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Effect of Fostair® on Biomarkers of Platelet Adhesion in Idiopathic Pulmonary Fibrosis

Hull University Teaching Hospitals NHS Trust · 2014
ClinicalTrials.gov · Datasets · License: Public Domain · 2014
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idiopathic-pulmonary-fibrosis
The investigator has recently studied markers of platelet activation in idiopathic pulmonary fibrosis (IPF) and found that in IPF patients there is a significantly increased platelet reactivity when compared with controls which is demonstrated by a concentration dependent increase in platelet-monocyte complex formation, platelet P-selectin expression and platelet fibrinogen binding in the presence of' the platelet agonists Adenosine diphosphate and L- Threonyl- L- phenylalanyl- L- leucyl- L- leucyl- L-argininamide (TFLLR). During platelet activation the platelets degranulate releasing numerous profibrotic cytokines including Transforming growth factor beta and Platelet derived growth factor that are recognised to be important in the pathogenesis of IPF. It is therefore plausible that the observed increased platelet reactivity in IPF contributes to the fibrotic process through local activation and degranulation with release of proinflammatory and profibrotic mediators within the pulmonary circulation. There is evidence that corticosteroid treatment may alter platelet adhesion, in a study of spontaneously hypertensive rat (SHR) increased circulating glucocorticoid, suppressed p-selectin expression. p selectin is a transmembrane protein present in the α granules of platelets. P selectin has a crucial role in platelet aggregation and platelet-leukocyte interactions, which are both potentially important mechanisms in the initiation and/or progression of tissue injury and development of thrombosis. In a study of patients with chronic obstructive pulmonary disease (COPD) exacerbation these were treated with either β agonists alone or β agonist and 40mg prednisolone and compared with a control group. At presentation the COPD patients had higher pulmonary artery pressure (PAP) higher p selectin and fibrinogen levels but lower Antithrombin III levels (AT III). The pulmonary artery pressure and fibrinogen levels were found to be significantly decreased in the steroid treated
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