Comparison of risk prediction scores for venous thromboembolism in cancer patients:A prospective cohort study

In ambulatory patients with solid cancer, routine thromboprophylaxis to prevent venous thromboembolism is not recommended. Several risk prediction scores to identify cancer patients at high risk of venous thromboembolism have been proposed, but their clinical usefulness remains a matter of debate. We evaluated and directly compared the performance of the Khorana, Vienna, PROTECHT, and CONKO scores in a multinational, prospective cohort study. Patients with advanced cancer were eligible if they were due to undergo chemotherapy or had started chemotherapy in the previous three months. The primary outcome was objectively confirmed symptomatic or incidental deep vein thrombosis or pulmonary embolism during a 6-month followup period. A total of 876 patients were enrolled, of whom 260 (30%) had not yet received chemotherapy. Fifty-three patients (6.1%) developed venous thromboembolism. The c-statistics of the scores ranged from 0.50 to 0.57. At the conventional positivity threshold of 3 points, the scores classified 13-34% of patients as high-risk; the 6-month incidence of venous thromboembolism in these patients ranged from 6.5% (95% CI: 2.8-12) for the Khorana score to 9.6% (95% CI: 6.6-13) for the PROTECHT score. High-risk patients had a significantly increased risk of venous thromboembolism when using the Vienna (subhazard ratio 1.7; 95% CI: 1.0-3.1) or PROTECHT (subhazard ratio 2.1; 95% CI: 1.23.6) scores. In conclusion, the prediction scores performed poorly in predicting venous thromboembolism in cancer patients. The Vienna CATS and PROTECHT scores appear to discriminate better between low-and high-risk patients, but further improvements are needed before they can be considered for introduction into clinical practice

Microparticles in vascular disorders: How tissue factor-exposing vesicles contribute to pathology and physiology

Coagulation is initiated by tissue factor (TF). Coagulant TF is constitutively expressed by extravascular cells, but there is increasing evidence that TF can also be present within the blood, in particular during pathological conditions. Such TF is exposed on circulating cell-derived vesicles, and its presence has been associated with development of disseminated intravascular coagulation and venous thrombosis. For example, the presence of TF-exposing vesicles in the blood of cancer patients may be associated with their high risk of developing venous thromboembolism. Remarkably, high levels of coagulant TF-exposing vesicles are present in other body fluids such as saliva and urine of healthy persons, suggesting that these vesicles play a physiological role. We postulate that the presence of TF-exposing vesicles in body fluids as saliva and urine provides an additional source of coagulant TF that promotes coagulation, thereby reducing blood loss and contributing to host defence by reducing the risk of microorganisms entering the "milieu interieur". (C) 2012 Elsevier Ltd. All rights reserve

A worldwide survey to assess the treatment approach of cancer associated venous thromboembolism (CAT)

Introduction: Low-molecular-weight heparin (LWMH) has been recommended as the preferred anticoagulant over vitamin K antagonists (VKAs) for CAT since the CLOT trial was published in 2003. We assessed the current anticoagulation practice of CAT in various countries. Methods: An electronic tool containing 49 questions on different aspects of the treatment of CAT was used for survey; personal links were sent to different specialists. Results: Of the 234 surveys sent between 12/2010 and 3/2012, 141(53 %) were available for analysis. Responses received from Europe, United States (US) and other countries were 58, 35 and 7 %, respectively, including 23 % haematologist, 18 % oncologist, 15 % pulmonologist and 15 % internists. The majority (82 %) use LMWH for long-term anticoagulation as first line. Use of LMWH is significantly higher (p = 0.004) among European respondents (90 %) vs US (69 %). 60 % use therapeutic dose of LMWH, while the remainder dose-reduce after a period of time. For long-term treatment, 44 % prefer LMWH and 10 % VKAs. For recurrent VTE, 44 % of the respondents increased the dose of LWMH, 8.2 % added VKA to LMWH and 30 % would insert IVC filter. Cost, reimbursement and administration of LMWH were the main concerns for not using LMWH. Discussion: With respect to the type of anticoagulant used for the long-term treatment of CAT, a relatively high number of respondent followed guidelines but as expected, a lesser use of LMWH in CAT in US compared to European mainly because of cost and reimbursement

Clinical course of upper extremity deep vein thrombosis in patients with or without cancer: a systematic review

The incidence of upper extremity deep vein thrombosis (UEDVT) is increasing. Information on the clinical course of UEDVT is scarce, especially in cancer patients. To summarize the clinical evidence regarding long-term clinical outcomes of UEDVT, in terms of recurrent venous thromboembolism (VTE), mortality, and anticoagulant-related bleeding, in patients with or without concomitant cancer. A systematic search of the literature was conducted in MEDLINE, EMBASE and BIOSIS Previews. Incidence rates for all outcome variables were calculated. In total, 45 studies comprising 4580 patients were included. No randomized controlled trials were identified. In most studies, patients were treated solely with anticoagulants. Among the prospective studies, the incidences of recurrent VTE and bleeding complications averaged 5.1% and 3.1% respectively, during 3 to 59months of follow-up. In the retrospective studies these figures were 9.8% and 6.7% respectively. Among the prospective studies, the mortality rate was 24% after one year. In the retrospective studies this rate was 35%. Cancer patients were found to have a 2- to 3-fold higher risk of recurrent VTE, an 8-fold increased risk of mortality, and a 4-fold increased risk of bleeding during anticoagulant therapy, compared to non-cancer patients. Studies were very heterogeneous in terms of study design, study populations and treatment approaches. Follow-up durations varied greatly, hampering combined analyses of average incidence rates. There is a need for large prospective studies to provide information on the best management of this disease, especially in high risk groups such as those with cance

A clinical decision rule and D-dimer testing to rule out upper extremity deep vein thrombosis in high-risk patients For the ARMOUR study investigators

In a management study, a diagnostic algorithm consisting of a clinical decision rule, D-dimer, and ultrasonography was shown to safely exclude upper extremity deep vein thrombosis (UEDVT). Efficiency may be lower in high-risk subgroups: those with a central venous catheter or pacemaker, inpatients, cancer, and elderly patients. Data of 406 patients with suspected UEDVT enrolled in a prospective management study were used for the present analysis. The aim was to evaluate the efficiency of the algorithm in subgroups, defined as the proportion of patients in whom imaging could be safely withheld based on the combination of a decision rule result indicating "UEDVT unlikely" and a normal D-dimer result. The strategy excluded UEDVT in 87 of 406 patients (21%); ultrasonography was withheld in these patients and none developed UEDVT during 3months of follow-up. In contrast, ultrasonography could be withheld in only 4 of 92 patients with a catheter or pacemaker (4.3%; 95% CI: 1.7% to 11%) and in 4 of 83 inpatients (4.8%; 95% CI: 1.9% to 12%). The efficiency was 11% in patients with cancer and 13% in those older than 75years. Although the combination of a decision rule and D-dimer testing is safe in excluding UEDVT in the overall population of patients with suspected UEDVT, its efficiency appears limited in some subgroups, in particular those with a central venous catheter or pacemaker, and inpatient

Safety and feasibility of a diagnostic algorithm combining clinical probability, D-dimer and ultrasonography in suspected upper extremity deep vein thrombosis::A prospective management study

Background: Traditionally, the focus of the diagnosis of venous thromboembolism (VTE) is on deep vein thrombosis (DVT) of the leg and pulmonary embolism. Until recently, upper extremity DVT (UEDVT) was regarded as an uncommon presentation of VTE; however, the more widespread use of central venous catheters has caused a significant increase in its incidence. Therefore, effective and safe diagnostic strategies are needed. Aims: This diagnostic management study assessed the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. Methods: In- and outpatients with suspected UEDVT were recruited from January 2010 until July 2012 in 16 hospitals in Europe and the United States, after approval of the protocol by the institutional review boards. Main exclusion criteria were previous UEDVT and the use of therapeutic doses of anticoagulants. Informed consent was obtained from all participants. The algorithm consisted of the sequential application of the Constans' clinical decision score1 (score), Ddimer testing and compression ultrasonography. Patients were first categorized as UEDVT likely or unlikely by the score. In patients with an unlikely score and a normal D-dimer, UEDVT was considered excluded and no further testing was done. All other patients underwent ultrasonography, which first assessed the presence of UEDVT and then superficial vein thrombosis (SVT). The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a diagnostic work-up excluding both UEDVT and SVT. To confirm an acceptable failure rate of excluding UEDVT (upper 95% confidence interval below 3%), approximately 400 patients needed to be included. Results: The study population comprised of 406 consecutive patients with suspected UEDVT. The algorithm was feasible and could be completed in 96%. Of the 406 patients, 203 had an unlikely probability score and D-dimer was measured, except in three cases. In 87 patients (22%) an unlikely score was combined with a normal D-dimer, and therefore UEDVT was excluded. All these patients had an uneventful 3 month follow up. The remaining 113 patients with an unlikely and 203 patients with a likely probability score underwent ultrasonography. Ultrasonography was repeated if indicated according to protocol; seven times (1.7%) because of an indeterminate ultrasonography result and in 45 of the 51 patients (13%) with the combination of a likely score, abnormal D-dimer and normal ultrasonography. To summarize, of the 406 included patients, 103 patients had UEDVT (25%), 55 had SVT (14%) and in 249 patients the algorithm excluded UEDVT and SVT. Of these, one patient developed UEDVT during follow-up, hence, an overall failure rate of 0.40% (95% CI: 0.0-2.2%). Summary/Conclusions: A new diagnostic algorithm which combines a clinical decision score, D-dimer and ultrasonography can safely and effectively exclude venous thrombosis of the upper extremity. This approach is attractive as it is simple, quick and non-invasive, and very similar to the well established algorithm for suspected DVT of the leg which could facilitate its implementation in clinical practice

Coagulation activation and microparticle-associated coagulant activity in cancer patients: An exploratory prospective study

Cancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VIE at study entry and 22 healthy volunteers, markers of in vivo and MP-dependent coagulation were measured and patients were prospectively followed for six months for the development of VTE. Procoagulant activity of MPs was measured in vitro using a tissue factor (TF)-independent phospholipid dependent test, a factor Xa-generation assay with and without anti-IF, and a fibrin generation test (FGT) with and without anti-factor VII(a). Markers of in vivo coagulation activation and total number of MPs at baseline were significantly elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/l, D-dimer 0.76 vs. 0.22 mg/l and 5.53 x 106 vs. 3.37 x 106 MPs/ml). Five patients (11.6%) developed VTE. Patients with VTE had comparable levels of coagulation activation markers and phospholipid-dependent MP procoagulant activity. However, median IF-mediated Xa-generation (0.82 vs. 0.21 pg/ml, p=0.016) and median Vila-dependent FGT (13% vs. 0%, p=0.036) were higher in the VIE group compared with the non-VTE group. In this exploratory study the overall hypercoagulable state in cancer patients was not associated directly with the MP phospholipiddependent procoagulant activity. However, in the patients who developed VTE within six months when compared to those who did not, an increased MP procoagulant activity was present already at baseline, suggesting this activity can be used to predict VI

A worldwide survey to assess the current approach to the treatment of patients with cancer and venous thromboembolism

<p>Low-molecular-weight heparin (LWMH) is recommended as the preferred anticoagulant treatment over vitamin K antagonists (VKA) for venous thromboembolism (VIE) 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 VIE. An electronic survey tool was used to disseminate a survey containing 49 questions on different aspects of the treatment of patients with cancer and VIE, 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 VIE 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.</p>