Development of a chemiluminescence assay for tissue plasminogen activator inhibitor complex and its applicability to gastric cancer.

BACKGROUND: Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. RESULTS: The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. CONCLUSION: Our chemiluminescence assay performs comparably to Sysmex's method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.

Epidemiological, clinical, therapeutic and evolutionary specificities of the association between venous thromboembolic event and cancer in sub-Saharan Africa: Case of Togo.

BACKGROUND: Our study aimed to describe the clinical, paraclinical, therapeutic and outcomes of patients with venous thromboembolic event (VTE) associated with cancer in the context of limited resources. MATERIALS AND METHODS: This was a descriptive cross-sectional study over a period of six years from March 1, 2016 to March 31, 2022, in the cardiology department and the oncology unit of the Sylvanus Olympio Teaching Hospital of Lome. Our study examined medical records of patients who were at least 18 years old and had venous thromboembolic disease and cancer that was histologically confirmed. This study did not include records that were incomplete or records from patients with coronavirus disease. RESULTS: Our study included 87 patients with average age of 56.36±15.26 years. The discovery of VTE occurred incidentally in 28.74%. Venous thrombosis was isolated in 68.96% and proximal in 95%. Pulmonary embolism was bilateral in 77.77%. Gynaecological and urological cancers were found in 33.33% and 32.19% respectively. Adenocarcinoma was the histological type of cancer found in 47.13%. Cancers were at a very advanced stage in 74.71%. Treatment with antivitamin K was prescribed in 12.65%. In our study, there were 58 patients who passed away with a mortality rate of 66.66%. The cause of death was a complication of VTE in 22.42% and related to the course of cancer in 63.79% of cases. CONCLUSION: VTE during cancer is particular with a fatal evolution due to the severity of VTE and the very advanced stage of cancer.

Predicting Pulmonary Embolism in Total Joint Arthroplasty Patients A Pilot Study.

Postoperative venous thromboembolism (VTE) is a common and costly complication following total joint arthroplasty (TJA). Development of a refined thrombophilic screening panel will better equip clinicians to identify patients at high-est risk for developing VTEs. In this pilot study, 62 high-risk TJA recipients who had developed pulmonary emboli (PE) within 90-days of surgery were eligible to participate. Of these patients, 14 were enrolled and subsequently adminis-tered a pre-determined panel of 18 hematologic tests with the aim of identifying markers that are consistently elevated or deficient in patients developing PE. A separate cohort of seven high-risk TJA recipients who did not report a symp-tomatic VTE within 90-days of surgery were then enrolled and Factor VIII and lipoprotein(a) levels were assessed. The most common aberrance was noted in 10 patients (71.4%) who had elevated levels of Factor VIII followed by five patients (35.7%) who had elevated levels of lipoprotein(a). Factor VIII was significantly prevalent (p < 0.001) while lipoprotein(a) failed to achieve statistical significance (p = 0.0708). Of the patients who were within normal limits of Factor VIII, three-fourths were "high-normal" with Fac-tor VIII levels within 5% of the upper limit of normal. This study demonstrates the potential utility of this hematologic panel as part of a perioperative screening protocol aimed at identifying patients at risk for developing VTEs. However, future larger scale studies assessing the capabilities and limitations of our findings are warranted.

Identification and management of pediatric venous thromboembolism in the emergency department.

Although the incidence of pediatric venous thromboembolism is increasing, it is often overlooked in children due to the overall low incidence. This issue reviews the epidemiology of pediatric venous thromboembolism, including the factors that have led to its increasing prevalence, and discusses the physiology of hemostasis and coagulation. Key features of the history and physical examination, as well as identification of risk factors, are reviewed, as these have the most diagnostic value for venous thromboembolism in pediatric patients. Recommendations are also provided for diagnostic testing and management in the emergency department.

Association of the neutrophil-to-lymphocyte ratio with the occurrence of venous thromboembolism and arterial thrombosis.

OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.

Evaluating of Existing VTE Risk Scales in Glioma Patients.

INTRODUCTION: Postoperative venous thromboembolism (VTE) is a frequently occurring complication among glioma patients. Several risk assessment models (RAMs), including the Caprini RAM, the IMPROVE Risk Score, the IMPROVED VTE Risk Score, and the Padua Prediction Score, have not been validated within the glioma patient population. The purpose of this study was to assess the predictive accuracy of established VTE risk scales in patients with glioma. MATERIALS AND METHODS: A single-center, retrospective, observational cohort study was conducted on 265 glioma patients who underwent surgery at the Almazov Medical and Research Centre between 2021 and 2022. VTE detection followed the current clinical guidelines. Threshold values for the Caprini, IMPROVE VTE, IMPROVEDD, and Padua scales were determined using ROC analysis methods, with cumulative weighting for sensitivity and specificity in predicting VTE development. The areas under the ROC curves (AUC) were calculated, and comparisons were made using the DeLong test. RESULTS: The area under the curve for the Caprini risk assessment model was 80.41, while the IMPROVEDD VTE risk score was 75.38, the Padua prediction score was 76.9, and the IMPROVE risk score was 72.58. No significant differences were observed in the AUC values for any of the scales. The positive predictive values of all four scales were low, with values of 50 (28-72) for Caprini, 48 (28-69) for IMPROVEDD VTE, 50 (30-70) for Padua, and 64 (35-87) for IMPROVE RAM. No significant differences were found in terms of PPV, NPV, positive likelihood ratio, and negative likelihood ratio among the analyzed scales. CONCLUSIONS: The Caprini Risk Assessment Model, the IMPROVE Risk Score, the IMPROVED VTE Risk Score, and the Padua Prediction Score exhibit acceptable specificity and sensitivity for glioma patients. However, their low positive predictive ability, coupled with the complexity of interpretation, limits their utility in neurosurgical practice.

Genetic risk stratification of inflammatory bowel disease-associated venous thromboembolism: An Asian perspective.

The utilisation of polygenic scoring models may enhance the clinician's ability to risk stratify an inflammatory bowel disease patient's individual risk for venous thromboembolism (VTE) and guide the appropriate usage of VTE thromboprophylaxis, yet there is a need to validate such models in ethnically diverse populations.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Current Topics from the Revised German S2k Guideline on Diagnosis and Treatment of Venous Thromboembolism.

It is an honor and a great pleasure for us to be guest editors for this special issue of Hämostaseologie - Progress in Haemostasis, which addresses important issues surrounding the complex of venous thromboembolism (VTE). In February 2023, the revised guideline on "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism" has been published on the website of the Association of the Scientific Medical Societies in Germany (AWMF)1. This guideline was drawn up under the leadership of the German Society of Angiology (DGA), and representatives of 17 scientific societies contributed to its content. As an S2k guideline, its recommendations are consensus based and are the result of a systematic review and evaluation of current evidence and consideration of the benefits and harms of diagnostic and therapeutic options. In this special issue, guideline authors provide a comprehensive overview of selected guideline topics which might be of clinical relevance to our readers and our community of haemostaseologists.

Design and validation of algorithms to identify venous thromboembolism in the French National Healthcare Database.

PURPOSE: This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value. METHODS: A case-identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra-database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de-identified pooled and formatted SNDS data (i.e., reconstituted electronic health records-rEHR) with a 6-month look-back period prior to the supposed VTE onset and a 12-month follow-up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert-confirmed VTE divided by the number of algorithm-identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE-identifying algorithm was updated based on expert recommendation. RESULTS: For the 150 patients identified with the first VTE-identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54-69]). The final VTE-identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86-98]) with a total of 87 algorithm-identified cases, including 80 retrieved from the 92 confirmed by experts. CONCLUSION: The identification of VTE in the SNDS is possible with a good PPV.

The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Anticoagulation in venous thromboembolism for the general physician.

Venous thromboembolism (VTE) is frequently encountered across various specialties. The management of VTE has become more nuanced, requiring consideration of several factors when deciding on the choice and duration of anticoagulation. This evidence-based review article summarises the current practice and evidence behind anticoagulation in VTE, incorporating national and international guidelines. Factors influencing decision-making around the choice and duration of anticoagulation, along with special circumstances such as cancer and antiphospholipid syndrome, are discussed. The clinical utility of thrombophilia screening is also addressed.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry / Diferencias relacionadas con la edad en la presentación, el tratamiento y los resultados clínicos de 100.000 pacientes con tromboembolismo venoso en el registro RIETE

Introduction: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. Methods: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. Results: From January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22–1.52) and major bleeding (OR, 2.08; 95%CI, 1.85–2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54–0.71). Conclusions: Compared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.(AU)

Venous thromboembolic outcomes in patients with lymphedema and lipedema: An analysis from the National Inpatient Sample.

BACKGROUND: Patients with lymphedema and lipedema share physical exam findings that may lead to misdiagnosis. Poor mobility is common in patients with obesity and patients with lymphedema and lipedema. This may constitute a risk factor for venous thromboembolism (VTE). Our objective was to evaluate the association of VTE in obese patients with lymphedema and lipedema. METHODS: The National Inpatient Sample (NIS) was searched from 2016 to 2020 to identify hospital admissions of obese female patients with lymphedema and lipedema. Patients were analyzed in the context of presence or absence of VTE while adjusting for complex cluster sampling techniques. Predictors of VTE were accessed by multivariable regression. RESULTS: Lymphedema was identified in 189,985 patients and lipedema in 50,645 patients. VTE was observed in 3.12% (n = 374,210) of patients with obesity. In patients with obesity, VTE was more common in patients with lymphedema than without (2.6% vs 1.6%; p < 0.01). Similarly, VTE was more common in patients with lipedema than without (0.6% vs 0.4%; p < 0.01). After multivariable logistic regression, VTE events in obese patients with lymphedema were higher versus without (OR 1.6; CI 1.08-2.43; p = 0.02). Similarly, VTE events were more common in obese patients with lipedema versus obese patients without lipedema (OR 1.20; CI 1.03-1.41; p = 0.02). CONCLUSIONS: In this hypothesis-generating study, lymphedema and lipedema show a positive association with VTE after adjusting for baseline patient characteristics such as obesity, which is a known independent risk factor for VTE. Mechanisms whereby lymphedema and lipedema are associated with VTE should be investigated.

Venous thromboembolism: diagnostic advances and unaddressed challenges in management.

PURPOSE OF REVIEW: This review summarizes recent advances in developing targeted diagnostics for venous thromboembolism (VTE) and unaddressed knowledge gaps in patient management. Without addressing these critical data needs, the morbidity in VTE patients will persist. RECENT FINDINGS: Recent studies investigating plasma protein profiles in VTE patients have identified key diagnostic targets to address the currently unmet need for low-cost, confirmatory, point-of-care VTE diagnostics. These studies and a growing body of evidence from animal model studies have revealed the importance of inflammatory and vascular pathology in driving VTE, which are currently unaddressed targets for VTE therapy. To enhance the translation of preclinical animal studies, clinical quantification of thrombus burden and comparative component analyses between modeled VTE and clinical VTE are necessary. SUMMARY: Lead candidates from protein profiling of VTE patients' plasma offer a promising outlook in developing low cost, confirmatory, point-of-care testing for VTE. Additionally, addressing the critical knowledge gap of quantitatively measuring clinical thrombi will allow for an array of benefits in VTE management and informing the translatability of experimental therapeutics.

Diagnostic strategies in postpartum individuals with suspected venous thromboembolism: A scoping review.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased postpartum and contributes to important morbidity and mortality. While there have been advances in evaluating diagnostic algorithms for suspected VTE during pregnancy, there is limited data for postpartum individuals. OBJECTIVE: We conducted a scoping review to describe and evaluate diagnostic strategies used to investigate suspected VTE in postpartum individuals. METHODS: A comprehensive search strategy was conducted in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (January 1, 2000-September 30, 2022) to identify original articles that reported on diagnostic strategies in postpartum individuals with suspected VTE. We extracted demographics, clinical decision rules used, D-dimer and imaging completed, including test performance and VTE outcomes. RESULTS: A total of 13 studies conducted across 11 countries with separate postpartum data were included for 759 individuals with suspected PE (n = 634) or DVT (n = 125), including unpublished data (n = 251). Among those with suspected PE, computed tomography pulmonary angiography was conducted more commonly (n = 522) than ventilation-perfusion scans (n = 69), with PE positivity rates that ranged from 4 %-27.6 % and 0-50 % across studies, respectively. Among 131 postpartum individuals with suspected PE who had a D-dimer measured, only 4.6 % (6/131) had a negative D-dimer test. For postpartum individuals with suspected DVT, the most common diagnostic test was compression ultrasonography (positivity rate 12.2 %-18.6 %). There were limited retrospective data evaluating the clinical decision rules. CONCLUSIONS: There are heterogeneous approaches globally in the diagnosis of suspected postpartum VTE. Limited high-quality data available underscores the need for more robust evidence to inform clinical practice.

Abbott D-dimer assay: analytical performance and diagnostic accuracy in management of venous thromboembolism.

This study aimed to assess analytical characteristics and diagnostic accuracy in management of venous thromboembolism (VTE) in the Emergency Department (ED) of the Abbott D-dimer assay applied on the Alinity c clinical chemistry analyzer (Abbott Laboratories, Chicago, IL) compared to the INNOVANCE D-dimer assay (Siemens Healthineers, Marburg, Germany). Precision was determined at three concentration levels following the CLSI EP15-A3 protocol. Method comparison and diagnostic accuracy were assessed using samples obtained from 85 patients who were referred for diagnostic imaging and D-dimer testing due to clinically suspected VTE. Within-run coefficients of variation (CVs) were 3.0%, 0.5% and 0.5% at D-dimer concentrations of 0.54, 1.42 and 2.68 mg/L FEU, while respective between-run CVs were 2.0%, 3.4% and 2.7%, hence fulfilling the desirable biological variation criteria for imprecision (<12.6%). Passing-Bablok regression analysis yielded a small proportional difference between the two compared assays (y = 1.09 (95% confidence interval (CI): 1.01-1.18) x + 0.09 (95%CI: -0.09 to 0.16)), while Bland-Altman analysis showed significant negative absolute (-0.6 mg/L FEU, 95%CI: -0.9 to -0.3) and relative mean bias (-14.1%, 95%CI: -20.3 to -7.9). Spearman's ρ was 0.979 (95%CI: 0.967-0.986). Inter-assay agreement relative to the cut-off was 92% (kappa coefficient = 0.547 (95%CI: 0.255-0.839)). Diagnostic sensitivity, specificity, positive and negative predictive values of the Abbott assay were 100%, 9.2%, 25.3% and 100%, respectively, compared to the following data for the INNOVANCE assay: 95.0%, 15.4%, 25.7% and 90.9%. Abbott D-dimer assay has shown excellent analytical precision, high comparability with the INNOVANCE D-dimer and high NPV at manufacturer's cut-off.