michael s
(Michael S)
#1
25 Which thrombolytics are currently available for
treating acute myocardial infarction? Who should
receive which one? What newer agents are there?
Anthony Gershlick
Thrombolysis
Natural thrombolysis occurs via the action of plasmin on fibrin
thrombi. Plasmin is formed from plasminogen by cleavage of a
single peptide bond. Plasmin is a non-specific protease and
dissolves coagulation factors as well as fibrin clots. Three
thrombolytic agents are currently available. Streptokinase (SK)
forms a non-covalent link with plasminogen. The resultant con-
formational change exposes the active site on plasminogen to
induce the formation of plasmin. Tissue plasminogen activator
(tPA) is a serine protease and binds directly to fibrin via a lysine
site, activating fibrin-bound plasminogen. The theoretical advan-
tages of tPA are its increased specificity and potency because of its
direct effect on fibrin-bound plasminogen. Being the product of
recombinant DNA technology, there should be no allergic
reaction to tPA. Unlike SK which should be used only once, tPA
can be used repeatedly. Some, but not all, of these theoretical
advantages translate into definite clinical benefit. Recently
reteplase, a variation of tPA, has become available.
The Fibrinolytic Therapy Trialists Collaborative Group^1
summarised results from thrombolytic trials encompassing
more than 100,000 patients. The overall relative risk reduction
in 35 day mortality with treatment was 18% (p < 0.00001). The
mortality at this time was ~13%, reduced to 8–9% with
treatment. However, in real life where the population is older
than in the trials the true mortality is about 18–20%.
Administration of a thrombolytic saves about 30 lives in a 1000
in those presenting within 6 hours of symptom onset but only
20 lives in a 1000 when patients receive treatment between 6
and 12 hours after symptom onset. Aspirin has an independent
beneficial effect on mortality and can be chewed.^2 The LATE
Trial showed no benefit 12 hours after onset of symptoms.^3
Judging the onset of symptoms can be difficult and may be
influenced by collateral flow from another artery. If a patient
presents with stuttering symptoms over 24 hours or so but has
