, the patient recovered and was discharged home with a thrombosed pump. For the next 2.5 years, the patient was in satisfactory condition during follow-ups, the pump was not explanted. Even sophisticated medical devices carry with them risks for the patient's life despite adequate management. Treatment of LVAD thrombosis depends on patient characteristics and pump-related factors.

Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis

Abstract Background The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs. Purpose We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy. Methods A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed. Results A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70). Conclusion In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors. Funding Acknowledgement Type of funding sources: None.