Cancer-associated Thrombosis Research Articles

Machine Learning Models for Risk Prediction of Cancer Associated Thrombosis: A Systematic Review and Meta-Analysis.

While the number of models for predicting the risk of cancer-associated thrombosis has been rising, there is still a lack of comprehensive assessment for machine learning prediction models. To critically appraise and quantify the performance studies using machine learning to predict cancer-associated thrombosis. We conducted searches on PubMed, Embase, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and other related databases for the related publications (from inception to December 1, 2023). The Prediction Model Risk of Bias Assessment Tool checklist was employed to evaluate the risk of bias and applicability. The Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of evidence in systematic reviews. Meta-analyses were conducted using R (version 4.3.2). A total of thirty-two studies were included. Mostly included literature exhibits a high risk of bias, and the applicability of the prediction models is deemed acceptable. The twenty-one included studies in the meta-analysis demonstrated the high predictive capacity of the machine learning models for cancer-associated thrombosis. Most of the prediction models included in the study showed good applicability and excellent prediction performance, but there was a high risk of bias.

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.

Impact of thrombocytopenia on bleeding and thrombotic outcomes in adults with cancer-associated splanchnic vein thrombosis

AbstractMalignancy is a risk factor for splanchnic vein thrombosis (SpVT). Data on the natural history of cancer-associated SpVT are limited. This was a single-center, retrospective cohort study of 581 adult patients with cancer and SpVT. We aimed to characterize the impact of thrombocytopenia on major bleeding and progression or recurrence of SpVT within 1 year of an initial cancer-associated SpVT diagnosis. Baseline thrombocytopenia (platelet <100 000 per μL within 15 days of SpVT diagnosis) was present in 39.5% of patients. A total of 39.2% of patients received therapeutic anticoagulation within 2 weeks of an SpVT diagnosis. The cumulative 1-year incidence of major bleeding was 10.7% (95% confidence interval [CI], 8.2-13.2) and 16.2% (95% CI, 13.2-19.2) for SpVT recurrence/progression. In the multivariable regression analysis, therapeutic anticoagulation was associated with increased major bleeding (adjusted risk ratio [aRR], 1.74; 95% CI, 1.08-2.81) and decreased progression/recurrence of SpVT (aRR, 0.55; 95% CI, 0.35-0.86). Baseline thrombocytopenia was not independently associated with either major bleeding (aRR, 0.76; 95% CI, 0.43-1.34) or progression/recurrence of SpVT (aRR, 1.14; 95% CI, 0.73-1.78). A secondary analysis using inverse probability of treatment weighting with propensity scores for baseline thrombocytopenia corroborated that patients with thrombocytopenia did not have an increased bleeding risk (adjusted hazard ratio [aHR], 0.81; 95% CI, 0.48-1.39). The multivariable analysis in which platelets were treated as a time varying covariate also did not reveal an association with major bleeding (aHR, 0.89; 95% CI, 0.55-1.45). Bleeding and thrombosis progression were frequent in patients with cancer-associated SpVT. Anticoagulation was associated with increased major bleeding and decreased thrombotic progression; thrombocytopenia did not impact the outcomes.

Direct oral anticoagulants for the treatment of cancer-associated thrombosis

Cancer-associated thrombosis (CAT) remains a challenging aspect of managing patients with cancer. This review discusses evidence regarding anticoagulants in the treatment of CAT, with particular emphasis on direct oral anticoagulants (DOAC). Apixaban, rivaroxaban and edoxaban have proven attractive alternatives to low-molecular weight heparins, and interactions with medical cancer treatment does not pose a major challenge. The majority of guidelines have endorsed the use of DOAC, and we highlight points to consider when choosing the optimal anticoagulant for the individual patient.

Primary Prevention of Cancer-Associated Thrombosis: Current Perspectives.

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.

Prevention and treatment of cancer-associated thrombosis during chemotherapy

In patients with malignant neoplasms, the incidence of symptomatic venous thromboembolism (VTE) is 4–7 times higher than in the general population. The presence of distant metastases of solid tumors increases the risk of VTE. Most often, VTE develops in pancreatic and stomach cancers. Chemotherapy increases the risk of VTE development. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients receiving chemotherapy.Prior to the start of chemotherapy, it is necessary to assess the risk of VTE development using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score &gt;3 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis.

Impact of applying machine learning to the electronic medical record on prediction of cancer-associated thrombosis.

409 Background: Cancer-associated thrombosis (CAT) is preventable among high-risk individuals with prophylactic anticoagulation. Risk assessment tools focus only on the initial period after cancer diagnosis; however, some patients may face different risks during different periods of their cancer journey. We developed a longitudinal machine learning system to predict the risk of CAT throughout cancer treatment. Methods: Using electronic health record data at Princess Margaret Cancer Centre, we assembled a cohort of people with thoracic and gastrointestinal cancer receiving systemic treatments between August 1, 2017 and December 31, 2019. We manually labelled 5,000 CT scans and 500 Doppler ultrasounds for the occurrence of CAT. We fine-tuned open-source large language models (LLMs) on those labelled reports, which we then used to automatically detect CAT among all 37,000 CT scans and Dopplers. Finally, we trained longitudinal machine learning systems to predict CAT within 90 days after each cancer treatment. LLMs and the CAT risk prediction system were evaluated among the held-out test cohort of people whose first treatment occurred in 2019. Results: The overall cohort included 2,031 patients and 21,375 treatment sessions. When classifying radiology reports, the fine-tuned LLM achieved an area under the receiver operating characteristic curve (AUROC) of 0.758 for DVT and 0.988 for PE in the test cohort. CAT occurred within 90 days after 6.23% of treatment sessions. The best ML system predicted the risk of CAT within 90 days with an AUROC of 0.651 (95% CI, 0.620-0.678). Considering only the first treatment per patient, treatments within the first 90 days after the first treatment, and treatments after 90 days, the system achieved AUROC of 0.639 (95% CI, 0.568-0.704), 0.599 (95% CI, 0.559-0.642), and 0.741 (95% CI, 0.699-0.783), respectively. Conclusions: Machine learning can longitudinally predict CAT among patients receiving systemic therapy for aerodigestive cancers. These systems could personalize prophylactic anticoagulation by identifying specific periods when patients face sufficient risk to warrant prevention.

The effects of an aggressive breast tumor on thrombosis after antithrombin downregulation in a hypercoagulable mouse model

BackgroundDespite improvements in therapy, breast cancer still contributes to high mortality rates. Survival of these patients becomes progressively worse upon diagnosis with cancer-associated thrombosis (CAT). Unfortunately, the mechanism causing CAT has remained unclear. ObjectiveSet up an acute and non-invasive hypercoagulable mouse model with an aggressive breast cancer and study the mechanism of cancer-associated thrombosis. MethodsMice were grafted with the aggressive breast cancer cell line MDA-MB-231 or sham-treated. Subsequently, an acute imbalance in coagulation was introduced by injecting a synthetic small interfering (si) RNA targeting hepatic Serpinc1 to knockdown antithrombin – a condition known to predispose to cause a hypercoagulant state in vivo. ResultsSilencing Serpinc1 with siRNA decreased plasma antithrombin levels. siRNA treatment had no short-term effects on tumor characteristics, but increased distant metastasis within the timeframe of this study. The systemic pro-inflammatory status, with elevated platelet counts and fibrinogen levels in tumor-bearing mice, was also not affected by antithrombin silencing. While elevated fibrin deposition in the liver upon Serpinc1 targeting was not significantly affected by the presence of breast cancer, knockdown of antithrombin did significantly increase intratumoral fibrin deposition and inflammation. Surprisingly, in the presence of an aggressive tumor, a protective outcome with less clinical features coinciding with venous thrombosis were observed in mice with antithrombin knockdown. ConclusionWe conclude that the presence of a breast tumor protects hypercoagulant mice from severe consumption of coagulation factors after lowering hepatic antithrombin levels, possibly due to elevated platelet counts. However, the consequences on cancer-associated thrombosis remained inconclusive.

Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer.

This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer.

Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study

BackgroundGuidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE). ObjectiveWe aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting. MethodsWe 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 six months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using c-statistics. ResultsWe included 12,471 patients from 2012 through 2020. Of these, 416 (3.3%) developed VTE. The c-statistic was 0.71 (95% confidence interval [CI]: 0.68–0.74) for the new CAT score and 0.66 (95% CI: 0.63–0.70) for the Khorana score. The six-month cumulative VTE incidence was 5.0% in 6,175 patients classified as high risk by the new CAT score, compared with 1.7% in 6,296 patients classified as low risk. The six-month cumulative VTE incidence was 5.2% in 4,263 patients classified as high risk by the Khorana score, compared with 2.4% in 8,208 patients classified as low risk. ConclusionThe 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 implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE.

P2.05A.01 Clinical Presentation, Outcomes, and Anticoagulant Strategies in Patients with Lung Cancer-Associated Isolated Distal Deep Vein Thrombosis

P2.05A.01 Clinical Presentation, Outcomes, and Anticoagulant Strategies in Patients with Lung Cancer-Associated Isolated Distal Deep Vein Thrombosis

Net Clinical Benefit of 12-Month Over 3-Month Edoxaban in Cancer-Associated Isolated Distal Deep Vein Thrombosis

Net Clinical Benefit of 12-Month Over 3-Month Edoxaban in Cancer-Associated Isolated Distal Deep Vein Thrombosis

Anticoagulant Management of Cancer-Associated Thrombosis and Thrombocytopenia: A Retrospective

Anticoagulant Management of Cancer-Associated Thrombosis and Thrombocytopenia: A Retrospective

Inferior Vena Cava Filter in Cancer-Associated Thrombosis: A Vade Mecum for the Treating Physicians: A Narrative Review.

Cancer is a remarkable prothrombotic disease, and cancer-associated thrombosis acts as a dreadful omen for poor prognosis. The cornerstone of venous thromboembolism therapy is anticoagulation; however, in patients with venous thromboembolism who are not suitable for anticoagulation (contraindication, failure, or complication), the inferior vena cava filter appears a valuable option in the therapeutic arsenal. The recently heightened trend of steady rise in filter placement mirrors the spread of retrievable devices, together with improvements in physicians' insertion ability, medico-legal issue, and novel and fewer thrombogenic materials. Nevertheless, the exact role of the inferior vena cava filter in cancer has yet to be endorsed due to a dearth of robust evidence. Indeed, data that support the inferior vena cava filter are weak and even controversial, resulting in discrepancies in the interpretation and application of guidelines in daily practice. In this narrative review, we aim at clarifying the state of the art on inferior vena cava filter use in malignancies. Furthermore, we provide a feasible, conclusive 4-step algorithm for the treating physicians in order to offer a practical strategy to successfully employ the inferior vena cava filter as a priceless device in the current armamentarium against cancer.

Abstract C005: Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer

Abstract Background: CM24 (mAb) blocks CEACAM1 interactions, has key roles in cancer progression, immune escape and metastasis. CEACAM1 is part of the neutrophil extracellular trap (NET) complex, involved in tumor immune evasion, metastasis and cancer-associated thrombosis, affecting patient survival. We demonstrated that CM24 binds to NET and suppresses NET-induced migration of cancer cells (AACR Cancer Metastasis Nov.2022) and that CM24+nivolumab (nivo) treatment of pancreatic ductal adenocarcinoma (PDAC) patients markedly reduced serum levels of the NET marker, Myeloperoxidase (MPO; AACR on pancreatic cancer Sept.2023). In a Phase 2 study (NCT04731467) 31 patients with advanced/metastatic PDAC progressed after 1st line therapy, were randomized for CM24 (20mg/kg q2wk), nivo (240mg/kg q2wk) and liposomal irinotecan, 5 fluorouracil and leucovorin (Nal-IRI/5FU/LV, q2wk) treatment (experimental arm) vs Nal-IRI/5FU/LV only (control arm). Interim analysis of the data showed Median OS for the experimental arm was 7.72m (95% CI: 4.00-8.11) vs. 5.62m (95% 3.22 -7.89) for the control arm (HR: 0.74; 95% CI: 0.31-1.77). Median PFS for the experimental group was 3.8m (95% 1.8-5.0) vs. 1.9m (95% 0.9, 3.6) for the control arm (HR 0.72; 95% CI: 0.33-1.60) (ASCO2024-LBA4143). Here we present a subgroup analysis evaluating serum MPO as a potential biomarker for CM24-based therapy. Methods: Patients were randomized as described above. Pre-dose serum samples were collected from 30 out of 31 pts and serum MPO levels were evaluated using ELISA (Cayman), where the measured mean serum MPO in healthy subjects (n=30) was 53 +/-7[SE]. NET-induced blood coagulation was tested using platelet aggregation assay. Results: Mean pre-dose MPO level in patients (n=30) was 359 +/- 46 [SE] and was selected as a threshold for biomarker analysis. OS for patients with MPO levels below the threshold (n=9/16) was 8.1 mo in the experimental arm (HR 0.34; (95% CI: 0.099-1.149)) vs 4.5mo in the control (n=9/15). PFS for patients with MPO levels below the threshold was 4.2mo in the experimental arm vs. 1.7 mo in the control (HR 0.24 (95% CI: 0.20-1.59)). NET-associated blood coagulation and the inhibitory effect of CM24 were tested in vitro. NETs induced platelet aggregation in a dose-dependent manner, and CM24 significantly reduced it (50-70% reduction, p value &amp;lt; 0.0001) at NET levels related to the selected biomarker range (MPO&amp;lt;357) but was less effective at higher NET levels (MPO&amp;gt;500), which relate to MPO above the threshold. These results are in line with the proposed CM24 MoA, affecting NET-related cancer complications. Conclusions: Exploratory biomarker analysis suggests serum MPO as a potential predictive biomarker for CM24-based therapy showing prolonged median OS, PFS and 66% reduction in risk of death vs control in PDAC patients with MPO levels below threshold compared to interim analysis that estimated OS and PFS risk reduction of 26% and 28%, respectively. These findings will be further evaluated in upcoming clinical studies. Citation Format: Teresa Macarulla, Michael Cecchini, Rocio Garcia-Carbonero, Talia Golan, Ruth Perets, Erkut Borazanci, Manuel Pedegral, Mariano Ponz-Sarvisé, Mohammed Najeeb Al Hallak, Shubham Pant, Valentina Boni, Omar Saavedra, María José de Miguel-Luken, Alexis D. Leal, Andrés J. Muñoz Martín, Tamara Sauri-Nadal, Michael Schickler, Hava Ben David, Hadas Reuveni. Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C005.

Diagnosis and treatment of venous thrombosis - part 2

The subject of this guideline from the Institute of Family Medicine at the University of Zurich (IHAMZ) is the management of venous thrombosis. The review summarizes the current evidence and recommendations from international guidelines (1-6). The IHAMZ-guidelines focus on primary care, they also provide guidance on the coordination of general and specialist medical care as well as on the transition between outpatient and hospital care taking into account the special features of the Swiss healthcare system. The guideline is devided in two parts. Part 1 discusses the diagnosis and treatment of deep vein thrombosis (DVT). A validated algorithm is recommended for the diagnostic process, which begins with the assessment of the clinical probability. With the inclusion of the D-dimer test, the need for subsequent imaging diagnostics can be reduced. The differences between the evaluation of an initial and recurrent DVT are shown and the indications and scope of evidence-based environmental diagnostics (thrombophilia and tumor search) are presented. All patients with DVT should receive anticoagulation (AC) for 3-6 months, as there is a high risk of recurrence with AC 3 months. The duration of the subsequent secondary prophylaxis depends on the presumed risk of recurrence on the one hand and the risk of bleeding on the other. Part 2 is dedicated to special thrombosis situations such as isolated distal thrombosis of the deep and muscle veins (idDVT, iMVT), shoulder-arm vein thrombosis (SAVT), cancer-associated thrombosis (CAT) and superficial vein thrombosis (SVT). The article on hormone- and pregnancy-associated DVT, developed together with the Department of Gynecology at the University Hospital of Zurich, discusses the importance of hormonal contraception and menopausal hormone replacement therapy (HRT) as thrombogenic risk factor as well as special features in the diagnosis and treatment of thrombosis in pregnancy.

Catheter – related thrombosis in cancer patients: Data from the registry of thrombosis and nEoplasia of SEOM (TESEO)

BackgroundCatheter related thrombosis (CRT) is the most frequent non-infectious complication associated with central venous access devices (CVAD), with a reported incidence between 13 % and 66 % in symptomatic and asymptomatic patients, respectively, with several factors influencing its development. MethodsCRT events recorded in TESEO, an international, multicentric, and prospective cancer-associated thrombosis registry were assessed. Descriptive analyses were conducted. ResultsBetween July 2018 and December 2023, 2,567 patients were included in TESEO. Of these, 245 patients developed CRT and were included in this analysis. Mean age was 60.5 years (SD 12.3). Peripherally inserted central catheters (PICC) were present in 42.1%, totally implanted ports (PORT) in 40.9% while 17% had missing data. The most common reported comorbidities were arterial hypertension (28.6%) and dyslipidemia (28.2%). Other thromboembolism associated risk factors were present in ≤10% of patients.Venous thromboembolism (VTE) related symptoms occurred in 70.2% of cases at presentation. Pulmonary embolism (PE) was present in 6.5%, being clinically suspected in 56.2% of cases. The diagnosis was mainly unilateral (81.3%) and 50% were central. Arterial and venous rethrombosis was present in 0.8% and 4.9% of cases respectively. Minor bleeding episodes occurred in 2.5% of cases, while major/clinically relevant episodes were present in 3.6%. ConclusionsUsual VTE associated risk factors were infrequent in the TESEO registry population. CRT was symptomatic in most cases, with reduced complication rates after treatment.

Venous thrombosis and thromboembolism in cancer patients

Deep vein thrombosis and pulmonary embolism are the most frequent cardiovascular complications of cancer, they can occur at any stage of its development. Treatment and prevention of these complications are undergoing great changes. The aim of the review is to analyze the special scientific literature, to evaluate the principles of prevention and treatment of cancer-associated thrombosis and thromboembolism.

Practical model for implementation of cancer-associated thrombosis prevention in the outpatient setting

IntroductionInternational guidelines recommend assessing venous thromboembolism (VTE) risk and outpatient thromboprophylaxis in selected high risk cancer patients. However, thromboprophylaxis rate in these patients is low in clinical practice. Therefore, we developed a multidisciplinary intervention algorithm to raise awareness about VTE and apply thromboprophylaxis in the outpatient setting. Materials and methodsIn a 12-month period, all single-center cancer patients were evaluated in an initial nursing consultation prior to first systemic therapy start. Consenting patients identified with a Khorana score ≥2 were referred to a specialist consultation in Oncology/Thromboembolic Risk, offering thromboprophylaxis with direct-acting anticoagulant or low molecular weight heparin if without excessive bleeding risk. The corresponding data was recorded in an observational and prospective manner. ResultsA total of 190 patients were evaluated from model implementation, of which 61 patients (32.1 %) had a Khorana score ≥2 (18.9 % with 2; 13.2 % with >2). Of these, 85.2 % consented to specialized assessment. In this group, a median age (med) of 65.5 years was observed [40–92]; the most common tumors were pancreas (26.9 %) and lung (26.9 %). Thromboprophylaxis was offered to 86.5 %; in these there was a non compliance rate of 4.4 %. In a med follow-up period of 116 days after thromboprophylaxis start there was a rate of major bleeding of 2.3 % and VTE of 4.7 %. ConclusionsThis is a feasible model for a generalized VTE risk assessment and subsequent thromboprophylaxis in an outpatient clinic setting. This methodology allows events and survival monitoring and evaluating other clinically relevant outcomes, such as quality of life.

Transcriptional Induction of SERPINE1 and Fibrinolysis Inhibition as Predominant Effects of Glucocorticoids on the Cancer Coagulome.

How tumors regulate the genes of the coagulome is crucial for cancer-associated thrombosis and the occurrence of venous thromboembolic complications in patients with cancer. We have previously reported potent yet complex effects of glucocorticoids (GC) on the expression of three genes that play a key role in the regulation of thrombin/plasmin activation (F3, PLAU, and SERPINE1). This study aimed to extend the investigation of GC effects to the whole tumor coagulome and assess the resulting impact on the ability of cancer cells to activate thrombin and plasmin. Cancer RNA expression data were retrieved from various sources. Additionally, oral squamous cell carcinoma (OSCC) cells exposed to GC in vitro were analyzed using QPCR, enzymatic assays measuring thrombin and urokinase-type Plasminogen Activator (uPA) activity, and D-dimer concentrations. Our findings highlight the potent and specific stimulatory effect of GC on SERPINE1 expression across different types of cancer. Consistently, GC were found to inhibit uPA proteolytic activity and reduce the concentrations of D-dimers in OSCC in vitro. Fibrinolysis inhibition is a key consequence of cancer cell exposure to GC, possibly leading to the stabilization of the fibrin clot in cancer.