Risk Of Venous Thromboembolism Research Articles

Cardiovascular disease burden and risk factor management in cancer survivors: insights from a large-scale East London cohort

Abstract Introduction Improvements in cancer survival have led to an urgent need to address long-term health issues among survivors, notably increased risk of cardiovascular disease (CVD). Shared risk factors may underpin at least part of this excess risk. Aims To investigate differences in cardiovascular risk profile between cancer survivors and controls; and to assesses the management of hypertension and statin use among cancer survivors compared with controls in a multi-ethnic and socio-economically diverse population. Methods The data were obtained from electronic health records of 1.2 million people registered with general practices in East London. It provides a snapshot of health records at the time of data extraction (01/01/2023). We identify individuals with record of past cancer (grouped into 20 cancer types) and their cardiovascular profile. Each cancer-exposed patient was age- and sex-matched to four non-cancer comparators. Multivariable logistic regression, with extensive adjustment for demographic and health-related variables, was used to elucidate the independent associations of past cancer with a range of cardiovascular outcomes. Patterns of guideline-directed risk factor control among cancer patients with hypertension and ischaemic CVDs (vs non-cancer controls) were assessed. Results The study consisted of 18,839 cancer survivors and 75,356 matched controls (64±15 years, 43% male), with marked ethnic diversity (cancer survivors: 48% White, 24% Black and 22% Asian) and socio-economic deprivation. Compared to matched controls, patients with past cancer had a higher prevalence of hypertension (44% vs. 41%) and chronic kidney disease (18% vs. 14%). We observed a higher prevalence of CVDs including venous thromboembolism (VTE) (5.6% vs. 2.8%), atrial fibrillation (AF) (6.5% vs. 5%), and heart failure (HF) (4.4% vs. 3.4%) among cancer survivors. Regression models fully adjusted for shared risk factors demonstrated an increased risk of a range of CVDs in patients with (any) past cancer, including VTE (OR 2.01), HF (OR 1.31) and AF (OR 1.27). CVD risk varied across cancer types (Figure 1). For example, lung cancer survivors had an elevated risk of VTE (OR 4.02), AF (OR 2.47), IHD (OR 1.45) and peripheral artery disease (OR 1.67) while colorectal cancer survivors had increased risks of VTE (OR 2.68), HF (OR 1.4) and AF (OR 1.32). In subgroup analyses, control of blood pressure and cholesterol did not differ significantly across cancer survivors and matched controls with hypertension and ischaemic CVDs, respectively. Conclusion We show higher burden of VRFs and an increased risk of CVDs among cancer survivors compared with non-cancer controls, with notable variation across cancer types. The lack of difference in control of blood pressure and cholesterol between cancer survivors and controls suggests that these risk factors did not explain the increased risk. Suggesting that an individualised approach to risk management is likely to be warranted.Risk of CVDs in Cancer Survivors

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

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 & 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

The incidence of cardiovascular conditions in patients admitted to hospital with and without COVID-19 in the South-East of Scotland

Abstract Background Multiple studies have reported an increased risk of acute myocardial infarction, cardiac arrhythmia, heart failure, myocarditis, and venous thromboembolism in patients admitted to hospital with COVID-19 infection. Whether the incidence of these cardiovascular conditions differ in patients hospitalised with COVID-19 compared to those who have COVID-19 excluded is not clear. Methods In a prospective, multi-centre, cohort study in secondary and tertiary care hospitals in Scotland, consecutive adults with symptoms of suspected COVID-19 were identified by the attending clinician using an electronic form integrated into the care pathway. Using linked electronic health record data, we evaluated the incidence of acute myocardial infarction, atrial fibrillation, heart failure hospitalisation, myocarditis, and venous thromboembolism during the index admission and the first 90 days following the index admission. In multivariable regression models the frequency of cardiovascular conditions at 90 days were compared in patients with confirmed COVID-19 infection defined by RT-PCR test with those in whom COVID-19 was excluded. Results Between April 2020 and May 2022, 53,644 (median age 68 [interquartile range, IQR 49-90] years, 54% women) consecutive patients were hospitalised and underwent RT-PCR for suspected COVID-19 infection. In total, 4,365 (8%) had COVID-19 confirmed and 49,279 (92%) had COVID-19 excluded. At 90 daythe myocardial infarction was less common (2% versus 5%) and venous thromboembolism was more common (6% versus 4%) in patients with COVID-19 compared to those without, but the proportion with atrial fibrillation (15% versus 14%), heart failure hospitalisation (10% versus 9%), and myocarditis (<0.1% versus <0.1%) were similar. Overall, the proportion with a cardiovascular condition at 90 days did not differ in patients with or without COVID-19 (Figure). Age (over 65 years, adjusted hazard ratio [aHR] 2.75, 95% confidence interval [CI] 2,61 to 2.89), male sex (aHR 1.35, 1.30 to 1.40), and risk factors (diabetes [aHR 1.13, 1.08 to 1.19], hyperlipidaemia [aHR 1.09, 1.01 to 1.18], hypertension [aHR 1.45, 1.39 to 1.52]) were independent predictors of cardiovascular complications, whilst COVID-19 status was not associated with increased risk (aHR 0.94, 0.88 to 1.01). Conclusion Cardiovascular conditions are common in patients hospitalised with suspected COVID-19, however the incidence at 90 days does not differ in those with or without COVID-19 and COVID-19 infection does not confer an increase in risk.

Life-Threatening Spontaneous Hematoma in Unusual Sites in Patients with COVID-19 on Anticoagulant Therapy: A Case Series

Thromboembolic manifestations are a common phenomenon in patients affected by corona virus (SARS CoV-2). Recent studies have shown that patients with acute renal failure are also at a greater risk of venous and arterial thromboembolism, 15-30% in ICU, and 7% inpatient care. However, frequently unjudicial use of anticoagulants may develop severe life-threatening hematoma. In our hospital settings we had a dedicated COVID Unit with a Hemodialysis facility. Our Nephrology department had managed 381 patients being COVID positive along with renal impairment from March 2020 to January 2022. Among these patients, four patients developed spontaneous non traumatic hematoma in unusual sites. On admission all the patients received treatment according to our national guidelines for COVID-19. Cases: It is a retrospective analysis in a single-centered hospital. Four cases with confirmed COVID-19 with acute kidney injury and on anticoagulant therapy had developed sudden concealed bleeding. These patients had no previous history of anticoagulant therapy before admission. Case 1 developed hemorrhage in Right lower anterior paramedian deep parietal wall of abdomen, Case 2 had hematoma in retroperitoneal space and in lower third of Iliopsoas, Case 3 developed hemorrhage in left cerebral hemisphere, Case 4 had Intramuscular Hematoma in left rectus abdominis. Out of these four patients two of them required Hemodialysis and one of them went into shock. All patients included were male. The mean age was 57±19.64years. All the four patients were initially managed conservatively with keen monitoring and with proper volume resuscitation, blood transfusion and discontinuation of the anticoagulants. Three of the patients survived with conservative management and one patient died due to sudden massive cardiac arrest. The use of therapeutic anticoagulant can increase the risk of bleeding in atypical sites and may exhibit higher patient death with COVID-19 if not identified at early stage. So a risk-benefit ratio of usage of anticoagulants should be kept in mind and further clinical trials needed to justify its random use in COVID-19. J Bangladesh Coll Phys Surg 2024; 42: 393-400

Venous thrombo-embolic events as the probable cause of arterial ischemic event in patients with patent foramen ovale

Abstract Introduction The origin of the emboli involved in patent foramen ovale (PFO)-related embolic events remains mostly unknown. Purpose To evaluate the venous thrombo-embolic (VTE) origin of patients with PFO-related embolic event. Methods Patients planned for PFO closure for secondary prevention of PFO-related arterial embolic event had a systematic venous thrombo-embolic (VTE) risk evaluation that included : an extensive questionnaire on past history of VTE events, clinical situations at high risk of VTE including complicated hemorrhoids, prior saphenectomy or venous sclerosis, varicocele, intrapelvic tumor, pregnancy, surgery or prolonged travel or presence of hyperthrombotic state (i.e., thrombophilia, active cancer or covid) and an abdominopelvic magnetic resonance venography (MRV) evaluation to identify any intrapelvic venous disease. Results From July 2020 to May 2023, 366 consecutive patients (Median age 51 [42-58] years, 42.9% female) were prospectively included. A past medical VTE events, a high risk VTE situation, a hyperthrombotic state and a pelvic venous abnormality on MRV were present in 8.5% (95%CI 6.0-11.8), 22.7% (95%CI 18.7-27.2), 7.1% (95%CI 4.9-10.2), and 36.3% (95%CI 31.6-41.4), respectively, and 58.5% (95%CI 53.4-63.4) of the patients presented at least one of the previous conditions. MRV identified various undiagnosed pelvic venous abnormalities with 20.0% of pelvic varices, 9.8% of May-Thurner-Cockett and 7.4% of Nutcracker phenomenons (Figure 1). Imaging abnormalities were more frequent among younger patients (aOR 1.02 95%CI:1.00-1.04) and women (aOR 1.94 ; 95%CI:1.25-3.02). Conclusion A majority of patients undergoing PFO closure for secondary prevention have a potential VTE source of paradoxical emboli suggesting that VTE events is the probable cause of arterial ischemic event in these patients.

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p<0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p<0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p<0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p<0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p< 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p< 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

Inherited thrombophilia and risk of venous thromboembolism in females in association with contraceptive use

Venous thromboembolism is a multifactorial disease and major cause of morbidity and mortality. Absolute risk of venous thromboembolism is less than 1 per 10,000 per year in women of reproductive age. Hormonal contraception is a common risk situation for venous thromboembolism in this part of the population. The risk of venous thrombosis depends on many factors, mainly female characteristics and also the type of contraception. Hematologists can help with the choice of contraception in females with inherited thrombophilia and females experiencing thrombosis. Intrauterine devices with levonorgestrel seem to be the best option in these settings.

Impact of Residual Vein Venous Thrombosis in Consecutive Patients with Cancer-Associated Thrombosis Treated with Tinzaparin—A Cohort Study

Background: The role of residual venous thrombosis (RVT) as a risk factor for recurrent venous thromboembolism (VTE) in patients with cancer-associated thrombosis (CAT) remains controversial. Methods: We conducted a cohort study on consecutive patients with CAT treated with tinzaparin recruited between 2007 and 2022. Primary outcome: RVT. Secondary outcomes: identification of variables associated with RVT and the role of RVT in VTE recurrences or clinically relevant bleeding (CRB). Results: Among 511 patients with CAT (age 64.1 years ± 13.4 years; 53.5% males) followed for 17.6 months (p25–75: 7.9–34), 35.8% (n = 183) presented RVT (at 6 months, 55.5%). Variables identified as being associated with RVT were ECOG performance status > 1, metastasis, and cancer location. Within 5 years, there were 57 CRB (11.2%; 95% CI: 8.6–14.2) and 67 VTE recurrences (13.1%, 95%CI: 10.3–16.4). Competing risk analysis identified that RVT at 6 months was associated with VTE recurrence within 5 years (sub-hazard ratio: 2.1; 95% CI: 1.2–3.7; p = 0.006), but not with CRB. Multivariate analysis confirmed that RVT at 6 months (HR: 2.1; 95% CI: 1.2–3.7) and metastases (HR: 1.7; 95% CI: 1.1–2.9) were associated with VTE recurrence within 5 years. Conclusions: RVT is high in patients with CAT. The presence of RVT at 6 months was associated with an increased risk of recurrent VTE over 5 years.

Clinical features, outcomes, and anticoagulant strategies in lung cancer-associated isolated distal deep vein thrombosis

IntroductionThe clinical presentation, outcomes, and anticoagulation strategies in patients with lung cancer-associated isolated distal deep vein thrombosis (LC-iDDVT) are not well-defined. Materials and methodsThe study included 593 patients with LC-iDDVT and 260 patients with lung cancer-associated proximal DVT (LC-Proximal DVT). LC-iDDVT was further classified into axial venous thrombosis (AVT; 112 patients) and muscular venous thrombosis (MVT; 481 patients). Cox proportional risk regression models with Fine-Gray tests and competing risk models were employed to evaluate short-term (90-day) and long-term (1-year) outcomes (hazard ratio [HR]; 95 % confidence interval [CI]). ResultsAt the 90-day follow-up, patients with MVT had lower adjusted risks of pulmonary embolism (PE; HR = 0.20 [0.07–0.55], p = 0.002) and venous thromboembolism (VTE) recurrence (HR = 0.54 [0.34–0.88], p = 0.013) than those with LC-Proximal DVT. Similar results were observed at the 1-year follow-up. However, adjusted risks for PE (HR = 0.74 [0.29–1.92], p = 0.540; HR = 0.87 [0.42–1.78], p = 0.700) and VTE recurrence (HR = 0.96 (0.54–1.71), p = 0.890; HR = 0.99 [0.63–1.56], p = 0.970) at 90-day and 1-year were not significantly different between patients with AVT and those with LC-Proximal DVT. Among patients with LC-iDDVT, those receiving anticoagulation had reduced risks of VTE recurrence (HR = 0.57 [0.35–0.95], p = 0.030) and DVT deterioration (HR = 0.28 [0.13–0.60], p = 0.001) compared to those without anticoagulation. Moreover, AVT patients on >3 months of anticoagulation had a lower VTE recurrence risk (HR = 0.23 [0.03–0.92], p = 0.038) than those on ≤3 months of anticoagulation. ConclusionIn the context of lung cancer, patients with AVT may have a higher tendency for recurrent thrombosis compared to those with MVT, especially if anticoagulation is refused or given briefly.

The Role of Screening for Venous Thromboembolism in Pelvic Trauma Patients: A Single-Centre Retrospective Study

Background: Venous thromboembolism (VTE) is a severe complication following pelvic trauma. Thromboprophylaxis has reduced the risk of VTE in the pelvic trauma population; nevertheless, the risk remains high. A substantial pulmonary embolism has emerged as the unexpected cause of death among patients presenting with ‘minor pelvic fractures’. The purpose of this study was to analyse the single-centre experience with a surveillance protocol. We hypothesised that DVT surveillance with VUS and CTPA may reduce the perioperative mortality–morbidity rate in the subpopulation of patients with pelvic or acetabular fractures. Methods: This is a retrospective analysis of patients admitted with pelvic or acetabular fractures between January 2001 and December 2021. In April 2013, a screening protocol for VTE was introduced. This protocol included venous ultrasound and CTPA for patients with chest injuries. Patients from two groups—one screened for VTE and one without screening—were compared. Results: Of the 3186 patients with pelvic and/or acetabular fractures who were admitted, 1975 were not screened for VTE and 1211 underwent screening. There were more VTE cases in the screening group (5.62% vs. 0.86%, p < 0.001). Nine (0.46%) cases of sudden death occurred in the non-screening group, and all of them died with symptoms of acute PE. Since the screening was introduced, we have not encountered any deaths in the perioperative period (0.46 vs. 0, p = 0.02). Conclusions: The combined use of VUS and CTPA in chest-injured patients is a trustworthy means of screening for VTE, resulting in decreased mortality rates for those with pelvic and acetabular fractures by accurately diagnosing VTE during the perioperative phase.

Venous thromboembolism and ovarian cancer risk: a Mendelian randomized study

IntroductionA potential link between venous thromboembolism and the risk of ovarian cancer has been identified in clinical practice. However, it is unclear whether there is a causal relationship between the two. In this study, we applied a univariate two-sample Mendelian randomization method to explain the possible link between venous thromboembolism and ovarian cancer pathogenesis at the genetic level, and pointed out that lipid metabolism and ovarian cancer pathogenesis have innovative basic experimental directions.ObjectiveThis study explored the causal effect between a history of venous thromboembolism and the risk of ovarian cancer.MethodsGenome-Wide Association Study (GWAS) data of venous thromboembolism patients (n = 9176) of the same ethnicity were selected as study exposures, and GWAS data of ovarian cancer patients (n = 1218) of the same ethnicity were selected as study exposures. In this study, univariate two-sample Mendelian randomization analysis (UVMR) was performed separately using inverse variance weighted (IVW), MR-Egger regression, and weighted median (WM) to assess causal effects. In this study, Cochran’s Q test, MR-Egger regression intercept term, MR-PRESSO, and leave-one-out method were used for sensitivity analysis to assess the stability and reliability of the results.ResultsThe GWAS data screened in this study were all European ethnicity data. In this study, we found that genetically predicted history of venous thromboembolism was associated with an upward trend in ovarian cancer incidence, and the results of Weighted median, Simple mode, Weighted mode, and MR Egger showed a similar trend (OR = 1.0006, 95% CI: 1.00007–1.0013, p < 0.05). There was no heterogeneity of results (p = 0.18) and no horizontal pleiotropy (p = 0.77). The instrumental variables selected for venous thromboembolism in this study were all strong instrumental variables (F = 669.7). The results of the sensitivity analysis remained consistent.ConclusionThe results of this study indicate that patients with a history of venous thromboembolism are at increased risk of developing ovarian cancer and point to possible associations between lipid metabolism genes, such as CYP4V2, and the development of ovarian cancer, which provide interesting directions for further basic research.

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.

Clinical Efficacy and Safety of Novel Anticoagulants for the Management of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis.

Cancer patients face a four- to sevenfold higher risk of venous thromboembolism (VTE) than the general population. Novel oral anticoagulants (NOACs) provide convenient alternatives to traditional therapies. We performed a systematic literature search across PubMed, Embase, and the Cochrane Library, targeting studies that examined the use of NOACs in cancer-associated VTE. The search included randomized controlled trials (RCTs). Selected studies compared NOACs with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKA) in cancer patients diagnosed with VTE. A meta-analysis using a random-effects model was applied to estimate pooled effect sizes for outcomes. In this meta-analysis, we included 12 RCTs. Results showed NOACs were more effective than LMWH in preventing VTE recurrence (RR 0.66, 95% CI 0.52-0.83, p = 0.0004). Compared with VKAs, NOACs showed no significant difference (RR 0.63, 95% CI 0.34-1.15, p = 0.13). However, this finding is limited by the small patient sample. Major bleeding outcomes were similar between NOACs and LMWH/VKAs (RR 1.24, 95% CI 0.85-1.80, p = 0.28; RR 0.77, 95% CI 0.39-1.53, p = 0.46, respectively). Meta-regression analysis indicated a statistically significant positive correlation between mortality and major bleeding events when comparing NOACs with LMWH (p = 0.049). There was no significant difference in all-cause mortality between patients treated with NOACs and those treated with LMWH (RR 1.04, 95% CI 0.92-1.18, p = 0.54) or VKAs (RR 0.94, 95% CI 0.72-1.23, p = 0.65). Meta-analysis shows NOACs, especially factor Xa inhibitors, reduce VTE recurrence in cancer patients more effectively than LMWH. Comparison between NOACs and VKAs is inconclusive due to limited patient data. Further research is needed to assess NOACs' efficacy and safety against VKAs.

Hereditary Angioedema and Venous Thromboembolism: Where There's Smoke, There's Fire.

C1-inhibitor deficiency-associated hereditary angioedema (C1INH-HAE) is a rare congenital swelling disorder caused by mutations in the SERPING1 gene. Despite evidence of a systemic procoagulant state in C1INH-HAE, dogma held that this disorder was not associated with thrombotic pathologies. Recent population scale epidemiological evidence has directly challenged this, with C1INH-HAE being associated with a significantly increased risk of venous thromboembolism (VTE). This review considers the growing body of evidence supporting associations between HAE and both a systemic procoagulant state and an increased risk of VTE. In the setting of C1INH-HAE, the relationship between the observed procoagulant and thrombotic phenotypes is a prime example of "where there's smoke, there's fire." This review also discusses the impact of C1INH-HAE disease modifying therapies on coagulation and VTE. Further, the utility of preclinical mouse models of C1-inhibitor deficiency is considered.

Risk of Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-analysis and Development of a Prediction Model.

About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions. To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT. For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot. After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies. The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.

Clinical analysis of bleeding and thrombotic events in haematological-oncology patients with severe thrombocytopenia and a high risk of thrombosis

Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 109/L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction. Results: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613–0.858, P = 0.003) and a cut-off value of 42.5 × 109/L. Conclusions: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 109/L.

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

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

Variation among venous thromboembolism risk assessment tools for postcesarean patients: a retrospective cohort study.

Venous thromboembolism (VTE) risk in pregnant women is four to five-fold higher than in nonpregnant women, and the risk of VTE is an additional four-fold higher after Cesarean section compared to normal vaginal delivery. Recommendations regarding anticoagulant prophylaxis are inconsistent across international guidelines, and VTE remains one of the leading causes of maternal morbidity and mortality. This study aimed to compare the need for postcesarean anticoagulation for VTE prophylaxis based on three major guidelines and our own institutional protocol. It was a retrospective cohort study that reviewed the medical records of patients who underwent a cesarean section at a tertiary-level care hospital in the United Arab Emirates (UAE). The need for anticoagulation was assessed using clinical tools from the American College of Obstetricians and Gynecologists (ACOG), Royal College Obstetricians and Gynecologists (RCOG), American College of Chest Physicians (ACCP), and the study site hospital protocol. A total of 1134 postcesarean women, aged 18-55 years, were included in the study. Most patients (87%) were at moderate risk for VTE. According to the study site hospital tool, 90.7% qualified for anticoagulant prophylaxis, while the ACOG, RCOG, and ACCP tools indicated that 0.5, 90.9, and 36.7% qualified, respectively. Enoxaparin was the primary anticoagulant used in 95% of cases. Only one patient developed VTE during the follow-up period. Anticoagulation needs assessment tools vary extensively in their estimations, highlighting the need for a uniform tool across multiple societies to establish a consistent standard of care and guide the development of evidence-based, site-specific protocols.

Role of PCSK9 Inhibitors in Venous Thromboembolism: Current Evidence and Unmet Clinical Needs.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have recently emerged as promising therapeutic agents for lowering low-density lipoprotein cholesterol and reducing the risk of cardiovascular events. Moreover, preliminary evidence from randomized controlled trials (RCTs) suggests that PCSK9i may also offer beneficial effects for patients following venous thromboembolism (VTE), with the most significant reductions in risk appearing over time, particularly beyond the first year of treatment. However, there is a lack of randomized controlled data supporting their efficacy and safety in conjunction with standard anticoagulation therapy. This article aims to critically evaluate the existing evidence for the use of PCSK9i as a complementary therapy for VTE risk reduction, while also identifying unmet clinical and research needs and proposing potential strategies to address these knowledge gaps.