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Background: Optimal anticoagulation management in patients with myeloproliferative neoplasms (MPN) experiencing splanchnic vein thrombosis (SpVT) requires balancing risks of bleeding and recurrent thrombosis., Objectives: We conducted a systematic review and meta-analysis to assess the incidence of bleeding and thrombosis recurrence in patients with MPN-SpVT., Methods: We included retrospective or prospective studies in English with ≥10 adult patients with MPN-SpVT. Outcomes included recurrent venous thrombosis (SpVT and non-SpVT), arterial thrombosis, and major bleeding. Pooled rates per 100 patient years with 95% CIs were calculated by DerSimonian-Laird method using random-effects model., Results: Out of 4624 studies screened, 9 studies with a total of 443 patients were included in the meta-analysis with median follow-up of 3.5 years. In the 364 patients with MPN-SpVT treated with anticoagulation, pooled event rate for major bleeding was 2.8 (95% CI, 1.5-5.1; I 2  = 95%), for recurrent venous thrombosis was 1.4 (95% CI, 0.8-2.2; I 2  = 72%), and for arterial thrombosis was 1.4 (95% CI, 0.6-3.3; I 2  = 92%) per 100 patient years. Among 79 patients (n = 4 studies) who did not receive anticoagulation, pooled event rate for major bleeding was 3.2 (95% CI, 0.7-12.7; I 2  = 97%), for recurrent venous thrombosis 3.5 (95% CI, 1.8-6.4; I 2  = 88%), and for arterial thrombosis rate 1.6 (95% CI, 0.4-6.6; I 2  = 95%) per 100 patient years., Conclusion: Patients with MPN-SpVT treated with anticoagulation have significant risks for both major bleeding and thrombosis recurrence. Further studies are necessary to determine the optimal anticoagulation approach in patients with MPN-SpVT., Competing Interests: Declaration of competing interests P.C., K.B., G.M.G., T.C., A.N., M.M., N.R., G.S., S.A., M.L., and J.B. have no conflict of interest. B.S. received grant support from AstraZeneca and Eisai, speaker honoraria from Eisai, and travel support from AbbVie, AstraZeneca, Ipsen, and Gilead, all not related to this study. P.E.R. has received research funding from Terrafirma; acted as a consultant for Hemostod, Mursla, Genfit, Boehringer Ingelheim, and Abbelight; received speaker fees from Tillots Pharma and AbbVie; and is supported by the Fondation pour la Recherche Médicale (FRM EQU202303016287), “Institut National de la Santé et de la Recherche Médicale” (ATIP AVENIR), the “Agence Nationale pour la Recherche” (ANR-18-CE14-0006-01, RHU QUID-NASH, ANR-18-IDEX-0001, ANR-22-CE14-0002), the “Émergence, Ville de Paris,” the Fondation ARC, the European Union’s Horizon 2020 research and innovation program under grant agreement number 847949, and by France 2030 Recherche Hospitalo-Universitaire Liver-Track, all not related to this study. W.A. has received research support from Bayer and has participated in advisory boards for AstraZeneca, Bayer, BMS-Pfizer, Leo Pharma, Norgine, Sanofi, and Viatris, all not related to this study. J.I.Z. has received research funding from Incyte and Quercegen; consultancy services to Sanofi, CSL, and Parexel; and honoraria from/advisory board participation with Pfizer/Bristol Myers Squibb (BMS), all outside current work. R.P. has received consultancy services from Merck Research Laboratory-Consultant, all outside the current work., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Introduction: There is unmet need in the treatment of ovarian and testicular germ cell tumors (GCTs). This study analyzed registered trials of interventions for GCTs., Materials and Methods: We included trials of interventions for GCTs registered on ClinicalTrials.gov by July 29, 2022. We analyzed their interventions, outcome measures and study design., Results: We included 142 trials registrations; 42 (30 %) for ovarian GCTs, 50 (35 %) for testicular GCTs, and 50 (35 %) trials for both. The majority of the trials were completed (56 %) and did not have results available (75 %). Most trials were in Phase 2. Information about the study design were not reported for many analyzed trials. Most trials had a single-group assignment (44 %) and were open-label (68 %). The median planned number of enrolled participants was 43. Most registrations used medicine(s) (87 %), either as a single type of intervention or in combination. The most commonly used type of medicine was chemotherapy (54 %). Primary outcome was not reported in 23 % of registrations, and secondary outcomes were not reported in 35 % of registrations. Overall survival was used in 6 % of registrations as a primary outcome and in 31 % of registrations as a secondary outcome., Conclusions: Few trials on GCTs were registered on ClinicalTrials.gov, and their number was declining in recent times. Most registrations did not report relevant information about the study design, or results if completed. More effort is needed to foster trials on GCTs, as well as to optimize the management of the registrations and foster the publication of research results., Competing Interests: Declaration of competing interest The authors declare they do not have any conflict of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain., Objectives: We aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients., Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883)., Results: We included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I 2  = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I 2  = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I 2  = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I 2  = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies., Conclusion: There is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE., (© 2024 The Authors.)

Background: The clinical characteristics of splanchnic vein thrombosis (SVT) in pediatric patients and its optimal treatment strategies are unknown., Objectives: This study aimed to assess the effectiveness and safety of anticoagulant therapy for pediatric SVT., Methods: MEDLINE and EMBASE databases were searched up to December 2021. We included observational and interventional studies that enrolled pediatric patients with SVT and reported anticoagulant treatment and outcomes, including rates of vessel recanalization, SVT extension, venous thromboembolism (VTE) recurrence, major bleeding, and mortality. Pooled proportions of vessel recanalization were calculated with their 95% CI., Results: A total of 506 pediatric patients (aged 0-18 years) across 17 observational studies were included. The majority of patients had portal vein thrombosis (n = 308, 60.8%) or Budd-Chiari syndrome (n = 175, 34.6%). Most events were triggered by transient provoking factors. Anticoagulation (heparins and vitamin K antagonists) was prescribed in 217 (42.9%) patients, and 148 (29.2%) patients underwent vascular interventions. The overall pooled proportions of vessel recanalization were 55.3% (95% CI, 34.1%-74.7%; I 2  = 74.0%) among anticoagulated patients and 29.4% (95% CI, 2.6%-86.6%; I 2  = 49.0%) among non-anticoagulated patients. SVT extension, major bleeding, VTE recurrence, and mortality rates were 8.9%, 3.8%, 3.5%, and 10.0%, respectively, in anticoagulated patients and 2.8%, 1.4%, 0%, and 50.3%, respectively, in non-anticoagulated patients., Conclusion: In pediatric SVT, anticoagulation appears to be associated with moderate recanalization rates and a low risk of major bleeding. VTE recurrence is low and comparable to that reported in pediatric patients with other types of provoked VTE., Competing Interests: Declaration of competing interests O.C. reports IIS grants from Pfizer and personal fees from PlasFree, outside the submitted work. S.L.-M. reports grants from Pfizer and Novonordisk and personal fees from Pfizer, outside the submitted work. W.A. reports grants and personal fees from Bayer and personal fees from BMS/Pfizer, Sanofi, Viatris, and Norgine, outside the submitted work. G.K. reports grants from Pfizer and Roche; other receipts from ASC therapeutics, Bayer, Novonordisk, Pfizer, Roche, and Sanofi-Genzyme; and personal fees from Bayer, BioMarine, BPL, CSL, Pfizer, Novonordisk, Roche, Sanofi-Genzyme, Sobi, Spark, Takeda, and Uniquore, outside the submitted work. All other authors have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined., Objectives: The objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT., Methods: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate., Results: In total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35)., Conclusion: Patients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT., Competing Interests: Declaration of competing interests E.V., M.C., N.R., S.M.B., M.M., J.A.D.P., J.M., A.M.D.B., V.P.C., M.S., and A.D.G. have nothing to disclose. M.D.N. received honoraria for participation at the advisory boards from Bayer, Daiichi Sankyo, Pfizer, Leo Pharma, Sanofi, and Viatris outside the submitted work. W.A. has received a research grant from Bayer to support a clinical study in patients with splanchnic vein thrombosis, received honoraria for participation at advisory boards from Bayer, BMS/Pfizer, Sanofi, Leo Pharma, and Portola, and reports grants and personal fees from Bayer, and personal fees from BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, Portola, and Werfen, outside the submitted work; M. Monreal received honoraria for participation at advisory boards from Bristol and Sanofi, outside the submitted work; S.S. has received research funding from Boehringer Ingelheim and Octapharma and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, and Sanofi; J.C.G.P. is a consulting for Cook Medical, Shionogi, WL Gore y Asociados, Vifor Pharma, and Boehringer Ingelheim and has received a research frant from Mallinckrodt and Noorik., (Copyright © 2023 International Society on Thrombosis and Haemostasis. All rights reserved.)

Background: Cancer represents a risk factor for splanchnic vein thrombosis (SVT) and usual site venous thromboembolism (VTE)., Objectives: To compare characteristics and outcomes of patients with cancer-associated SVT and usual site VTE., Patients/methods: Patients with solid cancer and SVT were enrolled in an international, prospective registry between May 2008 and January 2012. The comparison cohort included (1:1 ratio) patients with solid cancer and usual site VTE treated at two thrombosis centers who had a minimum of 12 months follow-up at December 2019 or experienced one of the outcomes within 12 months follow-up. Recurrent VTE, major bleeding, and all-cause mortality were evaluated at 12-month follow-up., Results: A total of 264 patients (132 in each cohort) were enrolled. Patients with SVT were less likely to have metastatic disease (36.1% vs 72.5%) or receive cancer therapy at thrombosis diagnosis (29.6% vs 64.9%). The most frequent cancer types were hepatobiliary and pancreatic in the SVT cohort and gastrointestinal in the usual site VTE cohort. Fewer patients with SVT received anticoagulation (68.9% vs 99.2%), and treatment duration was shorter (6.0 vs 11.0 months). The cumulative incidence of major bleeding (2.3% vs 4.7%) was nonsignificantly lower in the SVT cohort, whereas recurrent thrombosis (4.7% vs 5.5%) and all-cause mortality (41.7% vs 39.4%) were comparable between the two cohorts., Conclusions: The risk of recurrent thrombosis and bleeding appears to be similar in cancer patients with SVT and cancer patients with usual site VTE, despite some differences in baseline characteristics and anticoagulant treatment. Further prospective studies are warranted to confirm these findings., (© 2020 International Society on Thrombosis and Haemostasis.)

Treatment of splanchnic vein thrombosis (SVT) is challenging, and evidence to guide therapeutic decisions remains scarce. The objective of this systematic review and meta-analysis was to determine the efficacy and safety of anticoagulant therapy for SVT. MEDLINE, EMBASE, and clinicaltrials.gov were searched from inception through December 2019, without language restrictions, to include observational studies and randomized controlled trials reporting radiological or clinical outcomes in patients with SVT. Pooled proportions and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. Of 4312 records identified by the search, 97 studies including 7969 patients were analyzed. In patients receiving anticoagulation, the rates of SVT recanalization, SVT progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were 58% (95% CI, 51-64), 5% (95% CI, 3-7), 11% (95% CI, 8-15), 9% (95% CI, 7-12), and 11% (95% CI, 9-14), respectively. The corresponding values in patients without anticoagulation were 22% (95% CI, 15-31), 15% (95% CI, 8-27), 14% (95% CI, 9-21), 16% (95% CI, 13-20), and 25% (95% CI, 20-31). Compared with no treatment, anticoagulant therapy obtained higher recanalization (RR, 2.39; 95% CI, 1.66-3.44) and lower thrombosis progression (RR, 0.24; 95% CI, 0.13-0.42), major bleeding (RR, 0.73; 95% CI, 0.58-0.92), and overall mortality (RR, 0.45; 95% CI, 0.33-0.60). These results demonstrate that anticoagulant therapy improves SVT recanalization and reduces the risk of thrombosis progression without increasing major bleeding. The incidence of recurrent VTE remained substantial in patients receiving anticoagulation, as well. Effects were consistent across the different subgroups of patients. This trial was registered on the PROPERO database at (https://www.crd.york.ac.uk/prospero//display_record.php?ID=CRD42019127870) as #CRD42019127870., (© 2021 by The American Society of Hematology.)

Direct oral anticoagulants (DOACs) are currently the preferred oral anticoagulant treatment for most of the patients with deep vein thrombosis of the lower extremities and/or pulmonary embolism. DOACs have several advantages over vitamin K antagonists, such as availability of fixed dosages, fewer drug interactions, faster onset of action, shorter half-life, and lower risk of major and intracranial bleeding. Although the evidence on the use of DOACs in patients with unusual-site venous thromboembolism (VTE) is limited to a few, small randomized controlled trials, these drugs are increasingly used in clinical practice, and several observational cohort studies have been published recently. This narrative review will describe the latest evidence for the use of the DOACs in patients with thrombosis in atypical locations (splanchnic, cerebral, upper extremity, ovarian, and renal vein thrombosis) and will provide some practical advice for their use in patients with unusual-site VTE., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Abnormal clot structure has been identified in patients with thrombotic disorders. Anticoagulant therapy offers clear benefits for thrombosis prevention and treatment by reducing blood clot formation and size; nevertheless, there are limited data on the effects of different anticoagulants, where clotting is initiated with different triggers, on clot structure., Objectives: Our aim was to investigate the effects of vitamin K antagonists and factor Xa inhibitors on clot structure., Methods: Clots from pooled plasma spiked with rivaroxaban, apixaban, or enoxaparin, as well as plasma from patients on warfarin, were compared to plasma without anticoagulation. The kinetic profile of polymerizing clots was obtained by turbidity, fiber density was determined by confocal microscopy, clot pore size was investigated by permeation, and fiber size was analyzed using scanning electron microscopy. Clotting agonist was either tissue factor or thrombin., Results: Following clotting with tissue factor, all anticoagulated clots had a significantly increased lag time, with the exception of enoxaparin. Rivaroxaban additionally led to significantly less dense and more permeable clots, with thicker fibers. In contrast, turbidity analysis following initiation with thrombin showed few effects of anticoagulation, with only enoxaparin leading to a prolonged lag time. Enoxaparin clots made with thrombin were less dense and more permeable., Conclusion: Our results show that anticoagulants modulate clot structure particularly when induced by tissue factor, most likely due to reduction of thrombin generation. We propose that the effects of different anticoagulants could be assessed with a global clot structure measurement such as permeation or turbidity, providing information on clot phenotype., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Anticoagulant treatment of splanchnic (SVT) and cerebral vein thrombosis (CVT) can be challenging due to the rarity of these conditions, the concomitantly high thrombotic and bleeding risks, and the available low-quality evidence., Objectives: To explore the current therapeutic approaches to SVT and CVT, and the rationale behind the anticoagulant treatment choice., Methods: A cross-sectional survey was conducted (October 2018-April 2019) among members of three thrombosis and hemostasis societies. The survey consisted of four vignette cases: (i) SVT secondary to transient risk factor; (ii) cirrhotic SVT with esophageal varices; (iii) CVT secondary to transient risk factor; and (iv) unprovoked CVT with intracranial hemorrhage., Results: A total of 397 physicians responded to the survey. There was wide variability in anticoagulant treatment options, starting time, and duration. Vitamin K antagonists were the commonest choice across the four vignette cases (44.2%-63.0%). The direct oral anticoagulants (DOACs) were the second commonest choice in low-bleeding-risk scenarios (27.7% in case 1, 22.9% in case 3), while parenteral anticoagulation alone was the second commonest choice in high-bleeding-risk scenarios (39.9% in case 2, 39.8% in case 4). The most frequent reasons for selecting DOACs were oral route of administration (50.6%), lack of need for laboratory monitoring (48.1%), and favorable safety profile of these drugs (43.4%)., Conclusions: The results of our study showed that, despite being off-label, the DOACs were considered for the treatment of unusual-site venous thromboembolism. The wide variability among different physicians reflected the clinical difficulties and raised the need for more collaborative trials on these disorders., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Data extraction from reports about experimental or observational studies is a crucial methodological step informing evidence syntheses, such as systematic reviews (SRs) and overviews of SRs. Reporting discrepancies were defined as pairs of statements that could not both be true. Authors of SRs and overviews of SRs can encounter reporting discrepancies among multiple sources when extracting data-a manuscript and a conference abstract, and a manuscript and a clinical trial registry. However, these discrepancies can also be found within a single manuscript published in a scientific journal., Objectives: Hereby, we describe examples of internal reporting discrepancies that can be found in a single source, with the aim of raising awareness among authors of SRs and overviews of SRs about such potential methodological issues., Conclusions: Authors of SRs and overviews of SRs should check whether the same information is reported in multiple places within a study and compare that information. Independent data extraction by two reviewers increases the chance of finding discrepancies, if they exist. We provide advice on how to deal with different types of discordances and how to report such discordances when conducting SRs and overviews of SRs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Aim of the study is to evaluate the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infection among immigrants assigned to the immigrant centre of the province of Modena., Methods: At the time of arrival all immigrant were tested for: HBsAg, HBsAb, HBcAb, Ag p24/HIVAb, HCVAb, RPR, TPPA, Mantoux test (>10mm diameter of induration was considered to be positive), Chest X-rays. In case of positive samples, second level tests were performed (HbeAg, HBeAb, HDVAb, and baseline management and treatment of the infection detected)., Results: A total of 304 immigrant people were enrolled in the study. HBsAg positivity was 12.2%, HCVAb 3.3%, HIVAb 1.6%, TPPA+RPR positivity in the 0.7%; 10.2% had a positive Mantoux test; 5.6% had Chest X-rays positive for signs of infection and 6 patients had an active tuberculosis. 83.8% HBsAg were HBeAb positive/HBeAg negative. HDVAb resulted positive in 1 patient (2.7%). Previous HBV infection was detected in 28.6% of cases, isolated HBcAb in 2.3%; 5.6% of patients resulted to be positive to HbsAb alone (probable vaccinated)., Conclusion: Our study confirms the high prevalence of HBsAg positivity and latent tuberculosis among immigrants, underlying the importance of screening for infections in this special population., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore disagreements in multiple systematic reviews (SRs) assessing the benefit-to-harm ratio of thrombolytic therapy in patients with intermediate-risk pulmonary embolism (PE)., Study Design and Setting: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Database of Abstracts and Reviews of Effectiveness were searched up to April 14, 2016. We included SRs and guidelines that evaluated thrombolytic therapy, compared with anticoagulation alone, in intermediate-risk PE. We calculated pooled risk ratio (RR) and absolute risk difference (RD), with interquartile range (IQR), for all-cause mortality, recurrent PE, and major bleeding., Results: We marked the Pulmonary Embolism Thrombolysis trial, the largest trial, as a research milestone. Since its release in 2014, 12 SRs (2-15 included trials) and two major guidelines were published. Studies were concordant in reporting that thrombolysis reduced all-cause mortality (median RD -1.55%, IQR -1.60% to -1.40%; median RR 0.55, IQR 0.48-0.61). Discordant results were found for major bleeding (median RD 4.70%, IQR 0.90%-5.70%), with SRs reporting results in opposite directions. Relevant magnitude of effects and precision for benefits and harms were never prespecified., Conclusion: Fourteen evidence syntheses were published within 25 months. Conclusions suggested mortality reduction associated with thrombolytics. Therapy harm was more dispersed and alternatively considered. Interpretation of the benefit-to-harm ratio was elusive, and modest incremental advantages might or not be important, facilitating the origin of disputes., (Copyright © 2017 Elsevier Inc. All rights reserved.)