Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture.

BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking. METHODS: In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications. RESULTS: A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups. CONCLUSIONS: In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.).

Increased risk of venous thromboembolism in young and middle-aged individuals with hereditary angioedema: a family study.

ABSTRACT: Hereditary angioedema (HAE), caused by C1 inhibitor protein deficiency, was recently shown to be associated with an increased risk for venous thromboembolism (VTE). To our knowledge, this is the first national family study of HAE, which aimed to determine the familial risk of VTE. The Swedish Multi-Generation Register was linked to the Swedish National Patient Register for the period of 1964 to 2018. Only patients with HAE with a validated diagnosis were included in the study and were linked to their family members. Hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE were calculated for patients with HAE in comparison with relatives without HAE. Among 2006 individuals (from 276 pedigrees of 365 patients with HAE), 103 individuals were affected by VTE. In total, 35 (9.6%) patients with HAE were affected by VTE, whereas 68 (4.1%) non-HAE relatives were affected (P < .001). The adjusted HR for VTE among patients with HAE was 2.51 (95% CI, 1.67-3.77). Patients with HAE were younger at the first VTE than their non-HAE relatives (mean age, 51 years vs 63 years; P < .001). Before the age of 70 years, the HR for VTE among patients with HAE was 3.62 (95% CI, 2.26-5.80). The HR for VTE for patients with HAE born after 1964 was 8.29 (95% CI, 2.90-23.71). The HR for VTE for patients with HAE who were born in 1964 or earlier was 1.82 (95% CI, 1.14-2.91). HAE is associated with VTE among young and middle-aged individuals in Swedish families with HAE. The effect size of the association is in the order of other thrombophilias. We suggest that HAE may be considered a new rare thrombophilia.

How I treat acute venous thromboembolism in patients with brain tumors.

ABSTRACT: Venous thromboembolism (VTE) is a common complication in patients with brain tumors. The management of acute VTE is particularly challenging due to an elevated risk of intracranial hemorrhage (ICH). Risk of developing ICH on anticoagulation is influenced by a number of factors including tumor type, recent surgery, concomitant medications, platelet counts, and radiographic features. In patients with a heightened risk for ICH, the benefits of anticoagulation need to be balanced against a likelihood of developing major hemorrhagic complications. Management decisions include whether to administer anticoagulation, at what dose, placement of an inferior vena cava filter, monitoring for development of hemorrhage or progressive thrombus, and escalation of anticoagulant dose. This article discusses the complexities of treating acute VTE in patients with brain tumors and outlines treatment algorithms based on the presence or absence of ICH at the time of VTE diagnosis. Through case-based scenarios, we illustrate our approach to anticoagulation, emphasizing individualized risk assessments and evidence-based practices to optimize treatment outcomes while minimizing the risks of hemorrhagic events in patients with brain tumors.

How I treat the co-occurrence of venous and arterial thromboembolism: anticoagulation, antiplatelet therapy, or both?

ABSTRACT: Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.

How I approach the prevention and treatment of thrombotic complications in hospitalized patients.

This article uses case-based discussion to review prevention and management of thrombotic problems in hospitalized patients that involve a clinical hematologist. There is variation in the clinical hematologist's role in thrombosis practice throughout the world, and we discuss this where indicated. Hospital-associated venous thromboembolism (VTE), or hospital-associated thrombosis (HAT), is the term to cover VTE occurring during admission and for 90 days postdischarge and is a common patient safety problem. HATs are the most common cause of VTE accounting for 55% to 60% of all VTE, with an estimated 10 million occurring globally. VTE risk assessment alongside evidence-based thromboprophylaxis reduces this risk significantly. Many hospitalized patients, especially older patients, use direct oral anticoagulants (DOACs), mainly to prevent stroke in atrial fibrillation. DOACs require perioperative management and may need urgent reversal. Other complex interventions such as extracorporeal membrane oxygenation which require anticoagulation are also discussed. Lastly, those with uncommon high-risk thrombophilias, especially those with antithrombin deficiency, produce unique challenges when hospitalized.

Prediction of Venous Thromboembolism in Diverse Populations Using Machine Learning and Structured Electronic Health Records.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide. Current risk assessment tools, such as the Caprini and Padua scores and Wells criteria, have limitations in their applicability and accuracy. This study aimed to develop machine learning models using structured electronic health record data to predict diagnosis and 1-year risk of VTE. METHODS: We trained and validated models on data from 159 001 participants in the Mount Sinai Data Warehouse. We then externally tested them on 401 723 participants in the UK Biobank and 123 039 participants in All of Us. All data sets contain populations of diverse ancestries and clinical histories. We used these data sets to develop small, medium, and large models with increasing features on a range of optimizing portability to maximizing performance. We make trained models publicly available in click-and-run format at https://doi.org/10.17632/tkwzysr4y6.6. RESULTS: In the holdout and external test sets, respectively, models achieved areas under the receiver operating characteristic curve of 0.80 to 0.83 and 0.72 to 0.82 for VTE diagnosis prediction and 0.76 to 0.78 and 0.64 to 0.69 for 1-year risk prediction, significantly outperforming the Padua score. Models also demonstrated robust performance across different VTE types and patient subsets, including ethnicity, age, and surgical and hospitalization status. Models identified both established and novel clinical features contributing to VTE risk, offering valuable insights into its underlying pathophysiology. CONCLUSIONS: Machine learning models using structured electronic health record data can significantly improve VTE diagnosis and 1-year risk prediction in diverse populations. Model probability scores exist on a continuum, affecting mortality risk in both healthy individuals and VTE cases. Integrating these models into electronic health record systems to generate real-time predictions may enhance VTE risk assessment, early detection, and preventative measures, ultimately reducing the morbidity and mortality associated with VTE.

Association between epidermal growth factor receptor-tyrosine kinase inhibitors and venous thromboembolism among older patients with advanced non-small cell lung cancer.

BACKGROUND: Venous thromboembolism (VTE) risk is higher among patients with non-small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third-generation EGFR-TKI and first/second-generation EGFR-TKIs and stratify VTE risk by sex, age, and race/ethnicity in third-generation EGFR-TKI users. METHODS: Via the 2006-2019 Surveillance, Epidemiology, and End Results-Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third-generation EGFR-TKI (n = 493) and first/second-generation EGFR-TKIs (n = 1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model. RESULTS: A third-generation EGFR-TKI had a significantly higher VTE risk than first/second-generation EGFR-TKIs (HR, 1.26 [95% CI, 1.01-1.57]; p = .037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47-3.19]; p < .001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04-1.83]; p = .026), and non-Hispanic Whites (HR, 1.46 [95% CI, 1.10-1.95]; p = .010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29-4.80]; p = .007) and PE (HR, 2.00 [95% CI, 1.29-3.11]; p = .002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00-2.37]; p = .050) and PE (HR, 1.47 [95% CI, 1.06-2.05]; p = .021) was shown in patients aged ≥75 years and non-Hispanic Whites, respectively. Among third-generation EGFR-TKI users, non-Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03-4.02]; p = .041) and PE (HR, 2.88 [95% CI, 1.24-6.70]; p = .014) than non-Hispanic Asian/Pacific Islanders. CONCLUSIONS: Close monitoring of VTE events in high-risk patients is essential to promote early diagnosis and treatment.

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.

Thrombosis risk with haemoglobin C trait and haemoglobin C disease: A systematic review.

The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.

Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence-based guidelines to aid in the prevention of VTE in SCD.

Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

'X' marks the spot! Utilising factor Xa inhibitors to optimise thromboprophylaxis in multiple myeloma.

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality among multiple myeloma patients. Chang and colleagues' findings indicate that factor Xa inhibitors are as effective as warfarin in preventing VTE without raising the risk of gastrointestinal or intracranial bleeding complications. Commentary on: Chang et al. The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy. Br J Haematol 2024;205:473-477.

An Updated Systematic Review and Meta-analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients.

OBJECTIVE: To compare the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCSs) versus pharmacological thromboprophylaxis alone. BACKGROUND: Surgical inpatients have elevated VTE risk; recent studies cast doubt on whether GCS confers additional protection against VTE, compared with pharmacological thromboprophylaxis alone. METHODS: The review followed "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched up to November 2022. Randomized trials reporting VTE rate after surgical procedures, utilizing pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism, and VTE-related mortality were pooled through fixed and random effects. RESULTS: In a head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI: 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI: 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of pulmonary embolism for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI: 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants). CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Optimal Timing for Initiation of Thromboprophylaxis After Hepatic Angioembolization.

OBJECTIVE: To evaluate the optimal timing of thromboprophylaxis (TPX) initiation after hepatic angioembolization in trauma patients. BACKGROUND: TPX after hepatic trauma is complicated by the risk of bleeding, but the relative risk after hepatic angioembolization is unknown. METHODS: Patients who underwent hepatic angioembolization within 24 hours were retrospectively identified from the 2017 to 2019 American College of Surgeons Trauma Quality Improvement Project data sets. Cases with <24-hour length of stay and other serious injuries were excluded. Venous thromboembolism (VTE) included deep venous thrombosis and PE. Bleeding complications included hepatic surgery, additional angioembolization, or blood transfusion after TPX initiation. Differences were tested with univariate and multivariate analyses. RESULTS: Of 1550 patients, 1370 had initial angioembolization. Bleeding complications were higher in those with TPX initiation within 24 hours (20.0% vs 8.9%, P <0.001) and 48 hours (13.2% vs 8.4%, P =0.013). However, VTE was higher in those with TPX initiation after 48 hours (6.3% vs 3.3%, P =0.025). In the 180 patients with hepatic surgery before angioembolization, bleeding complications were higher in those with TPX initiation within 24 hours (72% vs 20%, P <0.001), 48 hours (50% vs 17%, P <0.001), and 72 hours (37% vs 14%, P =0.001). Moreover, deep venous thrombosis was higher in those with TPX initiation after 96 hours (14.3% vs 3.1%, P =0.023). CONCLUSIONS: This is the first study to address the timing of TPX after hepatic angioembolization in a national sample of trauma patients. For these patients, initiation of TPX at 48 to 72 hours achieves the safest balance in minimizing bleeding while reducing the risk of VTE. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Extended Pharmacologic Prophylaxis for Venous Thromboembolism After Colon Cancer Surgery Is Associated With Improved Long-term Survival: A Natural Experiment in the Chemotherapeutic Benefit of Heparin Derivatives.

OBJECTIVE: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. BACKGROUND: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. METHODS: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort. RESULTS: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests ( P =0.0017 overall, P =0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. CONCLUSIONS: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism.

Assessment of the CLOT (children's likelihood of thrombosis) real-time risk prediction model of hospital-associated venous thromboembolism in children with congenital heart disease.

BACKGROUND: Children with congenital heart disease (CHD) are at high risk for hospital-associated venous thromboembolism (HA-VTE). The children's likelihood of thrombosis (CLOT) trial validated a real-time predictive model for HA-VTE using data extracted from the EHR for pediatric inpatients. We tested the hypothesis that addition of CHD specific data would improve model prediction in the CHD population. METHODS: Model performance in CHD patients from 2010 to 2022, was assessed using 3 iterations of the CLOT model: 1) the original CLOT model, 2) the original model refit using only data from the CHD cohort, and 3) the model updated with the addition of cardiopulmonary bypass time, STAT Mortality Category, height, and weight as covariates. The discrimination of the three models was quantified and compared using AUROC. RESULTS: Our CHD cohort included 1457 patient encounters (median 2.0 IQR [0.5-5.2] years-old). HA-VTE was present in 5% of our CHD cohort versus 1% in the general pediatric population. Several features from the original model were associated with thrombosis in the CHD cohort including younger age, thrombosis history, infectious disease consultation, and EHR coding of a central venous line. Lower height and weight were associated with thrombosis. HA-VTE rate was 12% (18/149) amongst those with STAT Category 4-5 operation versus 4% (49/1256) with STAT Category 1-3 operation (P < .001). Longer cardiopulmonary bypass time (124 [92-205] vs. 94 [65-136] minutes, P < .001) was associated with thrombosis. The AUROC for the original (0.80 95% CI [0.75-0.85]), refit (0.85 [0.81-0.89]), and updated (0.86 [0.81-0.90]) models demonstrated excellent discriminatory ability within the CHD cohort. CONCLUSION: The automated approach with EHR data extraction makes the applicability of such models appealing for ease of clinical use. The addition of cardiac specific features improved model discrimination; however, this benefit was marginal compared to refitting the original model to the CHD cohort. This suggests strong predictive generalized models, such as CLOT, can be optimized for cohort subsets without additional data extraction, thus reducing cost of model development and deployment.

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. METHODS: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). CONCLUSIONS: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review.

Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.