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Title: The influence of neutrophils and mononuclear leucocytes on the fibrinolytic response to severe sepsis
Author: Haj, Montaser A.
ISNI:       0000 0001 3524 2024
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1995
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This study identified striking increase in plasma of plasminogen activator inhibitor 1(PAI-I), a major inhibitor of fibrinolysis levels in septic patients who are non-neutropenic. Neutropenic patients show less striking changes. Where shock occurs both groups of patients show very high levels of PAI-1. These observations suggest a role for leucocytes in PAI production. In the second section neutrophils are identified as containing PAI-1 in normal subjects, the levels rising significantly in sepsis. Monocytes contain no PAI-1 but do contain Plasminogen activator inhibitor 2(PAI-2) levels of which inhibitor also rise in sepsis. Normal neutrophils contained no PAI-2 but neutrophils from septic patients contained significant quantities of this inhibitor. In the third section mononuclear cells from septic patients are identified as enhancing PAI-1 production in cultured endothelial cell (EC). Septic neutrophils have a more complex effect on EC. Mononuclear cells and neutrophils therefore, both contribute to the fibrinolytic inhibition of septic disorders but by different mechanisms. Each cell type contains one of the major inhibitor of plasminogen activator and levels of these rise in sepsis. Both cell types from septic patients promote greater release of PAI-1 from endothelial cells than do cells from normal individuals. Inhibition of fibrinolysis by leucocytes may contribute to fibrin persistence in sepsis. This may be useful in localizing infection. If generalized, it may contribute to vascular occlusive complications of sepsis such as shock lung, acute renal failure or digital gangrene. Absence of leucocytes may account for the apparent reduction of vascular occlusive complications in leucopenic septic patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Infection; Haemostasis; PAI-1; Septic shock