Tissue Factor As a Predictor of Recurrent Venous Thromboembolism in Malignancy: Biomarker Analyses of the CATCH Trial

2017 ◽  
Vol 35 (10) ◽  
pp. 1078-1085 ◽  
Author(s):  
Alok A. Khorana ◽  
Pieter W. Kamphuisen ◽  
Guy Meyer ◽  
Rupert Bauersachs ◽  
Mette S. Janas ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Venous Thromboembolism ◽  
Tissue Factor ◽  
Competing Risk ◽  
Subdistribution Hazard ◽  
Patients With Cancer ◽  
Potential Biomarker ◽  
Recurrent Venous Thromboembolism ◽  
Multiple Variables ◽  
Recurrent Vte

Purpose Circulating tissue factor (TF) has been studied as a biomarker for predicting initial, but not recurrent, venous thromboembolism (VTE) in cancer, a setting in which predictors are incompletely understood. We evaluated the association of TF, clinical risk factors, and other biomarkers measured at the time of initial VTE with recurrent VTE in a prespecified analysis of the CATCH (Comparison of Acute Treatments in Cancer Hemostasis) trial. Methods CATCH was a randomized, multicenter trial that investigated tinzaparin 175 IU/kg once daily or dose-adjusted warfarin for 6 months in patients with cancer and acute, symptomatic VTE. TF ELISA, soluble P-selectin, d-dimer, FVIII, and C-reactive protein were assayed. Fisher’s exact test was used to screen for association with VTE; competing risk regression analysis of time to recurrent VTE was conducted, accounting for multiple variables. Results The study population comprised 900 patients (recurrent VTE, n = 76; 8.4%). Of these patients, 805 had samples available for TF assay. Mean and median TF levels were 72.5 pg/mL and 50.3 pg/mL, respectively (range, 15.6 pg/mL to 4,798 pg/mL). Patients in the highest quartile of TF experienced the greatest VTE recurrence (> 64.6 pg/mL; 38 [19%] of 203 patients v 34 [6%] of 602 patients; relative risk, 3.3; 95% CI, 2.1 to 5.1; P < .001). In competing risk regression analysis of time to recurrent VTE, TF remained strongly associated with recurrent VTE (subdistribution hazard ratio [SHR], 3.3; 95% CI, 1.7 to 6.4). Other significant variables included venous compression from mass (SHR, 3.1; 95% CI, 1.4 to 6.5) and hepatobiliary cancer (SHR, 5.5; 95% CI, 2.3 to 13.6). Conclusion This is the first report, to our knowledge, to describe TF as a potential biomarker of recurrent VTE in patients with cancer who are on anticoagulation treatment. A risk-adapted strategy could help identify high-risk patients who may benefit from more intensive anticoagulation approaches.

Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study

2021 ◽  
Author(s):  
Philippe Girard ◽  
Silvy LAPORTE ◽  
Céline Chapelle ◽  
Nicolas Falvo ◽  
Lionel Falchero ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Groups ◽  
Therapeutic Implications ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
C Statistic ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Introduction: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. Methods: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value >0.70 was needed to validate the Ottawa score. Results: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), digestive tract (18.3%) and breast (13.9%) cancers. The Ottawa score was high (≥1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95%CI: 2.3-10.8) vs 9.1% (95%CI: 6.1-13.6) in the Ottawa low vs high risk groups, respectively. The C-statistic value was 0.60 (95%CI: 0.55-0.65). Conclusion: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Risk of Recurrent Venous Thromboembolism and Mortality in Patients With Cancer Incidentally Diagnosed With Pulmonary Embolism: A Comparison With Symptomatic Patients

2011 ◽  
Vol 29 (17) ◽  
pp. 2405-2409 ◽  
Author(s):  
Paul L. den Exter ◽  
José Hooijer ◽  
Olaf M. Dekkers ◽  
Menno V. Huisman
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Bleeding Complications ◽  
Cancer Type ◽  
Oncology Patients ◽  
Patients With Cancer ◽  
Recurrent Venous Thromboembolism ◽  
Long Term Treatment ◽  
Recurrent Vte ◽  
Complications And Mortality

Purpose The routine use of modern computed tomography scanners has led to an increased detection of incidental pulmonary embolism (PE), in particular in patients with cancer. The clinical relevance of these incidental findings is unknown. Patients and Methods In this retrospective cohort study, oncology patients in whom PE was objectively proven between 2004 and 2010 and anticoagulant treatment was started, were included. Fifty-one patients with incidental PE and 144 with symptomatic PE were observed for 1 year to compare the risks of recurrent venous thromboembolism (VTE), bleeding complications, and mortality. Kaplan-Meier and Cox survival analyses were performed. Results Incidental and symptomatic patients did not differ with respect to mean age, sex, cancer type and stage, and risk factors for VTE. As a result from evolving treatment guidelines, approximately half of the patients in both groups received long-term treatment with vitamin K antagonists in stead of currently recommended low-molecular-weight heparin. The 12-month cumulative incidence of recurrent VTE was 13.3% in the incidental group versus 16.9% in the symptomatic group (P = .77). Notably, 20% VTE events recurred after premature termination of anticoagulant therapy. The risk of major bleeding complications was also comparable in the two groups (12.5% for incidental patients and 8.6% for symptomatic patients; P = .5). The respective 12-month mortality risks were 52.9% and 53.3% (P = .7). Conclusion Our findings suggest that oncology patients diagnosed with and treated for incidental PE, have similar high rates of recurrent VTE, bleeding complications, and mortality, as compared with oncology patients who develop symptomatic PE.

Anticoagulation outcomes in patients with venous thromboembolism following Whipple surgery for pancreatic cancer: Single center experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16255-e16255
Author(s):  
Nino Balanchivadze ◽  
James P Purtell ◽  
Philip Kuriakose ◽  
Julie Clark ◽  
Kylie Springer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Venous Thromboembolism ◽  
Upper Extremity ◽  
Major Bleeding ◽  
Cox Regression ◽  
Whipple Procedure ◽  
Cox Regression Analysis ◽  
Patients With Cancer ◽  
Multiple Variables ◽  
Recurrent Vte

e16255 Background: Venous thromboembolism (VTE) is a common complication in patients with pancreatic cancer (PC). Incidence of major bleeding and clinically relevant non-major bleeding is 14%-20% in patients with cancer who receive anticoagulation therapy (AT). Whipple procedure is a complex surgical intervention offering potential cure in patients with resectable PC; however, surgery can affect drug absorption, which may reduce effectiveness of AT or exacerbate drug related adverse events. Our aim was to assess incidence of bleeding in PC patients who had whipple procedure with subsequent VTE. Methods: Retrospective analysis of medical records for all adult patients with PC who underwent whipple procedure and developed VTE (between July 1, 2010, and July 1, 2020) at Henry Ford Hospital was performed. Multiple variables and outcomes were analyzed by two-group comparisons, univariate analysis, and Cox regression. Results: A total of 32 patients were included in the analysis. The mean (standard deviation [SD]) age was 67.4 (11 y) years, 16 (50%) patients were men, and 16 (50%) were women, (20 [63%] White; 11 [34%] Black; 1 [3%] Asian). The median Khorana score was 3 (range, 2–4). Of the 32 patients, 6 (19%) had upper extremity VTE, 11 (34%) had lower extremity VTE, 10 (31%) had a pulmonary embolism, 7 (22%) had intra-abdominal VTE, and 7 (22%) had recurrent VTE. All patients with upper extremity VTE had a peripherally inserted central catheter (PICC) or a venous port at the time of VTE diagnosis. Most of the patients (28 or 88%) received AT. Whereas 13 (41%) patients had at least one bleeding episode, 19 (59%) had no bleeding. Twenty-two (68%) patients did not need PRBC transfusion, while 4 (13%) patients required > 4 units packed red blood cell transfusion. No significant association between bleeding and AT was observed ( p = .590). Patients with a bleeding event had lower hemoglobin levels ( p = .030) and were more likely to receive blood transfusion ( p = .005). Cox regression analysis did not show patient age, ethnicity, type of AT used, recurrent VTE, and neoadjuvant chemotherapy treatment to be significantly associated with bleeding or death. A total of 14 (44%) patients were alive at the time of analysis. Conclusions: In patients with PC and VTE who received AT after whipple procedure, the incidence of bleeding was higher than what has been reported in patients with cancer in general, regardless of type of AT administration. Patients with central venous catheters might be at increased risk of upper extremity VTE and this subset of patients may benefit from various risk reducing strategies. Caution is recommended while managing AT in this complex patient population, and more studies are needed to assess factors specifically associated with AT and bleeding after whipple procedure.

A Meta-Analysis of Case Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding in Patients with Cancer

2020 ◽  
Vol 120 (04) ◽  
pp. 702-713 ◽  
Author(s):  
Alym Abdulla ◽  
Wendy M. Davis ◽  
Namali Ratnaweera ◽  
Elena Szefer ◽  
Brooke Ballantyne Scott ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Case Fatality Rate ◽  
Meta Analysis ◽  
Case Fatality ◽  
Fatality Rate ◽  
Patients With Cancer ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Abstract Background Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. Methods We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. Results Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1–27.8) and 1.9 (95% CI: 0.8–4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6–30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3–16.7) and 0.8 (95% CI: 0.3–2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5–21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. Conclusion In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.

Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
P Value ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

scholarly journals Predicting the Risk of Recurrent Venous Thromboembolism: Current Challenges and Future Opportunities

2020 ◽  
Vol 9 (5) ◽  
pp. 1582 ◽  
Author(s):  
Hannah Stevens ◽  
Karlheinz Peter ◽  
Huyen Tran ◽  
James McFadyen
Keyword(s):  
Venous Thromboembolism ◽  
Prediction Models ◽  
Clinical Prediction ◽  
Bleeding Events ◽  
Clinical Prediction Models ◽  
Disease Pathogenesis ◽  
Recurrent Venous Thromboembolism ◽  
Novel Biomarkers ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field.

Recurrent thrombosis followed by Lazarus response in ROS1 rearranged NSCLC treated with crizotinib: a case report

2020 ◽  
Vol 106 (6) ◽  
pp. NP41-NP45
Author(s):  
Teresa Beninato ◽  
Giuseppe Lo Russo ◽  
Marina Chiara Garassino ◽  
Filippo De Braud ◽  
Marco Platania
Keyword(s):  
Venous Thromboembolism ◽  
Genetic Alterations ◽  
Small Cell Lung ◽  
Recurrent Thrombosis ◽  
Right Heart ◽  
Thromboembolic Risk ◽  
Patients With Cancer ◽  
Recurrent Venous Thromboembolism ◽  
Progressive Respiratory Failure ◽  
Alk Positive

Introduction: Patients with cancer have higher risk of thrombosis compared to the general population and particularly lung adenocarcinoma is considered at high risk for venous thromboembolism. Some targetable oncogenic drivers are supposed to further increase this risk. Case description: A 35-year-old man who had developed a recurrent venous thromboembolism and pulmonary embolism (PE) was diagnosed with ROS1 rearranged non-small cell lung cancer (NSCLC). While molecular examinations were ongoing, he developed progressive respiratory failure. For PE and thrombosis worsening with detection of right heart thrombus, he underwent therapy with unfractionated heparin. Despite initial good radiologic results, only with the start of crizotinib did the patient’s clinical condition significantly improve to configure a Lazarus response. Conclusions: Cancer diagnosis should always be considered in patients with unprovoked thrombosis and, if NSCLC is diagnosed, genetic alterations should be always sought after. A possible relation between venous thromboembolism and oncogenic drivers, particularly for ALK translocations, has been hypothesized. Similarly to ALK-positive NSCLC, ROS1 rearranged disease has been associated with an increased thromboembolic risk. Further studies are needed to better evaluate this relation and to evaluate the potential benefit of a prophylactic anticoagulating treatment in this subset of patients.

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