•Cancer-associated thrombosis is a major health problem that affects morbidity and mortality of people with cancer.•Surgical and systemic pharmacological anticancer treatments have a significant ...impact on the thrombotic risk of patients.•Primary thromboprophylaxis may be considered in high-risk ambulatory cancer patients using validated risk models.•Anticoagulant treatment of VTE in cancer patients is effective but may be associated with increased bleeding.•LMWH or DOACs are effective treatments and generally safe options for cancer-associated thrombosis.
Background: Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide. Objectives: To establish ...a common international consensus addressing practical, clinically relevant questions in this setting. Methods: An international consensus working group of experts was set up to develop guidelines according to an evidence‐based medicine approach, using the GRADE system. Results: For the initial treatment of established VTE: low‐molecular‐weight heparin (LMWH) is recommended 1B; fondaparinux and unfractionated heparin (UFH) can be also used 2D; thrombolysis may only be considered on a case‐by‐case basis Best clinical practice (Guidance); vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients Guidance. For the early maintenance (10 days to 3 months) and long‐term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) 1A; idraparinux is not recommended 2C; after 3–6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit‐risk ratio, tolerability, patient preference and cancer activity Guidance. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion Guidance. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12–2 h preoperatively and continued for at least 7–10 days; there are no data allowing conclusion that one type of LMWH is superior to another 1A; there is no evidence to support fondaparinux as an alternative to LMWH 2C; use of the highest prophylactic dose of LMWH is recommended 1A; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding 2B; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy Guidance; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated 2C. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux 1B; for children and adults with acute lymphocytic leukemia treated with l‐asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients Guidance; in patients receiving chemotherapy, prophylaxis is not recommended routinely 1B; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic 1B or lung 2B cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low‐dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear 2C. Special situations include brain tumors, severe renal failure (CrCl < 30 mL min−1), thrombocytopenia and pregnancy. Guidances are provided in these contexts. Conclusions: Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.
Background: Although long‐term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC‐related thrombosis ...(CRT) in cancer patients and heterogeneity in clinical practices worldwide. Objectives: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. Methods: An international working group of experts was set up to develop GCPG according to an evidence‐based medicine approach, using the GRADE system. Results: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non‐randomized prospective studies and one retrospective study examining the efficacy and safety of low‐molecular‐weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting Guidance. The CVC can be kept in place if it is functional, well‐positioned and non‐infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established Guidance. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double‐blind randomized and one non randomized study on thrombolytic drugs and six meta‐analyses of AC and CVC thromboprophylaxis. Type of catheter (open‐ended like the Hickman® catheter vs. closed‐ended catheter with a valve like the Groshong® catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non‐randomized trials, three randomized trials and one meta‐analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended 1A; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium 1A. Conclusion: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.
Patients with cancer present with an elevated risk of thrombosis, which entails high morbidity and mortality. Various predictive scales that incorporate clinical and biological data have been ...developed to identify those at high risk of thrombosis, but, in general, they do not allow for the optimal selection of subjects who are candidates for thromboprophylaxis. Recent studies have demonstrated that the mutation profile has a high impact on the risk of thrombosis; this will facilitate developing new predictive models of thrombosis in patients with cancer.
Los pacientes con cáncer presentan un riesgo elevado de trombosis, que condiciona una elevada morbimortalidad. Se han desarrollado diversas escalas predictivas para la identificación de aquellos con alto riesgo trombótico, incorporando datos clínicos y biológicos, pero, en general, no permiten una selección óptima de los sujetos candidatos para recibir tromboprofilaxis. Estudios recientes demuestran que el perfil mutacional tiene un alto impacto sobre el riesgo trombótico, lo que va a facilitar el desarrollo de nuevos modelos predictivos de trombosis en pacientes con cáncer.
Summary
Background
Recommendations for management of cancer‐related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low‐quality evidence. This ...international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies.
Methods
Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression.
Results
We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low‐molecular‐weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio HR, 0.28; 95% confidence interval CI, 0.11–0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45–2.63). The bleeding rate did not increase significantly with dose escalation.
Conclusion
Morbidity and mortality are high after recurrence of cancer‐related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough ...cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.
Abstract Introduction The haemostatic system plays an important role in the process of cancer development and spread. Anticoagulants, mainly low molecular weight heparins, could prolong survival in ...cancer patients, particularly in patients with lung cancer, beyond prevention of thromboembolic events. Methods In a multicenter, investigator-initiated, open-label, randomized, sequential study, 38 patients with newly-diagnosed, limited-stage small-cell lung cancer were randomized to receive standard chemoradiotherapy or the same therapy plus 3,500 IU daily of bemiparin for a maximum of 26 weeks. The primary outcome was progression-free survival. Results The study was terminated early due to slow recruitment. Median progression-free survival was 272 days with chemoradiotherapy alone and 410 days in the bemiparin group; hazard ratio, 2.58 (95% confidence interval CI, 1.15-5.80); p = 0.022. Median overall survival was 345 days with chemoradiotherapy alone and 1133 days in the bemiparin group; hazard ratio, 2.96 (95% CI, 1.22-7.21); p = 0.017. The rate of tumor response was similar in both study arms. There was no significant between-group difference in the rates of major bleeding. Toxicity related with the experimental treatment was minimal. Conclusion The addition of bemiparin to first line therapy with chemoradiotherapy significantly increases survival in patients with newly-diagnosed, limited-stage small-cell lung cancer. (Funded by the Instituto Científico y Tecnológico, University of Navarra. ClinicalTrials.gov identifier: NCT00324558).
Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep ...vein thrombosis DVT, pulmonary embolism PE or both) and the anatomical relationship between occult cancer and VTE.
Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations.
A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79).
The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.
•The relationship between sites of VTE and occult cancer is unclear.•The 12-month prevalence of occult cancer was similar in DVT only, PE only, or both.•There were no relationship between unprovoked VTE and occult cancer locations.•Two thirds of cancers diagnosed after unprovoked VTE were located in the abdomen.
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