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Purpose: Cancer patients are at an increased risk of venous thromboembolism (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the prediction of VTE in patients with cancer.Experimental Design: Eight hundred four patients with newly diagnosed cancer or progression after remission were prospectively followed for 2 years until the occurrence of VTE or death [tumor sites: brain (n = 87), breast (n = 137), lung (n = 120), gastrointestinal (n = 143), pancreas (n = 53), prostate (n = 95), kidney (n = 22), myeloma and lymphoma (n = 99), and others (n = 48)]. Primary endpoint was symptomatic or fatal VTE. sVEGF was measured by immunoassay in baseline plasma.Results: Fifty-five patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level (25th–75th percentile) was 8.1 pg/mL (0–17.7). The cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4–14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2–7.9) in patients with lower levels (P = 0.03). The corresponding 2-year risk of death was 52.8% (95% CI, 46.0–60.0) and 43.9% (95% CI, 40.0–48.0), respectively (P = 0.02). In univariable time-to-VTE regression, elevated sVEGF was associated with VTE [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00–1.09; P = 0.04)]. The association between sVEGF and risk of VTE prevailed after multivariable adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00–1.09, P = 0.05).Conclusions: Elevated sVEGF is associated with an increased risk of VTE in patients with cancer. Clin Cancer Res; 22(1); 200–6. ©2015 AACR.

Table S1: Mean change in sVEGF according to selected variables - Simple linear regression models Table S2: Mean change in sVEGF* according to selected variables - "Multiple Model 1" Table S3: Mean change in sVEGF according to selected variables - "Multiple Model 2" Table S4: sVEGF and the risk of death-from-any-cause - Multivariable Cox regression model

A large proportion of patients experience functional limitations after an acute episode of venous thromboembolism (VTE). Recently, the post-VTE functional status (PVFS) scale was proposed to capture these limitations. We performed a prospective cohort study to validate this scale.The PVFS scale, PROMIS physical function 10a, EQ-5D-5L, and disease-specific quality of life (VEINES-QOL/Sym, PEmb-QoL) were assessed within three weeks of VTE diagnosis and after a median (IQR) follow-up of 13.4 (12.7-15.9) weeks. To evaluate construct validity of the PVFS scale, we determined correlations of PVFS scale with the other health measurements and investigated differences in patients above/below 70 years. Responsiveness was evaluated with a linear regression model, predicting change in PROMIS with change in PVFS scale.We included 211 patients (median (IQR) age: 55.1 (44.1-67.6) years, 40 % women). Pulmonary embolism was diagnosed in 105 (49.8 %) patients and 62.6 % of events were unprovoked. The PVFS scale correlated with PROMIS physical function (Spearman's rho (r): -0.67 and -0.63, p 0.001) and EQ-5D-5L index (r = -0.61 and -0.61, p 0.001) at baseline and follow-up. Furthermore, PVFS correlated moderately to strongly with disease-specific quality of life. Patients70 years had significantly higher PVFS grades at follow-up (median (IQR): 2 (0-3) vs. 1 (0-2), p = 0.010). Changes in PVFS scale over time were significantly associated with changes in PROMIS physical function.The PVFS scale showed adequate construct validity and responsiveness in a prospective cohort study of patients with VTE, suggesting that it can be incorporated as additional health measurement and outcome parameter in research and clinical practice.

Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes.In this prospective multicenter population-based cohort study, GDF-15 was measured in 594 ESKD patients on hemodialysis (median age: 66 years, 38% women), who were followed-up for in median 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE), and death was analyzed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment.GDF-15 levels were 5475ng/L in median (25th-75th percentile: 3964-7533) and independently associated with major bleeding (subdistribution hazard ratio [SHR] 1.31 per double increase, 95%CI 1.00-1.71), MACE (SHR 1.47, 1.11-1.94), and all-cause mortality (SHR 1.58, 1.28-1.95) but not arterial thromboembolism (SHR 0.91, 95%CI 0.61-1.36). Addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding (C-statistics increased from 0.61 (95%CI 0.52-0.70) to 0.68 (95%CI 0.61-0.78)). Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death.GDF-15 predicts risk of major bleeding, cardiovascular events, and death in ESKD patients on hemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.

BackgroundPatients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding the risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes.MethodsIn this prospective, multicentre, population-based cohort study, GDF-15 was measured in 594 ESKD patients on haemodialysis (median age 66 years, 38% female), who were followed up for a median of 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE) and death was analysed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment.ResultsGDF-15 levels were in median 5475 ng/l (25th–75th percentile 3964–7533) and independently associated with major bleeding {subdistribution hazard ratio [SHR] 1.31 per double increase [95% confidence interval (CI) 1.00–1.71]}, MACE [SHR 1.47 (95% CI 1.11–1.94)] and all-cause mortality [SHR 1.58 (95% CI 1.28–1.95)] but not arterial thromboembolism [SHR 0.91 (95% CI 0.61–1.36)]. The addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding [C-statistics increased from 0.61 (95% CI 0.52–0.70) to 0.68 (95% CI 0.61–0.78)]. Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death.ConclusionGDF-15 predicts the risk of major bleeding, cardiovascular events and death in ESKD patients on haemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.

Aims An interrelation between cancer and thrombosis is known, but population-based studies on the risk of both arterial thromboembolism (ATE) and venous thromboembolism (VTE) have not been performed. Methods and results International Classification of Disease 10th Revision (ICD-10) diagnosis codes of all publicly insured persons in Austria (0–90 years) were extracted from the Austrian Association of Social Security Providers dataset covering the years 2006–07 (n = 8 306 244). Patients with a history of cancer or active cancer were defined as having at least one ICD-10 ‘C’ diagnosis code, and patients with ATE and/or VTE as having at least one of I21/I24 (myocardial infarction), I63/I64 (stroke), I74 (arterial embolism), and I26/I80/I82 (venous thromboembolism) diagnosis code. Among 158 675 people with cancer, 8559 (5.4%) had an ATE diagnosis code and 7244 (4.6%) a VTE diagnosis code. In contrast, among 8 147 569 people without cancer, 69 381 (0.9%) had an ATE diagnosis code and 29 307 (0.4%) a VTE diagnosis code. This corresponds to age-stratified random-effects relative risks (RR) of 6.88 [95% confidence interval (CI) 4.81–9.84] for ATE and 14.91 (95% CI 8.90–24.95) for VTE. ATE proportion was highest in patients with urinary tract malignancies (RR: 7.16 [6.74–7.61]) and lowest in patients with endocrine cancer (RR: 2.49 [2.00–3.10]). The corresponding VTE proportion was highest in cancer of the mesothelium/soft tissue (RR: 19.35 [17.44–21.47]) and lowest in oropharyngeal cancer (RR: 6.62 [5.61–7.81]). Conclusion The RR of both ATE and VTE are significantly higher in persons with cancer. Our population-level meta-data indicate a strong association between cancer, ATE and VTE, and support the concept of shared risk factors and pathobiology between these diseases. Relative risk of ATE and VTE in persons with a cancer diagnosis code versus persons without a cancer diagnosis code.

Background The COVID-19 pandemic has focused medical attention on treating affected patients and protecting others from infection. However, concerns have been raised regarding the pandemic´s impact and associated containment measures (eg curfew, lockdown) on non-coronavirus disease 2019 (COVID-19)-related acute medical diseases. Objectives To investigate changes in the incidence of pulmonary embolism (PE) during the COVID-19 pandemic compared to the period before the pandemic and reference periods in previous years. Methods In this single-center study, we explored all diagnostic imaging tests performed for suspected PE between weeks 1 and 17 of the years 2018, 2019, and 2020. Incidence of PE (ie, primary outcome) was analyzed. Secondary outcomes included number of imaging tests for suspected PE. Results Compared to weeks 1 to 11, 2020, an abrupt decline in PE diagnosis (mean weekly rate, 5.2; 95% confidence interval [CI], 3.8-6.6 vs 1.8; 95% CI, 0.0-3.6) and imaging tests (mean weekly rate, 32.5; 95% CI, 27.5-37.6 vs. 17.3; 95% CI, 11.6-23.1) was observed from week 12, with beginning of the containment measures and public lockdown in Austria. Compared to weeks 12 to 17 of 2018 and 2019, PE incidence and imaging tests were similarly decreased from 5.3 (95% CI, 3.6-7.1) to 1.8 (95% CI, 0.0-3.6) and 31.5 (95% CI, 27.1-35.9) to 17.3 (95% CI, 11.6-23.1), respectively. The median simplified pulmonary embolism severity index (sPESI) score of PE patients during the pandemic was higher than in all other PE patients (3; interquartile range, 1-3 vs 1; interquartile range, 0-2; P = .002). Conclusion Our study demonstrates that the COVID-19 pandemic has an impact on non-COVID-19-related acute diseases as shown by the decline in incidence of PE and imaging procedures for diagnostic workup. Further studies from other hospitals are needed to confirm our findings.

Background Data on the effect of ABO blood group (ABO), von Willebrand factor (VWF) levels, and age on factor VIII (FVIII) in non-severe haemophilia A (HA) is scarce. Objective To investigate if ABO, VWF levels, and age have an influence on the variability of FVIII levels and consequently on the assessment of severity in non-severe HA. Patients/methods Eighty-nine patients with non-severe HA and 82 healthy controls were included. Data on ABO was collected and FVIII clotting activity (FVIII:C) with one-stage clotting assay (FVIII:C OSA) and chromogenic substrate assay (FVIII:C CSA), FVIII antigen (FVIII:Ag) and VWF antigen (VWF:Ag) and activity (VWF:Act) were determined. Results In HA, FVIII:C OSA and CSA and FVIII:Ag were not different between non-O (n = 42, median 15.5, interquartile range 10.4-24.0; 10.0, 6.8-26.0 and 15.2, 10.7-24.9) and O (n = 47, 14.1, 9.0-23.0; 10.0, 5.0-23.0 and 15.2, 9.3-35.5), whereas in healthy controls, non-O individuals had significantly higher FVIII levels. Fviii C showed no relevant correlation with VWF levels in HA, but we observed strong correlations in healthy controls. Age had only a minor influence in HA, but had a considerable impact on FVIII:C in healthy controls. In multivariable regression analysis ABO, VWF:Ag and age were not associated with FVIII:C in HA, whereas this model explained 61.3% of the FVIII:C variance in healthy controls. Conclusions We conclude that in non-severe HA ABO and VWF levels do not substantially influence the variability of FVIII levels and age has only minor effects on it, which is important information for diagnostic procedures.

Background and aims Cardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD. Methods In a cross-sectional population based cohort of chronic HD patients (n = 626) from Vienna, Austria, the medical histories of patients and use of antithrombotic treatment were recorded, and the distribution of antithrombotic therapies for primary (n = 260, 41.5%) or secondary (n = 366, 58.5%) prevention of CVD was analyzed. Results Single antiplatelet therapy (SAPT) was used in 234 patients (37.4%), dual antiplatelet (DAPT) in 50 (8.0%), combination of anticoagulation and antiplatelet in 59 (9.4%), anticoagulation monotherapy in 78 (12.5%), and no antithrombotics in 205 patients (32.7%). The prevalence of CVD was 58.5%. In primary CVD prevention, 23.5% (n = 61) of patients were treated with SAPT. For secondary prevention, SAPT was used in 173 (47.3%), DAPT in 49 (13.4%), and dual antithrombotic therapies in 50 patients (13.7%), while 55 (15.0%) patients received no antithrombotics. Age (odds ratio [OR] per 1 year increase 0.96, 95%CI 0.94–0.99, p = 0.004) and hereditary nephropathy (OR 4.13, 95%CI 1.08–15.78, p = 0.038) were independently associated with the absence of antithrombotic therapy in secondary CVD prevention. Conclusion The majority of patients did not receive antithrombotic therapy for primary prevention. Only 15% did not receive antithrombotic agents in the secondary prevention setting. The net-clinical benefit of antithrombotic therapy in ESRD needs to be determined.

Background Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) are at increased risk for bleeding. However, despite relevant clinical implications regarding dialysis modalities or anticoagulation, no bleeding risk assessment strategy has been established in this challenging population. Methods Analyses on bleeding risk assessment models were performed in the population-based Vienna InVestigation of Atrial fibrillation and thromboemboLism in patients on hemoDialysIs (VIVALDI) study including 625 patients. In this cohort study, patients were prospectively followed for a median observation period of 3.5 years for the occurrence of major bleeding. First, performances of existing bleeding risk scores (i.e., HAS-BLED, HEMORR2HAGES, ATRIA, and four others) were evaluated in terms of discrimination and calibration. Second, four machine learning-based prediction models that included clinical, dialysis-specific, and laboratory parameters were developed and tested using Monte Carlo cross-validation. Results Of 625 patients (median age: 66 years, 37% women), 89 (14.2%) developed major bleeding, with a 1-year, 2-year, and 3-year cumulative incidence of 6.1% (95% confidence interval [CI]: 4.2–8.0), 10.3% (95% CI: 8.0–12.8), and 13.5% (95% CI: 10.8–16.2), respectively. C-statistics of the seven contemporary bleeding risk scores ranged between 0.54 and 0.59 indicating poor discriminatory performance. The HAS-BLED score showed the highest C-statistic of 0.59 (95% CI: 0.53–0.66). Similarly, all four machine learning-based predictions models performed poorly in internal validation (C-statistics ranging from 0.49 to 0.55). Conclusion Existing bleeding risk scores and a machine learning approach including common clinical parameters fail to assist in bleeding risk prediction of patients on HD. Therefore, new approaches, including novel biomarkers, to improve bleeding risk prediction in patients on HD are needed.

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p &lt, 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.

Summary Background Cancer patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have an increased risk of mortality. Here, we investigated predictive factors for coronavirus disease 2019 (COVID-19) associated mortality in patients with neoplastic diseases treated throughout Austria. Methods In this multicentric nationwide cohort study, data on patients with active or previous malignant diseases and SARS-CoV‑2 infections diagnosed between 13 March 2020 and 06 April 2021 were collected. Collected data included the stage of the malignant disease and outcome parameters 30 days after the diagnosis of SARS-CoV‑2 infection. Results The cohort consisted of 230 individuals of which 75 (32.6%) patients were diagnosed with hematologic malignancies and 155 (67.4%) with solid tumors. At a median follow-up of 31 days after COVID-19 diagnosis, 38 (16.5%) patients had died due to COVID-19. Compared to survivors, patients who died were older (62.4 vs. 71.4 years, p p p = 0.03), lower lymphocyte counts (21.4% vs. 14%, p = 0.006) and lower albumin levels (32.5 g/l vs. 21.6 g/l, p p > 0.05). In 60.6% of the patients, therapy was postponed due to quarantine requirements or hospital admission. Conclusion Mortality of Austrian cancer patients infected with SARS-CoV‑2 is comparable to that of other countries. Furthermore, risk factors associated with higher mortality were evident and similar to the general population. Treatment delays were frequently observed.

Background Evidence supporting the use of anticoagulation for the prevention of stroke and thromboembolism in patients with kidney failure on hemodialysis (HD) and atrial fibrillation (AF) is limited. We prospectively assessed the incidences of stroke and major bleeding, as well as anticoagulation strategies in patients on HD with AF. Methods We recruited 625 prevalent HD patients into a population-based observational cohort study. The primary prospective outcomes were thromboembolic events (stroke, transient ischemic attack, systemic embolism) and major bleeding. Secondary outcomes included a composite of thromboembolic events, major bleeding, and cardiovascular death to determine net clinical harm. Results A total of 238 patients (38.1%) had AF, 165 (26.4%) already at baseline and 73 (15.9%) developed AF during a median follow up of 870 days. Forty (6.4%) thromboembolic events and 89 (14.2%) major bleedings occurred. Overall, 256 patients died (41.0%). In AF patients, use of vitamin K antagonists (VKAs) in 61 patients (25.6%) was not significantly associated with reduced risk of the primary thromboembolic outcome (subdistribution hazard ratio [SHR] 1.41 adjusted for age, sex, congestive heart failure, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes history score and antiplatelet co-medication (95% CI, 0.49-4.07), but with increased risk of major bleeding (SHR: 2.28; 95% CI, 1.09-4.79) compared with AF patients without anticoagulation (N = 139, 58.4%). Use of VKAs was associated with net clinical harm (adjusted SHR: 2.07; 95% CI, 1.25-3.42). Conclusions Although the nonrandomized nature of the study is prone to bias, anticoagulation with VKAs was not associated with decreased thromboembolic risk, but rather with increased risk of major bleeding and may be net harmful to patients with AF on HD.

Background: Growth-differentiation factor-15 (GDF-15) has recently been described as a potential biomarker for predicting risk of mortality and cardiovascular events in patients with atrial fibrillation (AF) but requires validation in clinical practice. Methods: The study population consisted of 362 patients (mean age: 71 years, 37% women) with non-valvular AF included in a prospective cohort study. Relationship of GDF-15 with all-cause mortality and major adverse cardiac events (MACE) was analyzed using Cox regression. Survival analysis stratified by GDF-15 was based on national death records, while MACE was recorded at personal follow-up. Further, we evaluated the recently developed GDF-15 based prognostic score towards prediction of all-cause mortality (ABC-death score). Results: Over a median observation period of 4.3 years, 81 (23.3%) patients died, and over a median personal follow-up of 316 days 47 MACE occurred. GDF-15 was independently associated with all-cause mortality (adjusted HR per double increase 2.33, 95%CI 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39). GDF-15 levels, measured at follow-up, were similarly associated with mortality, and longitudinal measurements of GDF-15 did not significantly differ. Six-year survival probability of patients above vs. below the median GDF-15 level was 44% (95%CI 34-57) and 84% (95%CI 76-93), respectively. The ABC-death score revealed a C-statistic of 0.80. Conclusion: GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, the ABC-death score showed good predictive accuracy in a “real-world” cohort. Therefore, introduction of GDF-15 into clinical practice would enhance risk prediction of morbidity and mortality in AF patients.

Although intraocular pressure is the main the risk factor for the development of glaucoma, other risk factors such as vascular dysfunction might play an additional pathogenic role. Hypertriglyceridemia, which may lead to vascular dysfunction, has been implicated in the development of glaucoma. The objective of this meta-analysis was to investigate the association of triglyceride levels with the risk of glaucoma in case-control studies. Seventeen case-control studies were included investigating the difference in triglyceride levels in patients with glaucoma (N = 1 391) compared to subjects without glaucoma (N = 25 575). In random effects meta-analysis, the pooled mean triglyceride level across all studies and patients with and without glaucoma was 132.9 mg/dL (95%CI: 124.0–141.7). Patients with glaucoma had significantly higher mean triglyceride levels than patients without glaucoma (absolute difference = 14.2 mg/dL, 95%CI: 5.8–22.5, p 2 = 66.2%, heterogeneity χ2 = 47.4 on 16 degrees of freedom, p

The thrombin generation potential is an in vitro measure for the capacity of an individual to generate thrombin and recognized as a reflection of a hypo- or hypercoagulable status. Measurement of the in vivo thrombin activity, however, may be of clinical significance. We evaluated a new assay for in vivo thrombin activity and compared it to the in vitro thrombin generation potential in patients with hemophilia A (N = 15), oral anticoagulation for atrial fibrillation (AF) (N = 20), subjects with active cancer (N = 21), and healthy volunteers (N = 10). Thrombin activity was measured with a commercially available oligonucleotide enzyme capture assay in argatroban-stabilized plasma samples. Thrombin generation potential was determined with a commercially available assay in citrated plasma. Thrombin activity was detected in 17 (30.4 %) patients (mean 0.30 mU/ml [SD 0.80]), and in 39 patients (69.6 %) no thrombin activity was present. In cancer patients, thrombin activity was detected in 11 patients (52 %) (range 0.14-5.00 mU/ml) and was particularly increased in 3 patients with vessel-invasive tumors (1.2, 1.5, and 5.0 mU/ml). In AF patients, thrombin activity was only measureable in two patients (10 %) (recent hematoma [0.4 mU/ml] and recent ischemic stroke [1.5 mU/ml]). Thrombin activity was detected in four patients (27 %) with hemophilia (range 0.29-1.75 mU/ml), all of whom had received a factor VIII infusion on the same day. Thrombin activity did not correlate with any of the parameters of the thrombin generation potential. Only patients in acute procoagulatory states or after clotting factor replacement had elevated in vivo thrombin activity, which was, however, unrelated to the in vitro thrombin generation potential.

Background. In cancer patients, reduced serum albumin has been described as a marker for global declining health and poor prognosis. Our aim was to investigate the association of albumin concentrations with the occurrence of venous thromboembolism (VTE) and mortality in patients with cancer. Methods. This investigation was performed in the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study. We included 1,070 patients with active cancer and assayed serum albumin from venous blood taken at study inclusion. Risk for occurrence of VTE was calculated in a proportional subdistribution hazard regression model with respect to competing risk of death and adjusted for cancer site, leukocyte count, estimated glomerular filtration rate, and cholinesterase. Results. Patients (630 males [58.9%] and 440 females [41.1%]) were observed for a median of 723 days. During follow-up, 90 VTE events (8.4%) and 396 deaths (37.0%) occurred. The median albumin was 41.3 g/L (25th–75th percentile, 37.6–44.2). Patients with albumin levels below the 75th percentile had a 2.2-fold increased risk of VTE (95% confidence interval [CI] 1.09–4.32), as well as a 2.3-fold increased risk of death (95% CI 1.68–3.20) compared with patients with albumin above the 75th percentile. Conclusion. Decreased serum albumin levels in cancer patients were significantly associated with increased risk of VTE and mortality. Serum albumin, a marker of a cancer patient’s overall prognosis, could be considered for risk assessment of important clinical outcomes such as VTE and mortality.

Patients with cancer are at risk of developing venous and arterial thromboembolism (VTE and ATE). Elevated platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte ratios (NLR) have been suggested as potential biomarkers for cancer-associated chronic inflammation, VTE and mortality. We investigated the association between PLR and NLR with VTE, ATE and mortality in patients with cancer. Within a prospective cohort study, we followed-up patients with newly diagnosed or progressing cancer for objectively confirmed, symptomatic VTE, ATE and death. Fine and Gray competing-risk regression was used to model the risk of VTE and ATE. Overall survival was analysed with Kaplan–Meier estimators. From 2003 to 2013, 1,469 patients with solid cancer (median age: 61 years; 47.3% female) were recruited and followed for 2 years. Overall, 128 (8.7%) patients developed VTE, 41 (2.8%) ATE and 643 (43.8%) patients died. The sub-distribution hazard ratios (SHRs) for VTE per doubling of PLR and NLR were 1.0 (95% confidence interval [CI]: 0.8–1.3, p = 0.899) and 1.2 (1.0–1.4, p = 0.059), respectively. For ATE, the SHR per doubling of PLR and NLR were 1.0 (0.7–1.5, p = 0.940) and 1.2 (0.9–1.6, p = 0.191), respectively. A higher PLR (hazard ratio [HR] per doubling = 1.5, 1.4–1.7, p

Monitoring of anti-coagulation with the direct factor Xa inhibitor rivaroxaban is considered unnecessary in a routine clinical setting. However, assessment of its anti-coagulant effect may be desirable in certain clinical situations. We assessed prothrombin time (PT) reagents and commercially available anti-Xa assays (Biophen) calibrated for rivaroxaban and heparin in comparison to liquid chromatography–mass spectrometry (LC-MS/MS) measurements of rivaroxaban concentration in samples from patients on treatment with rivaroxaban for stroke prevention in atrial fibrillation. Citrate plasma samples were obtained from 30 randomly selected patients on uninterrupted treatment with rivaroxaban for a minimum of 1 month. The anti-Xa assays, direct Xa inhibitor (DiXa-I®), and Heparin LRT® were conducted for both wide and low calibrations for rivaroxaban. Measurements were compared to LC-MS/MS using correlation, linear regression, intra-class correlation, and Bland–Altman analysis. In 30 patients (9 female) of median age 71.5 years and BMI 26.5 kg/m2, rivaroxaban concentrations between 2.4 and 625 ng/ml (median 82 ng/ml) were measured by LC-MS/MS. PT reagents were poorly correlated with rivaroxaban concentrations (r 2 = 0.52 and 0.09). Anti-Xa assays DiXa-I (r 2 = 0.95) and Heparin LRT (r 2 = 0.97) were correlated with rivaroxaban in all concentrations, but especially in low concentrations with low calibrations (r 2 = 0.97 and 0.98, respectively). The highest agreement occurred between Heparin LRT and low rivaroxaban concentrations with a mean difference of −5.3 ng/ml (limits of agreement, 12.9 to 2.4 ng/ml). Anti-Xa assays can indirectly determine the concentration of rivaroxaban for a wide range of concentrations in real-world patients. An interpretation of anti-Xa and PT measurements in treatment with rivaroxaban requires knowledge of the local reagents.

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p

Background Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) are at risk for occurrence of vascular access thrombosis and venous thromboembolism (VTE). Understanding the extent of these complications and identifying risk factors can help improve management strategies. Methods Adult HD patients were cross-sectionally recruited into the Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemoDIalysis (VIVALDI). In this investigation, retrospective data on the incidence and risk of VTE and vascular access thrombosis was analyzed using logistic regression and negative binomial regression for counts of vascular access thrombosis episodes. Results The analysis includes 626 patients on HD, which constitutes 73% of the total HD population in Vienna, Austria. One-hundred-seventy-eight patients (28.4%) had 275 vascular access thrombosis events during 2463.1 patient-years on HD, corresponding to an incidence rate (IR) of 111.6 events per 1000 patient-years on HD. In the multivariable negative binomial regression model, we found that patients suffered from vascular access thrombosis 2.5 times more often (IR ratio 2.63, 95% confidence interval [CI] 1.48–4.68, p = 0.001) if toxic nephropathy was their cause of ESRD (n = 28, 4.5%) compared to patients with other causes of ESRD. Sixty-one patients (9.7%) had a history of VTE and the IR of VTE events during the time on HD was 10.9 per 1000 patient-years on HD (women: IR 15.1, men IR 8.6). Female sex (odds ratio [OR] 1.90, 95%CI 1.07–3.36, p = 0.029) and atrial fibrillation (OR 2.00, 95%CI 1.10–3.64, p = 0.023) were independently associated with VTE. Conclusions Thromboembolic events including vascular access thrombosis and VTE are frequent complications in patients on HD. Risk evaluation for thromboembolism, including sex and clinical parameters, may identify high-risk patients and improve their clinical management.

The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients.Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death.The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m(2)) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations.In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death.

Venous thromboembolism (VTE) occurs frequently in patients with cancer and contributes to elevated morbidity and mortality. Risk factors for the occurrence of VTE events in patients with cancer have been investigated in numerous clinical studies. For now more than 10 years, the Vienna Cancer and Thrombosis Study (CATS) has focused on the identification of parameters predictive of future VTE occurrence. CATS has contributed to new findings, which may help identify patients at high risk of developing VTE, by means of biomarkers (such as D-dimer, prothrombin fragment 1+2, soluble P-selectin, platelet count, coagulation factor VIII activity, thrombin generation potential, etc.). The association of tissue factor bearing microparticles and the mean platelet volume with the risk of VTE was also elaborately investigated in the framework of CATS. More recently CATS has researched clinical and clinicopathologic parameters which contribute to identification of patients at risk of VTE. The type of cancer is one of the most important risk factor for VTE occurrence. Also the stage of cancer and the histological grade of a tumor have been found to be associated with the occurrence of cancer-related VTE. In further investigations, venous diseases including a history of previous VTE, a history of superficial thrombophlebitis and the presence of varicose veins, have been associated with the risk of VTE in CATS.

Background The clinical practice of stroke prevention in atrial fibrillation (AF) with direct oral anticoagulants (DOACS) differs from anticoagulation in randomized trial patients. We investigated the risk of thromboembolism, bleeding, and drug discontinuation in a hospital-based real-world setting. Methods All-comer patients with non-valvular AF were recruited into a registry at an academic tertiary care center. After informed consent, patients underwent a personal structured interview including medical history, past and current anticoagulation, and returned for follow-up after 6–12 months. Results The registry comprised 282 patients (42% women, median age 71 years) with a median CHA2DS2-Vasc-Score of 4 (25. to 75. percentile 2.5–5), who were prospectively followed 285 days in median. At inclusion, 118 patients took vitamin-K-antagonists, 33 dabigatran, 87 rivaroxaban, 30 apixaban, 5 low-molecular-weight heparin, and 9 were on no anticoagulant. Occurrence of stroke (rate 2.8/100 patient-years), was associated with prior stroke (hazard ratio [HR] 18.5, 95% confidence interval 2.16–159), increased HbA1c (HR per 1% increase 1.71, 1.20–2.45) and borderline significantly associated with vascular disease (HR 8.33, 0.97–71.3). Further we observed a high rate of major bleeding (2.8/100 patient-years), clinically relevant non-major bleeding (4.1/100 patient-years), and venous thromboembolism (2.8/100 patient-years). Anticoagulation was discontinued by 80 patients (36.9/100 patient-years), and diabetes (HR 2.31, 1.32–4.02), history of bleeding (HR 2.51, 1.44–4.37) and elevated leucocyte count (HR per 1G/l increase 1.02, 1.00–1.05) were associated with increased risk of discontinuation. Conclusions In this hospital-based registry, patients with atrial fibrillation had an increased risk of thromboembolic events despite anticoagulation. The low drug persistence may be attributable to distinct comorbid conditions and bleeding complications.

Introduction ABO blood group affects levels of von Willebrand Factor (VWF) and Factor (F) VIII, as individuals with blood group non-O have higher levels of VWF and FVIII. To the best of our knowledge there is no data available regarding the association between blood group and FVIII in non-severe haemophilia. Aim We aimed to explore the influence of ABO blood group on VWF and FVIII levels in patients with non-severe haemophilia A (HA). Methods We recruited persons with non-severe HA (FVIII levels of 1-40%). Adult patients (age ≥ 18 years), with platelet count > 105 /µl, without impaired renal and hepatic function, active cancer, surgery within the last 6 weeks, or overt infection within the last 2 weeks, who gave their informed consent were included. A blood sample was collected for laboratory analysis. The diagnosis of haemophilia was confirmed by molecular analysis of the FVIII gene in all patients. None of the patients had inhibitors against FVIII at the time of sample collection. The lowest FVIII level ever measured in each patient's history served as basis for the assessment of severity. Healthy male persons with a median age comparable to the patient group served as controls. We determined the following parameters: ABO blood group, FVIII, VWF activity (VWF:Act), and VWF antigen (VWF:Ag). FVIII was measured with a one-stage assay (Sysmex-CA7000 - Sysmex, Kobe, Japan, in multi-dilution mode with native FVIII-deficient plasma - Technoclone, Vienna, Austria and Aktin FS activator - Siemens, Marburg, Germany), VWF:Act (BC von Willebrand Reagent or Innovance VWF Ac - Siemens Healthcare, Marburg, Germany) and VWF:Ag levels with a latex agglutination assay (STA LIATEST VWF, Diagnostica Stago). Comparison of VWF and FVIII levels between blood group O and non-O was calculated with Mann-Whitney-U test, correlation between FVIII and VWF levels was calculated with Spearman's correlation, association of FVIII and VWF separated for blood group was calculated with univariable linear regression. Association of FVIII with VWF and blood group was calculated using multivariable linear regression. All calculations were performed with SPSS (IBM Version 25.0). Results A total of 89 persons with HA (71 with mild and 18 with moderate haemophilia) and 82 healthy controls were included. Patient characteristics are listed in Table 1. Median levels of VWF were significantly higher both in patients (p=0.002 for both VWF:Ag and VWF:Act) and healthy controls (p In HA there was no correlation between FVIII and VWF:Act (rho=0.180, p=0.095) or between FVIII and VWF:Ag (rho=0.028, p=0.795, Table 3). In univariable linear regression there was no significant association between VWF and FVIII in HA, neither in those with blood group non-O nor in those with blood group O (Figure 1). Also in multivariable linear regression there was no significant association between VWF (p=0.632) and blood group (p=0.929) with FVIII in patients with HA. In healthy controls, there was a strong positive correlation between FVIII and VWF:Act (rho=0.751, p Conclusions Neither the blood group nor the VWF had an influence on FVIII levels in non-severe HA patients. We conclude that the impact of the genetic mutation of the FVIII gene by far outweighs the influence of VWF levels and the blood group. Thus, for the diagnosis of HA and for determination of HA severity, the blood group needs not to be taken into account. Disclosures Pabinger: Roche: Honoraria; Sobi: Research Funding; Novo Nordisk: Research Funding; CSL Behring: Research Funding; Pfizer: Honoraria; Shire: Honoraria; Bayer: Honoraria; Sobi: Honoraria.

Introduction: Prior studies have indicated that Neutrophil extracellular traps (NETs) trigger arterial thromboembolism (ATE) and play a role in the pathogenesis of cancer-associated venous thrombosis. We investigated the association between NET biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE in patients with cancer. Methods: In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for objectively confirmed, symptomatic ATE and death. Fine&Gray competing-risk regression was used to model risk of ATE. Overall survival (OS) was analyzed with Kaplan-Meier estimators. Results: Nine-hundred and fifty-eight patients with cancer (median age: 61 years; 46.8% female; Table 1) were recruited. ATE occurred in 22 patients; the cumulative 6-, 12-, and 24-month risks of ATE were 1.1%, 1.8%, and 2.3%, respectively. The subdistribution hazard ratios (SHR) for ATE of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (95% confidence interval [CI]: 1.0-1.0, p=.882), 1.0 (1.0-1.0, p=.639), and 1.1 (1.0-1.2, p=.246) respectively. The 6-, 12-, and 24-month ATE probability was 1.3%, 1.7%, and 2.6% in patients with a H3Cit level ≤ 75thpercentile, and 0.8%, 1.3%, and 1.7% in patients above this cut-off (SHR=0.7, 0.2-2.0, p=.460). The 6-, 12-, 24-month overall survival of the study cohort was 87.0% (95%CI: 84.6-89.0), 73.6% (70.6-76.3), and 57.6% (54.3-60.8), respectively. The hazard ratio (HR) for mortality of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (1.0-1.0, p Conclusion: There was no significant association between H3Cit, cfDNA, and nucleosomes and ATE occurrence in patients with cancer. However, elevated levels of H3Cit, and cfDNA, were independently associated with an increased risk of mortality in patients with cancer. Table 1. Baseline characteristics of the total study population. Continuous data is reported as medians with first and third quartiles. Categorical variables are given as absolute frequencies and percentages. Data on body mass index, and cancer stage are missing in 2, and 76 patients, respectively. aPatients with brain and hematologic cancer Figure 1. Kaplan-Meier estimated for overall survival probability of patients with cancer according to baseline H3Cit, cfDNA, and nucleosome levels. MoM = Multiple-of-the-mean (i.e. Nucleosome results were compared to pooled plasma from 5 young male healthy controls to obtain a multiple-of-the-median) Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA) are current treatment options for cancer patients suffering from acute venous thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for the treatment of VTE in cancer patients, particular in comparison with the current standard of care which is LMWH, remains unclear. In this network meta-analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for the treatment of cancer-associated VTE. METHODS: A pre-specified search protocol identified 10 randomized controlled trials including 3242 cancer patients. Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were analyzed using a random-effects meta-regression model. RESULTS: LMWH emerged as significantly superior to VKA with respect to risk reduction of recurrent VTE (RR=0.60, 95%CI:0.45-0.79, p

Purpose: Cancer patients are at an increased risk of venous thromboembolism (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the prediction of VTE in patients with cancer. Experimental Design: Eight hundred four patients with newly diagnosed cancer or progression after remission were prospectively followed for 2 years until the occurrence of VTE or death [tumor sites: brain (n = 87), breast (n = 137), lung (n = 120), gastrointestinal (n = 143), pancreas (n = 53), prostate (n = 95), kidney (n = 22), myeloma and lymphoma (n = 99), and others (n = 48)]. Primary endpoint was symptomatic or fatal VTE. sVEGF was measured by immunoassay in baseline plasma. Results: Fifty-five patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level (25th–75th percentile) was 8.1 pg/mL (0–17.7). The cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4–14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2–7.9) in patients with lower levels (P = 0.03). The corresponding 2-year risk of death was 52.8% (95% CI, 46.0–60.0) and 43.9% (95% CI, 40.0–48.0), respectively (P = 0.02). In univariable time-to-VTE regression, elevated sVEGF was associated with VTE [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00–1.09; P = 0.04)]. The association between sVEGF and risk of VTE prevailed after multivariable adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00–1.09, P = 0.05). Conclusions: Elevated sVEGF is associated with an increased risk of VTE in patients with cancer. Clin Cancer Res; 22(1); 200–6. ©2015 AACR.

Background Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF. Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records. Results The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA2DS2-VASc Score was 4 [25th-75th percentile 3–5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03–1.07), male sex (1.7, 1.1–2.6), history of venous thromboembolism (2.0, 1.1–3.6), congestive heart failure (1.7, 1.1–2.5), history of or active cancer (1.5, 1.0–2.4) and time on HD (1.08 per year on HD, 1.03–1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%). Conclusions The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in HD patients with AF.

Introduction Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study. Materials and Methods Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE. Results Patients (n = 1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n = 96) and atorvastatin (n = 48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p = 0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray’s test: p = 0.04). Conclusion This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials.

Background Cancer patients are at high risk of developing venous thromboembolism (VTE). Red cell distribution width (RDW) has been reported to be associated with arterial and venous thrombosis and mortality in several diseases. Here, we analyzed the association between RDW and other red blood cell (RBC) parameters with risk of VTE and mortality in patients with cancer. Methods RBC parameters were measured in 1840 patients with cancers of the brain, breast, lung, stomach, colon, pancreas, prostate, kidney; lymphoma, multiple myeloma and other tumor sites, that were included in the Vienna Cancer and Thrombosis Study (CATS), which is an ongoing prospective, observational cohort study of patients with newly diagnosed or progressive cancer after remission. Primary study outcome is occurrence of symptomatic VTE and secondary outcome is death during a maximum follow-up of 2 years. Results During a median follow-up of 706 days, 131 (7.1%) patients developed VTE and 702 (38.2%) died. High RDW (>16%) was not associated with a higher risk of VTE in the total study cohort; in competing risk analysis accounting for death as competing variable the univariable subhazard ratio (SHR) was 1.34 (95% confidence interval [CI]: 0.80–2.23, p = 0.269). There was also no significant association between other RBC parameters and risk of VTE. High RDW was associated with an increased risk of mortality in the total study population (hazard ratio [HR, 95% CI]: 1.72 [1.39–2.12], p

Summary. Background: Cancer patients are at increasedrisk of venous thromboembolism (VTE). Objective: Weinvestigated the association of a history of VTE, superfi-cial thrombophlebitis, or the presence of varicose veinswith the occurrence of VTE during the course of cancer.Methods: Cancer patients were recruited in a prospectivecohort study, the Vienna Cancer and Thrombosis Study.Patients who had VTE within 3 months before studyinclusion were excluded. At study inclusion, history ofVTE, history of superficial thrombophlebitis, and pres-ence of varicose veins were recorded. Primary end pointwas the occurrence of symptomatic VTE. Hazard ratioswere obtained using the competing risk analysis accordingto Fine and Gray. Results: The cohort consisted of 1270patients followed over a median of 590 days. A history ofVTE was found in 66 patients (5.2%), superficial throm-bophlebitis in 79 patients (6.2%), and varicose veins in160 patients (12.6%). Ninety-eight patients (7.7%) devel-oped VTE during follow-up. The hazard ratios for therisk of VTE in patients with a history of VTE or superfi-cial thrombophlebitis were 1.44 (95% confidence interval:0.67–3.07) and 1.94 (1.04–3.61), respectively, and 2.01(1.26–3.21) in those with varicose veins. In multivariableanalysis including history of VTE, history of superficialthrombophlebitis, presence of varicose veins, and otherpatient-related factors, the presence of varicose veins(2.10 [1.29–3.41]) remained significantly associated withan increased risk of VTE. Conclusion: The presence ofvaricose veins is associated with an elevated risk of VTEin cancer patients. This clinical parameter could be usefulfor individual risk assessment of VTE in these patients.Keywords: neoplasm; risk; thrombophlebitis; varicoseveins; venous thromboembolism.IntroductionThe association of cancer and venous thromboembolism(VTE) is well established. Since VTE events in cancerpatients are accompanied with high mortality and morbid-ity [1–4], further research into the details of the associationbetween cancer and VTE is necessary. In the general pop-ulation, many risk factors for VTE have been identified.Superficial thrombophlebitis, varicose veins, and a historyof VTE in particular increase the risk of VTE [1,5,6].In cancer patients, several patient-specific risk factorsfor cancer-associated VTE have been described [7,8]. Sim-ilar to the general population, a history of previous VTEhas been regarded as a risk factor for recurrent VTEevents in cancer patients. For instance, Agnelli et al.reported that surgical cancer patients with a history ofVTE had a six-fold increased risk of new VTE eventsafter surgery [9]. Similarly, a four-fold increased VTE riskwas found for multiple myeloma patients and a 20-foldincreased VTE risk was found for patients with ovariancancer and a history of VTE [10,11]. In another prospec-tive observational study on a cohort of medical patientswith different cancer entities, a two-fold increase in VTEevents was found in patients with history of VTE [8].Prandoni et al. further demonstrated that cancer patientsare still at higher risk of recurrent VTE compared withnon-cancer patients, even while receiving anticoagulationtherapy [12].However, it has not been entirely elucidated whethera history of previous VTE that did not occur in close