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

2. Streptokinase (SK) – the definition
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
(Merrium Webster.com)

3. Streptokinase – the background haemolytic streptococci β.C
SK is a fibrinolytic, binds and converts PlG to Plasmin through its 3 domains collectively
It prevents the unwanted clot growth and its complications 2
It is on the WHOs List of Essential Medicine- 1.5 million/vial
It is a bacterial product, can build up immunity :
Should not be reused within 4 days to prevent allergic reactions
(Sk is ineffective if given within 4 days)

4. 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, a
protease, generated from the zymogen Plasminogen
PLG is located on the surface of fibrin clot
Plasmin acts on its substrate /Fibrin for its conversion to soluble fibrinogen degradation products.(unable to bind with PLG activators}
Removes thrombus; prevents it growth/embolism/complications and restores blood supply.
webster.com – Rev,2015

5. Fibrinolytic pathway

6. Fibrinolysis – Degrades the fibrin threads in the intravascular thrombus

7. PLG to Plasmin – Release of PLG activators Fibrin degradation products - FDPs

8. SK and Fibrinolysis - Mechanism of action
SK binds with the unbound PlG (in the blood clot) to form PlG SK complex which further activates the:
unbound PlG to form Plasmin
Plasmin is a Serine Protease that acts to degrade fibrin in blood clot to Soluble Degradation Products (FDPs)
FDPS cannot bind with tPA-1 to activate PLG for Plasmin
Plasmin also degrades many Plasma proteins

9. Fibrinolysis - Mechanism of action of SK

10. Fibrinolysis – Mechanism of action of SK

11. Plasminogen (PLG) - the structure 77Amino acids
Plasminogen is a glycoprotein synthesized mainly in liver that circulates in the blood with a half life of 2.2 days.
Plasma level of PLG in adults is 10 16mg/dl
It is a precursor of the Plasmin that degrades fibrin clots to soluble Fibrin Degradation Products(FDPs)
FDP cannot bind with the tPA -1 to convert PLG into active Plasmin
Plasmin is the initiator of the Fibrinolysis
and helps in tissue repair

12. Physiological mechanism - PLG – Plasmin-

13. 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 by the epithelium of the renal excretory ducts

14. PLG to active Plasmin – the activators

15. Urokinase for activation of tPA- 1 and PLG to Plasmin

16. PLG to Plasmin – the inhibitors at 3 levels- tPAI and antiplasmin and TAFI)
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
Thrombin Activated Fibrinolysis Inhibitor (TAFI)
tPAI- 1 is also inhibitor of the Thrombin activated Fibrinolysis Inhibitor(TAFA1)
Congenital deficiency of α- antiplasmin: A rare bleeding disorder that leads to excessive bleeding/defective Fibrinolysis

17. PLG to Plasmin – the inhibitors At 3 levels

18. PLG - Secretion abnormalities Deficiency/Ligneous disease
PLG can be secreted in excess or there can be its deficiency.
Both can be congenital or acquired
Deficiency leads to the development of fibrin rich pseudo membrane
(as Fibrin is not degraded normally)
That Impairs the functions of the tissues/organs – Ligneous disease
It affects the eyes; GIT, Respiratory and female reproductive system
(Ligneous conjunctivitis).

19. Ligneous conjunctivitis

20. Ligneous conjunctivitis

21. Ligneous gingivitis

22. SK – the administration 1.5million U
SK is given I/V in 60 mint. as soon as possible after the onset of ST elevation in adults – 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 as it is bacterial product
Overdose (>1.5 millions U) Is treated with amino Caproic acid
150mg aspirin for 4 wks as adjuvant therapy after MIS (

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

24. SK – Contra indications
SK should not be given in:
CVS : severe/uncontrolled Hypertension
CNS : stroke and Cerebral neoplasm/ haemorrhage
Women : Pregnancy and delivery

25. Streptokinase – Contra indications Conti.
SK may not be given in :
Age : Children. Have ↓PLG /PLG deficiency and potential allergy to SK
Trauma : Recent surgery and trauma:
Recent history of peptic ulcer

26. 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 function

27. Significance of SK cont.
Preservation of lung function and restoration of blood flow
Can be used as Plasminogen activator
Best results with in 4 hours till 24 hours
Usual dose for MI is 1.5 million IU- I/V infusion in 60 minutes
(Infusion: contents of vial+ 100 ml of Normal saline/

28. Streptokinase