Factors influencing patient's perception of long-term treatment with low-molecular-weight heparins for cancer-associated thrombosis: an updated analysis of TROPIQUE, a prospective observational study.

PURPOSE: Our objective was to compare patient's expectations to their experience and to identify factors predictive of patient's perception of long-term LMWH for the treatment of cancer-associated thrombosis (CAT). METHODS: Results from the validated Perception Anticoagulant Treatment Questionnaires (PACTQ) completed before inclusion (PACTQ1 for expectations) and at the end (PACTQ2 for convenience and satisfaction) of the 6-month TROPIQUE study were studied with principal component analysis. Possible predictive factors of improved perception of LMWH treatment were analyzed with the Kruskall-Wallis test. RESULTS: Among 409 included patients treated with LMWH, 269 PACT-Q1 and 139 PACT-Q2 were evaluable for treatment perception. Patients had high expectations (A1-A7 score of 26.7 ± 3.5, max = 35). Treatment cost (A7 = 1.90 ± 1.31) and concern about a mistake in anticoagulation (A5 = 1.93 ± 1.12) had little importance while LMWH treatment was considered easy to use (A4 = 4.20 ± 0.93). Six-month treatment with LMWH was associated with a high rate of convenience (B1-B11, C1-C2 = 55.1 ± 8.38, max = 65) and a high satisfaction score (D1-D7 = 25.1 ± 4.32, max = 35). Patients' confidence in treatment and perception of possible LMWH side effects were moderate while perception of autonomy and independence significantly improved at the end of the study compared to inclusion. PACT-Q2 satisfaction score was low in patients who experienced bleeding (PACT-Q2 24.1 ± 3.3 vs. 25.1 ± 4.3). LMWH twice daily tended to be found less convenient compared than once daily (53.3 ± 7.2 vs. 55.0 ± 8.3). CONCLUSION: CAT patients had a good perception of the 6-month LMWH treatment when comparing expectations and experience. Using a quantitative scale validated in the general population for VTE and subcutaneous injection and including a large number of patients, bleeding complications and LMWH twice daily were associated with a nonsignificant trend towards a worsen perception.

Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database.

OBJECTIVE: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years' duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. METHOD: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud's SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud's phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31-59, and ≥ 60 years. We performed descriptive and bivariate analyses. RESULTS: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud's. CONCLUSION: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice.

Autologous hematopoietic stem cell transplantation reverses skin fibrosis but does not change skin vessel density in patients with systemic sclerosis.

Hematopoetic stem cell transplantation (HSCT) improves survival in patients with severe systemic sclerosis (SSc) by resetting the immune system. We studied how HSCT acts on the key SSc skin pathology findings (fibrosis and vascularization). In mean, 3 skin punch biopsies per patient (range 2-6) were analyzed from 13 patients (5 females) with severe diffuse SSc before and up to 96 months after HSCT. Fibrosis of the four skin layers was graded semi-quantitatively and an overall fibrosis score was then calculated. Vessel numbers and calibers were assessed in the superficial and deeper dermis after immune-staining for endothelial antigens (CD31, VE-cadherin and vWF). The median age of patients at HSCT was 47 (24-64) years. The overall median modified Rodnan skin score decreased from 24 to 10 (P=0.003) at first follow-up within a median of 9 (6-36) months after HSCT as did the histological skin score (P=0.03). The modified Rodnan skin score and the fibrosis score correlated positively (r=0.589, P<0.001). The vessels density did not significantly change after HSCT nor did the expression of the tested endothelial markers. Although improving skin fibrosis in patients with SSc, HSCT does not alter vessel density within skin biopsies.

[Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC]. / Autogreffe des cellules souches hématopoïétiques dans les maladies auto-immunes : recommandations de la SFGM-TC.

Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

Systemic sclerosis, silica exposure and cellular therapies: The sand in the gears?

Systemic sclerosis (SSc) is a chronic orphan autoimmune disease with the highest mortality rate among rheumatic diseases. SSc-related interstitial-lung disease (ILD) remains among the leading causes of SSc-related mortality with still few therapeutic effective strategies. In patients with crystallin silica exposure, SSc is recognized as an occupational disease according to the French social security system (Table 25A of the general insurance regimen). Lympho-ablative or myeloablative immunosuppression followed by autologous hematopoietic stem-cell transplantation (aHSCT) is the only therapeutic approach with demonstrated efficacy, improved survival with disease modifying effects on SSc-fibrotic manifestations (skin disease and ILD) and quality of life. A documented past and/or present occupational silica exposure, with extensive exposure and/or silica-related ILD and/or with persistent silica content in the broncho-alveolar lavage fluid are contra-indications to aHSCT in SSc patients, due to the risk of silica-related malignancy or of SSc relapse. This article aims to discuss alternative options in SSc patients with a history of silica exposure, and how innovative cellular therapies (mesenchymal stromal cells, CAR cells) could represent new therapeutic options for these patients.

French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.

Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients. METHODS: This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008. RESULTS: Median disease duration before ASCT was 52 (nine to 396) months, 25/28 SLE patients (89%) were female, age 29 (16-48) years. At the time of ASCT, eight (one to 11) American College of Rheumatology (ACR) diagnostic criteria for SLE were present and 17 (60%) patients had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony stimulating factor in 93% of patients, and ex vivo CD34 stem cell selection was performed in 36%. Conditioning regimens were employed with either low (n = 10) or intermediate (18) intensities. With a median follow-up of 38 (one to 110) months after ASCT, the five-year overall survival was 81 ± 8%, disease-free survival was 29 ± 9%, relapse incidence (RI) was 56 ± 11% and non-relapse mortality was 15 ± 7%. Graft manipulation by CD34+ selection was associated with a lower RI (p = 0.001) on univariate analysis. There were five deaths within two years after ASCT: three caused by infection, one by secondary autoimmune disease and one by progressive SLE. CONCLUSIONS: Our data further support the concept of immunoablation and ASCT to re-induce long-term clinical and serologic remissions in refractory SLE patients even in the absence of maintenance therapy. This study also suggests a beneficial effect of ex vivo graft manipulation on prevention of relapses post-transplantation in SLE.

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage. OBJECTIVES: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. CONCLUSIONS: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

[Cytokines in systemic sclerosis]. / Les cytokines dans la sclérodermie systémique.

The balance in the production and release of cytokines "Th1/Th2" or "Th17" or "regulatory T" is one of the key events in the pathogenesis of systemic sclerosis (SSc). Specifically, the Th2 cytokine response, characterized by the production of IL-4, IL-10 and TGF-ß, leads to tissue fibrosis in patients with SSc. Many studies have shown the importance of analyzing the levels of cytokines as diagnostic or prognostic markers in the blood or in situ in patients with SSc. The restoration of the Th1/Th2/Th17/Treg balance will contribute to the effectiveness of treatment and the use of cytokine modulators may therefore be considered in developing new therapeutic approaches.

Long-term use of tinzaparin for the treatment of cancer-associated thrombosis in clinical practice: Insights from the prospective TROPIQUE study.

BACKGROUND: Real word data on the efficacy and safety of long-term use of tinzaparin for the treatment of cancer-associated thrombosis (CAT) are scarce. METHODS: We performed a post-hoc analysis of all cancer patients included in the prospective multicenter observational TROPIQUE study who received long-term treatment with tinzaparin for a first venous thromboembolism (VTE) event. We evaluated the patterns of anticoagulant prescription, the adherence to clinical practice guidelines (CPGs) for the treatment of CAT, and the clinical outcomes within a 6-month follow-up. RESULTS: In total, 301 patients were included in this post-hoc analysis. At study entry, their mean age was 64.6±11.9years and 143 (47.5%) patients were men. The most frequent cancer type was gastrointestinal (23.9%), followed by breast (17.9%) and lung (15.3%) cancer. At time of VTE diagnosis, 164 (57.8%) patients had metastatic disease and 245 (81.42%) were receiving chemotherapy. Based on the aggregation of all study pre-defined criteria, tinzaparin prescription was fully compliant with CPGs in 219 (72.8%) patients. The mean effective treatment duration with tinzaparin was 6.07±0.17months. At 6-month follow-up, the cumulative incidence of recurrent VTE was 5.4% (95% CI: 3.2-9.2%) and the cumulative incidence of major bleeding was 5.8% (95% CI: 3.6-9.6%). Clinical outcomes tended to differ across different types of cancer. Death from any cause occurred in 102 (33.9%) patients, mainly related to cancer progression. CONCLUSIONS: This post-hoc analysis of TROPIQUE confirms the favorable benefit-risk ratio of tinzaparin for the long-term treatment of CAT.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres.

OBJECTIVE: Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. METHODS: A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). RESULTS: Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. CONCLUSION: A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.

[Autologous hematopoietic stem cell transplantation for chronic inflammatory demyelinating polyneuropathy]. / Carrefour des spécialités : autogreffe de cellules souches hématopoïétiques périphériques pour la prise en charge thérapeutique des polyradiculonévrites inflammatoires démyélinisantes chroniques.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a dysimmune neuropathy with sensory and/or motor symptoms due to destruction of the myelin sheat secondary to an auto-immune attack. A quarter to a third of patients do not respond to immunomodulatory first line recommended therapies. No second line treatment has shown its effectiveness with a sufficient level of evidence. Autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapy for autoimmune disease, especially for CIDP in recent works. We present in this article an update on the diagnosis of CIDP, its conventional treatments as well as the results of AHSCT in this indication, which was the subject of French recommendations under the aegis of the SFGMTC and neuromuscular disease french faculty (FILNEMUS) as a third line therapy after failure of two first-line and one second-line treatments.

Patient education program at the forefront of cancer-associated thrombosis care.

INTRODUCTION: Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care. METHODS: Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020. RESULTS: In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P=0.05). Quality of life had improved significantly (P=0.025) and 90.0% of patients reported adhering to anticoagulant therapy. CONCLUSION: Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com) to improve the care and quality of life of patients with CAT.

Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis.

OBJECTIVES: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). METHODS: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. RESULTS: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. CONCLUSION: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

How to treat venous thromboembolism (TVE) in cancer patients: ten years of multidisciplinary team meetings (MDTM) at Saint-Louis Hospital.

BACKGROUND: - The management of venous thromboembolism (VTE) is particularly challenging in patients with cancer who undergo complex treatment protocols. Cancer patients often have comorbidities which may affect the efficacy and safety of anticoagulant treatments. Coordinated multidisciplinary management of these complex cases can help optimize delivery of individualized anticoagulant treatment. AIMS: - To describe the multidisciplinary team meeting (MDTM) for the management of VTE in cancer patients at our institution and to document outcomes in these patients. METHODS: - Bi-monthly MDTMs attended by different physicians and nurses were established at Saint-Louis Hospital in 2008. We performed a retrospective analysis of all cases discussed between September 2008 and January 2018. RESULTS: - Over a 10-year period, 520 patients were discussed a total of 551 times. Their mean age was 63 years with 278 (53%) women. The most frequent primary cancer sites were breast (23%), genitourinary (21 %), hematological (20%), digestive (15%), and lung (9%). Fifty-two percent of patients had metastatic cancer, and 54% of them were receiving chemotherapy. The optimal treatment for pulmonary embolism (17%), deep vein thrombosis (16%), catheter-related thrombosis (20%) or combined events (46%) was discussed. Twenty-three patients (4.4%) were discussed for one VTE recurrence and 4 (0.8%) for 2 recurrences. CONCLUSIONS: - A dedicated MDTM for the management of VTE in cancer patients allows to discuss a wide range of clinical scenarios and contributes to optimal adherence to evidence-based clinical practices guidelines. The MDTM evaluation was successfully carried out within a short time-frame of VTE diagnosis and helped optimize individualized treatment plans.

Drug-drug interaction (DDI) with direct oral anticoagulant (DOAC) in patients with cancer.

Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients after tumor progression. The treatment of CAT is challenging because of a high risk of VTE recurrence, a high risk of bleeding, common presence of comorbidities, poly-medication, and potential drug-drug interactions (DDI). Since 2018, direct oral anticoagulants (DOACs) represent a promising therapeutic alternative and have been recently included into the 2019 update of the International Initiative on Thrombosis and Cancer (ITAC-CME) clinical practice guidelines for management of CAT. However, pharmacokinetic studies suggest that concomitant treatment with P-gp or CYP3A4 inhibitors will result in an increased exposure to rivaroxaban and apixaban, but the clinical relevance of these studies is unknown. In addition, there is an important inter-individual variability in drug absorption, distribution, metabolism and elimination, even more in cancer patients. Overall, the risk of pharmacokinetic DDI should be estimated based on several individual (patient age, renal and liver function, number of comedications) and diseases-related factors, including inflammation, sarcopenia, and low body weight. In this context, DDI with clinical implications could be expected with anti-neoplastic agents or supportive care treatments, especially with drugs known to be moderate or strong inhibitors/inducers of CYP3A4 and P-gp. Consequently, in the presence of potential DDIs through CYP3A4, and/or P-gp, LMWHs remain the first-line anticoagulant of choice for the long-term treatment of CAT. Multidisciplinary consultation meetings and therapeutic patient education should be emphasized in the complex management of CAT.

How to screen and diagnose deep venous thrombosis (DVT) in patients hospitalized for or suspected of COVID-19 infection, outside the intensive care units.

INTRODUCTION: The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). MATERIAL AND METHODS: Non-systematic review of the literature. RESULTS: In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score>2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. DISCUSSION: Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis.

BACKGROUND: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts. OBJECTIVES: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19. METHODS: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59µg/L (95% CI 2.79-4.40µg/L), and the Z-score for overall effect was 8.74 (P<0.00001), with a high heterogeneity across studies (I2=95%). CONCLUSIONS: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group.

BACKGROUND: In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology. MATERIAL AND METHODS: A literature review (1990-2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts. RESULTS: For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present. CONCLUSIONS: Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.