A blood clot (thrombus) developed in the circulatory system can cause vascular
blockage leading to serious consequences including death. A healthy hemostatic system
suppresses the development of blood clots in normal circulation, but reacts extensively in
the event of vascular injury to prevent blood loss. Outcomes of a failed hemostasis include
stroke, pulmonary embolism, deep vain thrombosis and acute myocardial infraction
2. • A blood clot (thrombus) developed in the
circulatory system can cause vascular
• blockage leading to serious consequences
including death. A healthy hemostatic system
• suppresses the development of blood clots in
normal circulation, but reacts extensively in
• the event of vascular injury to prevent blood loss.
Outcomes of a failed hemostasis include
• stroke, pulmonary embolism, deep vain
thrombosis and acute myocardial infraction.
3. • Numerous trails have been conducted to
compare the clinical efficacy of recombinant
• tPA and streptokinase. Generally, these
investigations have not revealed a clear
preference
• for either drug. Streptokinase is as effective as
recombinant tPA in treating acute
• myocardial infarction
4. • A blood clot or thrombus consists of
• blood cells occluded in a matrix of the protein
fibrin. Enzyme-mediated dissolution of
• the fibrin clot is known as thrombolysis or
fibrinolysis. In mammalian circulation, the
• enzyme responsible for fibrinolysis is plasmin,
a trypsin-like serine protease
5. • Recombinant forms of normal human
plasminogen activators tPA and uPA are used
• in clinical intervention. Another commonly used
plasminogen activator is streptokinase
• (sPA), a bacterial protein that does not occur
naturally in human circulation. Streptokinase,
• tPA and uPA do not have a direct fibrinolytic
activity and their therapeutic action
• is via the activation of blood plasminogen to the
clot dissolving plasmin
6. • Unlike microbial streptokinase, human urokinase is not antigenic or
pyrogenic, but its
• recovery from urine is expensive and supply is limited for any extensive
use in therapy
• (Rouf et al., 1996). Like streptokinase, urokinase activates both the
circulating plasminogen
• and the clot-bound plasminogen. Because plasminogen activation by uPA
and
• streptokinase is not specific to the clot-bound plasminogen, the use of
these activators
• is associated with a serious risk of hemorrhage (Rouf et al., 1996).
• Attempts have been made to compare the fibrinolytic properties of
staphylokinase and
• streptokinase using animal models of venous thrombosis (Lijnen et al.,
1991b) and other
• methods (Collen et al., 1992).
7. • Although streptokinase is the best known microbial plasminogen activator,
it is not the
• only one. Staphylokinase (SAK) sourced from Staphylococcus sp. is a
potential alternative
• plasminogen activator (Lack, 1948; Matsuo et al., 1990; Collen et al., 1992;
Schlott et al.,
• 1994; Okada et al., 2001); 1991a. The structure and mechanism of action
of SAK are
• becoming better understood (Matsuo et al., 1990; Lijnen et al., 1991a;
Okada et al., 2001).
• Recombinant staphylokinase has been produced in bacteria such as
Escherichia coli
• (Sako, 1985; Collen et al., 1992; Schlott et al., 1994) and shown to induce
fibrin specific
• clot lysis in human plasma milieu in vitro (Matsuo et al., 1990; Lijnen et al.,
1991a).
8. • Streptokinase and, to a lesser extent,
staphylokinase are the best investigated
fibrinolytic
• proteins of microbial origin, but there are others.
Fibrinolytic proteins have been
• isolated from other species including microfungi
(Ba¨rwald et al., 1974) and anticoagulant
• proteins of potential therapeutic value occur in
higher animals such as leeches, mosquitoes,
• snakes and bats.