Advances and current research in primary thromboprophylaxis to prevent hospital-associated venous thromboembolism.

Hospital-associated venous thromboembolism (VTE) is defined as any case of VTE occurring during hospital admission and for up to 90 days post discharge. It accounts for over 50% of all cases of VTE internationally; indeed, there are an estimated 10 million cases of hospital-associated VTE annually. Over the last decade, there has been increasing interest in improving VTE risk assessment and thromboprophylaxis. This review summarises all the recent and ongoing major research studies and future challenges in the different areas, including medical, surgical and obstetric patients, as well as special areas such as lower limb immobilisation. We include sections on both pharmacological and mechanical thromboprophylaxis.

How to manage hemostasis in patients with liver disease during interventions.

Patients with advanced chronic liver disease (CLD) often need procedures to both treat and prevent complications of portal hypertension such as ascites or gastrointestinal bleeding. Abnormal results for hemostatic tests, such as prolonged prothrombin time, international normalized ratio, and/or thrombocytopenia, are commonly encountered, raising concerns about increased bleeding risk and leading to transfusion to attempt to correct prior to interventions. However hemostatic markers are poor predictors of bleeding risk in CLD, and routine correction, particularly with fresh frozen plasma and routine platelet transfusions, should be avoided. This narrative review discusses the hemostatic management of patients with CLD using 2 case descriptions.

The "lived" experience of menstruating women commencing anticoagulants.

Background: Although there is increased recognition that many menstruating women commenced on anticoagulants experience heavy menstrual bleeding, little research has been published describing what women go through and actually experience. Objectives: The aim of this study was to understand the "lived" experience of menstruating women commencing anticoagulants. Methods: We undertook a qualitative study using semistructured interviews. Women who had taken part in the parent PERIOD study and expressed an interest in an in-depth interview were recruited. Interviews were conducted online, and transcripts were generated through MS Teams. Data were analyzed using thematic analysis. Ethics committee approval: REC reference: 19/SW/0211. Results: A total of 15 participants were interviewed. The median age of the participants was 36 years (range, 20-49 years). The following 7 primary themes emerged from the interviews: (1) information received when commencing anticoagulation, (2) mood, (3) strategies used to manage heavy bleeding, (4) social/family life, (5) work life, (6) finances, and (7) multiple health issues-with saturation of themes achieved following 9 interviews. Women affected by heavy menstrual bleeding experienced a negative change in their work/social life and mood. Conclusion: Heavy menstrual bleeding experienced by women commencing anticoagulants has a significant impact on their lives. Recognized measures should be employed to support and minimize the problem for menstruating people.

How do anticoagulants impact menstrual bleeding and quality of life? - The PERIOD study.

Background: There is increasing recognition that menstruating women prescribed anticoagulants experience heavy menstrual bleeding. Objectives: The aim of this study is to report the extent of bleeding in menstruating women after commencing anticoagulants and the impact it has on their quality of life. Methods: Women aged 18 to 50, initiated on anticoagulant therapy, were approached to take part in the study. In parallel, a control group of women was also recruited. Women were asked to complete the menstrual bleeding questionnaire and a pictorial blood assessment chart (PBAC) during their next 2 menstrual cycles. Differences between the control and anticoagulated group were compared. Significance was considered at < .05. Ethics committee approval: REC reference: 19/SW/0211. Results: Fifty-seven women in the anticoagulation and 109 women in the control group returned their questionnaires. Women in the anticoagulated group reported an increase in the median length of their menstrual cycle from 5 to 6 days after commencing anticoagulation, compared to 5 days for women in the control group (P < .05). Anticoagulated women reported significantly higher PBAC scores as compared to the control group (P < .05), with two-thirds of women in the anticoagulation group reporting heavy menstrual bleeding. Women in the anticoagulation group reported worsening quality of life scores following the initiation of anticoagulation, compared with women in the control group (P < .05). Conclusion: Heavy menstrual bleeding occurred in two-thirds of women commencing anticoagulants, who completed a PBAC, which had negative impact on their quality of life. Clinicians commencing anticoagulation therapy should be mindful of this, and recognized measures should be taken to help minimize this problem for menstruating individuals.

A systematic approach to venous thromboembolism prevention: a focus on UK experience.

Venous thromboembolism (VTE) remains a leading cause of preventable morbidity and mortality associated with hospitalization. Despite evidence that providing appropriate thromboprophylaxis to those at risk of VTE in hospital, recent data suggest that the delivery of thromboprophylaxis remains suboptimal across the globe, with a lack of standardization in approach to VTE prevention. This review considers the role of VTE risk assessment and interventions to improve the implementation of the VTE prevention pathway and highlights the systematic approach to VTE prevention adopted in England and its impact. Finally, the critical areas for further research and the emerging data presented during the 2022 ISTH annual congress in London, UK, are summarized.

Prevention of hospital-associated venous thromboembolism - Insight from the Getting It Right First Time thrombosis survey in England.

A national Venous Thromboembolism (VTE) Prevention Programme was introduced in England in 2010, with limited subsequent study of its impact. Whilst the National Outcomes Framework reports VTE deaths related to hospitalisation annually, there are little data regarding VTE prevention practice or non-fatal VTE associated with hospitalisation. We report the first national thrombosis survey undertaken in collaboration with Getting It Right First Time. 98 Trusts (103 sites, 67% of 144 invited) participated in at least one survey, contributing data regarding VTE prevention in 9553 patients. Anti-coagulant thromboprophylaxis was prescribed to 88% (when indicated), with 8.1% of patients missing doses. Written patient information was provided to 31%. Of 4595 episodes of hospital-associated VTE, 13% were considered potentially preventable. The survey highlights the success of the national programme and areas for improvement in delivery of thromboprophylaxis and patient information.

Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH.

Hospital-associated venous thromboembolism (HA-VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA-VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis: We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies. We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis. We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case-by-case consideration of thromboprophylaxis. We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas.

Venous thromboembolism in patients hospitalised with COVID-19 in England.

BACKGROUND: The aim of this study was to detail the incidence of venous thromboembolism (VTE) in patients hospitalised with COVID-19 in England. METHODS: This was an exploratory retrospective analysis of observational data from the Hospital Episode Statistics dataset for England. All patients aged ≥18 years in England with a diagnosis of COVID-19 who had a hospital stay that was completed between 1st March 2020 and 31st March 2021 were included. A recorded diagnosis of VTE during the index stay or during a subsequent admission in the six weeks following discharge was the primary outcome in the main analysis. In secondary analysis, VTE diagnosis was the primary exposure and in-hospital mortality the primary outcome. RESULTS: Over the 13 months, 374,244 unique patients had a diagnosis of COVID-19 during a hospital stay, of whom 17,346 (4.6%) had a recorded diagnosis of VTE. VTE was more commonly recorded in patients aged 40-79 years, males and in patients of Black ethnicity, even after adjusting for covariates. Recorded VTE diagnosis was associated with longer hospital stay and higher adjusted in-hospital mortality (odds ratio 1.35 (95% confidence interval 1.29 to 1.41)). CONCLUSIONS: VTE was a common complication of hospitalisation with COVID-19 in England. VTE was associated with both increased length of stay and mortality rate.

Evaluation of novel coagulation and platelet function assays in patients with chronic kidney disease.

BACKGROUND: Hemostasis evaluation in chronic kidney disease (CKD) is critical for optimal management of thrombotic and bleeding events. Standard coagulation screens are inadequate for predicting coagulopathy in CKD. OBJECTIVE: To evaluate hemostasis parameters in patients with different stages of CKD using novel coagulation assays. PATIENTS/METHODS: Cross-sectional study of 30 healthy controls (HC) and 120 CKD patients (10 Stage 2, 20 Stage 3, 20 Stage 4, 20 Stage 5 not requiring renal replacement therapy, 20 transplant, 10 newly started on hemodialysis [HD], 20 established on HD). Standard laboratory tests were performed in addition to rotational thromboelastometry (ROTEM), multiple electrode aggregometry (MEA), thrombin generation assays, D-dimer, and markers of thrombogenesis (thrombin-antithrombin [TAT]), fibrinolysis, and endothelial activation (intercellular adhesion molecule-1 [ICAM-1]). RESULTS: D-dimer, TAT, and ICAM-1 concentrations were significantly higher in patients with CKD than HC (P < .01). ROTEM maximum clot firmness was significantly higher in patients than in HC (P < .01). In CKD Stage 5 patients (pre-HD and started HD) adenosine diphosphate and thrombin receptor activating peptide MEA tests were significantly lower than HC indicating platelet aggregation defect (P < .05). Multivariate analysis confirmed the direct effect of estimated glomerular filtration rate (eGFR) in the variance of ROTEM and MEA tests. Endogenous thrombin potential and peak thrombin were not statistically different between groups, but Stage 5 CKD patients had prolonged lag time (7.91 vs. 6.33, P < .001) and time to thrombin peak (10.8 vs. 9.5, P < .05) compared to HC. CONCLUSIONS: Patients with CKD exhibit features of concomitant hypercoagulability measured by ROTEM and platelet dysfunction measured with MEA. eGFR was an independent determinant of platelet dysfunction and hypercoagulability.

Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: Guidance from the SSC of the ISTH.

Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall hemostatic rebalance or bleeding risk in the periprocedural setting; however, attempts to correct these parameters remain frequent. We review the literature on periprocedural bleeding risk, bleeding risk factors, and the risk and benefits of hemostatic interventions in patients with cirrhosis. We provide guidance recommendations on evaluating bleeding risk in this patient group and management of hemostatic abnormalities in the periprocedural setting.

Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease.

INTRODUCTION: Hemorrhage and venous thromboembolism (VTE) are recognized complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients are uncertain. PATIENTS AND METHODS: We studied a retrospective cohort of patients with CLD nonelectively admitted to a specialist intensive care unit (ICU) determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48 hours; later, diagnosed >48 hours post-ICU admission). Associations with baseline clinical and laboratory characteristics, multiorgan failure (MOF), blood product administration, and mortality were explored. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: early VTE in 80 (13%) and involving the portal vein in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular carcinoma (HCC) and nonalcoholic liver disease were independently associated with early VTE (OR: 2.79, 95% CI: 1.5-5.2 and OR: 2.32, 95% CI: 1.4-3.9, respectively), and HCC, sepsis, and cryoprecipitate use with late VTE (OR: 2.45, 95% CI: 1.11-5.43; OR: 2.26, 95% CI: 1.2-4.3; and OR: 2.60, 95% CI: 1.3-5.1). CONCLUSION: VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD.

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.