Biomarker Signatures in Cancer Patients With and Without Venous Thromboembolism Events: A Substudy of CASSINI

Cancer is associated with an increased risk of venous thromboembolism (VTE). In the CASSINI study, ambulatory cancer patients with a Khorana risk score ≥2 had a reduced risk of VTE while receiving rivaroxaban. This analysis used blood samples from CASSINI to compare biomarker levels between patients with and without VTE. VTE occurred in 62 patients during the 6 months of CASSINI (cases), and they were matched by age, sex, cancer type, tumor stage, and Khorana score to 62 controls. Baseline blood samples were analyzed for 280 biomarkers, and biomarker distribution was compared using the Wilcoxon rank sum test between groups defined by VTE occurrence and vital status. Sparse Bayesian regression modeling was used to select a joint panel of potential VTE biomarkers. Biomarkers with the largest differences in baseline distribution among cancer patients with and without VTE included decreases in stromal cell-derived factor-1 (SDF-1), thyroid-stimulating hormone (TSH), and monocyte chemotactic protein 4 and increases in growth hormone (GH) and interleukin-1 receptor type 1 (IL-1R1). Between survivors and those who died, significantly different biomarkers included ST2, IL-8, and C-reactive protein. Regression analyses also identified decreases in SDF-1 and TSH. Pathway analysis indicated enrichment of cytokine and chemokine activity with IL-1R1, SDF-1, and GH, which are the strongest predictors of VTE or death. Our analyses highlight the interactions between hemostatic and inflammatory processes and identify candidate biomarkers of cancer-associated VTE. Prospective studies will determine clinical relevance of these biomarkers. This trial was registered at www.clinicaltrials.gov as #NCT02555878.

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Venous Thromboembolism in Pediatric Cancer Patients with Central Venous Catheter—A Systematic Review and Meta-analysis

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1729886 ◽

2021 ◽

Author(s):

Rasmus Søgaard Hansen ◽

Mads Nybo ◽

Anne-Mette Hvas

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Solid Tumors ◽

Pediatric Cancer ◽

Lymphoblastic Leukemia ◽

Meta Analysis ◽

Cancer Type ◽

Central Venous ◽

Increased Risk ◽

Pediatric Cancer Patients

AbstractPediatric cancer patients hold an increased risk of venous thromboembolism (VTE) due to their cancer. Central venous catheters (CVCs) further increase the VTE risk. This systematic literature review elucidates the VTE incidence in pediatric cancer patients with CVC. MEDLINE and EMBASE were searched in August 2020 without time limits. We included studies reporting original data on patients ≤18 years with any CVC type and any cancer type, who were examined for VTE with ≥7 days follow-up. In total, 682 unique records were identified, whereof 189 studies were assessed in full text. Altogether, 25 studies were included, containing 2,318 pediatric cancer patients with CVC, of which 17% suffered VTE. Fifteen studies (n = 1,551) described CVC-related VTE and reported 11% CVC-related VTE. Concerning cancer type, 991 children suffered from acute lymphoblastic leukemia (ALL) and 616 from solid tumors. Meta-analysis revealed VTE incidence (95% confidence interval) of 21% (8–37) for ALL and 7% (0.1–17) for solid tumors. Additionally, 20% of children with tunneled or nontunneled CVC and 12% of children with implantable ports suffered VTE. In conclusion, pediatric cancer patients with CVC have substantial VTE risk. Children with ALL and CVC have higher VTE incidence than children with solid tumors and CVC. Implantable port catheter should be preferred over tunneled or nontunneled CVC to reduce VTE risk. Thrombophilia investigation does not seem relevant in pediatric cancer patients with CVC and VTE. To prevent VTE, intensified catheter care is recommended, especially in children with ALL.

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Attention to diet, exercise, and weight in the oncology clinic: Results of a national patient survey.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10549 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10549-10549

Author(s):

Jennifer A. Ligibel ◽

Lori J. Pierce ◽

Catherine M. Bender ◽

Tracy E Crane ◽

Christina Marie Dieli-Conwright ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Online Survey ◽

Early Stage ◽

Cancer Type ◽

Breast Cancer Patients ◽

Related Factors ◽

Increased Risk ◽

Diet And Exercise ◽

To Receive

10549 Background: Obesity and related factors are increasingly associated with increased risk of developing and dying from cancer. The American Society of Clinical Oncology (ASCO) conducted a survey of cancer patients to assess their experience in receiving recommendations and referrals related to weight, diet and exercise as a part of their cancer care. Methods: An online survey was distributed to potential participants between March and June 2020 via ASCO channels and patient advocacy organizations, with an estimated reach of over 25,000 individuals. Eligibility criteria included being 18 years, living in the US, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns. Results: In total, 2419 individuals responded to the survey. Most respondents were female (75.5%), 61.8% had an early-stage malignancy, 38.2% had advanced disease, and 49.0% were currently receiving treatment. Breast cancer was the most common cancer type (36.0%). Average BMI was 25.8 kg/m2. The majority of respondents consumed £2 servings of fruits and vegetables per day (50.9%) and exercised £2 times per week (50.4%). Exercise was addressed at most or some oncology visits in 57.5% of respondents, diet in 50.7%, and weight in 28.4%. Referrals were less common: 14.9% of respondents were referred to an exercise program, 25.6% to a dietitian and 4.5% to a weight management program. In multiple regression analyses, racial and ethnicity minority respondents were more likely to receive advice about diet (Odds Ratio [OR] 1.92, 95% CI 1.56-2.38) and weight (OR 1.64, 95% CI 1.23-2.17) compared to non-Hispanic whites, individuals diagnosed with cancer in the past 5 yrs (vs > 5 yrs) were more likely to receive advice about exercise (OR 1.48, 95% CI 1.23-1.79), and breast cancer patients were more likely to receive advice about exercise (OR 1.37, 95% CI 1.11-1.68) and weight (OR 1.46, 95% CI 1.03-2.07) than other cancer patients. Overall, 74% of survey respondents had changed their diet or exercise after cancer diagnosis. Respondents reporting that their oncologist spoke to them about increasing exercise or eating healthier foods were more likely to report a change in behavior than those whose oncologists did not (exercise: 79.6% vs 69.0%, P < 0.001; diet 81.1% vs 71.4%, P < 0.001). Respondents whose oncologist had spoken to them about exercise were more likely to exercise > 2 times per week compared to respondents whose oncologists did not address exercise (53.5% vs 44.1%, P < 0.001). Conclusions: In a national survey of oncology patients, slightly more than half of respondents reported attention to diet and exercise during oncology visits. Provider recommendations for diet and exercise were associated with positive changes in these behaviors. Additional attention to diet and exercise as part of oncology visits is needed to help support healthy lifestyle change in cancer patients.

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Impact of cancer on the risk of unplanned 30-day readmissions.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6581 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6581-6581

Author(s):

Alexander Qian ◽

Edmund Qiao ◽

Vinit Nalawade ◽

Nikhil V. Kotha ◽

Rohith S. Voora ◽

...

Keyword(s):

Cancer Patients ◽

Cancer Diagnosis ◽

Hospital Admissions ◽

Reference Group ◽

Cancer Site ◽

Cancer Type ◽

Logistic Regression Models ◽

Increased Risk ◽

Initial Hospitalization ◽

The Impact

6581 Background: Hospital readmission are associated with unfavorable patient outcomes and increased costs to the healthcare system. Devising interventions to reduce risks of readmission requires understanding patients at highest risk. Cancer patients represent a unique population with distinct risk factors. The purpose of this study was to define the impact of a cancer diagnosis on the risks of unplanned 30-day readmissions. Methods: We identified non-procedural hospital admissions between January through November 2017 from the National Readmission Database (NRD). We included patients with and without a cancer diagnosis who were admitted for non-procedural causes. We evaluated the impact of cancer on the risk of 30-day unplanned readmissions using multivariable mixed-effects logistic regression models. Results: Out of 18,996,625 weighted admissions, 1,685,099 (8.9%) had record of a cancer diagnosis. A cancer diagnosis was associated with an increased risk of readmission compared to non-cancer patients (23.5% vs. 13.6%, p < 0.001). However, among readmissions, cancer patients were less likely to have a preventable readmission (6.5% vs. 12.1%, p < 0.001). When considering the 10 most common causes of initial hospitalization, cancer was associated with an increased risk of readmission for each of these 10 causes (OR range 1.1-2.7, all p < 0.05) compared to non-cancer patients admitted for the same causes. Compared to patients aged 45-64, a younger age was associated with increased risk for cancer patients (OR 1.29, 95%CI [1.24-1.34]) but decreased risk for non-cancer patients (OR 0.65, 95%CI [0.64-0.66]). Among cancer patients, cancer site was the most robust individual predictor for readmission with liver (OR 1.47, 95%CI [1.39-1.55]), pancreas (OR 1.36, 95%CI [1.29-1.44]), and non-Hodgkin’s lymphoma (OR 1.35, 95%CI [1.29-1.42]) having the highest risk compared to the reference group of prostate cancer patients. Conclusions: Cancer patients have a higher risk of 30-day readmission, with increased risks among younger cancer patients, and with individual risks varying by cancer type. Future risk stratification approaches should consider cancer patients as an independent group with unique risks of readmission.

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Genetic polymorphism of miR-218-2 (rs11134527) in cervical cancer: a case-control study in the Bangladeshi women

MicroRNA ◽

10.2174/2211536610666210715102554 ◽

2021 ◽

Vol 10 ◽

Author(s):

Farhana Nazneen ◽

Md. Shalahuddin Millat ◽

Md. Abdul Barek ◽

Md. Abdul Aziz ◽

Mohammad Sarowar Uddin ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Patients ◽

Case Control Study ◽

Case Control ◽

Recessive Model ◽

Cancer Type ◽

Increased Risk ◽

Hardy Weinberg Equilibrium ◽

Control Study ◽

Healthy Females

Background: The prevalence of Cervical Cancer (CC) is disproportionately higher in developing countries. It is the second most frequent cancer type among Bangladeshi women and the primary cause of morbidity and mortality. However, no previous data reported the association of miR-218-2 gene polymorphisms in Bangladeshi cervical cancer patients. Aim: This case-control study was designed to find the link between the rs11134527 polymorphism in miR-218-2 and CC. Methods: A total of 488 subjects were recruited, comprising 256 cervical cancer patients and 232 healthy females. Genotyping was conducted with the tetra-primer ARMS-PCR technique to detect the association. Results: The results of genotype data showed that rs11134527 obeyed the Hardy-Weinberg equilibrium in both CC cases and controls (P >0.05). Overall, the polymorphism was found to be significantly associated with an increased risk of cervical cancer with AG genotype (AG vs. GG: OR = 2.26, 95% Cl = 1.40-3.66, P = 0.0008), AA genotype (AA vs. GG: OR = 3.64, 95% Cl = 2.17-6.10, P <0.0001), dominant model (AG+AA vs. GG: OR = 2.75, 95% Cl = 1.75-4.31, P <0.0001), recessive model (AA vs. GG+AG: OR = 2.08, 95% Cl = 1.41-3.08, P = 0.0002), and A allele (A vs. G: OR = 1.94, 95% Cl = 1.51-2.51, P <0.0001). All of these correlations remained statistically significant after performing Bonferroni correction (P <0.008). Conclusion: Our study suggests that the rs11134527 polymorphism in the miR-218-2 gene contributes to the susceptibility of CC in Bangladeshi women.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.34 ◽

2011 ◽

pp. 191-204

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.191 ◽

2011 ◽

Vol 5 (3) ◽

pp. 191

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

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Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review

Cancers ◽

10.3390/cancers12030612 ◽

2020 ◽

Vol 12 (3) ◽

pp. 612 ◽

Cited By ~ 1

Author(s):

Anne Rossel ◽

Helia Robert-Ebadi ◽

Christophe Marti

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Absolute Risk ◽

Narrative Review ◽

Relative Reduction ◽

Number Needed To Treat ◽

Chemotherapeutic Regimen ◽

Patients With Cancer ◽

Increased Risk ◽

Risk Of Cancer

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk–benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

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Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽

10.1182/blood.v112.11.3824.3824 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3824-3824

Author(s):

Cihan Ay ◽

Rainer Vormittag ◽

Daniela Dunkler ◽

Ralph Simanek ◽

Alexandru-Laurentiu Chiriac ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Predictive Value ◽

Significant Risk ◽

Cumulative Probability ◽

Total Study Population ◽

Cox Regression Analysis ◽

Increased Risk ◽

Diagnosis Of Cancer ◽

D Dimer

Abstract Venous thromboembolism (VTE) is a frequent complication of cancer, which represents a major cause of morbidity and mortality in cancer patients. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. D-Dimer is a global indicator of coagulation activation and fibrinolysis and is frequently elevated in cancer patients, even without thrombosis. The measurement of D-dimer levels is a widely applied test in the diagnostic work-up of patients with suspected VTE. Prospective observational studies have shown that D-dimer levels have a predictive value for the risk of recurrence in non-cancer patients after the discontinuation of oral anticoagulant treatment. Whether testing for D-Dimer at diagnosis of cancer would be useful for prediction of cancer-associated thrombosis, is not elucidated because up to now appropriately designed prospective studies have not yet been carried out. Therefore, we have assessed D-Dimer levels in cancer patients as risk predictor for VTE and provide a report from the ongoing prospective observational CATS, which was initiated in October 2003. Patients with newly diagnosed cancer or progression of disease that had neither chemotherapy within the last three months, nor radiotherapy nor surgery within the last two weeks were recruited and followed prospectively. Occurrence of VTE and information on the patients’ anti-cancer-treatment within the follow up period were recorded. Observation ended with occurrence of VTE, death or after 2 years. VTE has always been confirmed by imaging. D-Dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan Meier and Cox regression analysis were applied for statistical calculation. Data on 821 patients with cancer (370 women/451 men, median age [IQR]: 62 [53–68] yrs) were available for analyses. Patients were followed for a median observation time of 454 days. Main tumour entities were malignancies of the breast (n=132), lung (n=119), upper (n=35) and lower gastrointestinal tract (n=106), pancreas (n=46), kidney (n=22) and prostate (n=101). Furthermore, 102 patients had high-grade glioma, 94 lymphomas, 17 multiple myeloma and 47 other tumour types. During the observation period VTE occurred in 62 patients (24 female/38 male, median age [IQR]: 60 [50–66] yrs). Elevated levels of D-Dimer (cut-off level 1.44 μg/ml, representing the 75th percentile of the total study population) [hazard ratio (HR): 2.4, 95% CI 1.4–4.0], surgery [HR: 2.3, 95% CI 1.0–5.3] and radiotherapy [HR: 2.3, 95% CI 1.2–4.4] were statistically significant risk factors for VTE in multivariate analysis including D-Dimer, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of developing VTE after 6 months was 11.2 % in patients with D-Dimer levels above and 4.2 % in those below the 75th percentile (p=0.003). In conclusion, cancer patients with elevated D-Dimer levels have an approximately 3-fold increased risk for future occurrence of VTE. High levels of D-Dimer independently predict VTE in these patients and D-Dimer measurement at diagnosis of cancer would help identify patients at increased risk for VTE.

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Statins and Venous Thromboembolism In Lung Cancer

Blood ◽

10.1182/blood.v116.21.5122.5122 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5122-5122

Author(s):

Moh'd Khushman ◽

Abdel-ghanie Abu-samra ◽

Shatha Farhan ◽

Gordon Jacobsen ◽

Amr Hanbali ◽

...

Keyword(s):

Lung Cancer ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Lipid Lowering ◽

Coagulation Cascade ◽

Controlled Study ◽

Increased Risk ◽

Statin Use

Abstract Abstract 5122 Background: Dyslipidemia plays a major role in the pathophysiology of atherosclerosis which may also contributed to an increased risk of and thromboembolism from the injury of the vascular endothelium and its activation of platelets, thereafter, the coagulation cascade. It has been well-established that the use of statins in patients with dyslipidemia reduces cardiovascular events and mortality, therefore, improves survival. In addition to a cholesterol-lowering effect, statins exhibit antithrombotic and anti-inflammatory properties that may confer a protective benefit to an increased risk of thromboembolism in cancer patients. Several case-controlled studies reported that cancer patients receiving long-term statins, but not other non-statin lipid lowering treatment, had a lower incidence of venous thromboembolism. Methods: To investigate any protective benefit from statin use in lung cancer patients, we have conducted this retrospective, case-controlled study. Total of 1548 patients with lung cancer were included from the tumor registery at Henry Ford Health System, Detroit, Michigan, between January 1999 and December 2004. The data were extracted from available electronic medical records of these patients. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 1,548 patients, 315 patients (average age was 68, range 46–90) were statin users at the time of their lung cancer diagnosis. The remaining 1233 patients (average age was 65.9, range 29–94) were non- statin users. After stratifying for statin use, 25 of the 315 statin users developed DVT/PE (7.9%), while 100 of the 1233 non-statin users developed DVT/PE (8.1%). This potential benefit from statin use can also be better visualized from comparing the development of DVT/PE between the statin and non-statin groups in a Kaplan-Meier curve for the probability of freedom from DVT/PE across time. Though statistical significance was not reached (log-rank p-value = 0.377), a trend towards a slightly decreased incidence of DVT/PE onset in the patients who receiving statin as the lipid-lowering agent has been observed. Conclusion: Based on our preliminary data, statin use in patients with lung cancer has demonstrated a weak but favorable protective effect on the development of a venous thromboembolism. The nature as a retrospective study and not well-balanced two group of patients (e.g., the average age of statin users were 2 years older than the non-statin users) may limit our results from reaching statistical significance. In addition, some of the patients who had no clear documentation of their home medications had also been categorized as non-statin users in our study. The results from our final data analysis will be presented. Disclosures: No relevant conflicts of interest to declare.

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Cancer-associated pathways and biomarkers of venous thrombosis

Blood ◽

10.1182/blood-2017-03-743211 ◽

2017 ◽

Vol 130 (13) ◽

pp. 1499-1506 ◽

Cited By ~ 90

Author(s):

Yohei Hisada ◽

Nigel Mackman

Keyword(s):

Cancer Patients ◽

Brain Cancer ◽

Cancer Type ◽

Increased Risk ◽

Different Types ◽

Multiple Biomarkers ◽

Podoplanin Expression ◽

Potential Factors ◽

Cancer Associated Thrombosis ◽

Pai 1

Abstract Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we summarize common and cancer type–specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets, and tissue factor–positive (TF+) microvesicles (MVs) are all potential factors that alone or in combination increase cancer-associated thrombosis. Patients with lung or colorectal cancer often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF. Thrombocytosis is often observed in gastrointestinal, lung, breast, and ovarian cancer and this could decrease the threshold required for VTE. Soluble P-selectin has been identified as a biomarker of cancer-associated thrombosis in a general cancer population and may reflect activation of the endothelium. P-selectin expression by the endothelium may enhance VTE by increasing the recruitment of leukocytes. Studies in patients with pancreatic or brain cancer suggest that elevated levels of PAI-1 may contribute to VTE. Although elevated levels of TF+ MVs have been observed in patients with different types of cancer, an association between TF+ MVs and VTE has been observed only in pancreatic cancer. Podoplanin expression is associated with VTE in patients with brain cancer and may activate platelets. Future studies should measure multiple biomarkers in each cancer type to determine whether combinations of biomarkers can be used as predictors of VTE. A better understanding of the pathways that increase VTE in cancer patients may lead to the development of new therapies to reduce the morbidity and mortality associated with thrombosis.

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