Impacto del perfil mutacional sobre el riesgo trombótico en pacientes con cáncer / Impact of the mutation profile on thrombotic risk in cancer patients

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 (AU)

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 (AU)

Impact of the mutation profile on thrombotic risk in cancer patients.

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.

Prevention of venous thromboembolism in hematologic neoplasms: an expert consensus from SEHH-SETH.

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.

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Improvement of appropriate pharmacological prophylaxis in hospitalised cancer patients with a multiscreen e-alert system: a single-centre experience.

PURPOSE: Thromboprophylaxis use among medical inpatients, including cancer patients, is suboptimal. We aimed to evaluate the impact of a novel multiscreen version (v2.0) of an e-alert system for VTE prevention in hospitalised cancer medical patients compared to the original software. METHODS: Prospective study including 989 consecutive adult cancer patients with high-risk of VTE. Patients were followed-up 30 days post-discharge. Two periods were defined, according to the operative software. RESULTS: E-alert v2.0 was associated with an increase in the use of LMWH prophylaxis (65.5% vs. 72.0%); risk difference (95% CI) 0.064 (0.0043-0.12). Only 16% of patients in whom LMWH prophylaxis was not prescribed lacked a contraindication. No significant differences in the rates of VTE (2.9% vs. 3.2%) and major bleeding (2.7% vs. 4.0%) were observed. CONCLUSIONS: E-alert v2.0 further increased the use of appropriate thromboprophylaxis in hospitalised cancer patients, although was not associated with a reduction in VTE incidence.

FOTROCAN Delphi consensus statement regarding the prevention and treatment of cancer-associated thrombosis in areas of uncertainty and low quality of evidence

Introduction. Decision-making in cancer-related venous thromboembolism (VTE) is often founded on scant lines of evidence and weak recommendations. The aim of this work is to evaluate the percentage of agreement surrounding a series of statements about complex, clinically relevant, and highly uncertain aspects to formulate explicit action guidelines. Materials and methods. Opinions were based on a structured questionnaire with appropriate scores and were agreed upon using a Delphi method. Questions were selected based on a list of recommendations with low evidence from the Spanish Society of Oncology Clinical Guideline for Thrombosis. The questionnaire was completed in two iterations by a multidisciplinary panel of experts in thrombosis. Results. Of the 123 statements analyzed, the panel concurred on 22 (17%) and another 81 (65%) were agreed on by qualified majority, including important aspects of long-term and prolonged anticoagulation, major bleeding and rethrombosis management, treatment in special situations, catheter-related thrombosis and thromboprophylaxis. Among them, the panelists agreed the incidental events should be equated to symptomatic ones, long-term and extended use of full-dose low-molecular weight heparin, and concluded that the Khorana score is not sensitive enough to uphold an effective thromboprophylaxis strategy. Conclusion. Though the level of consensus varied depending on the scenario presented, overall, the iterative process achieved broad agreement as to the general treatment principles of cancer-associated VTE. Clinical validation of these statements in genuine practice conditions would be useful (AU)

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FOTROCAN Delphi consensus statement regarding the prevention and treatment of cancer-associated thrombosis in areas of uncertainty and low quality of evidence.

INTRODUCTION: Decision-making in cancer-related venous thromboembolism (VTE) is often founded on scant lines of evidence and weak recommendations. The aim of this work is to evaluate the percentage of agreement surrounding a series of statements about complex, clinically relevant, and highly uncertain aspects to formulate explicit action guidelines. MATERIALS AND METHODS: Opinions were based on a structured questionnaire with appropriate scores and were agreed upon using a Delphi method. Questions were selected based on a list of recommendations with low evidence from the Spanish Society of Oncology Clinical Guideline for Thrombosis. The questionnaire was completed in two iterations by a multidisciplinary panel of experts in thrombosis. RESULTS: Of the 123 statements analyzed, the panel concurred on 22 (17%) and another 81 (65%) were agreed on by qualified majority, including important aspects of long-term and prolonged anticoagulation, major bleeding and rethrombosis management, treatment in special situations, catheter-related thrombosis and thromboprophylaxis. Among them, the panelists agreed the incidental events should be equated to symptomatic ones, long-term and extended use of full-dose low-molecular weight heparin, and concluded that the Khorana score is not sensitive enough to uphold an effective thromboprophylaxis strategy. CONCLUSION: Though the level of consensus varied depending on the scenario presented, overall, the iterative process achieved broad agreement as to the general treatment principles of cancer-associated VTE. Clinical validation of these statements in genuine practice conditions would be useful.

Implementation of a management protocol for massive bleeding reduces mortality in non-trauma patients: Results from a single centre audit / La aplicación de un protocolo de gestión para la hemorragia masiva reduce la mortalidad en pacientes con hemorragia no traumática: Resultados de la auditoría de un centro

OBJECTIVE: To audit the impact upon mortality of a massive bleeding management protocol (MBP) implemented in our center since 2007. DESIGN: A retrospective, single-center study was carried out. Patients transfused after MBP implementation (2007-2012, Group 2) were compared with a historical cohort (2005-2006, Group 1). BACKGROUND: Massive bleeding is associated to high mortality rates. Available MBPs are designed for trauma patients, whereas specific recommendations in the medical/surgical settings are scarce. PATIENTS: After excluding patients who died shortly (<6h) after MBP activation (n=20), a total of 304 were included in the data analysis (68% males, 87% surgical). INTERVENTIONS: Our MBP featured goal-directed transfusion with early use of adjuvant hemostatic medications. Variables of interest: Primary endpoints were 24-h and 30-day mortality. Fresh frozen plasma-to-red blood cells (FFP:RBC) and platelet-to-RBC (PLT:RBC) transfusion ratios, time to first FFP unit and the proactive MBP triggering rate were secondary endpoints. RESULTS: After MBP implementation (Group 2; n=222), RBC use remained stable, whereas FFP and hemostatic agents increased, when compared with Group 1 (n=82). Increased FFP:RBC ratio (p = 0.053) and earlier administration of FFP (p = 0.001) were also observed, especially with proactive MBP triggering. Group 2 patients presented lower rates of 24-h (0.5% vs. 7.3%; p = 0.002) and 30-day mortality (15.9% vs. 30.2%; p = 0.018) - the greatest reduction corresponding to non-surgical patients. Logistic regression showed an independent protective effect of MBP implementation upon 30-day mortality (OR=0.3; 95% CI 0.15-0.61). CONCLUSIONS: These data suggest that the implementation of a goal-directed MBP for prompt and aggressive management of non-trauma, massive bleeding patients is associated to reduced 24-h and 30-day mortality rates

OBJETIVO: Auditar el impacto en la mortalidad de un protocolo de manejo de hemorragia masiva (PHM) en pacientes médico-quirúrgicos, implementado en nuestro centro desde el 2007. DISEÑO: Estudio retrospectivo de cohortes. Grupo de intervención trasfundido con PHM (2007-2012, Grupo 2) comparado con cohorte histórica (2005-2006, Grupo 1). Ámbito: Los PHM existentes están diseñados para pacientes con politraumatismo, sin evidencia clara para pacientes médicos o quirúrgicos. PACIENTES: Se incluyeron 304 pacientes en el análisis (68% hombres, 87% quirúrgicos), tras la exclusión de aquellos con mortalidad inmediata (<6h) tras la activación del PHM (n=20). INTERVENCIONES: El PHM consta de transfusión dirigida por objetivos analíticos y uso precoz de adyuvantes hemostáticos. Variables de interés: Mortalidad a las 24h y a los 30 días. Las tasas transfusionales «plasma fresco congelado: concentrado de hematíes (PFC:CH)» y «plaquetas: CH (PLT:CH)», el tiempo hasta la primera unidad de PFC y la tasa de alerta proactiva del PHM fueron objetivos secundarios. RESULTADOS: Después de la implementación del PHM (Grupo 2; n=222), el uso de CH se mantuvo estable, mientras que el de PFC y el uso de hemostáticos aumentó comparativamente con respecto al Grupo 1 (n=82). La razón PFC:CH se incrementó (p = 0,053) y la administración de PFC fue más precoz (p = 0,001), especialmente en el grupo de alerta proactiva. El Grupo 2 mostró una menor mortalidad a las 24h (0,5 vs. 7,3%, p = 0,002) y a 30 días (15,9 vs. 30,2%, p = 0,018), con el mayor descenso para los pacientes no quirúrgicos. La regresión logística mostró un efecto protector independiente del PHM para mortalidad a 30 días (OR=0,3; IC 95% 0,15-0,61). CONCLUSIONES: Estos datos evidencian que la implementación de un PHM con gestión rápida y activa de la hemorragia masiva en pacientes médico-quirúrgicos se asocia a una reducción de las tasas de mortalidad a 24 h y 30 días

Búsqueda de cáncer oculto en pacientes con tromboembolismo venoso: un dilema por resolver / Search for occult cancer in patients with venous thromboembolism: A dilemma to resolve

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Implementation of a management protocol for massive bleeding reduces mortality in non-trauma patients: Results from a single centre audit.

OBJECTIVE: To audit the impact upon mortality of a massive bleeding management protocol (MBP) implemented in our center since 2007. DESIGN: A retrospective, single-center study was carried out. Patients transfused after MBP implementation (2007-2012, Group 2) were compared with a historical cohort (2005-2006, Group 1). BACKGROUND: Massive bleeding is associated to high mortality rates. Available MBPs are designed for trauma patients, whereas specific recommendations in the medical/surgical settings are scarce. PATIENTS: After excluding patients who died shortly (<6h) after MBP activation (n=20), a total of 304 were included in the data analysis (68% males, 87% surgical). INTERVENTIONS: Our MBP featured goal-directed transfusion with early use of adjuvant hemostatic medications. VARIABLES OF INTEREST: Primary endpoints were 24-h and 30-day mortality. Fresh frozen plasma-to-red blood cells (FFP:RBC) and platelet-to-RBC (PLT:RBC) transfusion ratios, time to first FFP unit and the proactive MBP triggering rate were secondary endpoints. RESULTS: After MBP implementation (Group 2; n=222), RBC use remained stable, whereas FFP and hemostatic agents increased, when compared with Group 1 (n=82). Increased FFP:RBC ratio (p=0.053) and earlier administration of FFP (p=0.001) were also observed, especially with proactive MBP triggering. Group 2 patients presented lower rates of 24-h (0.5% vs. 7.3%; p=0.002) and 30-day mortality (15.9% vs. 30.2%; p=0.018) - the greatest reduction corresponding to non-surgical patients. Logistic regression showed an independent protective effect of MBP implementation upon 30-day mortality (OR=0.3; 95% CI 0.15-0.61). CONCLUSIONS: These data suggest that the implementation of a goal-directed MBP for prompt and aggressive management of non-trauma, massive bleeding patients is associated to reduced 24-h and 30-day mortality rates.

Nuevos anticoagulantes orales en el tratamiento del tromboembolismo venoso: análisis crítico de los resultados clínicos / New oral anticoagulants in the treatment of venous thromboembolism: critical analysis of clinical trials

El tratamiento tradicional del tromboembolismo venoso ha consistido en la administración de heparina no fraccionada o de bajo peso molecular por vía parenteral, seguida de antagonistas de la vitamina K. En los últimos años se han realizado estudios clínicos con nuevos anticoagulantes orales que inhiben selectivamente la trombina (dabigatrán) o el factor Xa (rivaroxabán, apixabán, edoxabán), habiendo demostrado una eficacia similar o superior al tratamiento estándar, sin requerir monitorización y, en algunos caos, sin precisar anticoagulación parenteral. Sin embargo, existen algunas limitaciones derivadas del diseño de los estudios, las características de los pacientes y los esquemas terapéuticos, que aconsejan una aproximación individualizada en el tratamiento del tromboembolismo venoso empleando los nuevos anticoagulantes orales

The standard treatment of venous thromboembolism has been the use of parenteral unfractionated or low molecular weight heparin, followed by oral vitamin K antagonists. New oral anticoagulants that selectively inhibit coagulation proteins such as thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, edoxaban) have shown to be effective alternative treatments in venous thromboembolism patients in clinical trials, without requiring routine parenteral anticoagulation. However, these studies have a number of limitations relating to the patient enrollment and study design. All these factors will need to be considered when deciding which of the new oral anticoagulants to use in individual patients

Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis.

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.

Seguridad y eficacia de un concentrado de complejo protrombínico en pacientes con coagulopatía y hemorragia / Safety and efficacy of a prothrombin complex concentrate in patients with coagulopathy and hemorrhage

Fundamento: Los concentrados de factores del complejo protrombínico (CCP) están indicados para reversión del efecto de antagonistas de vitamina K (AVK). Recientemente se han utilizado en el manejo de la coagulopatía de la hemorragia masiva. El objetivo del presente trabajo es evaluar la seguridad y eficacia del CCP en dos situaciones clínicas, para reversión de AVK y manejo integral de la hemorragia masiva. Material y métodos: Revisión retrospectiva de los casos tratados con CCP entre enero de 2010 y febrero de 2013 en un único centro universitario. El objetivo primario fue la seguridad de administración del CCP en cuanto a reacciones inmediatas y episodios trombóticos. El objetivo secundario fue la eficacia, en 2 grupos: 1) Reversión de AVK y 2) Corrección de coagulopatía en hemorragia masiva. Resultados: El análisis de seguridad incluyó 31 pacientes (22 varones), edad mediana 61 años (rango 30-86). No se registraron reacciones adversas durante la infusión y solo se observó un evento trombótico. La eficacia en la reversión de AVK fue del 100% (6/6 pacientes), alcanzando normalización del INR en todos los pacientes. En hemorragia masiva, la supervivencia a las 24 horas fue 64% (16/25). Se requirieron procedimientos invasivos adicionales en 28% de los pacientes (7/25). El uso de CCP se asoció a cese de hemorragia en 44% de los pacientes (11/25), que correlacionó positivamente con la supervivencia (p=0,01). Conclusión: El uso de CCP es una alternativa segura y eficaz, para la reversión urgente del efecto de AVK, así como para el control de sangrado en situación de hemorragia masiva (AU)

Background: Prothrombin complex concentrates (PCC) are approved for urgent reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the management of massive bleeding-associated coagulopathy. The present work evaluates safety and efficacy of PCC in a case series of both VKA reversal and massive bleeding. Methods: Retrospective review of cases treated with CCP (January 2010 to February 2013). Safety endpoints were infusion reactions and incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality. Results: Thirty-one patients were included (22 male), median age 61 years (range 30-86). No infusion reactions were detected, and only 1 thrombotic episode was observed. VKA reversal was effective in 100% of patients (6/6), all of them with complete reversal of INR value. In massive bleeding, 24-hour survival was 64% (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25). CCP use was correlated with bleeding control in 44% of cases (11/25), and also significantly associated with survival (p=0.01). Conclusion: CCP are safe and effective for the novel indication of adjuvant treatment in massive bleeding patients, as well as for traditional urgent reversal of VKA (Au)

[Safety and efficacy of a prothrombin complex concentrate in patients with coagulopathy and hemorrhage]. / Seguridad y eficacia de un concentrado de complejo protrombínico en pacientes con coagulopatía y hemorragia.

BACKGROUND: Prothrombin complex concentrates (PCC) are approved for urgent reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the management of massive bleeding-associated coagulopathy. The present work evaluates safety and efficacy of PCC in a case series of both VKA reversal and massive bleeding. METHODS: Retrospective review of cases treated with CCP (January 2010 to February 2013). Safety endpoints were infusion reactions and incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality. RESULTS: Thirty-one patients were included (22 male), median age 61 years (range 30-86). No infusion reactions were detected, and only 1 thrombotic episode was observed. VKA reversal was effective in 100% of patients (6/6), all of them with complete reversal of INR value. In massive bleeding, 24-hour survival was 64% (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25). CCP use was correlated with bleeding control in 44% of cases (11/25), and also significantly associated with survival (p=0.01). CONCLUSION: CCP are safe and effective for the novel indication of adjuvant treatment in massive bleeding patients, as well as for traditional urgent reversal of VKA.

Adjuvant therapy with bemiparin in patients with limited-stage small cell lung cancer: results from the ABEL study.

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).

International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.

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.

International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer.

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.

Novedades en la enfermedad tromboembólica venosa / News on venous thromboembolic disease

Este artículo recoge las últimas novedades que se han producido en diferentes aspectos de la enfermedad tromboembólica venosa (ETEV): a) profilaxis de la ETEV en cirugía ortopédica mayor; b) profilaxis de la ETEV en pacientes médicos; c) avances terapéuticos en la embolia pulmonar; d) en la trombosis venosa superficial; y e) perspectivas de futuro en la ETEV. Se resumen las 5 ponencias desarrolladas en la II Jornada de Novedades en Tratamiento Anticoagulante (Madrid, 18 noviembre de 2011), organizada por la Fundación para el Estudio de la Enfermedad Tromboembólica en España y auspiciada por la Sociedad Española de Medicina Interna, Sociedad Española de Neumología y Cirugía Torácica, Sociedad Española de Cardiología, Sociedad Española de Trombosis y Hemostasia, y Sociedad Española de Angiología y Cirugía Vascular(AU)

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery(AU)