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.
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.
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.
