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

Blood ◽  
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.

High Plasma Levels of Soluble P-Selectin Are Predictive for Venous Thromboembolism in Cancer Patients - Results from the Vienna Cancer and Thrombosis Study (CATS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 701-701
Author(s):  
Cihan Ay ◽  
Ralph Simanek ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Guelay Alguel ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Plasma Levels ◽  
High Plasma ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Soluble P ◽  
Observation Period

Abstract Cancer patients are at high risk for venous thromboembolism (VTE), which represents an additional burden and a frequent cause of increased mortality. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. In recent studies the cell adhesion molecule P-selectin was identified to be a strong risk factor for VTE. However, the role of soluble P-selectin (sP-selectin) in cancer-associated VTE is not known because up to now clinical data are not available. Therefore, we assessed sP-selectin plasma levels in cancer patients as a risk predictor for VTE and provide a report from the ongoing prospective observational CATS. Patients with newly diagnosed cancer or progression of disease who had no chemotherapy within the last three months were enrolled from October 2003 to October 2006 and followed prospectively via phone and mail. Occurrence of VTE and information on the patientś anti-cancer-treatment within the follow up period were recorded. VTE has always been confirmed by imaging. sP-selectin levels were measured with a highly sensitive ELISA. Kaplan Meier and Cox regression analysis were applied for statistical calculation. We included 687 patients (319 female/368 male, median age [IQR]: 62 [54–68] yrs) with malignant disease and followed them for a median observation period of 415 days. Main tumour entities were malignancies of the breast (n=125), lung (n=86), upper (n=30) and lower gastrointestinal tract (n=100), pancreas (n=42), kidney (n=19) and prostate (n=72). Furthermore, 80 patients had high-grade glioma, 73 lymphomas, 18 multiple myeloma and 42 other tumour types. Distant metastases were found in 268 patients at the time of recruitment. During the observation period VTE occurred in 45 patients (21 female/24 male, median age [IQR]: 62 [48–66] yrs). Elevated plasma levels of sP-selectin (cut-off level 53.1 ng/mL representing the 75th percentile of the total study population, 173 patients) [hazard ratio (HR): 2.5, 95% CI 1.4 – 4.6], surgery [HR: 3.9, 95% CI 1.8 – 8.5] and radiotherapy [HR: 3.2, 95% CI 1.6 – 6.4] were statistically significant risk factors for VTE in multivariable analysis including sP-selectin, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin plasma levels above and 3.7% in those below the 75th percentile. In conclusion, high plasma levels of sP-selectin independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer would help to identify patients at increased risk for VTE.

High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2703-2708 ◽  
Author(s):  
Cihan Ay ◽  
Ralph Simanek ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Guelay Alguel ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cumulative Probability ◽  
Increased Risk ◽  
Soluble P

Abstract Cancer patients are at high risk for venous thromboembolism (VTE). Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups. The cell adhesion molecule P-selectin was recently identified as risk factor for VTE. To investigate soluble P-selectin (sP-selectin) in cancer patients as risk predictor for VTE, we performed a prospective cohort study of 687 cancer patients and followed them for a median (IQR) of 415 (221-722) days. Main tumor entities were malignancies of the breast (n = 125), lung (n = 86), gastrointestinal tract (n = 130), pancreas (n = 42), kidney (n = 19), prostate (n = 72), and brain (n = 80); 91 had hematologic malignancies; 42 had other tumors. VTE occurred in 44 (6.4%) patients. In multivariable analysis, elevated sP-selectin (cutoff level, 53.1 ng/mL, 75th percentile of study population) was a statistically significant risk factor for VTE after adjustment for age, sex, surgery, chemotherapy, and radiotherapy (hazard ratio = 2.6, 95% confidence interval, 1.4-4.9, P = .003). The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin above and 3.7% in those below the 75th percentile (P = .002). High sP-selectin plasma levels independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE.

D-Dimer and Prothrombin Fragment 1 + 2 Predict Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study

2009 ◽  
Vol 27 (25) ◽  
pp. 4124-4129 ◽  
Author(s):  
Cihan Ay ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Ralph Simanek ◽  
Alexandru-Laurentiu Chiriac ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Multivariable Analysis ◽  
High Grade Glioma ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Prothrombin Fragment ◽  
Patients With Cancer ◽  
Progression Of Disease ◽  
Tumor Types ◽  
D Dimer

Purpose Venous thromboembolism (VTE) is a well-recognized complication of cancer. Laboratory parameters might be useful to assess the VTE risk in patients with cancer. The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 (F 1 + 2), which reflect activation of blood coagulation and fibrinolysis, for prediction of cancer-associated VTE. Patients and Methods In a prospective, observational, cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy, radiotherapy, or surgery were enrolled and followed for a median of 501 days (interquartile range, 255 to 731 days). The malignancies in these patients were as follows: breast (n = 132), lung (n = 119), stomach (n = 35), lower gastrointestinal tract (n = 106), pancreas (n = 46), kidney (n = 22), and prostate (n = 101) cancers; high-grade glioma (n = 102); malignant lymphoma (n = 94); multiple myeloma (n = 17); and other tumor types (n = 47). The study end point was occurrence of objectively confirmed symptomatic or fatal VTE. Results VTE occurred in 62 patients (7.6%). The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population. In multivariable analysis that included elevated D-dimer, elevated F 1 + 2, age, sex, surgery, chemotherapy, and radiotherapy, the hazard ratios (HRs) of VTE in patients with elevated D-dimer (HR, 1.8; 95% CI, 1.0 to 3.2; P = .048) and elevated F 1 + 2 (HR, 2.0; 95% CI, 1.2 to 3.6; P = .015) were statistically significantly increased. The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 (15.2%) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 (5.0%; P < .001). Conclusion High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer.

Integrin genetic variants and risk of thromboembolic events in patients with colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 462-462
Author(s):  
Gerald Prager ◽  
Alexandra Schuler ◽  
Cihan Ay ◽  
Clemens Pausz ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Tumor Biology ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Direct Dna Sequencing ◽  
Increased Risk ◽  
Colorectal Cancer Patients ◽  
Integrin Beta 3

462 Background: Patients with colorectal cancer are at increased risk of venous thromboembolism (VTE). Integrin beta-3 are involved in tumor biology as well as platelet aggregation, thus, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in the integrin beta-3 gene could predict the risk of VTE in colorectal cancer patients. Methods: The study population comprises patients recruited into the Vienna Cancer and Thrombosis Study (CATS) (Ay, C et al; JCO 2011 vol. 29 no. 15), an ongoing prospective observational cohort study initiated in October 2003 at the Medical University of Vienna. In 114 out of 139 patients diagnosed with colon cancer DNA was assessable for integrin beta-3 germline SNPs rs3809865, rs5918, rs4642 characterization. Whole blood samples were analyzed using PCR-RFLP or direct DNA-sequencing. VTE events were statistical analyzed using one-way Anova testing. Results: The patient’s demographics and tumor characteristics were balanced between groups. VTE occurred in 14 patients (12.28%). In colorectal cancer patients with an rs3809865 A/A allele profile a statistical significant (p=0.0015) increased risk of VTE events was observed as 12 (25%) of 48 patients experienced VTE. Only 2 of 52 patients (3.85%) harboring an A/T allele VTE was diagnosed. None (0%) of the T/T subgroup had any VTE. Other SNPs revealed no predictive value for VTE. In multivariable analysis including age, sex, chemotherapy, and anti-VEGF therapy rs3809865 A/A allele profile remained a statistical significant risk factor for VTE. Conclusions: This study identifies germline polymorphisms in integrin genes as independent prognostic markers for VTE in colorectal cancer. These data may help to select subgroups of patients who may benefit from an enforced prophylaxis of venous thromboembolism (VTE).

High Soluble P-Selectin and Low Platelet Count as Thrombosis Risk Markers in Glioma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2985-2985
Author(s):  
Rainer Vormittag ◽  
Christine Marosi ◽  
Cihan Ay ◽  
Ralph Simanek ◽  
Ilse Schwarzinger ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Platelet Count ◽  
Cox Regression ◽  
Significant Risk ◽  
Cumulative Probability ◽  
Risk Markers ◽  
Cox Regression Analysis ◽  
Thrombosis Risk ◽  
Increased Risk ◽  
Soluble P

Abstract Abstract 2985 Poster Board II-961 Background Glioma patients are at high risk for venous thromboembolism (VTE). However, predictive laboratory parameters have not been identified. High platelet count (PLC) and increased soluble P-selectin (sP-selectin) have been reported as risk factors in cancer patients, so we investigated sP-selectin and PLC as risk markers in glioma patients. Methods The Cancer and Thrombosis Study (CATS) is a prospective observational study, whose endpoint is the occurrence of objectively confirmed VTE. sP-selectin was measured in the third week after neurosurgical intervention using a human sP-selectin Immunoassay (R&D Systems®, Minneapolis, USA). Multivariable Cox regression analysis was applied to calculate hazard ratios (HR) for VTE, including PLC, sP-selectin, age, sex and type of surgery. Results 140 patients with newly diagnosed high grade glioma were analysed (52 women; median age 54.5 years [interquartile range (IQR): 42.8-5.1]) during a median observation time of 309 (range: 3-1664) days. Twenty patients developed VTE (6 women, 14 men), of which 2 events were fatal pulmonary embolisms. The cumulative probability of VTE was 10% at six and 15% at twelve months. sP-selectin levels (ng/mL) were higher in patients with VTE compared to those without (median=51.8, IQR: 36.9–66.0 versus median=38.8, IQR: 30.7–52.1, p=0.011). Interestingly, PLC (G/l) was significantly lower in patients with (median=214, IQR: 166-248) than in those without VTE (median=255, IQR: 200-327; p=0.011). In multivariable regression analysis high sP-selectin (75th percentile: 55.1ng/mL) and low PLC (25th percentile: 198G/L) were significant risk markers of VTE (HR=3.4, 95% CI 1.3-9.0, and HR=3.3, 95% CI 1.2-8.8, respectively). Conclusion Our study revealed two strong predictive markers for VTE in glioma patients. Elevated sP-selectin is associated with a three-fold increased risk of thrombosis. In contrast to patients with other solid tumours, in glioma patients low PLC is associated with increased thrombosis risk. Disclosures: Pabinger: Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Prediction of Venous Thromboembolism in Patients With Cancer by Measuring Thrombin Generation: Results From the Vienna Cancer and Thrombosis Study

2011 ◽  
Vol 29 (15) ◽  
pp. 2099-2103 ◽  
Author(s):  
Cihan Ay ◽  
Daniela Dunkler ◽  
Ralph Simanek ◽  
Johannes Thaler ◽  
Silvia Koder ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Thrombin Generation ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Progression Of Disease ◽  
Tumor Types

Purpose Patients with cancer are at increased risk of venous thromboembolism (VTE). Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE. Patients and Methods The Vienna Cancer and Thrombosis Study (CATS) is a prospective observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. The study end point is occurrence of objectively confirmed symptomatic or fatal VTE within a follow-up period of 2 years. Thrombin generation was measured with a commercially available assay. Results One thousand thirty-three patients with malignancies of the breast (n = 151), lung (n = 148), upper (n = 44) and lower gastrointestinal tract (n = 125), pancreas (n = 67), kidney (n = 34), prostate (n = 122), and brain (n = 134) or lymphoma (n = 126), multiple myeloma (n = 26), and other tumor types (n = 56) were observed for a median observation period of 517 days. VTE occurred in 77 patients (7.5%). Patients with elevated peak thrombin (defined as values ≥ 611 nM thrombin, representing the 75th percentile of the total study population) had an increased risk of VTE with a hazard ratio of 2.1 (95% CI, 1.3 to 3.3, P = .002) in multivariable analysis including age, sex, surgery, chemotherapy, and radiotherapy. The cumulative probability of developing VTE after 6 months was significantly higher in patients with elevated peak thrombin than in those with lower peak thrombin (11% v 4%; log-rank test: P = .002). Conclusion Measurement of thrombin generation may help identify patients with cancer at high risk of VTE.

Predictive value of high-sensitive D-dimer determination for chemotherapy-associated venous thromboembolism in gastrointestinal cancer patients

2012 ◽  
Vol 108 (12) ◽  
pp. 1243-1245 ◽  
Author(s):  
Ilaria Portarena ◽  
Silvia Riondino ◽  
Francesca La Farina ◽  
Vincenzo Formica ◽  
Matteo Vergati ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Predictive Value ◽  
D Dimer

scholarly journals Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection

2020 ◽  
pp. 204887262090732 ◽  
Author(s):  
Vitali Koch ◽  
Moritz Biener ◽  
Matthias Müller-Hennessen ◽  
Mershad Vafaie ◽  
Ingo Staudacher ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Aortic Dissection ◽  
Positive Predictive Value ◽  
Cancer Patients ◽  
Upper Extremity ◽  
Predictive Value ◽  
Acute Aortic Dissection ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

Background: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons. Methods and results: We studied 1334 patients presenting to the emergency department with pulmonary embolism ( n=193), deep vein thrombosis ( n=73), acute aortic dissection ( n=22), thrombosis of the upper extremity ( n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349). Conclusion: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.

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