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Keywords:

General & Internal Medicine, 1103 Clinical Sciences

Abstract:

Despite enormous advances made in understanding of the biochemistry of fibrinolytic agents and their extensive clinical use in acute myocardial infarction a number of unresolved issues remain. There is an intriguing divergence of left ventricular response and reduction of mortality in patients with acute myocardial infarction treated with thrombolytic drugs. It is also difficult to explain why patients treated late have a reduced mortality after thrombolytic treatment. Uncertainty prevails on the validity of thrombolysis in patients with a low and very high risk of mortality. Resistance of coronary occlusion to any thrombolytic is another unexplained fact. Alteplase and saruplase are more fibrin specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. It is being explored whether prolonged intravenous maintenance infusions are more effective if replaced by a bolus injection, accelerated infusion or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules by deletion and domain substitution or hybrids of the two molecules have been constructed, without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets and await clinical testing.