Thrombolytic agents

The natural process of thrombosis functions to plug a damaged blood vessel, thus maintaining haemostasis until the damaged vessel can be repaired. Subsequent to this repair, the clot is removed via an enzymatic degradative process known as fibrinolysis. Fibrinolysis normally depends upon the serine protease plasmin, which is capable of degrading the fibrin strands present in the clot.

In situations where inappropriate clot formation results in the blockage of a blood vessel, the tissue damage that ensues depends, to a point, upon how long the clot blocks blood flow. Rapid removal of the clot can often minimize the severity of tissue damage. Thus, several thrombolytic (clot-degrading) agents have found medical application (Table 12.5). The market for an effective thrombolytic agent is substantial. In the USA alone, it is estimated that 1.5 million people suffer acute myocardial infarction each year, and there are another 0.5 million suffer strokes.

Table 12.5 Thrombolytic agents approved for general medical use

Product3

Company

Activase (rh-tPA)

Ecokinase (rtPA; differs from human tPA in that three of its five domains have been deleted) Retavase (rtPA; see Ecokinase) Rapilysin (rtPA; see Ecokinase)

Tenecteplase (also marketed as Metalyse) (TNK-tPA, modified rtPA) TNKase (tenecteplase; modified rtPA; see Tenecteplase) Streptokinase (produced by Streptokinase haemolyticus) Urokinase (extracted from human urine)

Staphylokinase (extracted from Staphylococcus aureus and produced in various recombinant systems

Genentech Galenus Mannheim

Boehringer Manheim/Centocor

Boehringer Manheim

Boehringer Ingelheim

Genentech

Various

Various

Various ar: recombinant; rh: recombinant human.

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