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Title: Functional aspects of thrombolytic therapy
Author: Gemmill, John Douglas
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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The benefits of thrombolytic therapy in acute myocardial infarction are established, yet there remain important questions, including the safe interval for effective readministration of the streptokinase-containing thrombolytic agents, and how to expedite the administration of therapy and the restoration of coronary patency. The work in this thesis addresses some aspects of these questions. The administration of thrombolytic agents by bolus injection has practical attractions. The pharmacokinetic properties of streptokinase (SK) and anistreplase in their standard administration regimens are compared, and demonstrate the significantly earlier, higher plasma concentrations and longer half-life achieved by bolus administration of anistreplase. Domiciliary administraiton reduces the delay to therapy. The feasibility of this approach was assessed comparing general practitioners' assessment of 139 patients, with and without electrocardiographs, with the coronary care unit diagnosis and the prescription of thrombolytic therapy. Domiciliary assessment is insufficiently reliable to recommend routine use of thrombolytic therapy at home at the present time. The significance of antibodies to SK-containing thrombolytic agents is largely unknown. Pretreatmet SK resistance titre and anti-SK IgG concentrations were measured in 128 patients with acute myocardial infarction treated with SK or anistreplase. A significant minor negative influence of SK resistance titre on coronary patency was observed. The haemodynamic responses to these agents were observed in detail, and blood pressure falls found to be usually short-lived and not require specific intervention. An association was sought between hypotensive episodes and markers of immunological resistance, markers of thrombin activity, and plasma viscosity. No relationship was found, refuting their implication in the hypotensive mechanism. The time course of the development of changes in SK resistance titre and anti-SK IgG concentration were documented in detail in the same patients over 30 months. Both indices peaked at 2 weeks following therapy, and declined slowly, with 50 & 58% of the population returning to within two standard deviations of pretreatment levels within 2 years. The functional sequelae of these antibody responses were studied in vitro using a pooled clot lysis assay. These data demonstrated near complete inhibition of lysis up to 9 months, with 75% recovery at 30 months.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available