Pathophysiological basis for anticoagulant and antithrombotic therapy in pulmonary hypertension.
In pulmonary hypertension (PH), thrombosis and thromboembolism may occur as primary events associated with inherited or acquired thrombophilia. Alternatively, in situ thrombosis may develop as a complication of pre-existing vasculopathy as in the case of idiopathic PH and related disorders (so called pulmonary arterial hypertension). In these disorders, a number of abnormalities has been described involving endothelial cells, platelets and other circulating cellular and soluble elements. These abnormalities are suggestive of a shift of pulmonary vascular microenvironment toward a procoagulant, prothrombotic and antifibrinolytic pattern. The abnormalities described so far include circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P-selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and cytokines. Also, decreased endothelial production of natural anticoagulants (thrombomodulin) and platelet antiaggregating substances (nitric oxide, prostacyclin) have been demonstrated. The present review is focused on the procoagulant, prothrombotic and antifibrinolytic mechanisms so far identified in PH, in both clinical setting and animal models. Understanding of these mechanisms is crucial for a proper selection of anticoagulant and antithrombotic therapies and provides the rationale for development of novel therapeutic options.
Lopes
Antonio Augusto
AA
Instituto do Coração -- InCor, Cardiologia Pediátrica e Cardiopatias Congênitas do Adulto, Av. Dr. Eneas de Carvalho Aguiar, 44, 05403-000 São Paulo-SP, Brazil. aablopes@usp.br
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D004727:Endothelium / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008954:Models, Biological; D010641:Phenotype; D012307:Risk Factors
D000925:Anticoagulants; D005343:Fibrinolytic Agents