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.

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.

Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry.

Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43-201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38-2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03-5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65-37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03-6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69-4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91-4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5-20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00-4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS: We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS: A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.

Rate and impact of venous thromboembolism in patients with ST-segment elevation myocardial infarction: Analysis of the Nationwide Inpatient Sample database 2003-2013.

Venous thromboembolism (VTE) and coronary artery disease are major health issues that cause substantial morbidity and mortality. New data have emerged suggesting that these two conditions could have a close relationship. Thus, we sought to determine the trends in annual rate of VTE occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and measure its impact on in-hospital mortality, bleeding complications, and cost and length of hospitalization. We queried the 2003-2013 Nationwide Inpatient Sample databases to identify adults with primary diagnosis of STEMI. VTE events were then allocated. Inpatient outcomes of patients with VTE were compared to those without VTE. Out of 2,495,757 hospitalizations for STEMI, VTE was diagnosed in 25,149 (1%) hospitalizations. Patients who experienced VTE were older (mean age: 67.5 vs 64.8, p < 0.01) and had a higher proportion of black patients (10.1% vs 7.7%, p < 0.001) and females (40.1% vs 35%, p < 0.001) compared to patients without VTE. There was an increasing trend in the rate of VTE during the study period (2003: 0.8% vs 2013: 1.0%, p < 0.001). Patients with VTE had a prolonged hospitalization (median: 9 vs 3 days, p < 0.001), increased cost, higher risk of gastrointestinal bleeding (OR: 2.13, p < 0.001), intracranial hemorrhage (OR: 2.14, p < 0.001), blood transfusions (OR: 1.94, p < 0.001), and mortality (OR: 1.39, p < 0.001). The rate of VTE occurrence in patients with STEMI in our study was 10 per 1000 admissions. VTE was associated with more bleeding complications, longer hospital stays, higher costs, and mortality. These findings suggest that a more aggressive approach for VTE prophylaxis may be warranted in this population.

Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.

Differences in galectin-3, a biomarker of fibrosis, between participants with peripheral artery disease and participants with normal ankle-brachial index.

The aim of this study was to determine if galectin-3 levels were different between participants with peripheral artery disease (PAD) and controls, and to describe its relationship with markers of early atherosclerosis. Sixty participants were recruited into two groups: a PAD group (n=31), ankle-brachial index (ABI) ⩽0.90 and a normal ABI group (n=29), ABI 1.0-1.4. PAD participants were older (68.6 vs 61.8 years, p=0.037), more commonly men (68% vs 38%, p=0.02), and with more cardiovascular risk factors (p<0.001). Galectin-3 was 22% higher in PAD participants (mean±SD: 17.6±4.7 vs 14.4±4.1 ng/mL, p<0.01). The odds ratio for galectin-3 in PAD to be 1 ng/mL higher than the participants with normal ABI was 1.19, after adjusting by age and gender (p=0.014). High-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment (HOMA) were positively associated with galectin-3 in the age- and gender-adjusted model, while arterial elasticity and microalbuminuria were not. In conclusion, galectin-3 levels were higher in participants with PAD.

Coated-platelets improve prediction of stroke and transient ischemic attack in asymptomatic internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis. METHODS: Three-hundred twenty-nine consecutive patients with technically adequate carotid Doppler evaluation without stroke or transient ischemic attack (TIA) in the previous 6 months were enrolled as part of a prospective cohort study conducted during a 40-month period. The main outcome was occurrence of stroke or TIA according to coated-platelet levels and internal carotid stenosis severity at enrollment. The optimal cutoff value of coated-platelet levels was determined by recursive partitioning analysis. Event-free survival was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: A cutoff of ≥45% for coated-platelet levels in combination with stenosis≥50% yielded a sensitivity of 0.78 (95% confidence interval, 0.51-1.0), specificity of 0.92 (0.89-0.95), positive predictive value of 0.21 (0.07-0.34), and a negative predictive value of 0.99 (0.98-1.0) for ipsilateral stroke or TIA. The incidence rate of ipsilateral stroke or TIA for patients with ≥50% stenosis and ≥45% coated-platelets was 21.5 per 100 person-years versus 1.27 per 100 person-years for patients with ≥50% stenosis and <45% coated-platelets (P<0.0001). CONCLUSIONS: Coated-platelet levels identify asymptomatic carotid stenosis patients at high risk for stroke or TIA, which suggests a role for coated-platelets in risk stratification before revascularization.

Primary venous thromboembolism prophylaxis in patients with solid tumors: a meta-analysis.

Venous thromboembolism (VTE) is a leading cause of death among outpatient chemotherapy patients. However the VTE preventive measures for outpatients are not widely advocated. We did a meta-analysis to evaluate the outpatient VTE prevention's effectiveness and safety. We searched electronic databases until the end of December 2012 and reviewed the abstracts and manuscripts following the PRISMA guidelines. Occurrence of first VTE event was the efficacy outcome. The safety end point was major bleeding. We calculated Q statistic and a homogeneity formal test. The odds ratio (OR) estimates were pooled by using the Mantel-Haenszel fixed-effects method in the absence of heterogeneity. Data were analyzed using the R META package). We identified 1,485 articles and reviewed 37 articles based on initial screening. The number of patients included in 11 selected trials was 7,805. The odds of VTE was lower in the prophylaxis group (OR 0.56; 95% CI 0.45-0.71) and improved when heparin-based prevention was analyzed (OR 0.53; 95% CI 0.41-0.70). We found strong prevention among patients with lung cancer (OR 0.46; 95% CI 0.29-0.74) and pancreatic cancer (OR 0.33; 95% CI 0.16-0.67). Major bleeding events were frequent in the intervention group (OR 1.65; 95% CI 1.12-2.44). Thromboprophylaxis reduced VTE episodes. The VTE events were reduced by 47% in heparin-based prophylaxis trials compared to placebo. The patients receiving heparin-based prophylaxis had a 60% increase in bleeding events. Improving risk stratification tools to personalize prevention strategies may enhance the VTE prevention applicability in cancer patients.

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.

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.

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.

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.

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.

Natural language processor as a tool to assess heparin induced thrombocytopenia awareness.

The life-threatening consequences of heparin induced thrombocytopenia (HIT) may be prevented with early recognition, prompt heparin withdrawal and direct thrombin inhibitor use. To determine the level of HIT awareness, electronic term recognition software can be used to query the electronic medical record (EMR) to assess the thought process and test ordering behavior of health care providers confronted with falling platelet counts. We sought to assess the awareness of HIT in a large teaching institution using these tools. Mayo Clinic databases were queried to identify a cohort of hospitalized adults receiving heparin (06/1/08-06/1/09). Serial platelet counts for each patient were scrutinized for a 50% decrement from baseline. "Clinician awareness" was defined by mention of HIT (determined by electronic term recognition software) within the hospital record by any member of the healthcare team or requisition of platelet factor 4/heparin antibody testing. During this time period, 34,694 adults were hospitalized and 24,956 received heparin. Only 3,239 (13%) patients had more than 1 platelet count during the hospital stay. Of 199 patients (6.1%) with ≥50% platelet count drop, clinician awareness was 36%. The absolute platelet count was the only independent variable associated with HIT awareness (P < 0.001). Both appropriate platelet count monitoring and HIT awareness are low at this large teaching institution. Software tools for monitoring awareness and providing realtime alerts of significant platelet count decrements may be useful.

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.