Long-term Venous Thromboembolism Research Articles

Abstract 3091: Long-term Association Between Hip Or Knee Replacement Surgery And Venous Thromboembolism Risk: A Prospective Matched Cohort Study In The Uk Biobank

Background: Hip and knee replacement surgeries have been linked to a transient increase in venous thromboembolism (VTE) risk in the short term. However, there is limited evidence regarding the extended impact of these surgeries on VTE risk beyond the first year. Objective: This prospective matched cohort study aimed to investigate the associations between hip or knee replacement surgery and VTE risk over a 10-year period, examining how these associations evolved over time. Methods: Analyzing data from 496,862 adults recruited between 2006 and 2010 in the UK Biobank study, 21,155 hip replacement surgery patients and 21,899 knee replacement surgery patients were identified and matched with the general population using exposure density sampling. The piecewise Cox proportional hazards model was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for VTE outcomes at different intervals within the 10 years post-surgery. Results: For the hip replacement surgery cohort (n=221,138), the mean age was 61.5 (standard deviation [SD] 6.8), 40.7% were men, and 407 (1.9%) patients with hip surgery developed VTE during follow-up. In the knee replacement surgery cohort (n=199,487), the mean age was 61.7 (SD 6.4), 44.5% were men, and 436 (2.5%) patients with knee surgery developed VTE. Adjusting for various factors, the elevated risk peaked within 30 days post-surgery, with HRs (95% CIs) of 21.4 (15.4-29.6) and 33.0 (23.4-46.4) for hip and knee replacement, respectively. The elevated risk persisted until the tenth year, with HRs (95% CIs) of 1.59 (1.23-2.04) and 1.68 (1.21-2.33) for hip and knee replacement, respectively. These associations were held across participant characteristics and in sensitivity analysis. Conclusions: In middle-aged and older British adults, hip or knee replacement surgery was associated with both short- and long-term VTE risk, with the heightened risk persisting for up to a decade.

Bariatric Surgery and the Long-Term Risk of Venous Thromboembolism: A Population-Based Cohort Study.

Bariatric surgery is associated with a greater venous thromboembolism (VTE) risk in the weeks following surgery, but the long-term risk of VTE is incompletely characterized. We evaluated bariatric surgery in relation to long-term VTE risk. This population-based retrospective matched cohort study within three United States-based integrated health care systems included adults with body mass index (BMI) ≥ 35kg/m2 who underwent bariatric surgery between January 2005 and September 2015 (n = 30,171), matched to nonsurgical patients on site, age, sex, BMI, diabetes, insulin use, race/ethnicity, comorbidity score, and health care utilization (n = 218,961). Follow-up for incident VTE ended September 2015 (median 9.3, max 10.7years). Our population included 30,171 bariatric surgery patients and 218,961 controls; we identified 4068 VTE events. At 30days post-index date, bariatric surgery was associated with a fivefold greater VTE risk (HRadj = 5.01; 95% CI = 4.14, 6.05) and a nearly fourfold greater PE risk (HRadj = 3.93; 95% CI = 2.87, 5.38) than no bariatric surgery. At 1year post-index date, bariatric surgery was associated with a 48% lower VTE risk and a 70% lower PE risk (HRadj = 0.52; 95% CI = 0.41, 0.66 and HRadj = 0.30; 95% CI = 0.21, 0.44, respectively). At 5years post-index date, lower VTE risks persisted, with bariatric surgery associated with a 41% lower VTE risk and a 55% lower PE risk (HRadj = 0.59; 95% CI = 0.48, 0.73 and HRadj = 0.45; 95% CI = 0.32, 0.64, respectively). Although in the short-term bariatric surgery is associated with a greater VTE risk, in the long-term, it is associated with a substantially lower risk.

Prevention of thromboembolism after a fracture: is aspirin enough?

Venous thromboembolism (VTE) is a serious complication that can arise during and after hospitalization, particularly following surgery under general anaesthesia. Particularly at risk are major orthopaedic surgical procedures such as elective knee or hip replacement and the treatment of hip fractures. In these patients, current guidelines recommend (low or low-moderate level of evidence) aspirin as a possible alternative to anticoagulant therapy for the prophylaxis of long-term venous thromboembolism after an initial period with anticoagulant drugs. Several randomized trials and meta-analyses demonstrate no significant differences in the risk of VTE when comparing aspirin with anticoagulants. However, it must be considered that most recommendations are based on elective orthopaedic surgery and that trials after fractures have excluded patients at high thrombotic risk. Consequently, the overall incidence of major clinical events (death and pulmonary embolism) was ∼1% with wide confidence margins in even large non-inferiority studies. The incidence of asymptomatic VTE, especially distal, appears to be higher with aspirin. Patient preference and lower costs could play an important role in the choice in favour of aspirin.

Long-Term Major Adverse Cardiovascular Events in Patients with Moderate and Severe COVID-19: A Focus on Early Statin Use and Previous CVD.

Limited data exist regarding the status of long-term cardiovascular disease (CVD) outcomes of hospitalized COVID-19 patients. We aimed to examine the efficacy of early statin use after SARS-CoV-2 pneumonia and the impact of prior CVD on the incidence of cardiovascular events. A prospective cohort study was performed on hospitalized COVID-19 patients. The primary endpoint was major adverse cardiovascular events (MACE) as a composite of cardiovascular mortality, stroke, heart failure, venous thromboembolism (VTE), revascularization, and nonfatal myocardial infarction (MI). The secondary endpoints comprised MACE components, all-cause mortality, readmission for COVID-19, and impaired functional classes. The mean age of the 858 participants was 55.52±13.97 years, and the median follow-up time was 13 months (11.5-15). Men comprised 63.9% of the patients. Overall, MACE occurred in 84 subjects (9.8%), and 98 patients (11.4%) received ventilation. A multivariate Cox regression model was employed to explore the association between statin use and outcomes, and the following hazard ratios were obtained: MACE (0.831 [0.529 to 0.981]; P=0.044), All-cause mortality (1.098 [0.935 to 1.294]; P=0.255), stroke (0.118 [0.029 to 0.48]; P=0.003), revascularization (0.103 [0.029 to 0.367]; P<0.0001), poor functional capacity (0.827 [0.673 to 1.018]; P=0.073), nonfatal MI (0.599 [0.257 to 1.394]; P=0.234), VTE (0.376 [0.119 to 1.190]; P=0.096), and decompensated heart failure (0.137 [0.040 to 0.472]; P=0.002). Prior CVD predicted MACE (2.953 [1.393 to 6.271]; P=0.005), all-cause death (1.170 [0.960 to 1.412]; P=0.102), and VTE (2.770 [0.957 to 8.955]; P=0.051). Previous CVD is a robust predictor of long-term MACE and VTE. Early statin use might decrease the incidence rates of MACE, ischemic stroke, revascularization, and readmission for heart failure.

Chronic thromboembolic pulmonary hypertension and mortality after venous thromboembolism: a nationwide population-based cohort study

Abstract Background One of the ultimate long-term complications of venous thromboembolism (VTE) is chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a condition defined as an increased mean pulmonary arterial pressure of at least 25 mmHg at rest and abnormal pulmonary artery resistance measured by right heart catheterization. To our knowledge, no study has compared mortality in VTE patients developing CTEPH to those who do not. Purpose We aimed to investigate the influence of CTEPH on long-term VTE mortality, by examining how receiving any pulmonary hypertension (PH) diagnosis following VTE influenced mortality. Methods We conducted a population-based cohort study of all adult Danish patients with an incident in or outpatient VTE diagnosis from 1995 through 2016. We excluded patients with a previous PH diagnosis. We defined CTEPH as receiving any PH diagnosis within two years following VTE. We categorized VTE by type (deep venous thrombosis [DVT] or pulmonary embolism [PE]) and provoking risk factors. We followed patients from two years after VTE until the first of death, emigration, or 31 December 2016. We calculated mortality rates and standardized mortality rate ratios (SMRs) of the association between PH and all-cause mortality and cause-specific mortality due to cancer and cardiovascular diseases. We also stratified the analyses by baseline presence of comorbidity (congestive heart failure, chronic pulmonary disease, and/or interstitial pulmonary disease). Results In 89,062 VTE patients alive two years after their VTE, 724 developed PH. The mortality rate per 1,000 person-years was 121 (95% confidence interval [CI]: 110–134) in patients with PH and 48 (95% CI: 47–48) in patients without PH. The SMR was 2.05 (95% CI: 1.77–2.37) for all VTE patients, 2.20 (95% CI: 1.53–3.16) for DVT patients, and 1.72 (95% CI: 1.47–2.01) for PE patients. The SMR was 1.79 (95% CI: 1.28–2.51) in VTE patients with a provoking VTE risk factor and 2.15 (95% CI: 1.83–2.53) in VTE patients without a provoking VTE risk factor. PH was associated with increased cause-specific mortality due to cardiovascular diseases (SMR=2.31, 95% CI: 1.75–3.06), but not cancer (SMR=0.94, 95% CI: 0.64–1.38). The SMR was 2.36 (95% CI: 2.06–2.71) in patients with comorbidity and 1.80 (95% CI: 1.45–2.24) in patients without comorbidity. Conclusion Development of PH, as a measure of CTEPH, within two years following incident VTE was associated with two-fold increased mortality in two-year VTE survivors. The increase in mortality was driven by cardiovascular causes. Funding Acknowledgement Type of funding sources: None.

Extended anticoagulation for venous thromboembolism: A survey of the American Venous Forum and the European Venous Forum

ObjectiveExtended anticoagulation therapy should always be considered after standard treatment of an unprovoked episode of venous thromboembolism (VTE). It can also be considered for selected patients with provoked VTE. However, the evidence-based protocols suggested by some clinical guidelines and risk assessment tools to guide this practice are limited and ambiguous. The goal of the present survey research was to analyze current practices in applying extended anticoagulation therapy for patients with VTE among members of the American Venous Forum (AVF) and European Venous Forum (EVF). MethodsAn online survey was created by the AVF Research Committee. The survey consisted of 16 questions to identify the country of practice, specialty, experience of the participating physicians, and their clinical practice patterns in applying extended anticoagulation therapy for VTE patients. The survey was distributed via e-mail to the members of the AVF and EVF. ResultsA total of 144 practitioners, 48 AVF members (33%) and 96 EVF members (66%), participated in the survey. Most of the respondents identified themselves as vascular specialists with primary certification in vascular surgery (70%), vascular medicine or angiology (9%), and venous disease or phlebology (3%). Of the 144 respondents, 72% believed that the risk of VTE recurrence will generally overweigh the risk of bleeding for patients with unprovoked VTE. Extended anticoagulation therapy might be used by 97% of providers. Different patterns in real world clinical practice were identified. More than one half of the practitioners estimated the VTE recurrence and bleeding risk subjectively. The antithrombotic drugs most commonly used for secondary prophylaxis were rivaroxaban, apixaban, warfarin, dabigatran, and aspirin, in decreasing order of frequency. Among the reasons selected for not regularly considering extended anticoagulation therapy were the lack of specific clinical practice guidelines (24%), lack of reported evidence (9%), and absence of valid VTE and/or bleeding risk prediction calculators (8%). Twelve participants (8%) stated that extended anticoagulation therapy would not be beneficial for most patients with VTE. Ten participants (7%) indicated that prescribing extended anticoagulation therapy was outside the scope of their specialty. ConclusionsDifferent practice patterns exist regarding extending anticoagulation therapy beyond the standard treatment for patients with VTE. Major gaps in knowledge remain a serious challenge at least partially explaining the inaccuracy and inconsistency in long-term VTE management. Appropriately designed studies are needed to evaluate risk stratification tools when contemporary best medical therapy is used, accurately predict VTE recurrence and its long-term outcomes, and tailor safe and effective secondary prophylaxis.

Long-term VTE treatment with rivaroxaban: Results from the DRESDEN NOAC REGISTRY

Data on long-term effectiveness and safety of venous thromboembolism (VTE) treatment with rivaroxaban are scarce and not available from randomized clinical trials. To supplement the positive results of phase III VTE treatment trials with rivaroxaban, we used data from the ongoing, prospective, non-interventional DRESDEN NOAC REGISTRY to evaluate long-term management patterns and clinical outcomes.Between December 1st 2011 and September 30th 2020, 812 patients with acute VTE (575 DVT; 237 PE) and rivaroxaban treatment were prospectively followed. During treatment (median rivaroxaban exposure 1.1 years IQR 0.3–5.0 years; median follow-up 6.1 years IQR 4.7–7.8 years) rates of recurrent VTE and ISTH major bleeding were 0.7/100 pt. years (95% CI 0.4–1.1) and 2.1/100 pt. years; 95% CI 1.5–2.8, respectively. Of the 427 patients still taking rivaroxaban at 12 months, 276 and 202 were still taking rivaroxaban at 3 and 5 years, respectively. “Scheduled end of treatment” was the leading discontinuation reason also beyond 12 months. When exposure days were divided by the number of major clinical outcomes (recurrent VTE + other major cardiovascular + ISTH major bleeding), continued rivaroxaban treatment had the longest “exposure per event” period (6398 days/event) compared to patients switching to alternative treatments (4658 days/event) or stopping anticoagulation completely (4337 days/event).Our results confirm low thrombotic and major bleeding rates for long-term VTE treatment with rivaroxaban. Beyond 12 months, scheduled treatment discontinuations still occur. Although 3–5% of patients planned for indefinite rivaroxaban therapy switched to other anticoagulants each year, the overall persistence to rivaroxaban was high.

Newer Oral Anticoagulants in Venous Thromboembolism

Abstract Venous thromboembolism (VTE) is an important medical condition for morbidity and mortality. Adequate anticoagulant treatment is necessary to reduce short- and long-term VTE related conditions. In the past low molecular weight heparin (LMWH) and Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for VTE patients. The patients require frequent monitoring with INR to keep balance between effectiveness and safety in clinical practice. NOACs have been the main stay of treatment in conditions requiring effective anticoagulation. They may prove to do the same in VTE. This article analyses, the present literature on use of NOACs in VTE.

Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.

Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0μg/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30days) developed in two patients (0.9%) and long-term VTE (30days-3years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.

Heart Failure Is Associated with Increased Risk of Long-Term Venous Thromboembolism.

Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), is highly prevalent in in-hospital HF patients and contributes to worse prognoses. However, the risk of VTE in out-patients with HF in long-term period is controversial. This study aimed to evaluate the associations between HF and the risk of VTE in a long-term follow-up duration. We searched for studies investigating the risk of VTE, PE, and DVT in patients with HF before April 15, 2020, in PubMed, MEDLINE, and Embase databases. Cohort studies and post hoc analysis of RCTs were eligible for inclusion if they reported relative risk of VTE, DVT or PE in patients with HF in more than 3-month follow-up period. We identified 31 studies that enrolled over 530,641 HF patients. Overall, patients with HF were associated with an increased risk of VTE (risk ratio [RR]=1.57, 95% confidence interval [CI]=1.34-1.84) and PE (RR=2.00, 95% CI=1.38-2.89). However, the risk of DVT was not significantly increased in HF patients (RR=1.33, 95% CI=0.67-2.63). Subgroup analysis showed that patients with chronic HF (RR=1.54, 95% CI=1.32-1.80) had a higher risk of VTE than those with acute HF (RR=0.95, 95% CI=0.68-1.32). In conclusion, HF was an independent risk for VTE and PE but not DVT in a long-term follow-up period. Patients with chronic HF were prone to suffer from VTE than acute HF.

Long-term recurrence risk after a first venous thromboembolism in men and women under 50 years old: A French prospective cohort

BackgroundData on long-term venous thromboembolism (VTE) recurrence risk according to gender are conflicting. ObjectiveTo evaluate long-term VTE recurrence risk after a first VTE in men and women under 50 years old. MethodsSince May 2000, 875 consecutive patients (315 men, 560 women) with a first symptomatic VTE under 50 years old were enrolled in a French prospective multicentre cohort study and were followed up as long as possible. The primary outcome was symptomatic recurrent VTE during follow-up. ResultsAt baseline, men were older and had more comorbidities than women. First VTE was mainly unprovoked in men (80.6%) and hormone-related in women (84.3%). During a median follow-up of 7.0 years (inter-quartile range, 5.0–11.0), recurrent VTE occurred in 97 men (30.8%) and in 72 women (12.9%) (annual incidence rates of recurrent VTE of 4.8% versus 1.8%-person-years, P<0.001). However, there was no difference according to gender in subgroups of patients with a first unprovoked VTE (5.8% versus 3.8%-person-years, P = 0.09). In women, duration of hormonal treatment before first VTE did not influence recurrence risk. In multivariable analysis, unprovoked VTE and family history of VTE were independently associated with recurrence (hazard ratio of 2.50 (95% confidence interval, 1.61 to 3.85) and 1.52 (1.11 to 2.09) respectively). LimitationsNumber of women with unprovoked VTE was low. ConclusionsIn patients with a first VTE under 50 years old, a first unprovoked episode and a family history of VTE, but not gender, were associated with a high risk of long-term recurrence.

Incident Heart Failure and Long-Term Risk for Venous Thromboembolism

BackgroundHeart failure (HF) hospitalization places patients at increased short-term risk for venous thromboembolism (VTE). Long-term risk for VTE associated with incident HF, HF subtypes, or structural heart disease is unknown. ObjectivesIn the ARIC (Atherosclerosis Risk In Communities) cohort, VTE risk associated with incident HF, HF subtypes, and abnormal echocardiographic measures in the absence of clinical HF was assessed. MethodsDuring follow-up, ARIC identified incident HF and subcategorized HF with preserved ejection fraction or reduced ejection fraction. At the fifth clinical examination, echocardiography was performed. Physicians adjudicated incident VTE using hospital records. Adjusted Cox proportional hazards models were used to evaluate the association between HF or echocardiographic exposures and VTE. ResultsOver a mean of 22 years in 13,728 subjects, of whom 2,696 (20%) developed incident HF, 729 subsequent VTE events were identified. HF was associated with increased long-term risk for VTE (adjusted hazard ratio: 3.13; 95% confidence interval: 2.58 to 3.80). In 7,588 subjects followed for a mean of 10 years, the risk for VTE was similar for HF with preserved ejection fraction (adjusted hazard ratio: 4.71; 95% CI: 2.94 to 7.52) and HF with reduced ejection fraction (adjusted hazard ratio: 5.53; 95% confidence interval: 3.42 to 8.94). In 5,438 subjects without HF followed for a mean of 3.5 years, left ventricular relative wall thickness and mean left ventricular wall thickness were independent predictors of VTE. ConclusionsIn this prospective population-based study, incident hospitalized HF (including both heart failure with preserved ejection fraction and reduced ejection fraction), as well as echocardiographic indicators of left ventricular remodeling, were associated with greatly increased risk for VTE, which persisted through long-term follow-up. Evidence-based strategies to prevent long-term VTE in patients with HF, beyond time of hospitalization, are needed.

P5587Elevated D-dimer level after 1 month anticoagulant therapy as a predictor for adverse outcomes in patients with venous thromboembolism: 10-year follow-up results

Abstract Background Our previous study showed that elevated D-dimer (D-D) level after 1 month of the anticoagulant therapy was an independent predictor of deep vein thrombosis (DVT) recurrences and combined endpoint (DVT recurrence and/or death from any causes) during 18 months. Prognostic value of elevated D-D level after 1 month of the anticoagulant therapy for the long-term venous thromboembolism (VTE) outcomes is unknown. Purpose To estimate the elevated D-D level influence after 1 month of the anticoagulant therapy on the 10-year prognosis in VTE pts. Methods One hundred and twelve pts (77 men) aged 18–76 (mean 54±14) years with DVT and/or pulmonary embolism were included in the study. Pts received unfractionated or low molecular weight heparin for at least 5 days followed by the long-term warfarin therapy (target international normalized ratio 2,0–3,0). D-D level was measured after 1 month from the start of the anticoagulant therapy by a quantitative assay with an estimated cut-off level of 0,5 ug/ml. The follow-up period was 10 years. Endpoints were VTE recurrence and combined endpoint (VTE recurrence and/or death from any causes). Results In all pts, median of follow-up was 2,77 years (min 2 weeks, max 11,61 years, IQR 1,44 to 10,31 years). Seventy seven (69%) pts had ended the 10-year follow-up period completely or achieved the endpoint. In these pts, median of follow-up was 9,23 years (IQR 1,70 to 10,53 years). Thirty-five cases were censored. During 10 years, the VTE recurrences rate was 27,7%, 14 pts died, the combined endpoint rate was 36,6%. Kaplan-Meier analysis showed that pts with elevated D-D level after 1 month of the anticoagulant therapy had higher 10-year cumulative risk for adverse outcomes (chi-square=6,0, p=0,014 for VTE recurrence; chi-square=13,7, p&lt;0,001 for combined endpoint). Cox regression confirmed that elevated D-D level after 1 month of the anticoagulant therapy was associated with a 2,5-fold increase in the 10-year VTE recurrences risk (HR 2,52; 95% CI 1,18–5,42; p=0,018) and a 3,2-fold increase in the 10-year combined endpoint risk (HR 3,21; 95% CI 1,68–6,15; p&lt;0,001) compared pts with normal D-D level after 1 month of the anticoagulant therapy. Conclusions During 10 years, the VTE recurrences rate was 27,7%, combined endpoint rate (VTE recurrence and/or death from any causes) was 36,6%. Elevated (&gt;0,5 ug/ml) D-D level after 1 month of the anticoagulant therapy had a prognostic value and was associated with the 2,5-fold increase in the 10-year VTE recurrences risk and the 3,2-fold increase in the 10-year adverse outcomes risk.

D-dimer levels at diagnosis and long-term clinical outcomes in venous thromboembolism: from the COMMAND VTE Registry.

The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0-4.9 µg/mL): N = 682, Quartile 2 (5.0-9.9 µg/mL) N = 694, Quartile 3 (10.0-19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P < 0.0001), as well as both within and beyond 30-day. After adjustment, the excess risk of Quartile 4 relative to Quartile 1 for all-cause death remained significant (HR 1.60, 95% CI 1.29-2.03). Similarly, the excess risk of Quartile 4 relative to Quartile 1 for recurrent VTE was significant (HR 1.57, 95% CI 1.02-2.41), which was more prominent in the cancer subgroup. The dominant causes of death in Quartile 4 were pulmonary embolism within 30-day, and cancer beyond 30-day. In conclusions, in VTE patients, elevated D-dimer levels at diagnosis were associated with the increased risk for both short-term and long-term mortality. The higher mortality risk of patients with highest D-dimer levels was driven by the higher risk for fatal PE within 30-day, and by the higher risk for cancer death beyond 30-day. Elevated D-dimer levels were also associated with the increased risk for long-term recurrent VTE, which was more prominent in patients with active cancer.

Полиморфизм гена тканевого активатора плазминогена и риск рецидива венозного тромбоза у пациентов молодого возраста

Introduction. The most frequent clinical manifestations of venous thromboembolism (VTE) — deep vein thrombosis (DVT) and pulmonary embolism (PE) are often complicated by recurrent episodes that lead to an increased risk of severe post-thrombophlebitic syndrome and/or life-threatening PE. The role of hereditary factors in the development of recurrent VTE in young people is still unclear. Aim: identification of genetic risk factors for recurrent VTE in young patients. Materials and methods. We examined 250 patients (117 men and 133 women, mean age — 37.4 years) with early VTE debut (aged up to 45 years inclusive). In 105 (42%) of them, a recurring course of thrombosis was observed. In all patients a molecular genetic study of DNA polymorphism of 9 genes involved in the regulation of hemostasis plasma activity was carried out: α- and β-subunits of factor (F) I (Thr312Ala and –455 G/A, respectively), FII (20210 G/A), FV (1691 G/A), FXII (46 C/T), FXIII A sub- unit (Val34Leu), plasminogen activator inhibitor type I (PAI-1, —675 4G/5G), tissue plasminogen activator (tPA, 311 bp Ins/Del), and the endothelial protein C receptor (EPCR, Ser219Gly). Assessment of statistical significance of differences in genotype distribution between the groups of patients with recurrent VTE and a single episode of thrombosis history was performed us- ing Fisher’s exact method. Results. In the long-term period VTE recurrence was revealed in 105 (42%) patients. The comparison group consisted of 103 (41.2%) patients with a single VTE episode in the anamnesis. In 42 (16.8%) patients the presence or absence of disease recur- rence was not revealed. Genotype «tPA Del Del» met 2 times less frequently in patients with recurrent VTE (14.3% vs 28.2% in individuals with a single episode of VTE; OR = 0.4; 95% CI: 0,2–0,9; p = 0.017) that indicates its possible protective effect on the risk of disease recurrence. For the remaining genes no significant differences in genotypes distribution between the compared groups were found. Study of «gene-gene interactions» of tPA and PAI-1 variants revealed significant differences between groups of patients: the combination «tPA Del/Del + PAI-1 4G5G» was 3.5 times less frequent in the group with recur- rent venous thrombosis (3.8% against 13.6%; OR = 0.3; 95% CI: 0.08–0.8; p = 0.011) while the combination of the genotypes «PAI-1 5G5G + tPA Ins/Del», in contrast, was typical for this group (13.3% vs. 5.8% in individuals with a single episode of VTE; OR = 2.5; 95% CI: 0.9–6.7; p = 0.054). Conclusion. Group of young patients with recurrent VTE is characterized by a significant reduction in the incidence of genotype tPA Del/Del as well as the combination of «tPA Del / Del + PAI-1 4G5G». To clarify the effect of polymorphism of these genes on the risk of developing of VTE recurrent episodes additional studies are needed.

Assessment of Anticoagulation in Patients Receiving Ultrasound-Assisted Catheter-Directed Thrombolysis for Treatment of Pulmonary Embolism.

Ultrasound-assisted, catheter-directed thrombolysis (USAT) has emerged as a popular treatment option for submassive pulmonary embolism (PE). The optimal strategy for transitioning patients from full-intensity to reduced-intensity heparin during the procedure has yet to be established. The goal of this study was to evaluate the anticoagulation management in patients receiving catheter-directed thrombolysis with USAT. A retrospective chart review was conducted of patients who received USAT for the treatment of PE. Institutional review board approval was obtained. The primary objective was to determine the proportion of patients with a therapeutic activated partial thromboplastin time (aPTT) prior to and during tissue-plasminogen activator (tPA) infusion. Secondary outcomes included heparin requirements, the rate of bleeding complications, and the appropriateness of long-term venous thromboembolism management. A therapeutic aPTT value was achieved in 32 patients (54.2%) prior to USAT and 35 patients (59.3%) during tPA infusion. Heparin requirements were reduced from 15.1 ± 4.1 to 12.8 ± 4.2 U/kg/h for patients who achieved a therapeutic aPTT both prior to and during tPA infusion. Bleeding occurred in 34.4% of patients and tended to be minimal (20.3%) or minor (10.9%). The majority of patients were discharged on a direct oral anticoagulant (63%), followed by warfarin (32%) and enoxaparin (5%). Conclusion and Relevance: To our knowledge, this is the first study that has assessed heparin management in the setting of USAT. The results of these data may aid in empirically dose adjusting unfractionated heparin to ensure safe and effective anticoagulation for patients receiving USAT.

Direct Oral Anticoagulants and the Paradigm Shift in the Management of Venous Thromboembolism.

The advent of direct oral anticoagulants (DOACs) has revolutionized anticoagulation management in both stroke prevention and venous thromboembolism (VTE) treatment/prevention. Clinical trials and secondary real-world data have shown that DOACs have similar efficacy and, in some cases, improved bleeding safety profiles compared with vitamin K antagonists. Together with benefits of patient convenience, this has shifted the risk-benefit ratio toward long-term anticoagulation. However, current VTE risk assessment models are based on vitamin K antagonists and do not take into account the new paradigm of DOACs. Therefore, challenges to the thrombosis community remain to determine patients who would benefit from long-term anticoagulation in the DOAC era. Here, the authors review the current literature on risks and benefits of DOACs and their potential role in long-term VTE thromboprophylaxis as well as in current risk assessment models. The increasing use of DOACs, led by their convenience of use and generally lower bleeding rates, calls for a reevaluation of the current models as the benefits of long-term anticoagulation may begin to outweigh risks and inconvenience associated with their predecessors.

Physicians' decision about long-term thromboprophylaxis in cancer outpatients: CAT AXIS, a case vignette study on clinical practice in France.

Data on long-term venous thromboembolism prophylaxis in cancer outpatients remain scarce. In the absence of clear and consistent treatment guidelines, our objectives were to describe and better understand clinical practice and to identify factors influencing the use of thromboprophylaxis. CAT AXIS was a multicentred cross-sectional study based on the completion of physician-profile questionnaires and the assessment of 10 e-mailed credible clinical scenarios of lung, colon and breast cancers by each of participants using the case vignette-validated method. A total of 224 physicians participated allowing the completion and the analysis of 2085 reviewed case vignettes corresponding to 765, 703 and 617 fictive clinical scenarios on lung, colon and breast cancers, respectively. The overall rate of thromboprophylaxis was 680/2085 (32.6%) among participants with a comparable proportion for the three types of cancer. Low-molecular-weight heparin (LMWH) was the most frequently used, by 92.7, 93.8 and 83.9% of participants for lung, colon and breast cancers, respectively; thromboprophylaxis duration of ≥ 3months was used by 74.4% of participants. Multivariate analyses revealed that the Eastern Cooperative Oncology Group index, metastatic malignancy, chemotherapy and history of thrombosis were significantly associated with the therapeutic decision unlike Khorana score and anaemia. In the absence of clear guidance, the use of thromboprophylaxis remains low and rather empiric even though the selection of LMWH by the majority of participants and treatment duration seems appropriate based on available data to date. Specific guidelines with corresponding awareness are required.

Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients.

Congenital heart disease (CHD) is a common condition in the pediatric population, affecting up to 1% of all live births (i.e., around 40,000 newborns/year in the United States). Although CHD does have a wide range of severity, by the age of 5 years approximately 80% of patients will require at least one surgical intervention to achieve a complete/palliative cardiac repair. Today, in light of their much-improved surgical survival, the care of these patients focuses on morbidity prevention and/or treatment. One such morbidity has been the increased frequency of thrombotic occlusions [e.g., cardioembolic arterial ischemic strokes; arterial, cardiac, and/or newly created shunt thrombosis; venous thromboembolism (VTE)]. Patients with CHD are at high risk of developing thrombosis due to the disruption of blood flow, CHD-related coagulopathy, inflammation, and/or platelet activation secondary to extracorporeal circulation support required during open-heart surgery or as a bridge to recovery, which can increase thrombus formation. In this article, we will discuss how the coagulation system is altered in patients with CHD in regard to the patient’s anatomy, procedures they undergo to correct their congenital heart defect, and other risk factors that may increase their thrombotic risk, focusing on VTE. We will also discuss the most recently published reports pertaining to guidelines on prophylaxis and treatment of VTE in this population. Finally, we will briefly address the long-term VTE outcomes for patients with CHD.

Factors influencing the use of thromboprophylaxis in cancer outpatients: CAT AXIS, a case-vignette study on clinical practice.

e18276 Background: Data on long-term venous thromboembolism (VTE) prophylaxis in cancer outpatients remain scarce. Our objective was to describe clinical practice and to identify factors influencing the use of thromboprophylaxis. Methods: CAT AXIS was a multicenter cross-sectional study based on the completion of physician-profile questionnaires and the assessment of 10 e-mailed credible clinical scenarios of lung, colon and breast cancer by each of participants using the case-vignettes validated method. Results: A total of 224 physicians participated allowing the completion and the analysis of 2,085 reviewed case vignettes corresponding to 765, 703 and 617 fictive clinical scenarios on lung, colon and breast cancers, respectively. The overall rate of thromboprophylaxis was 680/2085 (32.6%) among participants with a comparable proportion for the three types of cancer. Low-molecular-weight heparin (LMWH) was the most frequently used, by 92.7%, 93.8% and 83.9% of participants for lung, colon and breast cancer, respectively; treatment duration of ≥ 3 months was prescribed by 74.4% of participants. Multivariate analysis of factors influencing thromboprophylaxis based on patient’s characteristics is summarized in the table. Conclusions: In the absence of clear guidance, the use of thromboprophylaxis remains low and rather empiric even though the selection of LMWH by the majority of participants and treatment duration seems appropriate based on available data to date. ECOG index, metastatic malignancy, chemotherapy and history of thrombosis were significantly associated with the decision to use thromboprophylaxis in most situations. [Table: see text]