Taking a historical perspective, we review the discovery, pharmacology, and clinical evaluation of the old and new anticoagulants that have been approved for clinical use. The drugs are discussed chronologically, starting in the 1880s, and progressing through to 2024. The innovations in technology used to develop novel anticoagulants came in fits and starts and reflected the advances in science and technology over these decades, whereas the shift from anecdote to evidence-based use of anticoagulants was delayed until the principles of epidemiology and biostatistics were introduced into clinical trial design and to the approval process. Hirudin, heparin, and vitamin K antagonists were discovered by chance, and were used clinically before their mechanism of action was elucidated and before their net clinical benefits were evaluated in randomized clinical trials. Subsequent anticoagulants were designed based on a better understanding of the structure and function of coagulation proteins, including antithrombin, thrombin, and factor Xa, and underwent more rigorous preclinical and clinical evaluation before regulatory approval. By simplifying oral anticoagulation, the direct oral anticoagulants have revolutionized anticoagulation care and have enhanced the uptake of anticoagulation, but bleeding has not been eliminated and there is a need for more effective and convenient anticoagulants for thrombosis triggered by the contact pathway of coagulation. The newly developed factor XIa and XIIa inhibitors have the potential to address these unmet clinical needs and are undergoing clinical evaluation for several indications. SIGNIFICANCE STATEMENT: Anticoagulant therapy is the cornerstone of treatment and prevention of thrombosis, which remains a leading cause of morbidity and mortality worldwide. Elucidation of the structure and function of coagulation enzymes, their cofactors, and inhibitors, coupled with advances in structure-based design led to the discovery of more convenient, safer, and more effective anticoagulants that have revolutionized the management of thrombotic disorders.

In the field of global health, meeting the energy requirements of athletes has surfaced as an essential concern. This study seeks to evaluate the effectiveness of royal jelly (RJ) in improving exercise performance in endurance-trained men.

In this randomized, crossover, double-blind, placebo-controlled study, we will enroll 18 male endurance athletes. Participants will be randomly assigned to one of two conditions: the intervention condition, which will receive royal jelly (RJ) in 500 mg capsules taken orally twice daily for 2 weeks, or the control condition, which will receive a placebo consisting of 500 mg starch capsules taken orally twice daily for the same duration. The study will utilize a 2 × 2 crossover design with a 2-week washout period between treatments. To evaluate aerobic performance, we will determine each participant's maximal aerobic speed (MAS), followed by a test conducted at 80% of the MAS to measure time to exhaustion. Blood samples (5 cc) will be collected from all participants before and after the treadmill tests to analyze mRNA expressions of Nrf2 and PGC-1α, as well as oxidative stress parameters. Additionally, participants' dietary intake will be assessed using 3-day food records, and their blood pressure will be monitored before exercise, immediately after, and half an hour post-exercise.

This trial aims to evaluate the effectiveness of RJ as a nutraceutical agent for enhancing endurance athletic performance. We anticipate that the results will provide new insights into the clinical and molecular benefits of RJ. Additionally, these findings will offer valuable data to guide the design and execution of future clinical research involving RJ.

This study was registered in the Iranian Registry of Clinical Trials (registration No. IRCT20231209060310N1, date: December 21, 2023).

Data on the performance of the Khorana, PROTECHT, and ONKOTEV risk assessment models (RAMs) to predict venous thromboembolism (VTE) in patients with pancreatic cancer (PC) receiving outpatient chemotherapy remain limited. We performed a head-to-head comparison of these RAMs in patients with newly diagnosed PC enrolled in the nationwide, multicenter, and prospective BACAP cohort.

The Khorana, PROTECHT, and ONKOTEV scores were calculated at enrollment prior to chemotherapy. Patients were stratified into intermediate- and high-VTE-risk groups according to each RAM. The primary study outcome was VTE at a 6-month follow-up. The accuracy and discriminatory performance of the scores were assessed by calculating time-dependent Brier scores and c-indexes. Sub-distribution hazard ratios (SHRs) between high- and intermediate-risk patients were estimated.

Of 762 PC patients, 73 developed VTE within 6 months. In the competing risk analysis, the cumulative incidence of VTE at 6 months was 16.4% (95% CI, 13.8-19.1). The time-dependent Brier score was 0.14 (95% CI, 0.12-0.15) for all scores, indicating well-calibrated predictions. The respective time-dependent c-index of the Khorana, the PROTECHT, and the ONKOTEV scores was 0.50 (95% CI, 0.46-0.55), 0.50 (95% CI, 0.49-0.51), and 0.53 (95% CI, 0.48-0.58), indicating poor discrimination. The SHRs between high- and intermediate-risk patients ranged from 1.05 (95% CI, 0.76-1.44) for the ONKOTEV score to 1.06 (95% CI, 0.77-1.45) for the Khorana score.

In newly diagnosed PC patients receiving outpatient chemotherapy, the Khorana, PROTECHT, and ONKOTEV scores demonstrated a poor performance in predicting VTE at 6 months, highlighting the need for new tools to guide thromboprophylaxis decisions.

Coagulation disorders are increasingly recognized as significant complications in patients with solid tumors, affecting morbidity and mortality outcomes. Solid tumors can provoke a hypercoagulable state through the release of pro-coagulant factors, endothelial activation, and inflammation, leading to a heightened risk of coagulation disorders. These coagulation disorders may manifest as venous thromboembolism, arterial thromboembolism, thrombotic microangiopathy, or disseminated intravascular coagulation. These disorders can complicate surgical interventions and impact treatments, including chemotherapy and immunotherapy efficacy, leading to poor outcomes. Understanding the implications of coagulation disorders in solid tumors is essential for optimizing patient management, including identifying high-risk patients, implementing prophylactic measures, elucidating biomarkers for clinical outcomes, and exploring novel therapeutic agents. This review aims to provide insights into the current knowledge surrounding coagulation disorders in solid tumors and their clinical implications.

During the treatment of ovarian cancer, the risk of venous thromboembolism (VTE) post operatively is well established, however, patients may be at even greater risk during neoadjuvant chemotherapy (NACT). This study aimed to determine the incidence and timing of VTE amongst patients undergoing NACT, whether there was an association with survival, and examine risk factors associated with the development of VTE.

This was a retrospective cohort study of patients diagnosed with ovarian, fallopian tube and primary peritoneal cancer receiving neoadjuvant chemotherapy betweenApril 2011 and April 2022 at a gynaecological cancer centre in England. Clinical factors examined included: age at diagnosis, Body Mass Index (BMI), presence of inflammatory co-morbidity, tumour morphology, stage of disease, pelvic mass,ascites,retroperitoneal lymphadenopathy, Khorana score, serum albumin levels, chemotherapy regime, bevacizumab administration and Ca 125 levels.

Of 304 patients analysed, 73 (24%) patients developed venous thromboembolism. Of the patients who developed VTE, fifty-five patients developed pulmonary embolism (75%) and the stage of treatment at which most VTEs were diagnosed was neoadjuvant chemotherapy (32%). There was no correlation observed, between the incidence of VTE and any risk factors, including Khorana score, with the exception of low albumin (<35 g/L)(odds ratio (OR):2.1(95%CI 1.1-3.9; p = 0.06) and patients who did not receive paclitaxel chemotherapy (OR:2.04(95%CI 1.02-4.05; p = 0.08). There was no difference in survival rates between the VTE group and the non-VTE group.

This study demonstrates high rates of VTE, especially pulmonary embolism, in ovarian cancer patients undergoing NACT. The present study, amongst others in the literature also suggest that the risk of VTE in ovarian cancer patients undergoing NACT is underestimated by current risk stratification models. Therefore, prospective trials dedicated to ovarian cancer patients specifically, and a development of a risk model that takes into account factors established by higher levels of evidence, are strongly recommended.

Immune checkpoint inhibitors (ICIs), which offer previously unknown therapeutic advantages, have revolutionized cancer treatment. However, the risk of thromboembolic events (TEEs) associated with ICIs remains unclear. The aim of this network meta-analysis (NMA) was to evaluate the incidence of TEEs in cancer patients receiving different treatment regimens.

We searched for randomized clinical trials (RCTs) between January 2021 and December 2023 without restricting the cancer type. The percentages of TEEs were systematically extracted. An NMA was performed comparing atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, conventional therapy (which consists mainly of chemotherapy, targeted therapy, placebo, and their combinations), two ICI drugs, one ICI drug combined with conventional therapy, and two ICI drugs combined with conventional therapy. Additionally, subgroup analysis was conducted based on cancer type.

Eighty-three RCTs involving 54,736 patients were included. Patients receiving ICIs demonstrated comparable risks of arterial thromboembolism (ATE), deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVAs). Nivolumab (OR 0.39, 95 % CI 0.19 to 0.80) and two ICI drugs (OR 0.52, 95 % CI 0.29 to 0.89) had the lowest risk of venous thromboembolism (VTE) compared to two ICI drugs with conventional therapy. The risk of pulmonary embolism (PE) was greater for ipilimumab (OR 4.09, 95 % CI 1.13 to 15.51) than for nivolumab. For melanoma in the subgroup analysis, nivolumab significantly reduced the risk of VTE (OR 0.07, 95 % CI 0.00 to 0.76) compared to two ICI drugs. Among the single-ICI regimens, durvalumab was associated with the highest incidence of ATE, MI, and CVAs; ipilimumab had the highest incidence of VTE and PE; and pembrolizumab had the highest incidence of DVT. The combination of one ICI drug with conventional therapy was associated with a significantly greater risk of TEEs (except for MI) than the combination of two ICI drugs.

Various ICI regimens in cancer patients exhibit clinically significant differences in the risks of TEEs. Nivolumab exhibited a favorable safety profile regarding VTE, while ipilimumab had the highest risk of both VTE and PE. Different ICI regimens require tailored risk management strategies to reduce TEEs.

Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE).

We aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting.

We used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline-recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy. Patients were followed for 6 months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using C statistics.

We included 12 471 patients from 2012 to 2020. Of these, 416 (3.3%) developed VTE. The C statistic was 0.71 (95% CI, 0.68-0.74) for the new CAT score and 0.66 (95% CI, 0.63-0.70) for the Khorana score. The 6-month cumulative VTE incidence was 5.0% in 6175 patients classified as high risk by the new CAT score compared with 1.7% in 6296 patients classified as low risk. The 6-month cumulative VTE incidence was 5.2% in 4263 patients classified as high risk by the Khorana score compared with 2.4% in 8208 patients classified as low risk.

The new CAT score had a discriminatory ability similar to that reported in the derivation study. The C statistic was numerically higher than that of the Khorana score. Our findings support the implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE.

Patients with cancer undergoing systemic therapies have a high risk for venous thromboembolism (VTE). Risk assessment models were developed to select high-risk subgroups that might benefit from primary thromboprophylaxis, yet currently available models reportedly underperform in contemporary cancer treatment populations and risk models across multiple time points throughout therapy are not available.

We, therefore, aimed to validate the Vienna CATScore, a nomogram-based model including tumor type and continuous D-dimer levels, in a prospective cohort study of patients initiating contemporary systemic anticancer therapies. The validity of the model was tested at study inclusion, 3 weeks, and 3 months after start of therapy.

Overall, 598 patients were included [49% women, median age 62 years (interquartile range 53-70 years)]. Most patients had stage IV disease (68.2%). The 6-month cumulative incidence of VTE was 9.2% [95% confidence interval (CI) 6.8% to 11.5%]. The Vienna CATScore demonstrated good discriminatory ability (c-statistics: 0.69, 95% CI 0.61-0.76) at study baseline and across all evaluated time points (c-statistics: 0.68, 95% CI 0.63-0.73). Applying a 6-month predicted VTE risk threshold of 8%, the CATScore effectively distinguished between low- and high-risk groups at study inclusion (7.1% versus 15.1% observed VTE risk, P = 0.004) and across all three time points (6.3% versus 13.6% observed VTE risk, P < 0.001). Assuming a 50% risk reduction with thromboprophylaxis, this threshold resulted in a number needed to treat (NNT) of 13 and 15, respectively, in the high-risk group, while the NNT was 28 and 32, respectively, in the low-risk group.

This external validation of the Vienna CATScore confirms its effectiveness in predicting VTE risk in the initial months of state-of-the-art systemic anticancer therapies and across multiple time points.

The hemostatic system is tightly interconnected with cancer. Research has focused predominantly on thrombotic complications, but less is known about bleeding and bleeding risk prediction. Growth differentiation factor (GDF)-15 has previously emerged as a prognostic biomarker for bleeding.

The aim of this study was to investigate the association and predictive ability of GDF-15 for bleeding risk in patients with cancer.

The CAT-BLED (Vienna Cancer, Thrombosis, and Bleeding) study is a prospective, observational cohort study including cancer patients initiating systemic anticancer therapies. Patients were followed for up to 2 years for thrombotic and bleeding events. The primary outcome was major bleeding. GDF-15 was measured at inclusion and at 3 and 6 months of follow-up.

A total of 779 patients (48% women, median age 62 years, 15% on therapeutic anticoagulation) were included. During a median follow-up period of 18 months, 79 patients (10.1%) experienced major bleeding (12-month cumulative incidence 8.8%; 95% CI: 6.7-10.9). Higher GDF-15 levels were independently associated with increased major bleeding risk (adjusted subdistribution HR per doubling: 1.29; 95% CI: 1.04-1.59), and patients with levels greater than the cohort median (1,864 ng/L) had a significantly higher 12-month cumulative incidence (13.1% vs 4.6%; P < 0.001). This association remained robust in follow-up measurements at 3 and 6 months. GDF-15 showed moderate to good discrimination for predicting 6-month major bleeding risk (C statistic = 0.69; 95% CI: 0.60-0.77). GDF-15 was not associated with venous thromboembolism but was strongly associated with mortality (adjusted HR: 1.37; 95% CI: 1.25-1.50).

GDF-15 levels predict major bleeding risk in cancer patients and are not associated with venous thromboembolism, making GDF-15 a particularly promising biomarker for bleeding risk prediction.

Hemorrhagic complications associated with regional anesthesia are extremely rare. The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy reviews the published evidence since 2018 and provides guidance to help avoid this potentially catastrophic complication.The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy uses similar methodology as previous editions but is reorganized and significantly condensed. Therefore, the clinicians are encouraged to review the earlier texts for more detailed descriptions of methods, clinical trials, case series and pharmacology. It is impossible to perform large, randomized controlled trials evaluating a complication this rare; therefore, where the evidence is limited, the authors continue to maintain an 'antihemorrhagic' approach focused on patient safety and have proposed conservative times for the interruption of therapy prior to neural blockade. In previous versions, the anticoagulant doses were described as prophylactic and therapeutic. In this version, we will be using 'low dose' and 'high dose,' which will allow us to be consistent with other published guidelines and more accurately describe the dose in the setting of specific patient characteristics and indications. For example, the same 'high' dose may be used in one patient as a treatment for deep venous thrombosis (DVT) and in another patient as prophylaxis for recurrent DVT. Due to the increasing ability to obtain drug-specific assays, we have included suggestions for when ordering these tests may be helpful and guide practice. Like previous editions, at the end of each recommendation the authors have clearly noted how the recommendation has changed from previous editions.

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a highly malignant subtype of gastric cancer, but solely alpha-fetoprotein may fail to accurately predict the prognosis. Although the utilization of multi tumor markers could improve stratified patient management, such research in AFPGC is still blank. This study seeks to evaluate whether combining multiple tumor markers can enhance risk stratification and identify AFPGC subtypes with poor prognosis.

We first screened for patients with elevated serum CEA levels within the AFPGC cohort and evaluated their prognosis. Tumor characteristics and overall health conditions were analyzed to identify factors contributing to CEA elevation. Finally, the treatment responses of this group to different treatment modalities were also reviewed.

Approximately 45% of gastric cancer patients with elevated serum AFP also show increased CEA levels, classifying them as the dual-positive gastric cancer (DPGC) subgroup. These patients exhibit significantly shorter overall survival, heightened metastasis risk, and are more susceptible to systemic inflammation, immune response dysregulation, malnutrition, and cancer-related thrombosis. The elevation in serum CEA levels may indicate gastric cancer liver metastasis and increased neutrophils. While surgery is optimal for AFPGC, DPGC patients benefit significantly from immunotherapy combined with chemotherapy.

In AFPGC, combining serum AFP and CEA offers a more accurate prognosis. The poor prognosis in DPGC may be associated with aggressive local properties and systemic complications. Liver metastases and increased neutrophils are associated with increased serum CEA in AFPGC. Immunochemotherapy is a viable option for DPGC patients who cannot undergo surgery.

Improved efficacy has been shown for amivantamab and amivantamab-based combination therapies in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) compared to established treatment options in clinical trials. However, a high risk of venous thromboembolism (VTE) was observed in patients treated with amivantamab-based therapies, with considerable differences in VTE risk according to the line of systemic treatment, concomitant treatment with lazertinib, and intravenous vs. subcutaneous amivantamab administration. Based on early reports of high VTE rates, prophylactic anticoagulation has been implemented in ongoing clinical trials for the first 4 months of amivantamab-lazertinib therapy. However, open questions remain concerning the type, dosing, and duration of primary pharmacological thromboprophylaxis in patients treated with amivantamab-based therapies. Therefore, the aim of this clinical opinion piece is to provide provisional guidance on how to mitigate VTE risk in patients treated with amivantamab-based therapies following existing clinical practice guidelines on primary thromboprophylaxis and treatment of VTE in ambulatory patients with cancer.

The incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumour site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumour site.

We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumour-directed systemic therapy. The incidence of symptomatic ATE (acute ischaemic stroke, acute myocardial infarction, or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation, were meta-analysed by primary tumour site using random-effects modelling. We included 10 randomized controlled trials with 9875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2 = 0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2 = 0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2 = 0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumour sites.

Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed a lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Cancer patients have an increased risk of venous thromboembolism, which is their second cause of death after disease progression itself. Several thrombotic risk factors coexist in cancer patients, including the ability of both cancer and tumoral microenvironment's cells to directly or indirectly activate platelets and the enzymes of the coagulation cascade, resulting in a hypercoagulable state of blood. This narrative review gives an overview of the main mechanisms leading to venous thromboembolism in cancer patients, including the role that platelets and the clotting proteins may have in tumor growth and metastasis. Of note, the hemostatic balance is altered in cancer patients who may, next to a thrombosis tendency, also have an increased risk of bleeding. To highlight the complexity and the precariousness of the hemostatic balance of these patients, we discuss 2 specific gastrointestinal malignancies: hepatocellular carcinoma, which is frequently associated with liver cirrhosis, a condition that causes profound alterations of hemostasis, and colorectal cancer, which is characterized by a fragile mucosa that is prone to bleeding. Understanding the molecular mechanisms of cancer-associated thrombosis may give a unique opportunity to develop new innovative drugs, acting differently on distinct pathways and potentially allowing to reduce the risk of bleeding related to antithrombotic therapies. SIGNIFICANCE STATEMENT: The topic is significant because understanding the molecular mechanisms leading to cancer-associated thrombosis and bleeding, focusing on gastrointestinal malignancies, enables the development of more rationale and innovative antithrombotic strategies for cancer-associated thrombosis. Eventually, this will support an improved and patient-tailored antithrombotic management in vulnerable oncologic patients.

Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment models and the latest guideline recommendations. Finally, it summarizes gaps in knowledge, discusses future directions, and highlights recent advances and state-of-the-art research presented at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand.

Tumor thrombus can be associated with an increased risk of venous thromboembolism (VTE) and poor prognosis. The risks and benefits of anticoagulation remain unclear.

To evaluate the role of anticoagulation and associated outcomes in patients with tumor thrombus.

We conducted a single-center retrospective cohort study in patients with tumor thrombus from 2019 to 2022. All patients were followed for 12 months from the diagnosis of tumor thrombus or until death if death occurred earlier. The primary outcome was the percentage of patients prescribed any dose of anticoagulation for tumor thrombus (or concurrent bland thrombus/VTE). The secondary outcomes included new thrombosis, major bleeding, clinically relevant nonmajor bleeding, and mortality. We calculated the 6- and 12-month cumulative incidence of outcomes with 95% CI and compared those given anticoagulation vs not, considering death as a competing risk.

We included 211 patients, among whom 106 (50.2%; 95% CI, 47.9%-52.6%) were given anticoagulation for tumor thrombus or concurrent VTE (present in 21.8%). The most common type of cancer was hepatocellular carcinoma (28%). Splanchnic veins were the most commonly involved (49.3%). Anticoagulation was more likely used if tumor thrombus involved the inferior vena cava and/or the heart, with concurrent VTE, or if thrombosis service was consulted. The overall 12-month incidence of new VTE was 11.4% (95% CI, 7.3%-16.5%), that of major bleeding + clinically relevant nonmajor bleeding was 36.6% (95% CI, 29.6%-43.5%), and mortality of 52.5% (95% CI, 44.8%-59.6%), with no significant differences among groups given anticoagulation or not.

Patients with tumor thrombus carry high risks of VTE, bleeding, and mortality. The impact of anticoagulation remains unclear.

Cancer-associated venous thromboembolism (CAT) is common in patients with cancer and associated with significant morbidity and mortality. The incidence of CAT continues to rise, complicating patient care and burdening healthcare systems. Patients with cancer experiencing VTE face poorer prognoses, making prevention and effective management imperative. This narrative review synthesizes evidence on thromboprophylaxis in ambulatory patients with cancer receiving systemic therapy and acute treatment strategies for CAT. Risk assessment models (e.g., Khorana score) aid in identifying high-risk patients who may benefit from thromboprophylaxis. Pharmacological thromboprophylaxis with low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) has been shown to reduce the risk of CAT without significantly increasing the risk of bleeding complications. However, implementation of risk-based strategies remains limited in clinical practice. For acute CAT management, LMWHs have been the standard of care, but DOACs are increasingly favored due to their convenience and efficacy. However, challenges persist, including bleeding risks and drug interactions. Emerging therapies targeting Factor XI inhibitors present promising alternatives, potentially addressing current limitations in anticoagulation management for CAT.

Venous thromboembolic events (VTEs) are the second-leading cause of death in cancer patients, with an incidence of 5%-17% in lymphoma patients, particularly higher in those with non-Hodgkin lymphoma (NHL). Existing risk assessment models (RAMs) like the Khorana and ThroLy scores have limitations and are inadequately validated for NHL patients. Coagulation markers such as D-dimer, thrombin-antithrombin complex (TAT), and thrombomodulin (TM) show a potential predictive value for cancer-associated VTE but lack extensive research in NHL.

This study aimed to analyze characteristics and predictive risk factors for VTE in newly diagnosed NHL patients and to evaluate and improve the clinical applicability of the Khorana and ThroLy scores.

Data were collected from newly diagnosed NHL patients to analyze characteristics and potential predictive risk factors for VTE. The clinical applicability of the Khorana and ThroLy scores was evaluated, and the ThroLy score was improved by adjusting the hemoglobin cutoff and combining it with D-dimer testing. Sequential testing with TM and TAT levels was also performed.

VTE developed in 7.09% of NHL patients. Independent risk factors for VTE included clinical Stage III/IV, mediastinal involvement, history of VTE, D-dimer≥ 1345 μg/dL, and platelet (PLT)≥ 298 × 109, and Hb≥ 110 g/L was an independent protective factor for VTE. The ThroLy score was improved by adjusting the hemoglobin cutoff and combining it with D-dimer testing. Sequential testing of TM and TAT achieved a sensitivity of 66.7%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 96.7%.

VTE is a significant complication in NHL patients. The study highlighted independent risk factors and proposed a modified risk assessment model that effectively predicted VTE risk, potentially optimizing prevention and reducing healthcare costs.

 Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction. In this systematic review and meta-analysis, we aimed to evaluate candidate biomarkers and their association with cancer-associated VTE.

 We searched Medline, EMBASE, and Cochrane Central for studies that evaluated biomarkers in adult cancer patients from inception to September 2022. We included studies reporting on VTE after a cancer diagnosis with biomarker measurements performed at a defined time point. Median/mean differences (for continuous measures) and odds ratios (for dichotomous measures) with 95% confidence intervals were estimated and pooled using random-effects models.

 We included 113 studies in the systematic review. Of these, 50 studies were included in the meta-analysis. We identified two biomarkers at cancer diagnosis (factor VIII and time to peak thrombin), three biomarkers pre-chemotherapy (D-dimer, fibrinogen, and mean platelet volume), and one biomarker preoperatively (platelet count) that had significant median or mean differences. Additionally, we found that hemoglobin <100 g/L and white blood count >11 × 109/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil-to-lymphocyte ratio ≥3 and preoperative platelet count ≥400 × 109/L were also found to be associated with future VTE risk.

 In conclusion, this study identified nine candidate blood biomarkers that may help in optimizing VTE prediction in cancer patients that should be further explored in future studies.

A recent clinical trial demonstrated that the use of apixaban was safe and equal to enoxaparin (LMWH) in post-operative gynecologic oncology patients. This study aimed to determine if these findings are applicable in a diverse patient population at a single site urban academic medical center.

This was a retrospective cohort study of patients who underwent an exploratory laparotomy for confirmed or presumed gynecologic cancer from the years 2017-2023 at a single-site urban academic medical center. Venous thromboembolism (VTE) prophylaxis with LMWH was standard practice at our institution up until January 2021 after which apixaban became standard for post-operative prophylaxis in our division. Baseline demographic and clinical characteristics of patients receiving apixaban post-operatively were compared to the population previously receiving enoxaparin. The primary outcome was a VTE event within 90 days of surgery. Secondary outcomes included major and minor bleeding events.

Two hundred fifteen patients met inclusion criteria, of which 65 were discharged on enoxaparin and 150 were discharged on apixaban. Baseline characteristics in terms of age, race/ethnicity and BMI found no significant difference between the two groups. Rates of any VTE event within 90 days of surgery were similar for apixaban and LMWH (3.33 % vs. 4.61 %, p = 0.6). Secondary outcomes demonstrated that the rate of a major bleeding event in apixaban group was 1.31 % and LMWH group was 3.08 %, (p = 0.38). Minor bleeding events in the apixaban group were comparable to the LMWH group (10.60 % vs 10.16 %, p = 0.5).

In this real world, urban setting, for women undergoing laparotomy for gynecologic cancer, apixaban as post-operative VTE prophylaxis showed no increase in VTE events and appeared safe with no increase in bleeding events compared to LMWH. This study adds to the literature demonstrating that apixaban is safe and effective for VTE prophylaxis in our gynecologic oncology patients.

Hemostatic imbalances are frequent in patients with cancer. Although cancer-associated thrombotic complications have been well characterized, data on bleeding events in patients with cancer are sparse. Therefore, we aimed to investigate the incidence, risk factors, and impact on prognosis of bleeding events in patients with cancer initiating systemic anticancer therapies in a prospective cohort study, the Vienna Cancer, Thrombosis, and Bleeding Study. The primary study outcome was defined as clinically relevant bleeding (CRB), comprising major bleeding (MB) and clinically relevant nonmajor bleeding. In total, 791 patients (48% female), with median age of 63 years (interquartile range [IQR], 54-70), with various cancer types, 65.5% stage IV, were included. Over a median follow-up of 19 months (IQR, 8.7-24.0), we observed 194 CRB events in 139 (17.6%) patients, of which 42 (30.0%) were tumor related, 64 (46.0%) gastrointestinal, and 7 (5.0%) intracerebral. The 12-month cumulative incidence of first CRB and MB was 16.6% (95% confidence interval [CI], 13.7-19.6) and 9.1% (95% CI, 6.8-11.3), respectively, in the whole cohort, and 14.4% (95% CI, 11.2-17.5) and 7.0% (95% CI, 4.7-9.2), respectively, in those without anticoagulation. Patients with head and neck cancer had the highest risk of CRB. Lower baseline hemoglobin and albumin were associated with bleeding in patients without anticoagulation. Seven (5.0%) bleeding events were fatal, of which 6 occurred in patients without anticoagulation. Patients with CRB were at an increased risk of all-cause mortality (multivariable transition hazard ratio, 5.80; 95% CI, 4.53-7.43). In patients with cancer, bleeding events represent a frequent complication and are associated with increased mortality.

Chronic kidney disease (CKD) is a pervasive disease of the current century that usually affects the adult population, especially people with diabetes and hypertension. According to the recent studies, inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction are determining risk factors in the pathogenesis of CKD. Melatonin as a strong antioxidant is produced in various tissues including the kidneys. The present clinical trial aims to examine the efficacy of melatonin supplementation on metabolic parameters, oxidative stress, and inflammatory biomarkers in diabetic patients with CKD.

This is a double-blind, randomized, placebo-controlled clinical study that will be investigated the impacts of melatonin supplementation in diabetic patients with CKD. Laboratory findings will be applied to diagnose diabetic CKD. Forty-eight eligible diabetic subjects with CKD will be selected and randomly assigned to receive 5 mg melatonin tablets or identical placebo twice daily for 10 weeks. Participants will be asked to remain on their usual diet and physical activity. The primary outcome of this study is changes in oxidative stress and inflammatory biomarkers. The secondary outcomes include changes in lipid profile, renal function indicators, fasting blood sugar and serum insulin, systolic and diastolic blood pressure (SBP and DBP), serum phosphorous concentration, sleep quality, body weight, body mass index (BMI), and waist circumference (WC). Statistical analysis will be conducted using the SPSS software (version 25).

We hypothesize that melatonin administration may be useful for treating diabetic CKD by modulating oxidative stress, inflammation, regulating lipid metabolism, and increasing insulin sensitivity through different mechanisms. The current trial will exhibit the effects of melatonin, whether negative or positive, on diabetic CKD status.

The current trial received approval from Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.SHARIATI.REC.1402.072).

This study had been registered in Iranian Registry of Clinical Trials.

IRCT20170202032367N9 on 11 August 2023. https://www.irct.ir/trial/70709 .

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

To determine the incidence of venous thromboembolism in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy in UK gynecological cancer centers. Secondary outcomes included incidence and timing of venous thromboembolism since cancer presentation, impact on cancer treatment, and mortality.

All UK gynecological cancer centers were invited to participate in this multi-center retrospective audit through the British Gynecological Cancer Society. Data were captured on all patients undergoing neoadjuvant chemotherapy for International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian cancer within a 12-month period during 2021-2022. Patients on anticoagulation prior to cancer presentation were excluded. Patients who were diagnosed with venous thromboembolism between cancer presentation and commencing neoadjuvant chemotherapy were also excluded from our analysis of venous thromboembolism rates from neoadjuvant chemotherapy.

Fourteen UK gynecological cancer centers returned data on 660 eligible patients. The median age was 67 years (range 34-96). In total, 131/660 (19.8%) patients were diagnosed with venous thromboembolism from cancer presentation until discharge following cytoreductive surgery. Between commencing neoadjuvant chemotherapy and post-operative discharge, 65/594 (10.9%) patients developed venous thromboembolism (median 11.3%, IQR 5.9-11.3); 55/594 (9.3%) during neoadjuvant chemotherapy, 10/594 (1.7%) during post-operative admission. There was no significant difference across centers (p=0.47). Of these 65 patients, 44 (68%) were diagnosed with pulmonary embolism and 30 (46%) with deep-vein thrombosis (nine had both), including in major abdominal/pelvic vessels, with 36 (55%) presenting symptomatically and 29 (45%) diagnosed incidentally on imaging. Venous thromboembolism resulted in mortality (n=3/65, 5%), and delays/changes/cancelation of treatment (n=18/65, 28%).

Across a large, representative sample of UK gynecological cancer centers, one in five patients undergoing neoadjuvant chemotherapy were diagnosed with a potentially preventable venous thromboembolism, including one in nine diagnosed after commencing chemotherapy. This led to adverse clinical consequences for one third, including delay to oncological treatment and mortality. This high venous thromboembolism rate justifies the consideration of thromboprophylaxis in this patient group.

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow. Fibrinolysis is initiated when tissue plasminogen activator (tPA) converts plasminogen to plasmin, which binds to and degrades a fibrin fiber. The effects of apixaban on clot structure and lysis have been incompletely studied.

We aimed to study apixaban effects on clot structure, kinetics, and fibrinolysis using thrombin (low or high concentration) or tissue factor (TF) to activate clot formation.

We used a combination of confocal and scanning electron microscopy and turbidity to analyze the structure, formation kinetics, and susceptibility to lysis when plasma was activated with low concentrations of thrombin, high concentrations of thrombin, or TF in the presence or absence of apixaban.

We found that the clotting activator and apixaban differentially modulated clot structure and lytic potential. Low thrombin clots with apixaban lysed quickly due to a loose network and FXa cleavage product's cofactor with tPA; high thrombin clots lysed faster due to FXa cleavage product's cofactor with tPA; TF generated loose clots with restricted lysis due to their activation of thrombin activatable fibrinolytic inhibitor.

Our study elucidates the role of apixaban in fibrinolytic pathways with different clotting activators and can be used for the development of therapeutic strategies using apixaban as a cofactor in fibrinolytic pathways.

To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy.

We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding.

In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation.

In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Apixaban is a widely used direct oral anticoagulant that is recommended over warfarin therapy for many clinical indications. In patients with atrial fibrillation, dose reductions are recommended for patients with advanced age (≥80 years), low weight (≤60 kg) or elevated serum creatinine (≥1.5 mg/dL), but there is no routine laboratory monitoring necessary for long term-use. Furthermore, apixaban dose reductions due to renal dysfunction are not recommended when treating acute venous thromboembolism. Apixaban-calibrated anti-Xa assays are readily available at some medical centres, and they may be of clinical utility in certain circumstances such as in patients with renal insufficiency, medication adherence assessment, periprocedural planning, extremes in body weight and advanced age. Here, we describe the case of an elderly patient with chronic kidney disease taking apixaban for acute pulmonary embolism. The patient had an unanticipated prolonged apixaban half-life, with detectable apixaban-calibrated anti-Xa levels for >10 days after the last administered dose, which delayed a necessary surgical intervention by >1 week. This case is an example of appropriately using apixaban-calibrated anti-Xa levels to guide therapeutic decision making in perioperative planning.

Over the past two decades, the incidence of cancer-associated thrombosis (CAT) has increased. It is nowadays a common and often serious complication among patients with cancer. Although medical thromboprophylaxis is recommended for most surgical and nonsurgical cancer patients, it has been infrequently used in ambulatory patients with cancer because of the burden of treatment and concerns about bleeding. However, various risk assessment scores are now available and randomized placebo-controlled trials have established the efficacy of low-molecular-weight heparin or the direct oral Xa inhibitors rivaroxaban and apixaban in ambulatory patients with cancer at high risk of venous thromboembolism (VTE). This review provides an overview of (1) primary thromboprophylaxis in the setting of hospitalized surgical and medical patients, (2) extended thromboprophylaxis after hospital discharge, (3) performance of risk assessment tools for CAT, and (4) primary thromboprophylaxis in ambulatory patients with cancer. The aim is to provide support to physicians in identifying ambulatory patients with cancer at high VTE risk who benefit most from medical thromboprophylaxis according to current recommendations from international guidelines.

Migraine is a severe neurological disorder that is recognized as one of the most common debilitating diseases worldwide. Although the exact cause of migraine is not known, research suggests that inflammation, oxidative stress, mitochondrial dysfunction, and insufficient nutrients may contribute to its development. Studies indicate that nutrition-based approaches are safer and more cost-effective strategies for managing migraine symptoms compared to medication. In this regard, the impact of nutrition, as a complementary medicine, is largely attributed to that of certain nutrients on inflammation and mitochondrial function. It is hypothesized that alpha-linolenic acid and L-carnitine, which possess anti-inflammatory and antioxidant properties, may be synergically beneficial for migraine patients. Therefore, this study will be conducted to assess the efficacy of alpha-linolenic acid and L-carnitine co-supplementation in patients with migraine.

This is a parallel, randomized, triple-blind, placebo-controlled clinical trial, in which 80 women aged 20 to 50 years with migraine will be assigned to receive either intervention group (n = 40) receiving both 1000 mg/day flaxseed oil and 500 mg/day L-carnitine simultaneously for 12 weeks, or control group (n = 40) receiving both 1000 mg/day paraffin oil and 500 mg/day maltodextrin as the placebos for the same duration. The primary outcomes include changes in clinical symptoms of migraine, including frequency, severity, and duration of attacks, serum levels of C-reactive protein (CRP), total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD). Secondary outcomes include mental health, sleep quality, and quality of life (QOL).

In this study, we aim to investigate the potential benefits of combining alpha-linolenic acid and L-carnitine as a treatment option for migraine sufferers. Migraine, characterized by recurrent severe headaches, affects a significant portion of the population and can significantly impact an individual's quality of life. By studying alternative therapies such as alpha-linolenic acid and L-carnitine, researchers hope to expand the range of treatment options available and potentially provide relief to migraine sufferers.

Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20121216011763N57). Registration date: 29 March 2023.

The protocol is version 1.0 dated December 30, 2023. Recruitment began on July 10, 2023, and is expected to be completed by January 22, 2024.

While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes.

The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation.

Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues.

Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting.

Northern New England Clinical Oncology Society Research Funding Program.

Venous thromboembolism is a frequent complication of acute hospital care, and this extends to inpatient rehabilitation. The timely use of appropriate thromboprophylaxis in patients who are at risk is a strong, evidence-based patient safety priority that has reduced clinically important venous thromboembolism, associated mortality and costs of care. While there has been extensive research on optimal approaches to venous thromboembolism prophylaxis in acute care, there is a paucity of high-quality evidence specific to patients in the rehabilitation setting, and there are no clinical practice guidelines that make recommendations for (or against) thromboprophylaxis across the broad spectrum of rehabilitation patients. Herein, we provide an evidence-informed review of the topic with practice suggestions. We conducted a series of literature searches to assess the risks of venous thromboembolism and its prevention related to inpatient rehabilitation as well as in major rehabilitation subgroups. Mobilization alone does not eliminate the risk of venous thromboembolism after another thrombotic insult. Low molecular weight heparins and direct oral anticoagulants are the principal current modalities of thromboprophylaxis. Based on the literature, we make suggestions for venous thromboembolism prevention and include an approach for consideration by rehabilitation units that can be aligned with local practice.

Venous thromboembolism (VTE) poses a significant challenge in the context of multiple myeloma, with an incidence of up to 10% in newly diagnosed patients and varying frequency in the relapsed/refractory setting. Accurate VTE risk assessment and personalized thromboprophylaxis strategies are important parts of supportive care in myeloma. There are three validated risk assessment models for prediction of VTE risk in newly diagnosed myeloma-SAVED, IMPEDE-VTE, and PRISM. In this review, we delve into the practical applications of VTE risk prediction models in the context of current therapies. By emphasizing the necessity of a tailored approach, we underscore the importance of considering patient-specific, disease-specific, and treatment-specific risk factors in each clinical scenario, and using that data to complement the output from risk assessment models. We also provide a summary of currently available data on VTE thromboprophylaxis in myeloma, and highlight specific situations where direct oral anticoagulants should be strongly considered. Our objective is to fill the critical gaps in VTE prophylaxis and management through the analysis of specific patient cases and provide a practical overview for clinicians.

Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China.

A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses.

Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase.

Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

Venous and arterial thromboembolism (VTE/ATE) often coexist with onco-hematologic diagnosis. This study aimed to assess the time relationship between the diagnosis of VTE/ATE and blood cancers. The second aim was to identify VTE/ATE risk factors related to the type of hematology disease and cardiac history.

A total of 1283 patients underwent cardio-oncology evaluation at the Institute of Hematology and Transfusion Medicine in Warsaw from March 2021 through March 2023 (2 years), and 101 (7.8%) cases were identified with VTE/ATE.

ATE compared with VTE significantly occurred more often before the diagnosis and treatment of hematologic malignancy: 33/47 (70.2%) vs. 15/54 (27.8%), p < 0.0001. The risk of a VTE episode is exceptionally high in the first months after the diagnosis of an onco-hematological disease and the initiation of anticancer treatment. The higher frequency of VTE was associated with acute myeloid leukemia (17 cases/270 patients/6.30%/p = 0.055), acute lymphocytic leukemia (7 cases/76 patients/9.21%/p = 0.025), and chronic myeloproliferative disease (7 cases/48 patients/14.58%/p = 0.0003). Only the risk of VTE was significantly increased before (OR = 6.79; 95% CI: 1.85-24.95; p = 0.004) and after diagnosis of myeloproliferative disease (OR = 3.12; 95% CI: 1.06-9.16; p = 0.04).

ATEs occur more often than VTE before a diagnosis of blood cancer. The risk of VTE is exceptionally high before and after diagnosis of chronic myeloproliferative disease.

The purpose of this study was to evaluate the discriminatory capability of the Khorana, PROTECHT, CONKO, and COMPASS-CAT scores in ambulatory patients with lung cancer.

This retrospective cohort study included 591 patients with newly diagnosed lung cancer. A symptomatic or incidental VTE occurred in 108 patients.

The Khorana score at a 2-point threshold had a discriminatory capability with an odds ratio (OR) of 1.80 and an AUC of 0.57 for 6 months, and an OR of 1.51 and an AUC of 0.55 for 12 months. The CONKO score at a 2-point threshold had a stronger discriminatory capability for both 6 months and 12 months with ORs of 3.00 and 2.13, and AUCs of 0.63 and 0.59, respectively. Additionally, higher white blood cell counts, higher neutrophil counts, hypoalbuminaemia, and not undergoing lung surgery were related to VTE occurrence (p < 0.05).

The Khorana score with the 2-point threshold was validated in ambulatory patients with lung cancer, with the results indicating a decline in its discriminatory capability over time (at 12 months vs. 6 months from diagnosis). The CONKO score at the original 2-point threshold showed a stronger discriminatory capability but further validation with a larger sample size is recommended. The identified predictors should be further investigated in future research.

The hemostatic system and cancer display a tight interconnection, and hemostatic imbalance frequently occurs in patients with cancer. While extensive knowledge about thrombotic risk has been generated, less is known about bleeding risk and associated risk factors. However, bleeding risk is of high significance as patients with cancer frequently receive therapeutic anticoagulation for various indications and/or are candidates for primary thromboprophylaxis. The risk of bleeding in patients with cancer is variable and difficult to assess in clinical practice. Certain clinical settings such as hospitalization, specific underlying risk factors (e.g., tumor type), and medications (e.g., anticoagulation) can contribute to the individual bleeding risk of a patient with cancer. In addition, some dynamic factors such as platelet count or kidney function have an impact. Particularly, data on baseline risk of bleeding are lacking to allow for risk assessment in cancer patients without anticoagulation. In contrast, risk assessment models for the prediction of bleeding events in cancer patients receiving anticoagulation have been developed; however, these have yet to be validated. The recognition of the importance of bleeding risk in cancer patients is growing, leading to an increasing number of studies investigating and reporting bleeding complications. As study designs and reporting of bleeding events vary, it is challenging to offer a clear synthesis of evidence. In this narrative review, we provide an overview of currently available data about incidence, risk factors, and clinical impact of bleeding events in patients with cancer, and critically review risk assessment models for bleeding in cancer patients during anticoagulant therapy.

Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.