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      D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis

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          Abstract

          Background

          Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT.

          Methods

          Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence.

          Results

          Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3–15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19–52) and 5.81 for DD (95% CI: 1.1–31.7).

          Conclusions

          This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

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          Most cited references24

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          Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

          Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society
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            Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.

            We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was 4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
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              Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial.

              Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.
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                Author and article information

                Contributors
                +0034-667956480 , luisoneumo@hotmail.com
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                15 October 2018
                16 October 2018
                : 119
                : 8
                : 915-921
                Affiliations
                [1 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Medical Surgical Unit of Respiratory Diseases, , Virgen del Rocio Hospital, ; Seville, Spain
                [2 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), , Instituto de Salud Carlos III, ; Madrid, Spain
                [3 ]ISNI 0000 0004 1768 164X, GRID grid.411375.5, Internal Medicine, Emergency Service, , Virgen Macarena Hospital, ; Seville, Spain
                [4 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Institute of Biomedicine of Seville (IBIS), , Virgen del Rocío Hospital, ; Seville, Spain
                [5 ]Medical Oncology, Virgen de Valme Hospital, Seville, Spain
                [6 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, UGC Emergency Service, , Virgen del Rocío Hospital, ; Seville, Spain
                [7 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Diagnostic Imaging Unit, Radiology Service, , Virgen del Rocío Hospital, ; Seville, Spain
                [8 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Methodology and Research Evaluation Unit, , Hospital Virgen del Rocío, ; Seville, Spain
                [9 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Pharmacy, , Hospital Virgen del Rocío, ; Seville, Spain
                Author information
                http://orcid.org/0000-0002-4125-3376
                Article
                269
                10.1038/s41416-018-0269-5
                6203717
                30318508
                6d1c6b55-8691-43f0-b35c-10ad5e2608c3
                © Cancer Research UK 2018

                Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

                History
                : 26 April 2018
                : 27 August 2018
                : 31 August 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004587, Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III);
                Award ID: PI15/01085
                Award ID: PI15/01085
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100007509, Sociedad Española de Neumología y Cirugía Torácica (SEPAR);
                Award ID: 140/2013
                Award ID: 140/2013
                Award Recipient :
                Funded by: NEUMOSUR (5/2013); and the LEO Pharma Research Foundation.
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                © Cancer Research UK 2018

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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