1. Cardiac enzymes 3 - Streptokinase Lecture No: 1st MBBS
Dr Muhammad Ramzan

2. Streptokinase (SK) – the definition Is proteolytic
Streptokinase (SK) is an enzyme secreted by several species of streptococci that can bind with and catalyze the :
Conversion of  Plasminogen(PLG) to Plasmin
SK is used as an  thrombolytic medication for MI , pulmonary embolism and deep vein thrombosis
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3. Streptokinase – the background haemolytic streptococci β.C
SK is fibrinolytic and prevents the unwanted clot growth and its complications like embolism
SK is on the WHOs List of Essential Medicine million/vial
It is a bacterial product can build up immunity
SK may not be reused within 4 days 1.to prevent allergic reactions. 2. SK is ineffective if given within 4 days)
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4. Plasminogen - PLG glycoprotein with 77 AAs
PLG is a glycoprotein and is expressed in liver and kidneys
PLG is encoded by its own gene and is secreted as Zymogen in blood as well as in ECF
Genetic mutation in PLG gene may cause thrombophilia and Ligneous disease (Ligneous conjunctivitis) -
PLG ranges from mg/dl in adults with a half life of 2.2 days –

5. Fibrinolysis – resolves clots A Physiological process
Fibrinolysis is the enzymatic breakdown of the fibrin in the blood clot that is formed in response to vascular injury.
It is a physiological process and is catalyzed by the Plasmin
Plasmin is a Protease enzyme present in the blood as its precursor – the Plasminogen
The process clears fibrin deposits locally but does not cause systemic Fibrinolysis
webster.com –

6. Fibrinolysis

7. Fibrinolysis - Mechanism and significance
Plasmin acts on its substrate , the Fibrin for its conversion to soluble fibrinogen degradation products. (FDPs)
FDPs are unable to bind with PLG activators, so there is no further conversion of PLG to Plasmin
Fibrinolysis 1. Removes thrombus, 2. prevents its growth and complications like embolism
3. It restores blood supply.
webster.com – –

8. Vascular injury to Fibrinolysis

9. PLG to active Plasmin - the activators tPA is secreted in its inactive form
The conversion of PLG to Plasmin is mediated by the tPA- 1 and Urokinase Plasminogen activator(uPA)
Inactive tPA-1 is generated by the damaged vascular cells and is activated by the Urokinase
Urokinase is produced in inactive form by epithelium of renal excretory ducts

10. PLG to Plasmin – the inhibitors Major at 2 levels- tPAI and α2 antiplasmin
PLG to Plasmin is inhibited by the Tissue Plasminogen activator inhibitor tPAI (for tPA-1)
Generation of Plasmin is quickly inactivated by the main
Inhibitor - α2- antiplasmin (alpha2- AP)
Congenital deficiency of α2- antiplasmin produces:
.A rare bleeding disorder in females

11. PLG to Plasmin – activators and inhibitors

12. PLG to Plasmin – the inhibitors major at 2 levels

13. PLG - Secretion abnormalities Deficiency/Ligneous disease
PLG can be secreted in excess or there can be its deficiency.
Both can be congenital or acquired
PLG Deficiency leads to the development of fibrin rich pseudo- membrane as Fibrin is not degraded normally)
Fibrin gets deposited on various mucous membranes and tissues

14. PLG deficiency – Ligneous disease
PLG deficiency results in the failure of this mechanism, leading to deposition of fibrin that impairs:
functions of the various body tissues
PLG deficiency leads to Ligneous disease of body tissues
The affected ones include eye; mouth (gums), respiratory and female reproductive organs
– Medical problems in dentistry by Scully,7th edition,2007

15. Ligneous conjunctivitis

16. Ligneous conjunctivitis

17. Ligneous gingivitis

18. SK and Thrombolysis - Mechanism of action PLG SK complex formation
SK binds with the unbound PLG in blood clot to form :
PLG Streptokinase complex - PLG SK complex
The complex is activated by t-PA - 1 and Urokinase
PLG SK complex then activates unbound PLG in the blood clot to form Plasmin

19. Mechanism of action of SK cont.
Plasmin is a Serine Protease that degrades fibrin in blood clot to Soluble Degradation Products (FDPs)
FDPS cannot bind with tPA-1 to activate PLG for Plasmin
So there is no conversion of PLG to Plasmin
Plasmin also degrades many Plasma proteins

20. Mechanism of action of SK

21. Mechanism of SK action

22. Streptokinase – Major Indications
SK can be given in the following conditions.
Myocardial infarction
Pulmonary thrombosis/embolism
Deep vein thrombosis

23. SK – Contra indications
CVS : severe/uncontrolled Hypertension
CNS : stroke and Cerebral neoplasm/ haemorrhage
Women : Pregnancy and delivery
Age – children with PLG deficiency and allergy
Recent surgery and trauma
Recent history of peptic ulcer
Previous history of SK. Allergy

24. Significance of SK - major
Lyses of coronary, Pulmonary and deep vein thrombosis
Reduction of the mortality rate with MI
Reduction in infarct size and :
improvement in ventricular/ lung function and :
Restoration of blood flow

25. SK – the administration 1.5million U
SK is given I/V in 60 mint. (100ml saline) as soon as possible after the ST elevation – best results within 4- 24hrs
SK takes 90 minutes to be effective
Dose should not be repeated within 4 days as It is ineffective within this period. May cause allergy
Overdose is treated with amino Caproic acid or 150mg aspirin
for 4 wks as adjuvant therapy after MI