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OBJECTIVES: The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants. METHODS: This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%. RESULTS: Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed. CONCLUSION: Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants. TRIAL REGISTRATION: UMIN Clinical Trial Registry (UMIN000036734).

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Introduction: Antiphospholipid syndrome is an autoimmune disease that presents with thrombus hyperplasia. Although very rare, this disease is reported to become severe after the surgical invasion and other interventions. To our knowledge, there are no reports of partial nephrectomy in patients with antiphospholipid. Case presentation: A 45-year-old man visited our hospital for treatment of left renal cell carcinoma. He had a history of antiphospholipid syndrome and took two antithrombotic agents. We performed a robot-assisted partial nephrectomy. We selectively ligated only the feeding branch during the procedure. Postoperatively, there were no complications, and the patient was discharged on postoperative day 10. One year after surgery, there was no worsening of antiphospholipid syndrome. Conclusion: We reported the first case of robot-assisted partial nephrectomy for an antiphospholipid syndrome patient. Selective ligation of the renal artery might not have contributed to the severe antiphospholipid syndrome.

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OBJECTIVES: People with arteriosclerotic cardiovascular diseases (ASCVD) frequently use antithrombotic agents and statins. The objective of the study was to explore the prevalence and risk factors of cerebral microbleeds (CMBs) in elderly (≥ 65 years old) Chinese people with ASCVD. MATERIALS AND METHODS: We prospectively included 755 eligible participants with complete MRI data, and CMBs were discerned on the SWI sequence. Multivariate logistic regression was performed to analyze risk factors associated with CMBs. RESULTS: The average age was 74.9 ± 9.5 years, and the prevalence of CMBs was 37.9% (286/755). Of those with CMBs, 65.0% (186/286) had strictly lobar CMBs, 35.0% (100/286) had deep or infratentorial CMBs with or without lobar CMBs. We divided CMBs into two groups according to their locations, lobar CMBs group (strictly lobar CMBs) and deep CMBs group (with or without lobar CMBs). Age per 10 years (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.17-1.72, p < 0.001), statin use (OR 1.54, 95% CI 1.05-2.26, p = 0.03), and lacunes (OR 1.70, 95% CI 1.09-2.68, p = 0.02) were associated with any CMBs. Age per 10 years (OR 1.33, 95% CI 1.10-1.63, p < 0.001), statin use (OR 1.67, 95% CI 1.12-2.50, p = 0.01), and white matter hyperintensities (OR 1.71, 95% CI 1.17-2.51, p < 0.01) were associated with lobar CMBs. Only lacunes were associated with deep CMBs (OR 3.29, 95% CI 1.85-5.87, p < 0.001). CONCLUSIONS: In elderly people with risk factors of ASCVD, antithrombotic drug use was not associated with any CMBs, lobar CMBs, or deep CMBs. Statin use was correlated with lobar CMBs but not deep CMBs.

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BACKGROUND: Cold snare polypectomy is a high-risk endoscopic procedure with a low delayed post-polypectomy bleeding rate. However, it is unclear whether delayed post-polypectomy bleeding rates increase during continuous antithrombotic treatment. This study aimed to determine the safety of cold snare polypectomy during continuous antithrombotic treatment. METHODS: This single-center, retrospective cohort study enrolled patients who underwent cold snare polypectomy during antithrombotic treatment between January 2015 and December 2021. Patients were divided into continuation and withdrawal groups based on whether they continued with antithrombotic drugs or not. Propensity score matching was performed using age, sex, Charlson comorbidity index, hospitalization, scheduled treatment, type of antithrombotic drugs used, multiple medications used, indication for antithrombotic drugs, and gastrointestinal endoscopist qualifications. The delayed polypectomy bleeding rates were compared between the groups. Delayed polypectomy bleeding was defined as the presence of blood in stools and requiring endoscopic treatment or a decrease in hemoglobin level by 2 g/dL or more. RESULTS: The continuation and withdrawal groups included 134 and 294 patients, respectively. Delayed polypectomy bleeding was observed in 2 patients (1.5%) and 1 patient (0.3%) in the continuation and withdrawal groups, respectively (p = 0.23), before propensity score matching, with no significant difference. After propensity score matching, delayed polypectomy bleeding was observed in 1 patient (0.9%) in the continuation group but not in the withdrawal group, with no significant difference. CONCLUSION: Cold snare polypectomy during continuous antithrombotic treatment did not significantly increase delayed post-polypectomy bleeding rates. Therefore, this procedure may be safe during continuous antithrombotic treatment.

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Liposomes have been extensively explored as drug carriers, but their clinical translation has been hampered by their low drug-loading content and premature leakage of drug payloads. It was reasoned that vesicle-forming prodrugs could be incorporated into the lipid bilayer at a high molar fraction and therefore serve as a therapeutic agent as well as a structural component in liposomal nanomedicine. Boronated retinoic acid (BORA) was developed as a prodrug, which can self-assemble with common lipids to form liposomes at a high molar fraction (40%) and release all-trans retinoic acid (atRA) and hydroxybenzyl alcohol (HBA) simultaneously, in response to hydrogen peroxide (H2O2). Here, we report fucoidan-coated BORA-incorporated liposomes (f-BORALP) as clot-targeted antithrombotic liposomal nanomedicine with H2O2-triggered multiple therapeutic actions. In the mouse model of carotid arterial thrombosis, f-BORALP preferentially accumulated in the injured blood vessel and significantly suppressed thrombus formation, demonstrating their potential as targeted antithrombotic nanomedicine. This study also provides valuable insight into the development of vesicle-forming and self-immolative prodrugs to exploit the benefits of liposomal drug delivery.

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Thrombosis occurs in both macrovasculature and microvasculature, causing various cardio-cerebral vascular diseases. The lack of effective and safe antithrombotic drugs leads to a public health crisis. Mounting evidence suggests that protein disulfide isomerase (PDI) plays a critical role in the initial stage of thrombus formation, motivating the research of the feasibility of PDI inhibitors as novel anti-thrombotics. Rutin, one of the most potent PDI inhibitors, was reported to suppress platelet aggregation and thrombosis in animal models, but further studies and clinical translation were restricted due to its low aqueous solubility and oral bioavailability. In this work, we fabricated rutin-loaded lipid-based nano-formulation (NanoR) and characterized their physical-chemical properties, release profiles, pharmacokinetic process, and pharmacodynamic function against thrombosis in macrovessels and microvessels. NanoR provided increased solubility and dissolution of rutin to achieve earlier Tmax and higher Cmax than the sodium salt of rutin (NaR) after oral gavage. Ex vivo studies demonstrated that NanoR significantly inhibited thrombin generation and clot formation in the plasma of mice. Importantly, such effect was reversed by exogenous recombinant PDI, demonstrating the specificity of the NanoR. In direct current-induced arterial thrombosis model and ferric chloride-induced microvascular thrombosis model, NanoR exhibited greatly enhanced antithrombotic activity compared with NaR. NanoR also showed good safety performance according to tail bleeding assay, global coagulation tests, and histological analysis. Overall, our current results indicated that NanoR offers a promising antithrombotic treatment with potential for clinical translation.

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BACKGROUND: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. METHODS: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. RESULTS: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). CONCLUSIONS: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients.

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BACKGROUND: Despite the introduction of direct oral anticoagulants, the search for new oral anticoagulants remains an urgent task. OBJECTIVE: By using docking and scoring, based on physical methods, simple chemical rules, methods of synthesis, and activity measurement, develop new low-molecular-weight inhibitors of factor Xa, which are potential anticoagulants. METHODS: The development of leads was based on chemical synthesis and structure-based drug design methods. The basic idea was to combine the two approaches: one based on predictive modeling and the other based on the experimental data. RESULTS: In this study, we developed some nanomolar leads. Further chemical modification improved the inhibition constant by more than one order. DISCUSSION: The method proposed in this paper, as well as other methods, includes virtual screening, chemical synthesis, and activity measurement. However, the most time-consuming process in this method (chemical synthesis) was simplified, and the cost was reduced to the extent that was allowed; a very simple chemical reaction was chosen, i.e., the formation of an amide bond. CONCLUSION: In this work, we demonstrated how using simple chemical rules based on the structurebased drug design, substances with a nanomolar concentration of activity can be developed.

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BACKGROUND: The effect of antithrombotic drugs on intraoperative operative blood loss volume in patients undergoing emergency surgery for generalized peritonitis is not well defined. The purpose of this study was to investigate the effect of antithrombotic drugs on intraoperative blood loss in patients with generalized peritonitis using a nationwide surgical registry in Japan. METHOD: This retrospective cohort study used a nationwide surgical registry data from 2011 to 2017 in Japan. Propensity score matching for the use of antithrombotic drugs was used for the adjustment of age, gender, comorbidities, frailty, preoperative state, types of surgery, surgical approach, laboratory data, and others. The main outcome was intraoperative blood loss: comparison of intraoperative blood loss, ratio of intraoperative blood loss after adjusted for confounding factors, and variable importance of all covariates. RESULTS: A total of 70,105 of the eligible 75,666 patients were included in this study, and 2947 patients were taking antithrombotic drugs. Propensity score matching yielded 2864 well-balanced pairs. The blood loss volume was slightly higher in the antithrombotic drug group (100 [10-349] vs 70 [10-299] ml). After adjustment for confounding factors, the use of antithrombotic drugs was related to a 1.30-fold increase in intraoperative blood loss compared to non-use of antithrombotic drugs (95% CI, 1.16-1.45). The variable importance revealed that the effect of the use of antithrombotic drugs was minimal compared with surgical approach or type of surgery. CONCLUSION: This study shows that while taking antithrombotic drugs is associated with a slight increase in intraoperative blood loss in patients undergoing emergency surgery for generalized peritonitis, the effect is likely of minimal clinical significance.

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A selective and sensitive procedure for quantitation of a new antithrombotic drug (GRS) in rat plasma was developed and validated using an HPLC-UV. The method was validated according to recommendations of the FDA, EMA in terms of selectivity, linearity, accuracy, precision, recovery, matrix effect, stability, and carry-over. The preparation of the biological sample included liquid-liquid extraction with acetonitrile, separation of water-organic mixture with inorganic salts, organic phase clean-up with a sorbent (QuEChERS method), its evaporation to dryness and reconstitution of the residue with A:B eluents mixture (1:1). The chromatographic separations were performed on a micro-column 75 × 2 mm, 5 µm particle size sorbent ProntoSIL 120-5-C18 AQ. The flowrate was of 0.15 ml/min, detector wavelength was set at 360 nm for GRS and at 230 nm for papaverine (IS). It was found that GRS recovery from rat plasma is 94%, the response linearity is in the range of 10 to 1000 ng ml-1. The accuracy values for intra-day determination were of 93.2 to 101.8%, for inter-day determination were of 91.2 to 102.2%, coefficient of variation for intra- and inter-day precision did not exceed 4.1 to 9.3%. The application of the method was shown in pharmacokinetic studies of GRS in rats at a dose of 20 mg kg-1.

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BACKGROUND: Erector spinae plane block (ESPB) is useful for providing analgesia after thoracic surgery. Previous reports show that ESPB is safely performed in patients receiving antithrombotic drugs. We effectively performed continuous ESPB in a patient receiving aspirin after coronary artery bypass grafting. CASE PRESENTATION: A 62-year-old man with mediastinitis was scheduled for sternum closure using a latissimus dorsi muscle flap. He had gone coronary artery bypass grafting and was taking aspirin. After induction of general anesthesia and tracheal intubation, a catheter was inserted for ESPB from the T6 level under ultrasound monitoring and infusion of ropivacaine was started. Tracheal tube was removed in the operating room, cold sense was absent between T2-8, and analgesia was between T3-T8 after uneventful surgery. There were no complications associated with ESPB postoperatively. CONCLUSION: Continuous ESPB was a safe and useful analgesic method in a case undergoing sternum closure using a latissimus dorsi muscle flap.

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Antithrombotic therapy is a major risk factor for delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasia. A potassium-competitive acid blocker, vonoprazan, is expected to prevent delayed bleeding better than conventional proton pomp inhibitors (PPIs), but the evidence is controversial. We sought to clarify the efficacy of vonoprazan for prevention of delayed bleeding after gastric ESD in patients under antithrombotic therapy. We prospectively registered 50 patients who underwent gastric ESD while receiving antithrombotic therapy and vonoprazan in our institution between October 2017 and September 2018. The incidence of delayed bleeding was compared with that in a historical control group of 116 patients treated with conventional PPI. We also evaluated risk factors associated with delayed bleeding. Delayed bleeding was observed in 8 of 50 patients (16.0%), which was not dissimilar from the incidence in the historical control group (12.1%) (p=0.49). In the univariate analysis, age (> 70 years) (p=0.034), multiple antithrombotic drug use (p<0.01), procedure time (> 200 min) (p=0.038) and tumor size (> 40 mm) (p<0.01) were associated with delayed bleeding after gastric ESD, but vonoprazan was not (p=0.49). Vonoprazan may not be more effective than conventional PPIs in preventing delayed bleeding after gastric ESD in patients receiving antithrombotic therapy.

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Nucleotide pyrophosphatase/phosphodiesterase 4 (NPP4) is a membrane-bound enzyme that hydrolyzes extracellular diadenosine polyphosphates such as diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) yielding mononucleotides. NPP4 on the surface of endothelial cells was reported to promote platelet aggregation by hydrolyzing Ap3A to ADP, which activates pro-thrombotic G protein-coupled P2Y1 and P2Y12 receptors. Thus, NPP4 inhibitors have potential as novel antithrombotic drugs. In the present study we expressed soluble human NPP4 in Sf9 insect cells and established an enzyme assay using diadenosine tetraphosphate (Ap4A) as a substrate. The reaction product ATP was quantified by luciferin-luciferase reaction in a 96-well plate format. The sensitive method displayed a limit of detection (LOD) of 14.6 nM, and a Z'-factor of 0.68 indicating its suitability for high-throughput screening. The new assay was applied for studying enzyme kinetics and led to the identification of the first NPP4 inhibitors.

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Background: The use of antithrombotic drugs is increasing with the aging population. Prior to elective procedures, antithrombotic drugs are often discontinued. For emergency procedures in patients taking antithrombotic drugs, their effect cannot be attenuated which may lead to an increased risk of hemorrhagic events. However, there are few studies showing increased intraoperative blood loss in patients taking antithrombotic drugs who undergo emergency gastrointestinal surgery. The aim of this study is to determine whether the use of antithrombotic agents increases intraoperative blood loss in emergency gastrointestinal surgery. Methods: A retrospective review of patients who underwent emergency abdominal surgery between January 2013 and December 2017 was conducted. The primary outcome measure was intraoperative blood loss. Patients were divided into the antithrombotic drug group and a control group, and a propensity score was developed using multivariate logistic regression. We use 1:1 propensity score matching analysis to compare outcomes between the two groups. Results: Of 1555 patients included in this study, 1184 patients, including 170 patients taking antithrombotic drugs, were eligible for propensity score matching analysis. A 1:1 matching yielded 117 well-balanced pairs. There was no statistically significant difference in intraoperative blood loss (antithrombotic drug group vs control group, median (interquartile): 60 (225-10) vs 100 (243-10) ml, p = 0.43). Conclusions: This study suggests that antithrombotic drugs do not increase intraoperative blood loss in patients undergoing emergency gastrointestinal surgery. Emergency gastrointestinal surgery for patients currently taking antithrombotic drugs can be performed safely, and the use of antithrombotic drugs is not a reason to delay surgical intervention.

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Little is known about the health-related quality of life (HRQOL) following adverse bleeding events associated with antithrombotic drug therapy. This systematic review assesses the HRQOL of patients who suffered a bleeding event related to antithrombotic drug use. A literature search was performed using PubMed, EMBASE, and the Cochrane Library from inception through June 16, 2017. Studies measuring HRQOL after a bleeding event related to antithrombotic drug therapy for primary or secondary prevention of a thromboembolic event were included. Four studies with a total of 13,209 patients met the inclusion criteria, and of them, 3,649 patients developed a bleeding event. Patients who were included received antithrombotic drugs because of acute myocardial infarction or atrial fibrillation. EQ-5D, SF-36, and GHP MOS-13 were used to measure HRQOL. The follow-up time ranged from 6 to 29 months. Patients who suffered a bleeding event reported worse HRQOL compared to those who did not (EQ-5D - average increase on all domains of 0.09, p-values ranging from <0.001 to 0.003; SF-36 - average decrease on all domains of 21.4, p < 0.001; and GHP MOS-13 score - decrease of 11.9 points, p < 0.05) and an increased health concern (13.4-point increase; p < 0.05). In conclusion, adverse bleeding events occurring because of the use of antithrombotic agents are associated with a clinically relevant lower HRQOL and hence deserve more attention as part of the shared decision-making process between patients and providers. These data should be valuable for facilitating more substantive care and risk discussions regarding potential changes in outcome and rehabilitation.

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OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

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Lenalidomide (LD) was reported to increase the risk of thromboembolism when it was used along with dexamethasone (DEX). Prophylactic administration of antithrombotic drugs against thromboembolism has been recommended for proper use of LD, but none of the recommendation is stated in the package insert. The purpose of this study was to elucidate the usage of acetylsalicylic acid (ASA) for lenalidomide medication in patients withmultiple myeloma. We used the MDV analyzer to investigate clinical data retrospectively. The investigation period was from October 1, 2016 to September 30, 2017. Subjects were outpatients aged 20 years or older who were recorded in clinical data as multiple myeloma. There were 7,590 outpatients with multiple myeloma. They were divided into 4 groups by the combined use situation of LD and DEX: LD/DEX non-use group (n＝5,462), DEX alone group (n＝632),LD alone group (n＝203), and LD/DEX together group (n＝1,293), respectively. The prevalence rate of thromboembolism was 7.3% in the DEX alone group and 16.9% in the LD/DEX together group (p＜0.0001). Among the LD/DEX together group, ASA was prescribed at 63.6% in the group without thromboembolism (n＝1,074). The prevalence rate of thromboembolism was higher in the LD/DEX combined group than in the DEX alone group. Considering these findings, risk management for thromboembolism caused by administration of antithrombotic drugs should be considered. It is necessary to create more evidence concerning the necessity of administration of antithrombotic drug in combination with LD/DEX medication.

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The incidence of thrombotic diseases has increased in the past decade, a factor endangering human health. Currently, antithrombotic drugs used in the clinic have side effects such as inducing bleeding. Data from clinical observation indicate that congenital deficiency of factor XI (FXI) gene decreases the incidence of stroke and deep venous thrombosis, without causing spontaneous bleeding. This unique property of FXI makes it a potential new target for antithrombotic drugs development. Many studies have focused on the discovery of novel inhibitors targeting FXI. This review summarizes the research progress in searching for the inhibitors against FXI.

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BACKGROUND: Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation. OBJECTIVE: Our approach for the development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work. METHOD: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening methods, where R1, R2 and R3 are some chemical groups and (CONH) are amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be arbitrary for R1, R2 and R2, R3. RESULTS: Chemical modifications were made in the frame of the results, taking into account the structure of FXa, chemical synthesis capabilities, as well as patentability of the target compounds. Subnanomolar potency of several developed compounds was achieved. Several analyzers and various testing-suites have been used to measure the concentration that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2 concentration of the compound 217 (DD217) turned out to be 80±20 nM. The compound efficacy has proved by in vivo assays including oral administrations in rats, rabbits and monkeys. CONCLUSION: The pharmacodynamic profile of DD217 for oral administration in cynomolgus monkeys proves the efficacy of the compound, which makes it promising for the future preclinical trials.

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BACKGROUND: The clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) during antithrombotic drug therapy has not been fully investigated. METHODS: Patients who underwent video capsule endoscopy (VCE) for the investigation of OGIB at Okayama University Hospital from January 2009 to March 2016 were enrolled. We evaluated the VCE findings, the patterns of OGIB, and the rate of rebleeding within 1 year in antithrombotic drug users and antithrombotic drug nonusers. RESULTS: A total of 181 patients were enrolled. Among the antithrombotic drug users, the rate of VCE positivity in the patients with overt OGIB was significantly higher in comparison with patients with occult OGIB (45% versus 16%, p = 0.014), whereas there was no significant difference among the antithrombotic drug nonusers (27% versus 26%, p = 1.0). Among the antithrombotic drug users, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (50% versus 5.9%, p = 0.011). Moreover, among antithrombotic drug users who did not receive therapeutic intervention, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (75% versus 6.3%, p = 0.001). However, among the antithrombotic drug nonusers who did not receive therapeutic intervention, the rebleeding rate of the VCE-positive patients was not significantly different from that of the VCE-negative patients (20% versus 9.4%, p = 0.43). CONCLUSION: Therapeutic intervention should be considered for patients with overt OGIB who are VCE positive and who use antithrombotic drugs due to the high risk of rebleeding.