Current recommendations on thromboprophylaxis for foot and ankle (FA) surgery are often inconsistent and generally based on weak evidence. The aim of this survey study was to evaluate the current... Show moreCurrent recommendations on thromboprophylaxis for foot and ankle (FA) surgery are often inconsistent and generally based on weak evidence. The aim of this survey study was to evaluate the current practice among ortho-pedic surgeons regarding venous thromboembolism (VTE) prophylaxis following FA surgery. From February 2019 to March 2020, an online questionnaire was sent by e-mail to orthopedic societies across the world. The question-naire was hosted by the International Society of Thrombosis and Haemostais RedCAP platform. Topics of interest were VTE rates following FA surgery, duration and type of thromboprophylaxis, bleeding complications, VTE risk factors for prophylaxis and use of risk assessment. A total of 693 FA orthopedic surgeons from all continents completed the survey of whom 392 (57%) performed more than 200 FA procedures per year. A total of 669/693 (97%) respondents stated that thromboprophylaxis is necessary in FA surgeries. When thromboprophylaxis was prescribed, half of surgeons prescribed it for the duration of immobilization. Acetylsalicylic acid, low molecular weight heparin and direct-oral anticoagulants were, in this order, the preferred choice. Acetylsalicylic acid and low molecular weight heparin were predominantly prescribed in North America and Europe, respectively. Previous deep vein thrombosis, immobility, obesity and inherited thrombophilia were considered the main risk factors indicative of thromboprophylaxis use. In this survey, most surgeons agree that thromboprophylaxis is indicated for FA surgery, but the prescription, type and duration of prophylaxis differs greatly with a large intercontinental discrepancy. These survey results could be a foundation for developing uniform guidelines to optimize thromboprophylactic strategies in FA procedures around the world. (c) 2023 by the American College of Foot and Ankle Surgeons. All rights reserved. Show less
Camilleri, E.; Smit, D.L.; Rein, N. van; Cessie, S. le; Hon, O. de; Heijer, M. den; ... ; Ronde, W. de 2023
Background: Anabolic androgenic steroids (AAS) are thought to increase venous thromboembolism (VTE) risk. Objectives: We investigated whether AAS influence coagulation parameters associated with... Show moreBackground: Anabolic androgenic steroids (AAS) are thought to increase venous thromboembolism (VTE) risk. Objectives: We investigated whether AAS influence coagulation parameters associated with VTE by assessing their changes during and after AAS use. Methods: The HAARLEM study enrolled 100 male amateur athletes voluntarily starting an AAS cycle between 2015 and 2018. We measured procoagulant and anticoagulant protein levels, D-dimer levels, endogenous thrombin potential (ETP), and clot lysis time (CLT) at baseline and during 2 years of follow-up. Changes in coagulation during AAS cycle, 3 months after its discontinuation, and 1 year after its inclusion compared with baseline were estimated using linear mixed models. The associations between AAS dose and duration of use with these outcomes were studied through adjusted multivariable linear regression. Results: Participants used AAS for a median of 13 weeks (IQR: 10-23) with a median weekly dose of 901 mg (IQR: 634-1345 mg). Mean levels of multiple coagulation factors (F) increased during use compared with baseline, whereas FVIII and von Willebrand factor levels remained unchanged. Protein S and D-dimer showed the biggest increase (22% [95% CI: 15-29] and 1.3-fold [95% CI: 1.2-1.5], respectively). CLT was 8 minutes longer (95% CI: 5-10) and ETP was 165 nM*min (95% CI: -205 to -124) lower during the AAS cycle. A high weekly AAS dose and short cycle duration were associated with changes in protein S and ETP during use. All parameters returned to baseline values 3 months after discontinuation and remained similar after. Conclusion: During AAS use, procoagulant and anticoagulant protein levels increased in a reversible manner. The overall balance did not suggest a clear procoagulant state. Show less
Maanen, R. van; Martens, E.S.L.; Takada, T.; Roy, P.M.; Wit, K. de; Parpia, S.; ... ; Luijken, K. 2023
BackgroundIn patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation (“gestalt”) of PE presence. Although shown to be predictive, gestalt is... Show moreBackgroundIn patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation (“gestalt”) of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization.ObjectivesTo assess the diagnostic accuracy of gestalt in the diagnosis of PE and gain insight into its possible variation.MethodsWe performed an individual patient data meta-analysis including patients suspected of having PE. The primary outcome was diagnostic accuracy of gestalt for the diagnosis of PE, quantified as risk ratio (RR) between gestalt and PE based on 2-stage random-effect log-binomial meta-analysis regression as well as gestalts’ sensitivity and specificity. The variability of these measures was explored across different health care settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age.ResultsWe analyzed 20 770 patients suspected of having PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% vs 9.1%, respectively. The overall RR was 3.02 (95% CI, 2.35-3.87), and the overall sensitivity and specificity were 74% (95% CI, 68%-79%) and 61% (95% CI, 53%-68%), respectively. Although variation was observed across individual studies (I2, 90.63%), the diagnostic accuracy was consistent across all subgroups and health care settings.ConclusionA positive gestalt was associated with a 3-fold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and health care settings, exemplifying its diagnostic value for all patients suspected of having PE. Show less
Kapteijn, M.Y.; Zwaan, S.; Linden, E. ter; Laghmani, E.; Akker, R.F.P. van den; Rondon, A.M.R.; ... ; Buijs, J.T. 2023
Glioblastoma (GBM) patients have one of the highest risks of venous thromboembolism (VTE), which is even further increased upon treatment with chemotherapy. Tissue factor (TF) is the initiator of... Show moreGlioblastoma (GBM) patients have one of the highest risks of venous thromboembolism (VTE), which is even further increased upon treatment with chemotherapy. Tissue factor (TF) is the initiator of the extrinsic coagulation pathway and expressed by GBM cells. In this study, we aimed to examine the effect of routinely used chemotherapeutic agents Temozolomide (TMZ) and Lomustine (LOM) on TF procoagulant activity and expression in GBM cells in vitro. Three human GBM cell lines (U-251, U-87, U-118) were exposed to 100 µM TMZ or 30 µM LOM for 72 h. TF procoagulant activity was assessed via an FXa generation assay and TF gene and protein expression through qPCR and Western blotting. The externalization of phosphatidylserine (PS) was studied using Annexin V flow cytometry. Treatment with TMZ and LOM resulted in increased procoagulant activity in all cell lines. Furthermore, both agents induced procoagulant activity in the supernatant and tumor-cell-secreted extracellular vesicles. In line, TF gene and protein expression were increased upon TMZ and LOM treatment. Additionally, PS externalization and induction of inflammatory-associated genes were observed. Overall, the chemotherapeutic modalities TMZ and LOM induced procoagulant activity and increased TF gene and protein expression in all GBM cell lines tested, which may contribute to the increased VTE risk observed in GBM patients undergoing chemotherapy. Show less
A broad spectrum of long-term sequelae may be present in venous thromboembolism (VTE) survivors, affecting their quality of life and functioning. To monitor recovery and improve the prognosis of... Show moreA broad spectrum of long-term sequelae may be present in venous thromboembolism (VTE) survivors, affecting their quality of life and functioning. To monitor recovery and improve the prognosis of patients with persistent functional limitations, the development of a new outcome measure that could better capture the consequences of VTE was an unmet need. Starting as a call to action, the Post-VTE Functional Status (PVFS) scale was developed to meet this need. The PVFS scale is an easy-to-use clinical tool to measure and quantify functional outcomes after VTE by focusing on key aspects of daily life. As the scale was considered useful in coronavirus disease 2019 (COVID-19) patients as well, the Post-COVID-19 Functional Status (PCFS) scale was introduced early in the pandemic after slight adaptation. The scale has been well incorporated into both the VTE and COVID-19 research communities, contributing to the shift of focus toward patient-relevant functional outcomes. Psychometric properties have been evaluated, mainly for the PCFS scale but recently also for the PVFS scale, including validation studies of translations, showing adequate validity and reliability. In addition to serving as outcome measure in studies, guidelines and position papers recommend using the PVFS and PCFS scale in clinical practice. As broad use of the PVFS and PCFS scale in clinical practice is valuable to capture what matters most to patients, widespread implementation is a crucial next step. In this review, we discuss the development of the PVFS scale and introduction in VTE and COVID-19 care, the incorporation of the scale in research, and its application in clinical practice. Show less
Winter, M.A. de; Dorresteijn, J.A.N.; Ageno, W.; Ay, C.; Beyer-Westendorf, J.; Coppens, M.; ... ; Nijkeuter, M. 2021
Background Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not... Show moreBackground Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice.Objectives To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.Methods In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED").Results Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration).Conclusion Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated. Show less
Mahe, I.; Agnelli, G.; Ay, C.; Bamias, A.; Becattini, C.; Carrier, M.; ... ; Laporte, S. 2021
Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them... Show moreCancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed >= 6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (beta=80%; alpha one-sided=0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding. Show less
Giustozzi, M.; Connors, J.M.; Blanco, A.B.R.; Szmit, S.; Falvo, N.; Cohen, A.T.; ... ; Agnelli, G. 2021
Background Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical features and outcomes... Show moreBackground Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical features and outcomes of cancer patients with incidental or symptomatic VTE randomized in the Caravaggio study. Objectives We performed a predefined sub-analysis of the Caravaggio study in order to investigate the clinical features and outcomes of incidental and symptomatic VTE in patients with cancer. The relative efficacy and safety of apixaban and dalteparin in patients with incidental and symptomatic VTE was also assessed. Methods The Caravaggio study compared apixaban to dalteparin for the 6-month treatment of cancer-associated VTE. The primary efficacy and safety outcomes were recurrent VTE and major bleeding. Results Two hundred thirty patients (20%) had incidental and 925 (80%) symptomatic VTE. Pulmonary embolism with or without deep vein thrombosis as index event, colorectal cancer, Eastern Cooperative Oncology Group (ECOG) score of 0, and locally advanced or metastatic cancer were more frequent in patients with incidental VTE. Deep vein thrombosis as index event, hematological cancer, and ECOG score of 2 were more frequent in patients with symptomatic VTE. Ten patients (4.3%) with incidental and 68 (7.4%) with symptomatic VTE had recurrent VTE (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.29-1.10). Major bleeding occurred in 12 (5.2%) patients with incidental VTE and in 33 (3.6%) patients with symptomatic VTE (HR 1.43, 95% CI 0.74-2.77). When comparing apixaban to dalteparin in patients with symptomatic and incidental VTE, the HR for recurrence was 0.73 (95% CI 0.45-1.19) and 0.41 (95% CI 0.11-1.56), respectively, and the HR for major bleeding 0.93 (95% CI 0.47-1.83) and 0.96 (95% CI 0.31-2.96), respectively. Conclusions Compared to cancer patients with symptomatic VTE, those with incidental VTE have different clinical features at presentation, with a numerically lower incidence of recurrent VTE and a numerically higher incidence of major bleeding. Show less
Although direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and... Show moreAlthough direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and safety in patients with obesity. We reviewed available data for use of DOACs for VTE treatment and prevention in patients with obesity, including phase 3, phase 4, meta-analyses, and pharmacokinetic and pharmacodynamics studies. In addition, we reviewed available data regarding DOACs in bariatric surgery. We provide updated guidance recommendations on using DOACs in patients with obesity for treatment and prevention of VTE, as well as following bariatric surgery. Show less
Introduction: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports.Methods: We analyzed global PE-related mortality by... Show moreIntroduction: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports.Methods: We analyzed global PE-related mortality by focusing on the latest year available for each member state in the World Health Organization (WHO) mortality database, which provides age-sex-specific aggregated mortality data transmitted by national authorities for each underlying cause of death. PE-related deaths were defined by International Classification of Diseases, Tenth Revision codes for acute PE or nonfatal manifestations of venous thromboembolism (VTE). The 2001 WHO standard population served for standardization.Results: We obtained data from 123 countries covering a total population of 2 602 561 422. Overall, 50 (40.6%) were European, 39 (31.7%) American, 13 (10.6%) Eastern Mediterranean, 13 (10.6%) Western Pacific, 3 (2.4%) Southeast Asian, and 2 (1.6%) African. Of 116 countries classifiable according to population income, 57 (49.1%) were high income, 42 (36.2%) upper-middle income, 14 (12.1%) lower-middle income, and 3 (2.6%) low income. A total of 18 726 382 deaths were recorded, of which 86 930 (0.46%) were attributed to PE. PE-related mortality rate increased with age in most countries. The reporting of PE-related deaths was heterogeneous, with an age-standardized mortality rate ranging from 0 to 24 deaths per 100 000 population-years. Income status only partially explained this heterogeneity.Conclusions: Reporting of PE-related mortality in official national vital registration was characterized by extreme heterogeneity across countries. These findings mandate enhanced efforts toward systematic and uniform coverage of PE-related mortality and provides a case for full recognition of PE and VTE as a primary cause of death. Show less
Accumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients... Show moreAccumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients is lacking. Diagnosing PE in these patients is challenging as signs and symptoms of PE and COVID-19 show wide overlap, D-dimer levels are often elevated in the absence of thrombosis and computed tomography pulmonary angiography (CTPA) may be unfeasible in the case of severe renal impairment and/or hemodynamic instability. This narrative review discusses available literature and guidelines on current diagnostic algorithms for suspected PE in special patient populations, in particular COVID-19. A special focus is on reviewing the literature aimed at identifying symptoms with a high suspicion for PE and on the diagnostic performance of diagnostic algorithms for suspected PE in the setting of COVID-19. Based on available literature, the index of suspicion for PE should be high in the case of unexplained abrupt worsening of respiratory status, typical symptoms of deep-vein thrombosis and/or acute unexplained right ventricular dysfunction. Despite the lack of prospective diagnostic management studies, we propose to adhere to current diagnostic algorithms applying assessment of pretest probability and D-dimer testing as available evidence suggests that these might be considered safe. Preferably, algorithms using adjusted D-dimer thresholds are recommended as it likely improves the yield of the clinical decision rule/D-dimer combination. Show less
OBJECTIVE The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has in-creased significantly. The Eastern Association for the Surgery of Trauma recommends... Show moreOBJECTIVE The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has in-creased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight hepa- rin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH.METHODS The authors performed a 4-year (2014 & ndash;2017) analysis of the pediatric American College of Surgeons Trau-ma Quality Improvement Program. All trauma patients (age <= 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes.RESULTS A total of 2479 patients met the inclusion criteria (mean age 15.5 +/- 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients re-ceiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03).CONCLUSIONS LMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this are needed. Show less
COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ... Show moreCOVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients. Show less
Objective This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery.Background Patients undergoing... Show moreObjective This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery.Background Patients undergoing orthopedic surgery are at high risk for VTE. Although patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery.Methods Data from a large population-based case-control study (the Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention.Results Of 4721 cases and 5638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year before the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9-4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI, 4.1-73.6), non-O blood group (OR 11.2; 95% CI, 3.4-34.0), or elevated plasma levels of factor VIII (OR 18.6; 95% CI, 7.4-46.9) all relative to patients without these defects, not undergoing orthopedic surgery.Conclusions Patients with factor V Leiden, high levels of factor VIII, or blood group non-O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment to efficiently reduce VTE risk. Show less
Gal, G. le; Carrier, M.; Castellucci, L.A.; Cuker, A.; Hansen, J.B.; Klok, F.A.; ... ; ISTH CDE Task Force 2021
Clinical research in venous thromboembolism (VTE) is hindered by variability in the collection and reporting of data and outcomes. A consistent data language facilitates efficiencies, leads to... Show moreClinical research in venous thromboembolism (VTE) is hindered by variability in the collection and reporting of data and outcomes. A consistent data language facilitates efficiencies, leads to higher quality data, and permits between-study comparisons and evidence synthesis. The International Society on Thrombosis and Haemostasis (ISTH) launched an international task force of more than 50 researchers to develop common data elements for clinical research in venous thromboembolism.The project was organized in seven working groups, each focusing on a topic area: General Core Data Elements; Anticoagulation and Other Therapies; Chronic VTE and Functional Outcomes; Diagnosis of VTE; Malignancy; Perioperative; and Predictors of VTE. The groups met via teleconference to collaboratively identify key data elements and develop definitions and data standards that were structured in a project-specific taxonomy. A Steering Committee met by teleconference and in-person to determine the overall scope of the project and resolve questions arising from the working groups. ISTH held an open public comment period to enable broader stakeholder involvement and feedback. The common data elements were then refined by the working groups to create a set of 512 unique data elements that are publicly available at .The ISTH VTE Common Data Elements are intended to be a living project with ongoing curation, future expansion, and adaptation to meet the needs of the thrombosis and hemostasis research community. Show less
Aims Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2... Show moreAims Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk.Methods Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE.Results There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14).Conclusions Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this. Show less
Ageno, W.; Vedovati, M.C.; Cohen, A.; Huisman, M.; Bauersachs, R.; Gussoni, G.; ... ; Agnelli, G. 2020
Background Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding... Show moreBackground Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study.Methods The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population.Results Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin.Conclusion Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer. Show less
Nemeth, B.; Nelissen, R.; Arya, R.; Cannegieter, S. 2020
Venous thromboembolism (VTE) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Many guidelines advise on the ideal pharmacological... Show moreVenous thromboembolism (VTE) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Many guidelines advise on the ideal pharmacological thromboprophylaxis strategy; however, despite its use, approximately 1.5% of patients still develop symptomatic VTE. Considering the large number of THAs and TKAs performed worldwide (2.5 million in total), the impact of VTE following these interventions is enormous. This paper discusses a concept how to further lower rates of VTE and bleeding complications following surgery. By stratifying patients according to their risk, we can optimize the balance between VTE and bleeding for each individual. This way, low-risk patients may be safely withheld from treatment (and avoid unnecessary bleeding complications and costs), whereas high-risk patients should receive adequate therapy (for instance, an increased thromboprophylaxis dosage and duration). An individualized strategy requires a well-functioning VTE prediction model following THA and TKA to help physicians to decide on optimal thromboprophylaxis therapy. Show less
Background: The primary objective of this study was to determine the incidence of symptomatic venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), in the... Show moreBackground: The primary objective of this study was to determine the incidence of symptomatic venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), in the hip fracture population. Secondary objectives included determining timing of VTE diagnosis, VTE thromboprophylaxis given, and identifying any factors associated with VTE. Methods: Using data from the FAITH and HEALTH trials, the incidence of VTE, including DVT and PE, and the timing of VTE were determined. A multivariable Cox regression analysis was used to determine which factors were associated with increased risk of VTE, including age, treatment for comorbidity, thromboprophylaxis, time to surgery, and method of fracture management. Results: 2520 hip fracture patients were included in the analysis. Sixty-four patients (2.5%) had a VTE [DVT: 36 (1.4%), PE: 28 (1.1%)]. Thirty-five (54.7%) were diagnosed less than 6 weeks postfracture and 29 (45.3%) more than 6 weeks postfracture. One thousand nine hundred ninety-three (79%) patients received thromboprophylaxis preoperatively and 2502 (99%) received thromboprophylaxis postoperatively. The most common method of preoperative (46%) and postoperative (73%) thromboprophylaxis was low molecular weight heparin. Treatment with arthroplasty compared to internal fixation was the only variable associated with increased risk of VTE (hazard ratio 2.67, P = 0.02). Conclusions: The incidence of symptomatic VTE in hip fracture patients recruited to the 2 trials was 2.5%. Although over half of the cases were diagnosed within 6 weeks of fracture, VTE is still prevalent after this period. The majority of patients received thromboprophylaxis. Treatment with arthroplasty rather than fixation was associated with increased incidence of VTE. Show less
Direct oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are... Show moreDirect oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are considered optimal, clinical events still occur. Given that anticoagulation treatment is a delicate balance between clotting and bleeding, it is possible that an optimal target spot exists where the effect of anticoagulation achieves both the lowest possible risk of bleeding and thrombosis. Other currently available anticoagulants (ie, vitamin K antagonists and heparins) provide important clues for this. If such a target spot exists, tailored DOAC therapy may further benefit patients. This opinion article summarizes the current available evidence that suggests that such a tailored strategy could work. It also describes research suggestions for conducting studies in patient populations such as patients with extremes of body weight or impaired kidney function to evaluate whether tailored treatment with DOACs could lead to better patient outcomes. Show less
