Thromboembolism In Cancer Patients Research Articles

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis.

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 timepoint. 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 114 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 <100g/L and white blood count >11 x 109/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil lymphocyte ratio >3 and preoperative platelet count ≥400 x 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.

Gynecological Cancer and Venous Thromboembolism: A Narrative Review to Increase Awareness and Improve Risk Assessment and Prevention.

The prevention and appropriate management of venous thromboembolism in cancer patients is of paramount importance. However, the literature data report an underestimation of this major problem in patients with gynecological cancers, with an inconsistent venous thromboembolism risk assessment and prophylaxis in this patient setting. This narrative review provides a comprehensive overview of the available evidence regarding the management of venous thromboembolism in cancer patients, focusing on the specific context of gynecological tumors, exploring the literature discussing risk factors, risk assessment, and pharmacological prophylaxis. We found that the current understanding and management of venous thromboembolism in gynecological malignancy is largely based on studies on solid cancers in general. Hence, further, larger, and well-designed research in this area is needed.

Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Cancer Patients with Central Venous Catheters: A Literature Review.

Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory settings. The endothelial injury associated with the use of these catheters adds to the risk of VTE to already high-risk patients. The introduction of direct oral anticoagulants (DOACs), with its proven efficacy and safety in multiple clinical indications, have renewed the attention to VTE prophylaxis in cancer patients with CVC. Several clinical trials and meta-analyses had shown that both apixaban and rivaroxaban are effective in lowering the risk of VTE, without increasing the risk of bleeding. Several risk assessment models (RAM) have utilized patient-related, tumor-related, and treatment-related factors, in addition to widely available biomarkers, like Hemoglobin (Hb) level, white blood cell (WBC) and platelets counts to stratify patients into two or three VTE risk levels. In this manuscript, we review the published clinical trials and meta-analyses that attempted to study the efficacy and safety of anticoagulants, mostly the DOACs, in cancer patients with CVCs. We will also propose a practical risk-directed approach to enhance VTE prophylaxis rate.

Abstract WP237: Anticoagulant Utilization and Risk of Thromboembolic Events Following Ischemic Stroke Among Adults With Cancer

Rationale: Ischemic stroke and cancer frequently coexist, but there are limited data from population-based cohorts regarding prevalence, risk of subsequent thromboembolic events, and treatments. Methods: We leveraged large-scale healthcare data to assess recurrent thromboembolic events in the 6 months following discharge for ischemic stroke among a nationally representative U.S. population with active cancer. Landmark analyses were undertaken with anticoagulant exposure status based on dispensations in the week following hospital discharge. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within propensity score-matched pairs. Results: Among 86,365 adults discharged after an ischemic stroke between 10/2020-09/2021, 10.2% had active cancer. Based on eligibility criteria (including removal of those with known atrial fibrillation), 4,819 were assessed [median age 74 years; 48.7% female; common cancer types: 25.3% gastrointestinal, 20.3% prostate, 18.4% lung]. Anticoagulants were dispensed to 14.7% of the cohort in the week following discharge. Incidence of thromboembolic event recurrence was 37.5 per 100 person-years (66.7% ischemic stroke). Initial anticoagulation was associated with an increased risk of thromboembolism recurrence (aHR=1.42, 95% CI: 1.06-1.90). Conclusions: This large-scale real-world study demonstrates an estimated 10% of patients with ischemic stroke had active cancer, and they faced a very high 6-month incidence of recurrent thromboembolism. Anticoagulants were not commonly prescribed after discharge, suggesting that clinicians use them less commonly for stroke than for venous thromboembolism in cancer patients. The higher risk of recurrent events on anticoagulants likely reflects residual confounding by indication. Clinical trials are needed to further assess optimal antithrombotic strategies in this population.

The Contribution of Inherited Thrombophilia to Venous Thromboembolism in Cancer Patients.

Although the relationship between venous thromboembolism (VTE) and cancer has been a subject of study, knowledge of the contribution of thrombophilia to thrombosis in patients with cancer is still very limited. The aim of this article is to collect present knowledge on the contribution of inherited thrombophilia to VTE in cancer patients. We performed a search in Google Scholar and PubMed and selected 21 from 76 returned articles. Then we made a narrative review of the selected articles. We describe 11 studies on the contribution of inherited thrombophilia to VTE in cancer patients in general and 10 on that contribution in specific types of cancer: 1 in colorectal cancer, 4 in breast cancer, 1 in gynecologic cancer and 4 in hematopoietic malignancies. All studies investigate the relation of factor V Leiden (FVL) to VTE, 13 that of the prothrombin G20210A mutation (PTG20210A) and 7 studies also investigate other inherited thrombophilias, such methylenetetrahydrofolate reductase gene mutations, although only 2 investigate the contribution of deficiencies of the natural anticoagulants. Studies are very heterogeneous, in design and sample size and conclusions differ considerably. There is no consensus on the contribution of inherited thrombophilia to VTE in cancer patients except for acute lymphoblastic leukemia in children. Probably, that contribution is not the same for all types of cancer and more studies are needed to bring more knowledge on this subject.

Association between TSPAN15 (rs78707713) and SLC44A2 (rs2288904) Genetic Polymorphisms and Venous Thromboembolism in Cancer Patients

Association between TSPAN15 (rs78707713) and SLC44A2 (rs2288904) Genetic Polymorphisms and Venous Thromboembolism in Cancer Patients

Influencing factors of venous thromboembolism in cancer patients and effect analysis of early nursing interventions

Influencing factors of venous thromboembolism in cancer patients and effect analysis of early nursing interventions

Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Patients with cancer have an increased risk of venous thromboembolism (VTE). Currently, several VTE risk prediction tools have been developed to identify candidates for primary VTE thromboprophylaxis. However, the availability of reliable and highly discriminatory prediction models for VTE risk assessment in cancer patients is limited, warranting further improvement of VTE risk stratification strategies. The implementation of biomarkers in risk assessment models might lead to refined VTE risk prediction, but it remains to be more comprehensively investigated. In this systematic review and meta-analysis, we aimed to evaluate and summarize all candidate biomarkers and their association with cancer-associated VTE. We conducted an electronic search in Medline, EMBASE and Cochrane central databases for studies that evaluated biomarkers in adult patients with cancer from inception to September 26 th 2022. We included observational and interventional studies reporting on subsequent VTE occurring after a cancer diagnosis. The baseline or index event of the biomarker measurements had to be definitively and uniformly applied to all enrolled patients. Two reviewers independently screened titles, abstracts and full-text articles for inclusion. Median differences (for continuous measures) and Odds Ratios (OR) (for dichotomous cut-off measures) with 95% confidence intervals (95% CI) were estimated and pooled using random-effects models. We assessed each studies risk of bias using the Quality in Prognostic Studies (QUIPS) risk of bias tool. Our search identified 4274 studies that were screened for inclusion (Figure 1). Following the screening, 109 studies (with 520 biomarker measurements) met the inclusion criteria and were included in the systematic review. Of these, 51 studies (with 174 biomarker measurements) were included in the meta-analysis. The majority of the studies were cohort studies (n=47; 32 prospective and 15 retrospective), while the other 4 studies were nested case-control studies. Eighteen studies had a study population of mixed cancer types and the remaining studies had a study population of specific cancer types, including: lung (n=6), gynecologic (n=5), breast (n=3), stomach (n=3), lymphoma (n=2), myeloma (n=2), ovarian (n=2), pancreas (n=2), brain (n=1), colorectal (n=1), gastrointestinal (n=1), genitourinary (n=1), gynecologic or breast (n=1), head and neck (n=1), liver (n=1), and prostate (n=1). We calculated the median difference and 95% CI for 23 different biomarkers. Cancer patients who experienced subsequent VTE events had significantly higher pre-treatment factor VIII activity, peak thrombin, platelet count and prothrombin fragment F1+2 levels compared to patients who did not experience VTE events (Table 1). Pre-treatment d-dimer levels were also higher in cancer patients who developed VTE, however, considerable heterogeneity was observed (Table 1). Contrastingly, pre-treatment hemoglobin, lag time - thrombin generation, prothrombin time and time to peak thrombin levels were significantly lower in those experiencing VTE events compared to patients who did not experience any events (Table 1). D-dimer levels on day-1 after cancer surgery were reported in two studies which, when pooled, revealed that cancer patients with subsequent VTE had higher d-dimer levels post-operatively compared to those with no events (Table 1). Moreover, pre-treatment hemoglobin levels 100 g/L was significantly associated with future VTE risk [OR: 1.42 (95%CI: 1.03-1.97), I 2=0%, n=11] while neutrophil lymphocyte ratio 3 was associated, yet insignificant [OR: 1.60 (95%CI: 0.99-2.60), I 2=43%, n=4]. Pre-treatment platelet count 350 x 10 9/L and white blood count levels 11 x 10 9/L were not significantly associated with future VTE risk [OR: 0.84 (95%CI: 0.66-1.06), I 2=0%, n=9 and 1.32 (0.86-2.03), I 2=56%, n=8, respectively]. From the 51 studies included in the meta-analyses, 27 studies had a low risk of bias, 19 studies had a moderate risk of bias and 5 studies had a high risk of bias. In conclusion, nine blood biomarkers were found to be significantly associated with VTE in cancer patients. Their utility as predictors of VTE in thrombotic risk assessment models may help in optimising VTE prediction and should be further explored in future studies.

Abstract 12787: Efficacy and Safety of Apixaban versus Low Molecular Weight Heparin for the Treatment of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Introduction: Current guidelines recommend the use of low molecular weight heparin (LMWH) for the management of venous thromboembolism (VTE) in cancer patients. However, direct oral anticoagulants (DOACs) have emerged as promising alternative for reducing VTE events. Moreover, apixaban shows a higher safety profile among DOACs. Hypothesis: This study aims to compare the efficacy and safety of apixaban versus LMWH (Enoxaparin or Dalteparin) in the treatment of venous thromboembolism in cancer patients. Methods: A systematic search was conducted in electronic databases (Pubmed, Embase, Scopus, and Cochrane libraries) from inception until June 2023, using appropriate Mesh terms for ‘apixaban’, ‘LMWH’, and ‘VTE’. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CI) were calculated using random effects models. A p-value of &lt;0.005 was considered statistically significant. Results: Five randomized trials involving 2311 patients (apixaban: 1088 and LMWH: 1223) with mean ages of 64.5±11.45 and 64.2±10.8, respectively, were included in the analysis. At a median follow-up of six months, the occurrence of clinically relevant non-major bleeding (CRNMB) (OR, 1.04, 95% CI: 0.66 - 1.64, I2=37.72%, p=0.87), composite of major and CRNMB (OR, 1.11, 95% CI: 0.84 - 1.46, I2=0.00%, p=0.47), were higher with apixaban treatment. However, the rates of recurrent VTE (OR, 0.72, 95% CI: 0.50 - 1.04, I2=3.91%, p=0.08), major bleeding (OR, 0.83, 95% CI: 0.55 - 1.25, I2=0.00%, p=0.38), and mortality (OR, 0.91, 95% CI: 0.79 - 1.05, I2=0.00%, p=0.19) were lower with apixaban compared to LMWH treatment. However, none of the observed differences reached statistical significance. Conclusions: In cancer patients with VTE, apixaban demonstrates non-inferior efficacy and a comparable safety profile to LMWH. Further randomized trials are warranted to confirm these findings.

Cancer-Associated Abdominal Vein Thrombosis.

Cancer is associated with an increased risk of developing venous thromboembolism, due to its direct influence on the three pillars of Virchow's triad (e.g., compression on the blood vessels by the tumour, blood vessels invasion, and cytokine release), together with the effect of exogenous factors (such as chemotherapy, radiotherapy, surgery). In cancer patients, the risk of thrombosis at unusual sites, such as splanchnic, ovarian and renal vein thrombosis, is also increased. Abdominal vein thromboses are frequently incidental findings on abdominal imaging performed as part of the diagnostic/staging workup or the follow-up care of malignancies. There is little evidence on the management of unusual site venous thromboembolism in cancer patients since there are only a few specific recommendations; thus, the management follows the general principles of the treatment of cancer-associated deep vein thrombosis and pulmonary embolism. This narrative review summarises the latest evidence on cancer-associated abdominal vein thrombosis, i.e., thrombosis of the splanchnic, ovarian and renal veins.

Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study.

Despite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study. Using Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidity and frailty using the Charlson Comorbidity Index Score and Hospital Frailty Risk Score, marital status, use of selected medications, and recent surgery (<90 days). During the study period, 886,536 patients were diagnosed with cancer. Of 1882 cancer patients diagnosed at the time of their venous thromboembolism, 44.4% (835/1882) had distant metastases. In this cohort, the one- and five-year mortality cumulative incidences were 68% (1284/1882) and 84% (1578/1882), respectively, in contrast to 38% (2135/5549) and 67% (3653/5549) in the comparison cohort. The mortality rate ratio was 4.34 (95% confidence interval [CI], 3.95-4.78) for the first year of follow-up and 3.44 (95% CI 3.17-3.73) for the five-year follow-up period. Of the 23,366 patients diagnosed with venous thromboembolism after cancer diagnosis, 18% (4183/23,366) had distant metastases at the time of cancer diagnosis. The cumulative incidence of death at one year was 45% (10,465/23,366; mortality rate ratio 3.48, 95% CI 3.37-3.60) and at five years 69% (15,669/23,366; mortality rate ratio 2.57, 95% CI 2.50-2.63). Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis. The study was supported by grants from the Independent Research Fund Denmark (record no. 3101-00102B) and the Karen Elise Jensen Foundation.

458P Association between TSPAN15 and SLC44A2 genetic polymorphisms and venous thromboembolism in cancer patients

458P Association between TSPAN15 and SLC44A2 genetic polymorphisms and venous thromboembolism in cancer patients

Thromboembolism in Cancer Patients With COVID-19 Infection Compared With Other Infections—A Case Series

Abstract An increased risk of venous thromboembolism (VTE) with COVID-19 infection has been well documented, particularly in critically ill-hospitalized patients. The presence of cancer, in addition to several anticancer treatments, can further elevate the risk of VTE. The following case reports describe an increased risk of extensive thrombosis that can be seen with COVID-19 infection in cancer patients. We report 3 cases of pulmonary embolism and deep vein thrombosis in cancer patients with COVID-19 infection. All 3 cases are unique with the timeline of COVID-19 infection and diagnosis of VTE. The current pandemic has alerted the clinician to the potential increased risk for thrombus formation in cancer patients with COVID-19, even days to months after acute infection.

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

Immune checkpoint inhibitors: risk of venous thromboembolism in cancer patients examined

Immune checkpoint inhibitors: risk of venous thromboembolism in cancer patients examined

Diagnostic Approach for Venous Thromboembolism in Cancer Patients.

Venous thromboembolic disease (VTE) is a common complication in cancer patients. The currently recommended VTE diagnostic approach involves a step-by-step algorithm, which is based on the assessment of clinical probability, D-dimer measurement, and/or diagnostic imaging. While this diagnostic strategy is well validated and efficient in the noncancer population, its use in cancer patients is less satisfactory. Cancer patients often present nonspecific VTE symptoms resulting in less discriminatory power of the proposed clinical prediction rules. Furthermore, D-dimer levels are often increased because of a hypercoagulable state associated with the tumor process. Consequently, the vast majority of patients require imaging tests. In order to improve VTE exclusion in cancer patients, several approaches have been developed. The first approach consists of ordering imaging tests to all patients, despite overexposing a population known to have mostly multiple comorbidities to radiations and contrast products. The second approach consists of new diagnostic algorithms based on clinical probability assessment with different D-dimer thresholds, e.g., the YEARS algorithm, which shows promise in improving the diagnosis of PE in cancer patients. The third approach uses an adjusted D-dimer threshold, to age, pretest probability, clinical criteria, or other criteria. These different diagnostic strategies have not been compared head-to-head. In conclusion, despite having several proposed diagnostic approaches to diagnose VTE in cancer patients, we still lack a dedicated diagnostic algorithm specific for this population.

A cohort study on blood coagulation in childhood cancer survivors

Cancer survivors are at an increased risk of thromboembolism compared to the general pediatric population. Anticoagulant therapy decreases the risk of thromboembolism in cancer patients. We hypothesized that pediatric cancer survivors are in a chronically hypercoagulable state compared to healthy controls. Children who survived for more than five years from cancer diagnosis at the UT Health Science Center at San Antonio Cancer Survivorship Clinic were compared to healthy controls. The exclusion criteria were recent NSAID use or a history of coagulopathy. Coagulation analysis included platelet count, thrombin-antithrombin complexes (TAT), plasminogen activator inhibitor (PAI), routine coagulation assays, and thrombin generation with and without thrombomodulin. We enrolled 47 pediatric cancer survivors and 37 healthy controls. Platelet count was significantly lower in cancer survivors at a mean of 254 × 109/L (95%CI: 234–273 × 109/L) compared at 307 × 109/L (283–331 × 109/L) in healthy controls (p < 0.001), although not outside the normal range. Routine coagulation assays showed no differences, except for a significantly lower prothrombin time (PT) in cancer survivors (p < 0.004). Cancer survivors has significantly elevated biomarkers of the procoagulant state, such as TAT and PAI, compared to healthy controls (p < 0.001). A multiple logistic regression model controlling for age, BMI, gender, and race/ethnicity documented that a low platelet count, short prothrombin clot time, and higher procoagulant biomarkers (TAT and PAI) were significantly associated with past cancer therapy. Survivors of childhood cancer have a persistent procoagulant imbalance for more than five years after diagnosis. Further studies are needed to establish whether procoagulant imbalance increases the risk of thromboembolism in childhood cancer survivors.

Hypercoagulability State Combined with Post-Treatment Hypofibrinolysis in Invasive Breast Cancer: A Seven-Year Follow-Up Evaluating Disease-Free and Overall Survival.

(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation and fibrinolysis components in invasive breast cancer. (2) Methods: Tissue factor pathway inhibitor (TFPI), tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) antigen (concentration) and TFPI and TF activities were examined in the blood samples of 60 breast cancer patients treated by adjuvant chemotherapy, endocrine therapy, radiotherapy and immunotherapy. Blood samples were taken 24 h before primary surgery and 8 months after tumour removal surgery. (3) Results: Adjuvant therapy administrated to breast cancer patients significantly increased the concentration of plasma TF, the PAI-1 antigen and also the activity of TFPI and TF, but significantly decreased the level of the t-PA antigen. Combined chemotherapy and endocrine therapy, but not monotherapy, has an important effect on haemostatic biomarker levels. (4) Conclusions: Breast cancer patients receiving adjuvant therapy have an elevated risk of developing a hypercoagulability and hypofibrinolysis state leading to venous thromboembolism.

Managing cancer associated thrombosis (cat): a dedicated service may help

Cancer is single most important risk factor for developing thromboembolism (VTE). Cancer patients are at increased risk of bleeding due to various reasons [1]. Low molecular weight heparin (LMWH) remained the standard of care for many years [2]. Direct acting oral anticoagulants (DOACs) are simpler to administer and equally effective and safe as compared to LMWH [2]. However, there are several concerns associated with DOACs in cancer patients. They are related to drug-to-drug interactions and risk of bleeding in gastrointestinal and urothelial malignancies [3]. Authors have comprehensively summarized the available evidence related to managing venous thromboembolism in cancer patients.

Factor Xa inhibitors in the prevention and treatment of venous thromboembolism in cancer patients

Venous thromboembolism is a common complication of cancer. The prevalence varies according to cancer type and increases proportionally with the stage of cancer. In the past 15-20 years, low molecular weight heparin has been recommended as the first-line treatment. New international guidelines now allow for use of direct factor Xa inhibitors both as prophylaxis and treatment for venous thromboembolism. Prophylaxis should as a general rule only be initiated in patients with moderate to high risk. Bleeding risk assessment is important before starting anticoagulation. Both thrombosis and bleeding risk can change and should therefore be assessed on an ongoing basis. In this clinical review, use of anticoagulation therapy in cancer patients is discussed with particular emphasis on the use of direct factor Xa inhibitors.