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.

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.

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.