Some patients who have presented a thromboembolic event persist with a high risk of recurrence despite anticoagulant treatment. It has been suggested that adding an inferior vena cava filter may reduce this risk, but the clinical effects of this measure are not clear. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified three systematic reviews including four randomized trials answering this question. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded there might be little or no difference on the occurrence of deep venous thrombosis by adding an inferior vena cava filter in anticoagulated patients, and it is not clear whether there are differences in the occurrence of pulmonary embolism or mortality because the certainty of evidence is very low.
The preferred dosification for low molecular weight heparins is in two doses for most patients with venous thromboembolic disease. A daily dose would make treatment simpler, less expensive and more comfortable while retaining a similar benefit and safety. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including five randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether the risk of recurrence differs between the two alternatives because the certainty of the evidence is very low, and that administering low molecular weight heparin in two doses might be associated to little or no difference in the risk of major bleeding and mortality.
BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy.
DESIGN AND SETTINGS: As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer.
METHODS: Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.
RESULTS: Question 1. Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?
RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence).Question 2. Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?
RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence).Question 3. Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?
RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence).Question 4. Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?
RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence).Question 5. Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism?
RECOMMENDATION: In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence).Question 6. Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE?
RECOMMENDATION: In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).
Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.
This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
BACKGROUND: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.
METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.
RESULTS: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).
CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted.
CONTEXTE: Cet article porte sur le traitement de la maladie de TEV.
MÉTHODES: Nous avons généré une forte (Grade 1) et la faiblesse des recommandations (Grade 2) Sur la base (Grade A), (Grade B), et les preuves de haute qualité de qualité moyenne à faible qualité (grade C).
RÉSULTATS: Pour thrombose veineuse profonde aiguë ou d'embolie pulmonaire (EP), nous recommandons un traitement initial de l'anticoagulant par voie parentérale (Grade 1B) ou anticoagulation par rivaroxaban. Nous suggérons héparine de bas poids moléculaire (HBPM) ou le fondaparinux sur IV héparine non fractionnée (Grade 2C) ou sous-cutanée d'héparine non fractionnée (Grade 2B). Nous suggérons un traitement thrombolytique pour PE avec hypotension (Grade 2C). Pour TVP proximale ou une EP, nous recommandons un traitement de 3 mois sur des périodes plus courtes (Grade 1B). Pour une première thrombose veineuse profonde proximale ou EP qui est provoquée par une chirurgie ou par un facteur de risque transitoire non chirurgicale, nous recommandons 3 mois de traitement (1b année; Grade 2B si provoquée par un facteur de risque non chirurgicale et le risque faible ou modéré saignements), qui est sans provocation , nous vous proposons un traitement prolongé si le risque de saignement est faible ou modérée (Grade 2B) et nous recommandons 3 mois de traitement si le risque de saignement est élevé (Grade 1B), et qui est associée à un cancer actif, nous recommandons un traitement prolongé (Grade 1B, 2B grade en cas de risque élevé de saignement) et de proposer des HBPM sur les antagonistes de la vitamine K (Grade 2B). Nous suggérons des antagonistes de la vitamine K ou HBPM sur dabigatran ou rivaroxaban (Grade 2B.) Nous suggérons des bas de contention pour éviter le syndrome post-thrombotique (Grade 2B). Pour une thrombose veineuse superficielle, nous vous suggérons fondaparinux prophylactique à dose unique ou HBPM plus aucune anticoagulation (Grade 2B), et suggérons fondaparinux sur HBPM (Niveau 2C).
CONCLUSION: Des recommandations fortes s'appliquent à la plupart des patients, alors que les recommandations faibles sont sensibles aux différences entre les patients, y compris leurs préférences.
INTRODUCTION: Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of people with untreated DVT may die from pulmonary embolism. Risk factors for DVT include immobility, surgery (particularly orthopaedic), malignancy, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for proximal DVT? What are the effects of treatments for isolated calf DVT? What are the effects of treatments for pulmonary embolism? What are the effects of interventions on oral anticoagulation management in people with thromboembolism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticoagulation; compression stockings; low molecular weight heparin (short and long term, once or twice daily, and home treatment); oral anticoagulants (short and long term, high intensity, abrupt discontinuation, and computerised decision support); prolonged duration of anticoagulation; thrombolysis; vena cava filters; and warfarin.
INTRODUCTION: avantages et les inconvénients relatifs des anticoagulants sont nécessaires pour les décisions concernant l'anticoagulation appropriée chez les patients atteints de cancer.
OBJECTIFS: Examiner les avantages et les inconvénients des anticoagulants pour des indications d'amélioration prophylactiques, thérapeutiques et de survie chez les patients atteints de cancer.
Patients et méthodes: Vue d'ensemble de 6 recensions systématiques de l'anticoagulation dans le cancer de la suite de la Cochrane Collaboration et classement des recommandations d'évaluation, de développement et d'évaluation méthodologie.
RÉSULTATS: Central veineuse cathéters thromboprophylaxie avec de l'héparine ou la warfarine ne réduit pas significativement l'incidence de la thrombose veineuse profonde symptomatique (TVP) (risque relatif [RR] 0,43, IC 95% 0,18 à 1,06 et RR = 0,62, IC 95% de 0,30 à 1,27 respectivement) . Pour la thromboprophylaxie périopératoire, à faible poids moléculaire héparine (HBPM) et l'héparine non fractionnée (HNF) ont des effets similaires sur la mortalité (RR 0,89, IC 95% 0,61 à 1,28) et la morbidité. Pour le traitement initial de la maladie thromboembolique veineuse (MTEV), les HBPM par rapport à l'héparine non fractionnée réduit la mortalité à 3 mois (RR 0,71, IC 95% de 0,52 à 0,98). Pour le traitement à long terme de la TEV, les HBPM par rapport à des antagonistes de la vitamine K réduit la récurrence de TEV (hazard ratio [HR] 0,47, IC 95% de 0,32 à 0,71), mais pas la mortalité (HR 0,96, IC 95% 0,81 à 1,14). Comme les interventions visant à améliorer la survie, la warfarine suggère un bénéfice de survie à 6 mois dans le sous-groupe de cancer du poumon à petites cellules (SCLC) (RR = 0,69, IC 95% de 0,50 à 0,96), tandis que l'héparine suggèrent un bénéfice de survie chez les patients atteints de cancer en général (RH 0,77, IC 95% 0,65 à 0,91) et chez ceux ayant limité CPPC en particulier (HR 0,56, IC 95% 0,38 au 0,83).
CONCLUSIONS: Chez les patients atteints de cancer, les données actuelles ne supporte pas l'utilisation systématique de la thromboprophylaxie pour les cathéters veineux centraux ou un anticoagulant spécifique pour la thromboprophylaxie postopératoire. Anticoagulants peut améliorer la survie, mais davantage de données seront utiles dans le choix des sous-groupes qui bénéficient le plus.
Some patients who have presented a thromboembolic event persist with a high risk of recurrence despite anticoagulant treatment. It has been suggested that adding an inferior vena cava filter may reduce this risk, but the clinical effects of this measure are not clear. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified three systematic reviews including four randomized trials answering this question. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded there might be little or no difference on the occurrence of deep venous thrombosis by adding an inferior vena cava filter in anticoagulated patients, and it is not clear whether there are differences in the occurrence of pulmonary embolism or mortality because the certainty of evidence is very low.
