Biomedical Engineering Reference
In-Depth Information
12.4.4 Streptokinase
Streptokinase is a 48 kDa extracellular bacterial protein produced by several strains of
Strepto-
coccus haemolyticus
group C. Its ability to induce lysis of blood clots was fi rst demonstrated in
1933. Early therapeutic preparations administered to patients often caused immunological and
other complications, usually prompted by impurities present in these products. Chromatographic
purifi cation (particularly using gel fi ltration and ion-exchange columns) overcame many of these
initial diffi culties. Modern chromatographically pure streptokinase preparations are usually sup-
plied in freeze-dried form. These preparations (still obtained by non-recombinant means) often
contain albumin as an excipient. The albumin prevents fl occulation of the active ingredient upon
its reconstitution.
Streptokinase is a widely employed thrombolytic agent. It is administered to treat a variety of
thrombo-embolic disorders, including:
•
pulmonary embolism (blockage of the pulmonary artery - which carries blood from the heart
to the lungs for oxygenation - by an embolism), which can cause acute heart failure and sudden
death;
•
deep-vein thrombosis (thrombus formation in deep veins, usually in the legs);
•
arterial occlusions (obstruction of an artery);
•
acute myocardial infarction.
Streptokinase induces its thrombolytic effect by binding specifi cally and tightly to plasminogen.
This induces a conformational change in the plasminogen molecule that renders it proteolytically
active. In this way, the streptokinase-plasminogen complex catalyses the proteolytic conversion
of plasminogen to active plasmin.
As a bacterial protein, streptokinase is viewed by the human immune system as an antigenic
substance. In some cases, its administration has elicited allergic responses that have ranged from
mild rashes to more serious anaphylactic shock (an extreme and generalized allergic response
characterized by swelling, constriction of the bronchioles, circulatory collapse and heart failure).
Another disadvantage of streptokinase administration is the associated increased risk of haem-
orrhage. Streptokinase-activated plasminogen is capable of lysing not only clot-associated fi brin,
but also free plasma fi brinogen. This can result in low serum fi brinogen levels and, hence, com-
promise haemostatic ability. It should not be administered to, for example, patients suffering from
coagulation disorders or bleeding conditions such as ulcers. Despite such potential clinical com-
plications, careful administration of streptokinase has saved countless thousands of lives.
12.4.5 Urokinase
The ability of some component of human urine to dissolve fi brin clots was fi rst noted in 1885. It
was not until the 1950s, however, that the active substance was isolated and named urokinase.
Search WWH ::
Custom Search