Incidence Of Venous Thromboembolism Research Articles

Brisk walking pace offsets venous thromboembolism risk equivalent to established monogenic mutations.

Mendelian mutations in F2 and F5 genes are known risk factors for venous thromboembolism (VTE). This study aimed to explore the association between walking pace and VTE, compare its risk with Mendelian mutations, and identify if blood biomarkers mediate this effect. We followed 445,261 UK Biobank participants free of VTE at baseline. Walking pace was self-reported, and carrier status for F2 and F5 gene mutations was determined by rs1799963 and rs6025 genotypes. We used a Cox proportional hazard model to estimate walking pace's effect on VTE risk, bidirectional Mendelian randomization (MR) analysis to assess causality, and mediation analysis to explore blood biomarkers. Over a median follow-up of 12.8 years, 11,155 incident VTE cases were identified. The 10-year incidence rates for brisk and slow walking paces were 1.32% and 3.90%, respectively. For F5 carriers, the rates were 1.70% (brisk pace) and 3.62% (slow pace). Brisk walking pace reduced VTE risk in F5 carriers (2.65%) compared to non-carriers with a slow pace (3.66%). MR analysis confirmed a causal relationship from walking pace to VTE risk. Mediation analysis revealed that serum albumin and cystatin C mediated 8.7% to 11.7% of the effect of brisk walking pace on VTE risk. A slow walking pace is causally associated with increased VTE risk. A brisk walking pace mitigates VTE risk, particularly in individuals with F5 gene mutations, and this effect is partially mediated by serum albumin and cystatin C.

The Effects of Perioperative Gender-affirming Hormone Therapy on Facial Feminization Surgery Adverse Events, Facial Features Addressed, and Esthetic Satisfaction: A Multimodal Analysis.

Facial feminization surgery (FFS) treats gender dysphoria in transfeminine patients by addressing the facial bony and soft tissue components. Individuals seeking FFS may be taking gender-affirming hormone replacement therapy [gender-affirming hormone therapy (GAHT)]. This study aims to better characterize the GAHT's impact on venous thromboembolism (VTE) risk, surgical planning, and outcomes. A systematic review and meta-analysis of the literature were carried out to assess the effect of perioperative GAHT continuation on VTE. Cochrane Q and I2 statistics measured study heterogeneity with the following meta-regression exploring these results. Simultaneously, a retrospective review of the senior author's FFS cohort was conducted to investigate GAHT duration's impact on FFS revision rate, complication incidence, and facial structures operated on. Eleven articles were included: 602 patients stopped GAHT, of whom 3 VTEs were recorded (0.49%). This is compared with one episode among the 925 who continued GAHT perioperatively (0.11%). Study heterogeneity was low (0%), but limited VTE sample size precluded meta-analytic conclusions. Gender-affirming hormone therapy duration does not impact the incidence of all-cause complications (P = 0.478), wound infection (P = 0.283), hematoma (P = 0.283), or VTE (P = 1). The only procedures significantly less associated with higher GAHT were tracheal shaving (P = 0.002) and mandibuloplasty (P = 0.003). Finally, the FFS revision rate was not associated with GAHT duration (P = 0.06). There is a paucity of data to assess the safety or harm of continuing GAHT in the FFS perioperative period. Thus, a shared provider-patient decision-making process examining the risks and benefits of GAHT perioperative continuation is warranted. As patients seeking gender-affirming care are diverse, a "one-protocol-fits-all" is not appropriate.

UK Foot and Ankle Thromboembolism (UK-FATE).

Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE. This was a multicentre, prospective national collaborative audit with data collection over nine months for all patients undergoing foot and ankle surgery in an operating theatre or TA rupture treatment, within participating UK hospitals. The association between VTE and thromboprophylaxis was assessed with a univariable logistic regression model. A multivariable logistic regression model was used to identify key predictors for the risk of VTE. A total of 13,569 patients were included from 68 sites. Overall, 11,363 patients were available for analysis: 44.79% were elective (n = 5,090), 42.16% were trauma excluding TA ruptures (n = 4,791), 3.50% were acute diabetic procedures (n = 398), 2.44% were TA ruptures undergoing surgery (n = 277), and 7.10% were TA ruptures treated nonoperatively (n = 807). In total, 11 chemical anticoagulants were recorded, with the most common agent being low-molecular-weight heparin (n = 6,303; 56.79%). A total of 32.71% received no chemical prophylaxis. There were 99 cases of VTE (incidence 0.87% (95% CI 0.71 to 1.06)). VTE-related mortality was 0.03% (95% CI 0.005 to 0.080). Univariable analysis showed that increased age and American Society of Anesthesiologists (ASA) grade had higher odds of VTE, as did having previous cancer, stroke, or history of VTE. On multivariable analysis, the strongest predictors for VTE were the type of foot and ankle procedure and ASA grade. The 90-day incidence of symptomatic VTE and mortality related to VTE is low in foot and ankle surgery and TA management. There was notable variability in the chemical prophylaxis used. The significant risk factors associated with 90-day symptomatic VTE were TA rupture and high ASA grade.

Rescue of COVID-19 Patient Complicated by Spontaneous Pneumothorax and Acute Pulmonary Thromboembolism

Abstract Pulmonary thromboembolism is a common cardiovascular disease, with high morbidity and mortality rates in hospitalized patients. Because of clotting disorders and hypoxemia caused by COVID-19, critically ill patients are highly susceptible to thrombotic complications. A study published in the Journal of the American Medical Association in 2022 showed that the incidence of venous thromboembolism (VTE) in critically ill COVID-19 patients was approximately 10% to 35%, whereas the incidence of VTE in autopsy cases was as high as 60% (JAMA Intern Med 182:1063-1070). Clinicians need increased awareness of VTE in COVID-19 patients, to reduce the risk of deep vein thrombosis and pulmonary thromboembolism and to be alert to life-threatening complications.

Evaluation of the Khorana score and association with venous thromboembolism incidence among patients with uterine cancer: Implications for patient care

Evaluation of the Khorana score and association with venous thromboembolism incidence among patients with uterine cancer: Implications for patient care

Venous thromboembolism incidence and risk factors in patients undergoing hematopoietic stem cell transplantation

BackgroundMalignancy is a well-known risk factor for venous thromboembolism (VTE), and the Khorana risk score is effective for screening solid tumor patients. However, there is a lack of validated screening tools and established risk factors for patients undergoing hematopoietic stem cell transplant (HCT). Current literature reports VTE incidence in HCT patients ranging from 2.5% to 8.5%. Anticoagulation is difficult to manage post-transplant given prolonged thrombocytopenia and the likelihood of bleeding. By identifying risk factors, a predictive model may be developed to prospectively test prophylaxis strategies in patients at the highest thromboembolic event (TE) risk. ObjectivesThis study evaluated the cumulative incidence of TE at 6 months following allogeneic and autologous HCTs. This study also aimed to identify risk factors for developing TE, to evaluate time from HCT to TE, and to compare one-year survival following HCT between patients experiencing TE and those who did not. Study DesignThis is a retrospective single-center study evaluating the incidence of TE events in adult subjects undergoing HCT between March 2014 and December 2019. ICD-9 and ICD-10 codes were used to determine cancer diagnosis, TE events up 180 days after HCT, and comorbidities of interest. Each subject was reviewed for data accuracy by manual retrospective chart review. The study employed statistical tests such as the cumulative incidence method with competing risks, Gray's test, and univariate and multivariate Cox proportional hazards models to analyze the time to first thromboembolic (TE) event, evaluate risk factors, and assess 1-year survival post-HCT in relation to TE events within 180 days of HCT. Variables examined included age, sex, body mass index (BMI), transplant type, hospital length of stay, history of TE prior to transplant, active infections, graft-versus-host disease (GVHD), veno-occlusive disorder (VOD), cytomegaly virus (CMV) and other factors. ResultsThe study included 636 evaluable patients; the majority were male (57.9%), white (68.7%), and underwent an autologous HCT (68.4%). Twenty-nine patients (4.6%) experienced a TE event within 180 days post-transplant. TE events were more common in the allogeneic transplant group (n=13/201, 6.5%) than the autologous transplant group (n=16/435, 3.7%) (p=0.122). The cumulative incidence of TE was higher in patients who developed an active infection than those who did not (7.6% vs 3.1%, P=.011). Hospital LOS [HR 1.03, 95% CI 1.0-1.06, p=0.036] and active infection [HR 2.34, 95% CI 1.1-4.95, p=0.027] were significantly associated with TE in the univariate analysis but were not retained in the final multivariate model. There was no difference in one-year survival among all patients who experienced a TE event and those who did not; however, in the autologous HCT subgroup, one-year survival rate was significantly lower in those with TE compared to those without TE (Figure 3c, 80.4% vs 95.3%, P=.01). Examined variables, including history of TE event and GVHD, were not associated with TE event risk. ConclusionWhile the overall incidence of TE in our study was low, many patients received pharmacologic or mechanical prophylaxis, suggesting such strategies may be effective in mitigating TE risk. Factors such as infection and hospital LOS may further increase TE risk. Providers should continuously monitor for risk factors and signs and symptoms of TE post-transplant. It is also imperative to consider chemical prophylaxis if counts are recovered while hospitalized.

Venous thromboembolism in adolescents and young adults with acute lymphoblastic leukemia treated on a pediatric-inspired regimen

Asparaginase (ASP)-containing regimens for acute lymphoblastic leukemia (ALL) are associated with venous thromboembolism (VTE). We evaluated the prevalence, risk factors, role of prophylaxis and clinical impact of VTE among adolescents and young adult (AYA) patients (15–50 years) treated on Dana-Farber Cancer Institute (DFCI) ALL protocols. The 1- and 2-year cumulative incidence of VTE were 31.9% (95% CI: 27.0%, 36.9%) and 33.5% (95% CI: 28.5%, 38.5%) respectively, with most events occurring during ASP-based consolidation phase (68.6%). VTE was more frequent in patients with overweight/obese vs. normal BMI (39.2% vs. 29.0%, p = 0.048). In a 1-year landmark analysis, the 4-year overall survival was 91.5%, without difference between patients with vs. without VTE (93.8% vs. 90.0%, p = 0.93). Relapse and non-relapse mortality rates were also similar. Among patients treated at Dana-Farber/Harvard Cancer Center, cerebral sinus vein thrombosis occurred in 3.6% of patients (8.5% of VTE events) in comparison to pulmonary embolism (32.9%) and deep vein thromboses (58.6%, 24.4% line-associated). In a Cox regression model for VTE free-time, elevated BMI was associated with shorter VTE free-time (HR 1.94 [95% CI 1.13-3.35], p = 0.018), while low molecular weight heparin (LMWH) prophylaxis as time-varying covariate was not. In conclusion, we found that VTE was frequent in AYAs treated on DFCI ALL protocols but did not impact survival outcomes. Overweight/obese BMI increased risk for VTE.

Estimated glomerular filtration rate versus creatinine clearance to determine anticoagulant dosage after lower-limb orthopedic surgery.

Anticoagulation is recommended for thromboprophylaxis after lower-limb orthopedic surgery. The suggested dosage is based on creatinine clearance (CCr) in the labels. However, most facilities only provide estimated glomerular filtration rate (eGFR) as laboratory data. Because the eGFR equation adjusts for a body surface area (BSA) of 1.73 m2, it may overestimate renal function in patients with a small BSA. This retrospective study aimed to determine whether different renal function estimation formulas affect the incidences of venous thromboembolism (VTE) and bleeding when determining anticoagulant dosages. This study included patients who underwent lower-limb orthopedic surgery and received anticoagulants (edoxaban, enoxaparin, and fondaparinux) between 2017 and 2020 at Yaizu City Hospital. Anticoagulant dosing was evaluated using CCr, eGFR, and de-indexed eGFR (without correction for BSA), and the incidences of VTE and bleeding were compared among these formulas. The median values for BSA, CCr, eGFR, and de-indexed eGFR were 1.40 m2, 56.0mL/min, 73.0mL/min/1.73m2, and 60.9mL/min, respectively. There was no significant difference in the VTE incidence among these formulas. However, when dose reduction or contraindication threshold was determined by eGFR vs. CCr, the bleeding incidence was significantly higher in the group that was overdosed by CCr (6.0% vs. 25.7%, p < 0.05). Similarly, using de-indexed eGFR vs. CCr, the bleeding incidence was significantly higher in the group that was overdosed by CCr (7.5% vs. 28.6%, p < 0.05). In orthopedic surgery, anticoagulant dosages should be based on CCr for patients with a small BSA to avoid bleeding risks.

Incidence, patient characteristics, and treatment patterns of U.S. active-duty service members diagnosed with COVID-19-associated VTE in the outpatient setting

Abstract Background Venous Thromboembolism (VTE) is a well-established complication of acute coronavirus disease 2019 (COVID-19) infection. We sought to clarify the incidence, patient characteristics, and treatment patterns of VTE within United States active-duty service members (ADSM) diagnosed with COVID-19 infection in the outpatient setting. Methods Our team conducted a multicenter retrospective review of the outpatient healthcare records for all U.S. ADSM diagnosed COVID-19-associated VTE between January 1, 2020, and April 30, 2022. The data was obtained from the COVID-19 surveillance case list maintained by the Armed Services Health Surveillance Division (ASHSD) of the U.S. Defense Health Agency (DHA). The Defense Medical Surveillance System (a database containing inpatient and outpatient electronic medical records for active-duty service members) was used to capture all appropriate medical encounters using ICD-10 coding for venous thromboembolic events within 365 days of COVID-19 diagnosis. Chart review for data adjudication was performed by the physician investigator team. Results Among 365,788 ADSM who were diagnosed with COVID-19 in the outpatient setting, a total of 159 patients were identified as having COVID-19-associated VTE. The overall incidence rate of VTE was 43.47 per 100,000 people within 365 days of diagnosis (90-day incidence rate of 32.5/100,000). The median time from COVID-19 diagnosis to VTE was 23 days (IQR 13-87). Of 159 patients, 33 (20.7%) were diagnosed with DVT, 143 (90%) with PE, and 20 (12.5%) with both PE and DVT. The median age was 30 years old (IQR 23-38). The majority of patients were male (85%). 49% were white. The most common medical comorbidity was obesity (33%), 11% had a history of active tobacco use, and 9.4% of patients had a prior VTE diagnosis. Only 34% of patients were vaccinated for COVID-19 prior to their diagnosis (35 Pfizer–BioNTech, 13 Moderna, and 4 other). 148 (93%) of patients were treated with a direct oral anticoagulant, 10 (6.2%) were treated with low molecular weight heparin, and 1 (0.8%) was treated with a vitamin K antagonist. 96 (60.3%) required hospitalization with 4 (2.5%) requiring subsequent thrombectomy. None experienced major bleeding events. Only 2 (1.3%) of the patients died within 22 days from VTE diagnosis. The remaining 98.7% were alive at 875 days (SD 230) of follow-up. Conclusion The incidence of venous thromboembolism in active-duty military patients with COVID-19 was rare, affecting mostly unvaccinated, minority men in their 30s with risk factors such as obesity, prior VTE, and prior tobacco use. Of the women with VTE, 54% were non-white minorities. While VTE diagnosis was associated with a low mortality rate, the majority of patients required hospitalization.

A novel dynamic risk score to predict venous thromboembolism (VTE) recurrences after 3 months of anticoagulation in patients with incident VTE and without active cancer

Abstract Background Predicting the risk of recurrent venous thromboembolism (rVTE) during and following anticoagulation is complex. Current models lack the ability to adapt to changing patient conditions over time and fail to account for the direct impact of anticoagulation in real-world clinical settings. Purpose To develop a dynamic risk prediction model for rVTE to help clinicians decide on the duration of anticoagulant therapy in conjunction with a model for bleeding (also submitted to the conference). Methods UK Clinical Practice Research Datalink data (2001-2020) was used to generate a retrospective cohort with first VTE who had received 3 months of anticoagulation. Patient episodes of rVTE were evaluated. Covariates were collected at baseline and subsequently as time-varying data to capture changes post-VTE. Hazards with 95% confidence intervals (CI) were estimated and covariates included in a Fine &amp; Gray model used as predictors of rVTE. An additive (logarithmic) scoring scheme was developed from subdistribution hazard ratios, discrimination (expressed by the C-statistic) estimated from 10-fold cross-validation. Results 51,465 patients with a first VTE were included; 4041 rVTE were identified in 200,698 person-years of observation. Incidence rates for rVTE were 2.01 per 100 person-years. Nineteen independent predictors of rVTE (recorded before or after the VTE diagnosis) were included in the model, 13 associated with increased risk and 6 with decreased risk, Table 1. Patients recognised as lower-risk, medium and higher-risk (10.5%, 37% and 52.5% of the population, respectively, at 90 days after first VTE, assuming no anticoagulation treatment) had an annualised rVTE incidence rate of 2.20, 3.84, and 7.44 per 100 person-years. The C-statistic for rVTE was 0.65 (95%CI, 0.64-0.66). The points scored can be added or subtracted to predict risk (Table 2). Conclusions Our dynamic risk score effectively identifies patients at risk of rVTE three months post their initial VTE diagnosis. It allows for continuous monitoring of risk, and modelling of treatment impact, providing clinicians with a pragmatic tool to help determine treatment duration, and adapt their strategies in response to evolving patient conditions.Table 1:Predictors for VTE recurrenceTable 2:VTE recurrence risk score

A novel dynamic risk score to predict Clinically Significant Bleeding (CSB) after 3 months of anticoagulation in patients with incident Venous ThromboEmbolism (VTE) and without active cancer

Abstract Background Predicting the risk of clinically significant bleeding (CSB), bleeding requiring hospitalisation or fatal bleeding, during and following anticoagulation is complex. Current models lack the ability to adapt to changing patient conditions over time and fail to account for the direct impact of anticoagulation in real-world clinical settings. Purpose To develop a dynamic risk prediction model for CSB to help clinicians decide on the duration of anticoagulant therapy in conjunction with a model for recurrences of VTE (also submitted to the conference). Methods UK Clinical Practice Research Datalink data (2001-2020) was used to generate a retrospective cohort with first VTE who had received 3 months of anticoagulation. Patient episodes of CSB and recurrent VTE were evaluated. Covariates were collected at baseline and subsequently as time-varying data to capture changes post-VTE. Hazards with 95% confidence intervals (CI) were estimated and covariates included in a Fine &amp; Gray model used as predictors of CSB. An additive (logarithmic) scoring scheme was developed from subdistribution hazard ratios, discrimination (expressed by the C-statistic) estimated from 10-fold cross-validation. Results 51,621 patients with a first VTE were included; 3307 CSB were identified in 206,292 person-years of observation. Incidence rates for CSB were 1.60 per 100 person-years. 18 independent predictors of CSB (recorded before or after the VTE diagnosis) were included in the model, Table 1. Patients recognised as lower-risk, medium and higher-risk (67.5 %, 15.9 % and 16.7 % of the population, respectively, at 90 days after first VTE, assuming no anticoagulation treatment) had an annualised incidence rate of 0.84, 2.94, and 9.45 per 100 person-years. The C-statistic for CSB was 0.78 (95%CI, 0.77-0.79). The points scored can be added to predict risk (Table 2). Conclusions Our dynamic score effectively identifies patients at risk of CSB three months post their initial VTE diagnosis. It allows for continuous monitoring of risk, and modelling of treatment impact, providing clinicians with a pragmatic tool to help determine treatment duration, and adapt their strategies in response to evolving patient conditions.Table 1:Predictors for CSBTable 2:CSB risk score

The initial high-dose versus maintenance-dose anticoagulation therapy with direct oral anticoagulants for cancer-associated venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Initial high-dose anticoagulation therapy with rivaroxaban and apixaban has been a standard treatment for venous thromboembolism (VTE), although there could be concerns of an increased risk of bleeding events especially among high bleeding-risk patients including those with active cancer. Purpose The present study aimed to evaluate the clinical outcome of initial high-dose anticoagulation therapy comparing to maintenance-dose anticoagulation therapy in patients with cancer-associated VTE using propensity score-matching analysis. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Among 1507 patients with cancer-associated VTE, we evaluated 180-day clinical outcomes before discontinuation of anticoagulation therapy using a 1:1 propensity score-matching model with 21 risk-adjusting variables Results After the propensity score-matching, we enrolled 324 patients with initial high-dose anticoagulation therapy and 324 patients with initial maintenance dose anticoagulation therapy. Of patients with initial high-dose anticoagulation therapy, rivaroxaban and apixaban were administered in 198 and 126 patients, respectively. Of those with initial maintenance-dose anticoagulation therapy, rivaroxaban, apixaban, and edoxaban were administered in 34, 46 and 244 patients, respectively. The median durations of initial high-dose anticoagulation therapy were 18 [IQR: 15-21] days for rivaroxaban and 7 [IQR: 7-7] days for apixaban. In the current study population, the mean age was 67±12 years, 346 were women, and the mean body weight was 58±12 kg. There was no significant difference in the distribution of gastrointestinal cancer such as stomach and colorectal cancer between the 2 groups (4.6% vs. 4.9%, P=1.0, 8.3% vs. 11.4%, P=0.22). The cumulative 180-day incidence of discontinuation of anticoagulation was not significantly different between the 2 groups (27.8% vs. 30.5%, P=0.50). There were no significant differences in the cumulative 180-day incidences of recurrent VTE (3.1% vs. 1.0%, P=0.08), nor major bleeding (8.1% vs. 7.0%, P=0.66), nor all-cause death (25.1% vs. 21.6%, P=0.33) between the 2 groups. There were also no significant differences in the cumulative 180-day incidences of all clinically relevant bleeding (14.9% vs. 13.3%, P=0.72), gastrointestinal bleeding (8.4% vs. 5.4%, P=0.15), nor major gastrointestinal bleeding (5.4% vs. 2.7%, P=0.10). Conclusions There was no signal of an increased risk of recurrent VTE in the initial maintenance-dose anticoagulation therapy. Considering a numerically slightly higher incidence of gastrointestinal bleeding in the initial high-dose anticoagulation therapy for cancer-associated VTE, the initial maintenance-dose anticoagulation therapy could be a potential treatment option for selected patients including patients at a high risk of gastrointestinal bleeding.Study flow chartResults

The association between steroid use and recurrent venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background It is well known that use of oral steroids is a risk factor for development of venous thromboembolism (VTE). However, the impact of use of oral steroids on VTE recurrence has not been fully evaluated in the era of direct oral anticoagulants (DOAC), which has been a clinically relevant issue in the decision-making of anticoagulation strategies for patients who need oral steroids after VTE diagnosis. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with oral steroids after VTE diagnosis in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population were divided into 2 groups according to the use of oral steroids after VTE diagnosis; the steroid group and the non-steroid group. We compared clinical characteristics, management strategies, and outcomes including recurrent VTE, major bleeding and all-cause death, between the 2 groups. Results Patients with steroids and those without accounted for 693 (13%) and 4,504 (87%), respectively. Patients with steroids more often had chronic kidney disease (29% vs. 18%, P&amp;lt;0.001), autoimmune disease (50% vs. 5.4%, P&amp;lt;0.001), thrombocytopenia (7.7% vs 4.9%, P=0.002), and anemia (64.4% vs 54.1%, P&amp;lt;0.001), whereas there was no significant difference in the mean age (68.5 vs. 67.6 years old, P=0.16), the prevalence of women (62% vs 58%, P=0.06), active cancer (30% vs. 29%, P=0.42), and history of VTE (8.4% vs 6.8%, P=0.12) between the 2 groups. The cumulative 5-year incidence of discontinuation of anticoagulation therapy were not significantly different between the 2 groups (61.5% vs. 58.5%, log-rank P=0.16). The cumulative 5-year incidences of recurrent VTE nor major bleeding were not significantly different between the 2 groups (10.4% vs. 9.4%, log-rank P=0.55; 16.9% vs. 13.3%, log-rank P=0.16, respectively). Even after adjusting confounders, the risks of recurrent VTE nor major bleeding were not significantly different (adjusted hazard ratio = 0.97, 95% confidence interval = 0.65-1.45, P = 0.89; adjusted hazard ratio = 1.12, 95% confidence interval = 0.84-1.50, P = 0.44). The cumulative 5-year incidences of all-cause death was significantly different between the 2 groups (44.2% vs. 30.2%, log-rank P&amp;lt;0.001). Even after adjusting confounders, the risk of all-cause death remained significantly different (adjusted hazard ratio = 1.82, 95% confidence interval = 1.56-2.12, P&amp;lt;0.001). Conclusions Use of oral steroids after VTE diagnosis was not significantly associated with an increased risk of VTE recurrence in the DOAC Era, which might suggest that there could be no major concerns on an increased risk of recurrent VTE with oral steroids after VTE diagnosis under appropriate anticoagulation therapy.

Clinical outcomes of edoxaban treatment without parenteral anticoagulation therapy for acute venous thromboembolism: Insight from the COMMAND VTE Registry-2

Abstract Background Direct oral anticoagulants (DOACs) including edoxaban are currently widely used all over the world. Each DOAC has a specific usage for the treatment and second prevention of venous thromboembolism (VTE) in the acute phase as well as in the chronic phase. Edoxaban is recommended to be administered after an appropriate initial treatment including parenteral anticoagulation therapy such as heparin. However, because of the rapid anticoagulant effect of edoxaban after oral intake, some physicians could administer edoxaban initially without parenteral anticoagulation therapy in the daily clinical practice, which has not been investigated so far. Purpose The purpose of this study is to explore the effectiveness and safety of edoxaban treatment for VTE without initial parenteral anticoagulation therapy. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Of those, 1842 patients received edoxaban including 848 patients with pulmonary embolism (PE) and 994 patients with deep vein thrombosis (DVT) alone, who were divided into 2 groups based on the presence or absence of initial parenteral anticoagulation therapy with heparin. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the 2 groups. Results PE and DVT patients with initial parenteral anticoagulation therapy with heparin accounted for 623 (73.5%) and 244 (24.5%), respectively. After the PSM, 195 pairs of PE patients and 226 pairs of DVT patients were matched. In PE patients, those matched by the PSM were relatively mild cases compared to the unmatched cases (simplified PESI score=0: 25.9% vs. 12.4%, P&amp;lt;0.001). Whereas, in DVT patients, those matched were relatively severe cases compared to unmatched cases (isolated distal DVT: 24.1% vs. 71.0%, P&amp;lt;0.001). In the matched cohort, there was no significant difference in baseline characteristics between the 2 groups, including simplified PESI score in PE patients and thrombus location profile in DVT patients. In both PE patients and DVT patients, the 30-day cumulative incidences of all-cause death were not significantly different between the 2 groups (PE patients: 3.7% vs. 2.6%, P=0.56; DVT patients: 2.7% vs. 4.5%, P=0.31). Similarly, the 30-day cumulative incidences of recurrent VTE and major bleeding were not significantly different between the 2 groups (recurrent VTE: PE patients: 0% vs. 0.5%, P=0.32; DVT patients: 0.6% vs. 0.9%, P=0.99; major bleeding: PE patients: 1.5% vs. 3.2%, P=0.32; DVT patients: 2.2% vs. 3.2%, P=0.54) Conclusion In this current real-world VTE registry, a certain number of patients received edoxaban without parenteral anticoagulation therapy, who did not show a signal of worse clinical outcomes.

The influence of concomitant antiplatelet therapy in venous thromboembolism patients treated with anticoagulants in the DOAC era: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction The mainstay of treatment and second prevention of venous thromboembolism (VTE) is anticoagulation therapy, and recently direct oral anticoagulant (DOAC) for VTE have prevailed all over the world as oral anticoagulation therapy. Although concomitant antiplatelet therapy in addition to oral anticoagulation therapy could have an influence on both recurrent VTE and bleeding events, there have been still limited real-world data on the issue in the DOAC era. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with concomitant antiplatelet therapy in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulation therapy, the current study population was consisted of 4790 VTE patients with oral anticoagulation therapy, who were divided into 374 patients (7.8%) treated with concomitant antiplatelet therapy and 4416 patients (92.2%) treated with only oral anticoagulation therapy. Results Patients with concomitant antiplatelet therapy were older (Concomitant antiplatelet therapy: 74.1 vs. Only oral anticoagulation therapy: 67.3 years, P&amp;lt;0.001), were less often women (52% vs 59%, P=0.005) and more frequently had history of major bleeding (9.8% vs 6.0%, P=0.003), myocardial infarction (16% vs 0.9%, P&amp;lt;0.001) and stroke (33% vs 6.8%, P&amp;lt;0.001). The cumulative incidences of recurrent VTE were not significantly different between the 2 groups (5.9% vs 9.6% at 5-year, Log rank P=0.06). Similarly, the cumulative incidences of major bleeding (14.6% vs 13.3% at 5-year, Log rank P=0.11) and stroke (8.3% vs 6.0% at 5-year, Log rank P=0.12) were not significantly different between 2 groups. However, the cumulative incidences of clinically relevant all bleeding (29.0% and 23.0% at 5-year, Log rank P=0.007) were significantly higher in concomitant antiplatelet therapy group, which was statistically significant even after adjusting confounders. Conclusion In the current large VTE registry in the DOAC era, concomitant antiplatelet therapy in addition to oral anticoagulation therapy for patients with VTE was not significantly associated with the risks recurrent VTE, major bleeding or stroke, but was associated with an increased risk of clinically relevant all bleeding.Study Flow ChartMain results

Neutrophil Extracellular Traps: Potential Thrombotic Markers and Therapeutic Targets in Colorectal Cancer.

Neutrophil extracellular traps (NETs) are promising promoters in venous thromboembolism (VTE). In the present study, we have investigated the potential thrombogenic role of NETs in colorectal cancer (CRC). A total of 583 patients with gastrointestinal malignancies who were diagnosed with or without VTE by extremities arteriovenous ultrasound and computed tomography were enrolled. The incidence of VTE in CRC was as high as 17.53%. In serological ELISA experiments, Cit-H3, MPO and cfDNA were significantly overexpressed in CRC patients with VTE compared to CRC patients without VTE and healthy individuals. Neutrophils from CRC patients with VTE produced appreciable amounts of NETs after stimulation with phorbol-12-myristate-13-acetate, which were lacking in CRC patients without VTE and healthy individuals. CfDNA was positively correlated with plasmin-α2-antiplasmin complex and tissue plasmin activator inhibitor-1 complex, and Cit-H3 was positively correlated with plasmin-α2-antiplasmin complex, suggesting that NETs are associated with increased fibrinolytic activity. We screened some NETs-related genes by analysing several high-throughput sequencing datasets of VTE and NETs. FCGR1A was identified as the optimal target gene by pan-cancer expression analysis and survival analysis. FCGR1A was significantly overexpressed in the peripheral blood of CRC patients without VTE compared to healthy individuals and showed a positive correlation with cfDNA. Neutrophil-derived NETs were significantly reduced by FCGR1A inhibitor exposure. These findings indicate that NETs are actively involved in VTE in CRC. NETs are promising thrombotic marker and therapeutic target in CRC to prevent the thrombotic consequences of cancer.

Contribution of an Artificial Intelligence Tool in the Detection of Incidental Pulmonary Embolism on Oncology Assessment Scans

Introduction: The incidence of venous thromboembolism is estimated to be around 3% of cancer patients. However, a majority of incidental pulmonary embolism (iPE) can be overlooked by radiologists in asymptomatic patients, performing CT scans for disease surveillance, which may significantly impact the patient’s health and management. Routine imaging in oncology is usually reviewed with delayed hours after the acquisition of images. Nevertheless, the advent of AI in radiology could reduce the risk of the diagnostic delay of iPE by an optimal triage immediately at the acquisition console. This study aimed to determine the accuracy rate of an AI algorithm (CINA-iPE) in detecting iPE and the duration until the management of cancer patients in our center, in addition to describing the characteristics of patients with a confirmed pulmonary embolism (PE). Materials and Methods: This is a retrospective analysis of the role of Avicenna’s CE-certified and FDA-cleared CINA-iPE algorithm in oncology patients treated at Gustave Roussy Cancer Campus. The results obtained from the AI algorithm were compared with the attending radiologist’s report and were analyzed by both a radiology resident and a senior radiologist. In case of any discordant results, the reason for this discrepancy was further investigated. The duration between the exact time of the CT scan and analysis was assessed, as well as the duration from the result’s report and the start of active management. Results: Out of 3047 patients, 104 alerts were detected for iPE (prevalence of 1.3%), while 2942 had negative findings. In total, 36 of the 104 patients had confirmed PE, while 68 alerts were false positives. Only one patient reported as negative by the AI tool was deemed to have a PE by the radiologist. The sensitivity and specificity of the AI model were 97.3% and 97.74%, while the PPV and NPV were 34.62% and 99.97%, respectively. Most causes of FP were artifacts (22 cases, 32.3%) and lymph nodes (11 cases, 16.2%). Seven patients experienced delayed diagnosis, requiring them to return to the ER for treatment after being sent home following their scan. The remaining patients received prompt care immediately after their testing, with a mean delay time of 8.13 h. Conclusions: The addition of an AI system for the detection of unsuspected PEs on chest CT scans in routine oncology care demonstrated a promising efficacy in comparison to human performance. Despite a low prevalence, the sensitivity and specificity of the AI tool reached 97.3% and 97.7%, respectively, with detection of all the reported clinical PEs, except one single case. This study describes the potential synergy between AI and radiologists for an optimal diagnosis of iPE in routine clinical cancer care. Clinical relevance statement: In the oncology field, iPEs are common, with an increased risk of morbidity when missed with a delayed diagnosis. With the assistance of a reliable AI tool, the radiologist can focus on the challenging analysis of oncology results while dealing with urgent diagnosis such as PE by sending the patient straight to the ER (Emergency Room) for prompt treatment.

Unfractionated Heparin Administered Every 8 h Outperforms 12 Hourly Administration for Venous Thromboembolism Prophylaxis in Reconstructive Head and Neck Tumor Patients: A 12 Year Retrospective Cohort Study.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), poses a significant risk of morbidity and mortality in surgical patients, especially those undergoing head and neck cancer surgery with microvascular free flap reconstruction. These patients are at a heightened risk of VTE due to numerous patient and surgical risk factors. VTE chemoprophylaxis guidelines in these patients are limited due to a distinct paucity of research. This study aims to contribute to this scarcity of information, providing guidance for surgeons. This retrospective cohort study evaluated the efficacy and safety of subcutaneous unfractionated heparin administered every 8 h versus every 12 h for postoperative VTE prophylaxis in patients undergoing head and neck resections with immediate free flap reconstruction. Data was collected from hospital medical records between January 2010 to December 2021. Patient demographics, operative details, and outcomes, including incidence of VTE and bleeding complications, were analyzed. Among 622 patients, those receiving heparin every 8 h (n = 393) demonstrated a significantly lower rate of VTE (0.8%) compared to 12-hourly group (n = 229; 3.9%) (p = 0.006). Additionally, there were no significant differences in the rates of postoperative hematoma between the two groups (9.4% versus 7.9% respectively, p = 0.510). Our study suggests that an increased daily dose of unfractionated heparin every 8 h for VTE chemoprophylaxis is superior to a 12-hourly regimen with comparable bleeding profiles. Further multicentre, prospective studies are needed to validate these results and compare the efficacy and safety of unfractionated heparin with other agents such as low-molecular-weight heparin in this patient group.

Clots and bleeds: the outcomes of percutaneous coronary intervention in hemophilia patients with acute coronary syndrome.

Hemophilia is a disease characterized by a high risk of bleeding. With advances in treatment, life expectancy and aging-associated diseases such as coronary artery disease have increased. Our primary objective is to assess for major adverse outcomes, mortality, and length of hospital stay in individuals with hemophilia presenting for acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI). Our retrospective cohort study analyzed data from the Nationwide Inpatient Sample Database (NIS) for 2018 to investigate the outcomes of ACS management with PCI in adults with and without hemophilia. We used ICD-10 codes to exclude patients with significant comorbidities and identify those with ACS undergoing PCI. Propensity score matching and multivariable logistic regression were employed to account for over 20 baseline characteristics, mitigating confounding factors. The incidence of gastrointestinal bleeding (11.0% vs. 2.8%, p < 0.001), hemorrhagic stroke (10.0% vs. 1.4%, p < 0.001), and retroperitoneal hemorrhage (5.6% vs. 1.4%, p < 0.001) was significantly higher in individuals with hemophilia undergoing PCI compared to those without hemophilia. Additionally, venous thromboembolism (VTE) incidence was notably higher in the hemophilia cohort (6.6% vs. 2.4%, p = 0.027). The hemophilia cohort also experienced a higher mortality rate (7.1% vs. 3.3%, p = 0.037) and longer hospital stays. Patients with hemophilia undergoing PCI are at a significantly greater risk of adverse events, increased mortality, and longer hospital stays than the general population. To mitigate the risk of unfavorable outcomes, it is crucial to ensure adequate replenishment of coagulation factors and establish close collaboration between cardiologists and hematologists.

Ten-Year Trends in Venous Thromboembolism Prophylaxis at a High-Volume Arthroplasty Center

Introduction: Venous thromboembolism (VTE) prophylaxis is the standard of care after total joint arthroplasty. However, there have been changes in the prevalence of certain medication classes used by institutions over time driven by the literature and national clinical practice guidelines. The purpose of this study was to analyze the patterns of VTE medications over the past 10 years at our institution. Methods: We identified 25,095 patients who underwent a primary total joint arthroplasty between 2012 and 2022. Medications for VTE prophylaxis included aspirin, warfarin, unfractioned heparin (UFH), low-molecular-weight heparin (LMWH), factor-Xa inhibitors (FXa), and antiplatelet agents different from aspirin and thrombin inhibitors. Tranexamic acid use was recorded. The rates of symptomatic VTE were calculated and categorized as deep vein thrombosis or pulmonary embolism. Results: Venous thromboembolism rates decreased from 1.1% in 2012 to 0.2% in 2022 and ranged between 0.4% and 1.2% during the ten-year period. Although VTE incidence decreased in the past 4 years, an isolated increase was noted in 2021(1%). In 2012, the use of aspirin, warfarin, FXa, and UFH were 52.1%, 30.7%, 0%, and 16.2%, respectively, whereas in 2022, the rates for the same medications were 83.3%, 0.3%, 10.4%, and 1.8%, respectively. The use of LMWH, thrombin inhibitors, and other antiplatelet agents had minimal variation, and none of these medications surpassed 5% during this period. The aspirin dose changed from 325 mg in 2012 (96.5%) to 81 mg in 2022 (98.8%). Similarly, TXA use increased from 30.8% in 2012 to 84.9% in 2022. Conclusion: In the past 10 years, our institution has transitioned from warfarin, UFH, and high-dose aspirin to low-dose aspirin and FXa, exhibiting acceptably low deep vein thrombosis and diminishing pulmonary embolism rates during that time.