Anticoagulation Stewardship to Bridge the Implementation Gap in Perioperative Anticoagulation Management.

Lack of alignment of care protocols among providers in health care is a driver of increased costs and suboptimal patient outcomes. Perioperative anticoagulation management is a good example of a complex area where protocol creation is a clinical challenge that demands input from multiple experts. Questions regarding the need for anticoagulation interruptions are frequent. Yet, due to layers of complexity involving analysis of anticoagulation indication, surgical risk, and anesthesia-associated bleeding risk as well as institutional practices, there is heterogeneity in how these interruptions are approached. The recent perioperative anticoagulation guidelines from the American College of Chest Physicians summarize extensive evidence for the management of anticoagulant and antiplatelet medications in patients who undergo elective interventions. However, implementation of these guidelines by individual clinicians is highly varied and often does not follow the best available clinical evidence. Against this background, anticoagulation stewardship units, which exist to improve safety and quality monitoring for the anticoagulated patient, are of growing interest. These units provide a bridge for the implementation of value-based, high-quality guidelines for patients who need perioperative anticoagulation interruption. We use a case to pragmatically illustrate the problem and tactics for change management and implementation science that may facilitate the adoption of perioperative anticoagulation guidelines.

In medical inpatients, the IMPROVE risk score had moderate predictive power for 14-d in-hospital bleeding.

SOURCE CITATION: Villiger R, Juillard P, Darbellay Farhoumand P, et al. Prediction of in-hospital bleeding in acutely ill medical patients: external validation of the IMPROVE bleeding risk score. Thromb Res. 2023;230:37-44. 37634309.

Dissecting the rationale for thromboprophylaxis in challenging surgical cases.

Pulmonary embolism (PE) is a leading preventable cause of death in surgical patients, and rates of fatal PE are increasing. Individual assessment, to balance the risks of thrombosis and bleeding, is the key to providing appropriate prophylaxis. The risk assessment process includes use of evidence-based guidelines, literature published since the latest guidelines, large registries, and risk scoring systems together with clinical experience and judgment. Risk assessment is a dynamic process and needs to be updated both during the hospital stay and just prior to discharge since clinical events may change the level of risk. The final assessment may identify patients who require ongoing anticoagulant prophylaxis after discharge. The Caprini risk score is widely used in surgical patients and is a composite of the number of risk factors and their relative weights. The Caprini risk score set point for risk levels requiring anticoagulant prophylaxis varies depending on the type of surgical procedure, surgical population, and number of risk factors. Mandatory implementation of evidence-based care pathways is helpful in lowering PE-related mortality. This review presents several challenging cases, emphasizing the importance of employing all available assessment tools, including dynamic assessment of risk during hospitalization. Finally, the limitations of evidence-based guidelines in complex scenarios and the need to employ all available tools to properly protect very high-risk patients are emphasized.

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification. AIM: To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE. METHODS: Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC). RESULTS: The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined. CONCLUSION: Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

A Patient with Recurrent Strokes: Approach to Coagulopathy.

Despite anticoagulation recommendations, patients may present with recurrent events. While medication adherence is always a concern, assessment of anticoagulation failure demands a systematic approach, taking into account the potential limitations of anticoagulants and a review of differential diagnoses for comorbidities. We illustrate our approach in a case presentation.

Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis.

The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.

Cancer-associated thrombosis by cancer sites and inherited factors in a prospective population-based cohort.

Cancer-associated thrombosis (CAT) is common and associated with mortality. We estimated CAT rate by cancer sites and inherited factors among cancer patients from the UK Biobank (N =70,406). The 12-month CAT rate after cancer diagnosis was 2.37% overall but varied considerably among cancer sites. Among the 10 cancer sites classified as 'high-risk' of CAT by the National Comprehensive Cancer Network guidelines, 6 had CAT rate <5%. In contrast, 5 cancer sites classified as 'average-risk' by the guidelines had CAT rate >5%. For inherited risk factors, both known mutation carriers in two genes (F5/F2) and polygenic score for venous thromboembolism (VTE) (PGSVTE) were independently associated with increased CAT risk. While F5/F2 identified 6% patients with high genetic-risk for CAT, adding PGSVTE identified 13 % patients at equivalent/higher genetic-risk to CAT than that of F5/F2 mutations. Findings from this large prospective study, if confirmed, provide critical data to update guidelines for CAT risk assessment.

Perioperative management of antithrombotic therapy: an American college of chest physicians clinical practice guideline

The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management

Executive Summary: Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

A Prospective Study Evaluating Patterns of Responses to the Caprini Score to Prevent Venous Thromboembolism After Interventional Treatment for Varicose Veins.

BACKGROUND: Venous thromboembolism (VTE) is a critical complication of varicose vein treatments. The Caprini Score (CS) is an established tool to assess patients' VTE risks. One disadvantage is the number of questions required, some of them referring to a low incidence of disease, even lower in patients seeking an elective procedure. These elements take time and may result in filling errors if the CS is not filled out by a properly trained health professional. OBJECTIVE: To establish a response pattern in CS, with emphasis on questions that usually have a negative answer and propose a simpler adaptative digital version without changing the original structure of the tool. METHODS: two hundred and twenty-seven patients in the pre-surgical treatment of varicose veins were enrolled prospectively and submitted to the CS evaluation. RESULTS: The pattern of dichotomous responses could be divided arbitrarily into four subgroups considering the percentage of positive responses: none (11 items), less than 3% (13 items), between 3% and 20% (5 items), and more than 20% (8 items). Of the 12 CS questions related to illnesses that occurred in the last month, ten had had no responses, and 2 were less than 3%. CONCLUSION: There is a pattern in the CS responses of patients with an indication of surgical treatment of varicose veins. Many of the CS questions are not helpful in this scenario and may result in filling errors performed by untrained providers. An adaptative version of the CS might benefit varicose veins surgery VTE risk stratification.

Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis.

OBJECTIVE: To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT). METHODS: We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com. RESULTS: The results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I2, 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I2, 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding. CONCLUSION: DOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs. REGISTRATION: Open Science Framework (https://osf.io/dth86).

Comparison of a nonpneumatic device to four currently available intermittent pneumatic compression devices on common femoral blood flow dynamics.

OBJECTIVE: The purpose of the present study was to compare common femoral vein blood flow enhancement during external mechanical compression using the novel, nonpneumatic Recovery Force Health Movement and Compressions (MAC) System (Recovery Force USA, Fishers, Ind), and four currently available intermittent pneumatic compression devices. METHODS: The MAC device was compared with the Kendall SCD 700 (Cardinal Health, Dublin, Ohio), Arjo Huntleigh Flowtron ACS900 (Arjo, Malmö, Sweden), ActiveCare+S.F.T. (Zimmer Biomet, Warsaw, Ind), and Circul8 (Ortho8, Rocklin, Calif). Doppler ultrasound measurements for each device were directly obtained from the right common femoral vein by a registered vascular technologist. The peak flow velocity and the time taken to reach the peak were calculated. For the MAC system only, the subjects were asked to walk a minimum of 500 steps while wearing the system, which was then checked for slippage. Leg size measurements were obtained using the noncontact Sigvaris Legreader XT5 (Vialis Ortopedia, Turin, Italy). The MAC device is not yet commercially available, and the present study was a prequel to clinical studies of venous thromboembolism prevention. RESULTS: We recruited a broad range of 20 subjects who varied in age (mean ± standard deviation [SD], 50.5 ± 16.2 years), body mass index (mean ± SD, 26 ± 5.5 kg/m2), gender (male, 25%; female, 75%), and right calf circumference (mean ± SD, 37.2 ± 5.5 cm). The peak flow velocity compared with the baseline measurements was significantly greater for the Recovery Force Health MAC System for three (Kendall SCD 700, P = .02; ActiveCare+S.F.T., P = .003; Circul8, P < .001) of the four comparisons. Although the difference was not significant, the Arjo Huntleigh Flowtron ACS900 (SD, 3.4 cm/s) had more measurement variability in the peak flow velocity compared with baseline than did the MAC System (SD, 1.9 cm/s). The MAC had a significantly (P < .001) faster rise time to peak flow compared with the comparison devices. It was the only device to achieve the target peak flow velocity over baseline of at least three times in every body mass index group. Finally, the MAC System met the goal of <2.5 cm of movement after ambulation in 100% of the measurements, with 75% of the measurements showing no movement. CONCLUSIONS: The MAC System is a mobile device that remained in place during ambulation and provided more consistent external mechanical compression in the desired range compared with the other three devices included in the present study.

Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study.

Background In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30-day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07-2.99; P=0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08-2.71; P=0.021). Surgical bleed risk classification (high- versus low-risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020.

This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.