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Obesity is associated with increased thrombotic risk and hypercoagulability whose main driver is an excess of coagulation factor VIII relative to protein C. The aims of this study were to evaluate the association between factor VIII, protein C, factor VIII-to-protein C ratio and bioimpedance parameters of body composition in obese patients. We analysed blood from 69 obese patients and 23 non-obese healthy controls. Plasma levels of factor VIII, protein C, and factor VIII-to-protein C ratio were correlated with total fat, visceral fat, and muscle mass. Compared to controls, obese patients had significantly higher factor VIII (110.5% vs 78.05%, p 1 was significantly associated with body-mass index (odds ratio 1.08, 95% CI 1.02 to 1.14) and fat-to-muscle ratio (odds ratio 2.47, 95% CI 1.10 to 5.55). Factor VIII-to-protein C ratio strongly correlated with D-dimer levels in the overall population (rho 0.44, p

Background The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. Methods We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months. Results In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD], 4.4%; 95%-CI, −4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, −0.3%; 95%-CI, −10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, −10.1–12.4), 3.1% and 11.7% for breast cancer (RD, −8.6; 95%-CI, −19.3–2.2), 8.9% and 10.9% for hematological malignancies (RD, −2.0; 95%-CI, −13.1–9.1), and 10.4% and 17.4% for gynecological cancer (RD, −7.0; 95%-CI, −19.8–5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. Conclusion Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.

The authors regret that panel E of Fig. 1 was missing, showing the cumulative incidence of the primary outcome in hematologic cancer. The authors would like to apologise for any inconvenience caused.

Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation. SummaryBackground Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Patients and Methods Consecutive patients with active cancer and an objective IDDVT diagnosis (January 2011 to September 2014) were included from our files. We collected information on baseline characteristics, IDDVT location and extension, VTE risk factors, and type and duration of anticoagulant treatment. Results A total of 308 patients (mean age 66.2 [standard deviation (SD), 13.2 years]; 57.1% female) with symptomatic IDDVT and a solid (n = 261) or hematologic (n = 47) cancer were included at 13 centers. Cancer was metastatic in 148 (48.1%) patients. All but three (99.0%) patients received anticoagulant therapy, which consisted of low-molecular-weight heparin in 288 (93.5%) patients. Vitamin K antagonists were used for the long-term treatment in 46 (14.9%) patients, whereas all others continued the initial parenteral agent for a mean treatment duration of 4.2 months (SD, 4.6 months). During a total follow-up of 355.8 patient-years (mean, 13.9 months), there were 47 recurrent objectively diagnosed VTEs for an incidence rate of 13.2 events per 100 patient-years. During anticoagulant treatment, the annual incidence of major bleeding was 2.0 per 100 patient-years. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Additional studies are warranted to investigate the optimal intensity and duration of anticoagulant treatment for these patients.

Essentials A stand-alone D-dimer below 750 μg/L has been proposed to rule out acute pulmonary embolism (PE). This was a post-hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The negative predictive value of a D-dimer

Essentials The Constans score and D-dimer can rule out upper extremity deep vein thrombosis without imaging. We evaluated the performance of an extended Constans score and an age-adjusted D-dimer threshold. The extended Constans score did not increase the efficiency compared to the original score. Age-adjusted D-dimer testing safely increased the efficiency by 4%, but this needs validation. SummaryBackground Among patients with clinically suspected upper extremity deep vein thrombosis (UEDVT), a clinical decision rule based on the Constans score combined with D-dimer testing can safely rule out the diagnosis without imaging in approximately one-fifth of patients. Objectives To evaluate the performance of the original Constans score, an extended Constans score and an age-adjusted D-dimer positivity threshold. Methods Data of 406 patients with suspected UEDVT previously enrolled in a multinational diagnostic management study were used. The discriminatory performance, calibration and diagnostic accuracy of the Constans score were evaluated. The Constans score was extended by selecting clinical variables that may have incremental value in detecting UEDVT, conditional on the original Constans score items. The performance of the Constans rule was evaluated in combination with fixed and age-adjusted D-dimer thresholds. Results The original Constans score showed good discriminatory performance (c-statistic, 0.81; 95% confidence interval [CI], 0.76–0.85). An extended Constans score with five additional clinical items improved discriminatory performance and calibration, but this did not translate into a higher efficiency in avoiding imaging tests. Compared with a fixed threshold, age-adjusted D-dimer testing increased the proportion of patients for whom imaging and anticoagulation could be withheld from 21% to 25% (gain, 3.7%; 95% CI, 2.3–6.0%). Conclusions The Constans score has good discriminatory performance in the diagnosis of UEDVT. Age-adjusted D-dimer testing is likely to safely increase the efficiency of the diagnostic algorithm, but this approach needs prospective validation.

[Background] Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE., [Methods] Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations., [Results] A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79)., [Conclusion] The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

Essentials Few data exist on outcome of upper extremity deep and superficial vein thrombosis (UEDVT and UESVT). We followed 102 and 55 patients with UEDVT or UESVT, respectively, for a median of 3.5 years. Risk of recurrent venous thromboembolism was low in both diseases, and the mortality high. Postthrombotic symptoms were infrequent and cancer patients had a higher risk of recurrent VTE. Background There is scant information on the optimal management and clinical outcome of deep and superficial vein thrombosis of the upper extremity (UEDVT and UESVT). Objectives To explore treatment strategies and the incidence of recurrent venous thromboembolism (VTE), mortality, postthrombotic symptoms, and bleeding in patients with UEDVT and UESVT and to assess the prognosis of cancer patients with UEDVT. Patients/methods Follow-up of patients with UEDVT or UESVT, who were enrolled previously in a diagnostic management study. Results We followed 102 and 55 patients with UEDVT and UESVT, respectively, both for a median of 3.5 years. Anticoagulant treatment was started in 100 patients with UEDVT (98%) and in 40 (73%) with UESVT. Nine patients with UEDVT (9%) developed recurrent VTE, 26 (26%) died, 6 (8%) of 72 patients had moderate postthrombotic symptoms, and 5 (5%) experienced major bleeding. One patient with UESVT had a recurrent VTE, 18 (33%) died, none had moderate postthrombotic symptoms, and none had major bleeding. Of the cancer patients with UEDVT, 18% had recurrent VTE vs. 7.5% in non-cancer patients (adjusted hazard ratio 2.2, 95%CI 0.6-8.2). The survival rate was 50% in cancer patients with UEDVT vs. 60% in those without (adjusted HR 0.8, 95%CI 0.4-1.4). Conclusions The risk of recurrent VTE was low in patients with UEDVT, and negligible for UESVT. Mortality was high for both diseases. Postthrombotic symptoms were infrequent and mild. Anticoagulant therapy of UEDVT carried a substantial risk of major bleeding. Cancer patients had a significant risk of recurrent VTE

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30Kg/m2 and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events.

Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. In patients with unprovoked VTE, the risk is approximately 5% in the year following VTE diagnosis. Cancer-specific screening is therefore often considered in these patients, but the optimal screening strategy remains controversial. Recently, two risk classification scores have been proposed that may help in identifying patients at high risk of occult cancer in whom extensive screening may be warranted. In the present post hoc analysis of the Hokusai-VTE study, we evaluated the performance of the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica (RIETE) and Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) scores for occult cancer in patients with acute VTE. A total of 8,032 patients were included in the analysis of whom 218 (2.7%; 95% confidence interval [CI], 2.4–3.1) developed cancer between 30-day and 12-month follow-up. The c-statistics of the RIETE and SOME scores were 0.62 (95% CI, 0.57–0.66) and 0.59 (95% CI, 0.55–0.62), respectively. In patients classified as ‘high risk’, the cumulative incidence of cancer diagnosis during follow-up was 2.9% (95% CI, 2.1–3.9) for the RIETE score and 2.7% (95% CI, 1.9–3.7) for the SOME score, corresponding to hazard ratios of 1.8 (95% CI, 1.3–2.5) and 1.5 (95% CI, 1.04–2.2), respectively. In conclusion, the performance of both scores was poor. When used dichotomously, the scores were able to identify a group of patients with a significantly higher risk of occult cancer, although it remains unknown whether this translates into improved clinical important outcomes.

Essentials Cancer patients are at risk for venous thromboembolism (VTE). The risk of VTE in less advanced stage cancer on neoadjuvant chemotherapy is unclear. In over 7800 patients, we found a 7% pooled incidence of VTE during neoadjuvant therapy. Highest VTE rates were observed in patients with bladder and esophageal cancer. Summary Background Venous thromboembolism (VTE) is a frequent complication in cancer patients receiving adjuvant treatment. The risk of VTE during neoadjuvant chemo-radiotherapy remains unclear. Objectives This systematic review evaluated the incidence of VTE in patients with cancer receiving neoadjuvant treatment. Methods MEDLINE and EMBASE databases were searched from inception to October 2017. Search results were supplemented with screening of conference proceedings of the American Society of Clinical Oncology (2009-2016) and the International Society of Thrombosis and Haemostasis (2003-2016). Two review authors independently screened titles and abstracts, and extracted data onto standardized forms. Results Twenty-eight cohort studies (7827 cancer patients, range 11 to 1398) were included. Twenty-five had a retrospective design. Eighteen cohorts included patients with gastrointestinal cancer, representing over two-thirds of the whole study population (n = 6002, 78%). In total, 508 of 7768 patients were diagnosed with at least one VTE during neoadjuvant treatment, for a pooled VTE incidence of 7% (95% CI, 5% to 10%) in the absence of substantial between-study heterogeneity. Heterogeneity was not explained by site of cancer or study design characteristics. VTE presented as pulmonary embolism in 22% to 96% of cases (16 cohorts), and it was symptomatic in 22% to 100% of patients (11 cohorts). The highest VTE rates were observed in patients with bladder (10.6%) or esophageal (8.4%) cancer. Conclusions This review found a relatively high incidence of VTE in cancer patients receiving neoadjuvant therapy in the presence of some between-study variation, which deserves further evaluation in prospective studies.

Cancer patients hospitalized for an acute medical illness are at increased risk of venous thromboembolism (VTE). Pharmacological thromboprophylaxis is considered standard practice for these patients and current guidelines recommend prophylactic doses of low-molecular-weight heparins (LMWHs), unfractionated heparin (UFH), or fondaparinux in the absence of bleeding or other contraindications [1-4]. These recommendations are extrapolated from large placebo-controlled randomized clinical trials (RCTs) of VTE thromboprophylaxis in broad mixed populations of medical inpatients, none involving exclusively cancer patients or presenting efficacy and safety data for this subgroup [5-8]. Because cancer inpatients represent a unique population with increased risk of VTE and major hemorrhage, validation of the efficacy and safety of thromboprophylaxis in this group is critical. This article is protected by copyright. All rights reserved

SummaryLow-molecular-weight heparin (LWMH) is recommended as the preferred anticoagulant treatment over vitamin K antagonists (VKA) for venous thromboembolism (VTE) in patients with cancer. However, there is uncertainty about the duration and dose of LMWH treatment. Therefore, we designed this multinational survey to assess the current approach to the treatment of patients with cancer and VTE. An electronic survey tool was used to disseminate a survey containing 49 questions on different aspects of the treatment of patients with cancer and VTE, among both thrombosis and non-thrombosis specialists. A total of 229 invitations were sent, and 141 completed the survey (60% of the total). Fifty-eight percent of the respondents were from Europe, 35% from the US and the remaining 7% from other countries. Respondent’s specialties included haematology (23%), oncology (18%), pulmonology (15%) and general internal medicine (15%). LMWH was indicated as the first choice for the long-term treatment by 82% of the respondents, of whom 60% used full therapeutic doses and 40% chose a dose reduction. When continuing anticoagulants after the long-term treatment period, 44% of respondents preferred LMWH, 10% VKA, while the remaining 45% chose per individual patient for either LMWH or VKA. In conclusion, we observed a relatively high observance rate of the guidelines with respect to the use of LMWH for the long-term treatment of VTE in cancer. In contrast, the dose of LMWH and the type of anticoagulant chosen after the initial 3–12 months varied substantially, probably reflecting the limited available evidence.

Background: Although in patients with cancer the risk of venous thromboembolism (VTE) is increased, the incidence is too low to routinely give prophylactic treatment. Procoagulant microparticles (MPs), especially tissue factor (TF)-bearing MPs, contribute to the risk of VTE in cancer patients. In the present study, we assessed the MP-associated procoagulant activity using a functional assay, the fibrin generation test (FGT), to identify cancer patients prone to develop VTE. Methods: As an ongoing study, plasma was collected from cancer patients, mainly with stage III or IV pancreatic, gastro-intestinal, breast or lung cancer. The MPassociated procoagulant activity was determined via the FGT with the addition of an inhibitory antibody to factor VII. The prolongation of the clotting time in the presence of anti-factor VII is a measure for the contribution of TF-bearing MPs to the clotting time. Patients were followed up for 6 months. Results: 100 patients were included, of which 77 have completed follow-up until now. The first 43 patients were used to establish a cut-off value of the FGT. Receiver operating characteristics showed that a prolongation of the clotting time of 13% after addition of anti-factor VII, was the optimal cut-off value. In the entire group, 8 of 77 patients (10%) developed VTE, of which 7 could have been predicted by the FGT. Using this cut-off value, 23 patients (30%) had a FGT-result above the cut-off (positive test) and 54 patients had a FGT-result below the cut-off (negative test). The prevalence of VTE was 30% in the FGT-positive patients and 2% in the FGTnegative patients (sensitivity 88%, specificity 77%). Conclusions: The FGT seems an excellent predictor for VTE in cancer patients. The next step will be to test the efficacy of prophylactic anticoagulants in patients with cancer and a high thrombosis risk based on the FGT.

Summary. Background: Hemato-oncology patients treated with intensive chemotherapy usually require the placement of a central venous catheter (CVC). CVCs are frequently complicated by catheter-related central venous thrombosis (CVT), which has been associated with an increased risk of pulmonary embolism and catheter-related infection. Objectives: To determine the efficacy and safety of thromboprophylaxis with s.c. low-molecular-weight heparin (nadroparin) administered once daily in a randomized placebo-controlled, double-blind trial in patients with hematologic malignancies. Patients and methods: Consecutive patients with hematologic malignancies requiring intensive chemotherapy including autologous stem cell transplantation were eligible. The patients were randomized to receive nadroparin 2850 antifactor Xa units once daily or placebo s.c. for 3 weeks. Venography was performed on day 21 after CVC insertion. Secondary outcomes were bleeding and catheter-related infection. Results: In total, 113 patients were randomized to nadroparin or placebo, and 87 patients (77%) underwent venography. In total, 11 venographically proven catheter-related CVTs were diagnosed. The frequency of catheter-related CVT was not significantly different between study groups, namely four catheter-related CVTs in the placebo group [9%; 95% CI: 0.002–0.16] vs. seven catheter-related CVTs in the nadroparin group (17%; 95% CI: 0.06–0.28). In addition, no difference in the incidence of catheter-related infection or bleeding was observed between the groups. Conclusion: This study showed that the actual risk for catheter-related CVT in patients with hematologic malignancies is lower than suggested in earlier studies in cancer patients. Although prophylactic administration of nadroparin appeared to be safe in this group of patients with a high risk of bleeding, it cannot be recommended for the prevention of catheter-related CVT or catheter-related infection in patients with hematologic malignancies.

Summary. Background: The SOMIT trial randomized patients with idiopathic venous thromboembolism (IVTE) and without signs of cancer at routine medical examination, to extensive screening for cancer plus 2 years of follow-up or to just 2-year follow-up. Methods: The data of the SOMIT-trial were used to perform a decision analysis. The screening tests were divided in several possible strategies. The number of detected cancer patients and the number of patients investigated further for an eventually benign condition were calculated for each strategy. The total costs for the screening strategy and for each detected cancer patient were determined. Based on the tumor type, stage, age and gender of the individual cancer patient, the difference in live years gained (LYG) was calculated between the two study groups. Results: Computed tomography (CT) of the abdomen combined with sputum cytology and mammography detected 12 of the 14 patients with cancer and had one false-positive result. In general, screening strategies including abdominal/pelvic ultrasonography (US) or tumor markers yielded a higher number of patients needed to screen in comparison with those using abdominal/pelvic CT. Furthermore, the strategies which included colonoscopy, tumor markers, and abdominal/pelvic US were significantly more costly, had inferior LYG and higher costs per LYG, when compared with strategies using abdominal/pelvic CT. Conclusions: Despite the limitations of this analysis, the screening for cancer with a strategy including abdominal/pelvic CT with or without mammography and/or sputum cytology appears potentially useful for cancer screening in patients with IVTE. The cost-effectiveness analysis of this strategy needs confirmation in a large trial.

Modern computer tomography (CT) with its higher sensitivity and resolution has increased the detection of incidental venous thromboembolism (VTE) in the venous and pulmonary vasculature during routine imaging for cancer staging and response assessment [1]. As a result, up to half of all VTEs diagnosed in oncology centers are incidental [1-5]. Although widely accepted, the diagnosis of incidental VTE is made without using the standard imaging studies required for confirming the presence of symptomatic VTE (i.e. compression ultrasonography for deep vein thrombosis [DVT] and CT pulmonary angiography [CTPA] or ventilation/perfusion lung scan for pulmonary embolism [PE]). The accuracy and reliability of staging imaging in making a diagnosis of DVT or PE have not been established. This article is protected by copyright. All rights reserved

Introduction Isolated distal deep vein thrombosis (IDDVT) accounts for one-fourth to one-half of all deep vein thrombosis (DVT) of the leg. Patients with IDDVT are frequently treated for a shorter period of time compared to patients with proximal DVT and/or pulmonary embolism (PE) due to a perceived lower risk of recurrence. About 10-20% of patients with venous thromboembolic events (VTEs) have concomitant cancer. Guidelines recommend long-term anticoagulant treatment in this group of patients due to their high risk of VTE recurrence. Unfortunately, information on the clinical history of IDDVT patients is limited and, to date, no study has evaluated the long-term risk of VTE recurrence in IDDVT patients with cancer. Aim To provide information on the clinical history of IDDVT patients with active cancer. Materials and Methods A multicenter, cohort study including active-cancer patients with an objective diagnosis of IDDVT (between January 2011 and September 2014) was conducted. Information on baseline characteristics, thrombosis location and extension, concomitant risk factors, type and duration of treatment was collected. All patients were followed for a minimum of 12 months and up to 24 months. During follow-up, VTE recurrence, major bleeding episodes and death were registered. Potential risk factors for VTE recurrence were evaluated. Results 308 patients (mean age 66.2 ± 13.2 years, female 57.1%) in 13 centers were included, Table 1; 261 patients had solid cancer and 47 patients hematologic cancer. At the time of IDDVT diagnosis, the disease was metastatic in 148 patients (48.1%); 99.0% of patients received anticoagulant treatment: 288 patients (93.5%) were initially treated with low molecular weight heparin, 15 with fondaparinux (5.2%) and 1 with unfractionated heparin; vitamin K antagonists were used in 46 patients (14.9%) only. Total follow-up was 389 patient-years, mean follow-up 15.2 months. Mean duration of treatment was 4.2 months. During the study period there were 47 episodes of VTE recurrence (36 proximal DVT or PE) for a incidence rate of 13.2 events per 100 patient-years; 7 patients had major bleeding (2.3%) and 137 died (44.5%). At multivariate analysis, previous VTE was associated with an increased risk of recurrence (OR 2.10; 95% 1.06, 4.14), whereas patients with gastrointestinal cancer had a lower risk of recurrence (OR 0.26; 95% CI 0.08, 0.86). Table 1 . Baseline characteristics of the population Number of patients 308 Age (years), mean ± SD 66.2 ± 13.2 Women 176 (57.1%) Men 132 (42.9%) Body-mass index > 30 Kg/m 2 25 (8.1%) Concomitant risk factors for VTE Recent surgery or trauma 79 (25.6%) In-patients/immobilization 45 (14.6%) Prolonged bed rest 47 (15.3%) Local or systemic infections 19 (6.2%) Qualifying distal venous thrombosis Axial calf veins 135 (43.8%) Muscolar calf veins 149 (48.4%) Medial gastrocnemius veins 113 (36.7%) Lateral gastrocnemius veins 45 (14.6%) Soleal veins 73 (23.7%) Bilateral venous thrombosis 22 (7.1%) More than one vein involved 127 (41.2%) Previous history of VTE 45 (14.6%) Family history of VTE 16 (5.2%) Primary cancer site Breast 54 (17.5%) Gastrointestinal 51 (16.6%) Pancreas 18 (5.8%) Hepatic 9 (2.9%) Lung 44 (14.3%) Hematologic 47 (15.3%) Prostate 17 (5.5%) Brain 15 (4.9%) Other 53 (17.2%) Metastases 148 (48.1%) Cancer therapy Systemic chemotherapy 174 (56.5%) Radiotherapy 20 (6.5%) Hormonal therapy 36 (11.7%) Anticoagulant therapy 305 (99%) Low-molecular-weight heparin 288 (93.5%) Fondaparinux 16 (5.2%) Unfractionated heparin 1 (0.3%) Heparin-Vitamin K antagonists 46 (14.9%) VTE = venous thromboembolism. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Other studies are warranted to address the adequate management of these patients.

Summary. Background: The best available test for the diagnosis of upper extremity deep venous thrombosis (UEDVT) is contrast venography. The aim of this systematic review was to assess whether the diagnostic accuracy of other tests for clinically suspected UEDVT is high enough to justify their use in clinical practise and to evaluate if any test can replace venography. Methods: MEDLINE and EMBASE databases were searched from inception to June 2009. Two reviewers independently evaluated study eligibility, extracted data, and assessed study quality. Results: We identified 17 papers, reporting on 793 patients. Overall, the methodological quality was poor, sample sizes were small, and large between-study differences were observed in spectrum and design. The summary estimates of sensitivity (95% confidence interval) were 97% (90–100%) for compression ultrasonography, 84% (72–97%) for Doppler ultrasonography, 91% (85–97%) for Doppler ultrasonography with compression, and 85% (72–99%) for phleboreography. The corresponding summary estimates of specificity were, respectively, 96% (87–100%), 94% (86–100%), 93% (80–100%), and 87% (71–100%). Clinical findings, a clinical score, D-dimer, magnetic resonance imaging, rheography and plethysmography were evaluated in one study each, involving a median number of 46 patients (range 21–214). Sensitivity and specificity ranged from 0% to 100% and from 14% to 100%. Conclusions: Methodological limitations, large between-study differences and small sample sizes limit the evidence of tests for clinically suspected UEDVT. Compression ultrasonography may be an acceptable alternative to venography. The addition of (color) Doppler does not seem to improve the accuracy. Adequately designed studies are warranted to confirm these findings.

Summary. Background: The reported diagnostic accuracy of the D-dimer test for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE) varies. It is unknown to what extent this is due to differences in study design or patient groups, or to genuine differences between D-dimer assays. Methods: Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of venous thromboembolism were systematically searched for in the MEDLINE and EMBASE databases up to March 2005. Reference lists of all included studies and of reviews related to the topic of the present meta-analysis were manually searched for other additional potentially eligible studies. Two reviewers independently extracted study characteristics using standardized forms. Results: In total, 217 D-dimer test evaluations for DVT and 111 for PE were analyzed. Several study design characteristics were associated with systematic differences in diagnostic accuracy. After adjustment for these features, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (DVT 96%; PE 97%), microplate enzyme-linked immunosorbent assay (ELISA) (DVT 94%; PE 95%), and latex quantitative assay (DVT 93%; PE 95%) were superior to those of the whole-blood D-dimer assay (DVT 83%; PE 87%), latex semiquantitative assay (DVT 85%; PE 88%) and latex qualitative assay (DVT 69%; PE 75%). The latex qualitative and whole-blood D-dimer assays had the highest specificities (DVT 99%, 71%; PE 99%, 69%). Conclusions: Compared to other D-dimer assays, the ELFA, microplate ELISA and latex quantitative assays have higher sensitivity but lower specificity, resulting in a more confident exclusion of the disease at the expense of more additional imaging testing. These conclusions are based on the most up-to-date and extensive systematic review of the topic area, including 184 articles, with 328 D-dimer test evaluations.

Summary. Background: The value of the D-dimer (DD) test in combination with the clinical pretest probability (PTP) has not been evaluated in cancer patients with suspected deep vein thrombosis (DVT), whereas this group of patients usually accounts for 10–25% of clinically suspected DVT. Methods: A cohort of 2066 consecutive patients with clinically suspected DVT was investigated. Patients were judged to be positive or negative for DVT according to the outcomes of serial compression ultrasound and a 3-month follow-up period with imaging test verification of the symptomatic cases. Diagnostic accuracy indices of the DD test according to the PTP score were assessed in patients with and without cancer. Results: Of the cohort, 244 (11%) were known to have cancer at presentation. A venous thromboembolic event was diagnosed in 41% of the patients with cancer and in 22% of the patients without malignancy. Among the cancer patients, 17% were considered to have a low PTP, 35% a moderate and 41% a high PTP. The negative predictive value (NPV) of the DD test was 100% (95%CI, 85–100) and 97% (95% CI, 88–99) among cancer patients with low PTP or low-moderate PTP. In the absence of malignancy, the corresponding NPV were 98% and 97%, respectively. The specificity of the DD test progressively decreased moving from the low to the higher PTP. Conclusions: In cancer patients with clinically suspected DVT, a negative DD might be useful in excluding the diagnosis within the low or low-moderate PTP groups. More studies are warranted to confirm these findings.

Item does not contain fulltext BACKGROUND: The safety of a D-dimer (DD) measurement in cancer patients with clinically suspected pulmonary embolism (PE) is unclear. OBJECTIVES: The aim of this study was to assess the accuracy of the DD test in consecutive patients with clinically suspected PE with and without cancer. METHODS: The diagnostic accuracy of DD (Tinaquant D-dimer) was first retrospectively assessed in an unselected group of patients referred for suspected PE (n = 350). Subsequently, the predictive value of the DD was validated in a group of consecutive inpatients and outpatients with clinically suspected PE prospectively enrolled in a management study (n = 519). The results of the DD test in cancer patients were assessed according to the final diagnosis of PE and the 3-month clinical follow-up. RESULTS: In the first study group, DD showed a sensitivity and a negative predictive value (NPV) of 100% and 100% in patients with cancer and 97% and 98% in those without malignancy, respectively. In the validation cohort, the sensitivity and NPV of DD were both 100% (95% CI 82%-100% and 72%-100%, respectively), whereas in patients without malignancy, the corresponding estimates were 93% (95% CI 87%-98%) and 97% (95% CI, 95%-99%), respectively. The specificity of DD was low in patients with (21%) and without cancer (53%). CONCLUSIONS: A negative DD result safely excludes the diagnosis of PE in patients with cancer. Because of the low specificity, when testing 100 patients with suspected PE, a normal DD concentration safely excludes PE in 15 patients with cancer and in 43 patients without cancer.

Background: In cancer patients, clinically unsuspected pulmonary embolism (PE) represents a relatively common finding on computed tomography scans performed as part of the oncological follow-up. Patients with unsuspected PE may be at risk to develop symptomatic venous thromboembolism (VTE) and appear to have an increased mortality rate compared to patients without VTE. Current guidelines suggest the same initial and longterm anticoagulation for unsuspected VTE as for patients with symptomatic thrombosis. Based on these indications, cancer patients with unsuspected PE would be anticoagulated for at least 6 months or until the disease is active, which in most cases would mean indefinite treatment. In fact, dedicated studies on the treatment of unsuspected PE are missing, leaving doubts over the need for (indefinite) anticoagulation which exposes these patients to an increased risk of major bleeding events. Objectives: to evaluate the current treatment approaches for unsuspected PE and to assess their efficacy and safety in a large prospective cohort of cancer patients. Design and study population: Multicenter, international, prospective registry. All ambulatory or hospitalized cancer patients with a first diagnosis of unsuspected PE will be eligible for the study. Both solid and hematological cancers at any stage of disease will be considered for inclusion. Patients will be excluded in case of: 1) age

Background: Although in patients with cancer the risk of venous thromboembolism (VTE) is increased, the incidence is too low to routinely give prophylactic treatment. Procoagulant microparticles (MPs), especially tissue factor (TF)-bearing MPs, contribute to the risk of VTE in cancer patients. In the present study, we assessed the MP-associated procoagulant activity using a functional assay, the fibrin generation test (FGT), to identify cancer patients who will develop VTE. Methods: As an ongoing study, plasma was collected from cancer patients, mainly with stage III or IV pancreatic, gastro-intestinal, breast or lung cancer. The MP-associated procoagulant activity was determined via the FGT with the addition of an inhibitory antibody to factor VII. The prolongation of the clotting time in the presence of anti-factor VII is a measure for the contribution of TF-bearing MPs to the clotting time. Patients were followed up for 6 months. Preliminary results: 100 patients were included, of which 77 had complete follow-up. The first 43 patients were used to establish a cut-off value of the FGT. Receiver operating characteristics showed that a prolongation of the clotting time of 13% after addition of anti-factor VII, was the optimal cut-off value. In the entire group, 8 of 77 patients (10%) developed VTE, of which 7 could have been predicted by the FGT. Using this cut-off value, 23 patients (30%) had a FGT-result above the cut-off (positive test) and 54 patients had a FGT-result below the cut-off (negative test). The prevalence of VTE was 30% in the FGT-positive patients and 2% in the FGT-negative patients (sensitivity 88%, specificity 77%). Conclusion: The FGT seems an excellent predictor for VTE in cancer patients. The next step will be to test the efficacy of prophylactic anticoagulants in patients with cancer and a high thrombosis risk based on the FGT.

Background: Patients with cancer and a first venous thromboembolic event (VTE), who have been treated with molecular weight heparin (LMWH) for 6 months, usually continue anticoagulant treatment in case of active disease (metastatic cancer and/or ongoing cancer treatment). However, it is unknown whether LMWH or vitamin K antagonists (VKA) should be used for the long-term treatment. Aim: The aim of this study is to determine whether LMWH (Enoxaparin, Dalteparin, Nadroparin, Tinzaparin) is superior to VKA (Acenocoumarol, Phenprocoumon or Warfarin) for the long-term treatment of cancer patients who have completed 6-12 months of anticoagulation for VTE. Design: Multicenter, multinational, randomized, open label trial. Patients: Cancer patients who have received 6-12 months of anticoagulation for VTE will be randomly assigned to 6 additional months of LMWH or VKA (target INR 2.0-3.0). Allocation to treatment will be done centrally by block randomisation via a web-based system (concealed allocation) and will be stratified by center. The primary efficacy outcome is symptomatic recurrent VTE, i.e. deep vein thrombosis and pulmonary embolism. The primary safety outcome is major bleeding. Organization: A total of 65 to 87 recurrent VTE events are needed to show a 50% reduction with LMWH as compared to VKA (type I error 0.05, two-sided, power respectively 80 and 90%). To observe 75 events, with a 10% event rate per half year in the VKA arm and 5% in the LMWH arm a total of 1,000 patients will need to be included. Outcomes will be adjudicated by a central adjudication committee. A steering committee will be formed, preferably consisting of one member of every participating center. An electronic case report form will be used for data collection. (www.examinethrombosis.com).

Background: Ultrasonography is currently used as the reference test for clinically suspected upper extremity deep vein thrombosis (UEDVT) although the diagnostic accuracy of the test for this indication remains less well established compared to DVT of the legs. The safety of withholding anticoagulant therapy without additional testing in patients with suspected UEDVT who have an unlikely clinical probability score and a normal D-dimer test has not been evaluated. Moreover, no study has so far evaluated the safety and feasibility of (serial) ultrasonography in patients with either a likely clinical decision rule or abnormal D-dimer. Aim: Aim of this study is to assess the safety and feasibility of a diagnostic algorithm that combines a clinical score, D-dimer test, and compression ultrasonography as a diagnostic work-up for UEDVT. Design: This is a prospective multicenter management study. Patients: All patients with suspected UEDVT, including patients with central venous catheters for chemotherapy, will be included in this study. Patients with suspected UEDVT will be handled according to the attached flow-chart. All patients will be followed for 3 months. The primary outcome will be the cumulative 3-month incidence of objectively confirmed symptomatic venous thromboembolic events. Based on a maximum failure rate of the diagnostic work-up of 3%, 400 patients will be needed to test the safety of the diagnostic strategy. Organization: We aim for an inclusion rate of 20 patients per center per year; with an inclusion period of 1.5 years and to compensate for inactive centers, we will need approximately 20 centers. A steering committee will be formed and outcomes will be adjudicated by a central adjudication committee. An electronic case report form will be used for data collection. (Graph presented).

EssentialsCancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are associated with the occurrence of VTE in cancer.SummaryBackground Patients with cancer are at high risk of venous thromboembolism (VTE). ADAMTS-13 regulates von Willebrand factor (VWF) activity, which plays a role in the development of cancer and in VTE.Objectives The aim of this study was to search for an association between the levels of VWF and ADAMTS-13 and VTE in patients with cancer and to compare current scoring systems for prediction of VTE before and after addition of these parameters.Patients/Methods In a case-control study, in which patients with recently diagnosed cancer were followed-up for 6 months, we compared 20 patients who developed VTE (cases) and 140 patients with cancer without VTE (controls), matched for sex, age, and type and stage of cancer. We measured VWF, ADAMTS-13 (activity and antigen), P-selectin, D-dimer and F1 + 2 levels at baseline, and calculated both the Khorana score and the Khorana score expanded after addition of P-selectin and D-dimer levels.Results VWF levels were significantly higher in cases when compared with controls (326 185% vs. 242 +/- 158%) and correlated with advanced stage of cancer: localized, 185 [142; 222]; locally advanced, 240 [146; 257]; metastatic, 267 [153; 324] (mean [interquartile range]). The addition of two biomarkers, ADAMTS-13 activity and F1 + 2 levels, to the Khorana score improved receiver operating curves.Conclusions von Willebrand factor and ADAMTS-13 are associated with the occurrence of VTE in patients with cancer. Moreover, addition of ADAMTS-13 and F1 + 2 levels to the Khorana score considerably increases the predictive value for VTE.