Altered hemostasis in pulmonary hypertension.
Pulmonary hypertension is characterized by increased pressure in the pulmonary circulation and, in some cases, inflammation. Significant vascular remodeling occurs in response to these stresses and histopathology demonstrates in-situ thrombosis in a significant number of cases. Elevated shear stresses and inflammation, based on in-vitro data, would be expected to enhance platelet activation and aggregation/adhesion, increase release of von Willebrand factor, increase tissue factor expression, downregulate surface thrombomodulin with diminished thrombin inactivation and decreased protein C activation, and alter fibrinolytic factors with a net loss of fibrinolysis. Data from animal and human studies of pulmonary hypertension provide evidence for increased platelet activation, decreased platelet survival, increased release of von Willebrand factor antigen without an increase in activity, decreased soluble thrombomodulin and a net loss of fibrinolytic activity with excessive release of plasminogen activator inhibitor-1. These changes may result in in-situ thrombosis, which may occur as an inciting event of pulmonary hypertension, or as a consequence of other initiating factors. Chronic anticoagulation has been used in pulmonary hypertension based on observations of increased survival. However, the direct link between altered coagulation and the development or persistence of pulmonary hypertension awaits confirmation.
Hassell
K L
KL
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. hassellk@jove.uchsc.edu
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D018180:Thrombomodulin / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology
D000925:Anticoagulants; D018180:Thrombomodulin; D014841:von Willebrand Factor