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      The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis

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          Abstract

          We aimed to evaluate the performance of the Khorana score in predicting venous thromboembolic events in ambulatory cancer patients. Embase and MEDLINE were searched from January 2008 to June 2018 for studies which evaluated the Khorana score. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Additional data on the 6-month incidence of venous thromboembolism were sought by contacting corresponding authors. The incidence in each Khorana score risk group was estimated with random effects meta-analysis. A total of 45 articles and eight abstracts were included, comprising 55 cohorts enrolling 34,555 ambulatory cancer patients. For 27,849 patients (81%), 6-month follow-up data were obtained. Overall, 19% of patients had a Khorana score of 0 points, 64% a score of 1 or 2 points, and 17% a score of 3 or more points. The incidence of venous thromboembolism in the first six months was 5.0% (95%CI: 3.9-6.5) in patients with a low-risk Khorana score (0 points), 6.6% (95%CI: 5.6-7.7) in those with an intermediate-risk Khorana score (1 or 2 points), and 11.0% (95%CI: 8.8-13.8) in those with a high-risk Khorana score (3 points or higher). Of the patients with venous thromboembolism in the first six months, 23.4% (95%CI: 18.4-29.4) had been classified as high risk according to the Khorana score. In conclusion, the Khorana score can be used to select ambulatory cancer patients at high risk of venous thromboembolism for thromboprophylaxis; however, most events occur outside this high-risk group.

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          Epidemiology of cancer-associated venous thrombosis.

          Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increased mortality compared with cancer patients without. This may be explained by the more aggressive type of malignancies associated with this condition. It is hypothesized that thromboprophylaxis in cancer patients might improve prognosis and quality of life by preventing thrombotic events. However, anticoagulant treatment leads to increased bleeding, particularly in this patient group, so in case of proven benefit of thromboprophylaxis, only patients with a high risk of venous thrombosis should be considered. This review describes the literature on incidence of and risk factors for cancer-associated venous thrombosis, with the aim to provide a basis for identification of high-risk patients and for further development and refinement of prediction models. Furthermore, knowledge on risk factors for cancer-related venous thrombosis may enhance the understanding of the pathophysiology of thrombosis in these patients.
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            A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts

            Venous thromboembolism (VTE) is a frequent complication of cancer, however the risk is highly variable among individuals depending on various factors, including types of cancer. To enable a personalized risk prediction of VTE we developed and externally validated a clinical prediction model for cancer-associated VTE. The prospective Vienna Cancer and Thrombosis Study (CATS, n=1,423) was used for model development, and the prospective Multinational cohort study to Identify Cancer patients at risk of VTE (MICA, n=832) was used for external validation. Primary outcome was objectively confirmed VTE at 6 months. The cumulative 6-month VTE risk was 5·7% in CATS (95% CI: 4·5-6·9), and 6·3% (95%CI: 4·7-8·2) in MICA. Tumor sites were categorized into low/intermediate, high, and very high VTE categories. Predictive variables were selected from a broad set of clinical and laboratory factors. The final prediction model included two variables: tumor site category (hazard ratio for “high” vs. “low/intermediate”, and “very high” versus “high” VTE-risk tumor site=1·96 (95% CI: 1·41-2·72, p=0·0001). and D-Dimer (hazard ratio per doubling=1·32, 95% CI: 1·12-1·56, p=0·001). The C-Indices of the model were 0·66 (95%: 0·63-0·67) in internal validation (CATS), and 0·68 (95%: 0·62-0·74) in external validation (MICA), respectively. The clinical prediction model was adequately calibrated in both cohorts. An externally-validated clinical prediction model incorporating only one clinical factor (tumor site category) and one biomarker (D-Dimer) predicts the risk of VTE in ambulatory patients with solid cancers. This simple model considerably improves on previous models for predicting cancer-associated VTE, and can aid physicians in selecting patients who will likely benefit from thromboprophylaxis. Austrian Science Fund, Austrian National Bank Memorial Fund, Unrestricted grants from participating hospitals
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              Efficacy of Prophylactic Low-Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial.

              Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low-molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer.
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                Author and article information

                Journal
                Haematologica
                Haematologica
                haematol
                Haematologica
                Haematologica
                Ferrata Storti Foundation
                0390-6078
                1592-8721
                June 2019
                03 January 2019
                : 104
                : 6
                : 1277-1287
                Affiliations
                [1 ]Tergooi Hospitals, Department of Internal Medicine, Hilversum, the Netherlands
                [2 ]Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Science, Amsterdam, the Netherlands
                [3 ]University G. D’Annunzio, Department of Medicine and Ageing Sciences, Chieti, Italy
                Author notes
                Correspondence: FRITS I. MULDER f.i.mulder@ 123456amc.nl
                Article
                1041277
                10.3324/haematol.2018.209114
                6545838
                30606788
                65190326-4ec1-4e7e-a550-4af12e8ab739
                Copyright© 2019 Ferrata Storti Foundation

                Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.

                History
                : 12 October 2018
                : 02 January 2019
                Categories
                Article
                Coagulation & Its Disorders

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