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9780521704632c23 CUFX213A/Peck 9780521618168 December 29, 2007 14:58
23 Drugs affecting coagulationUses
Streptokinase is used to dissolve clot in arterial (acute MI, occluded peripheral arter-
ies and PE) and venous (DVT) vessels.Mechanism of action
Streptokinase activates the fibrinolytic system by forming a complex with plasmino-
gen, which then facilitates the conversion of further plasminogen to active plasmin.
The clot can then be lysed.Side effects
Haemorrhage – streptokinase is contraindicated in patients for whom a risk of
serious bleeding outweighs any potential benefit of therapy (i.e. active internal
bleeding, recent stroke, severe hypertension).
Cardiovascular – it may precipitate reperfusion arrhythmias and hypotension dur-
ing treatment of acute MI.
Allergic reactions may occur as it is very antigenic. Where high antibody titres
are expected (5 days to 12 months from previous exposure to streptokinase), an
alternative should be sought.Kinetics
Streptokinase is administered intravenously as a loading dose followed by an infu-
sion. The loading dose is sufficient to neutralize any antibodies that are often present
from previous exposure to streptococcal infection. The streptokinase–antibody com-
plex is cleared rapidly and the streptokinase–plasminogen complex is degraded to a
number of smaller fragments during its action.
Alteplase(rt-PA, tissue-type plasminogen activator) is a glycoprotein that becomes
activated only when bound to fibrin, inducing the conversion of plasminogen to
plasmin. Because of its mode of activation, systemic fibrinolysis occurs to a lesser
extent than with streptokinase.
Urokinasewas originally extracted from human adult male urine but is now pre-
pared from renal cell cultures. Recombinant DNA technology is currently used to
produce pro-urokinase. It is not antigenic and is used in the lysis of clots in arteri-
ovenous shunts and in hyphaema (anterior chamber haemorrhage with refractory
thrombi).Antifibrinolytics
Aprotinin
Aprotinin is a polypeptide with 58 amino acids and has a molecular weight of 6512 Da.
Itis a naturally occurring proteolytic enzyme inhibitor acting on trypsin, plasmin and
tissue kallikrein. It inhibits the fibrinolytic activity of the streptokinase–plasminogen