Blood clots, or thrombi, form normally to repair damaged blood vessels but can become problematic if they form in the wrong place. Tissue plasminogen activator (tPA) is an enzyme that plays a key role in dissolving blood clots by converting plasminogen to plasmin, which breaks down fibrin. tPA is used medically as a thrombolytic agent to treat conditions caused by abnormal clotting like heart attacks, strokes, and deep vein thrombosis. While lifesaving, tPA must be carefully administered due to risks of bleeding and is only used within narrow time windows after symptoms occur.

1. SUBMITTED BY,
ANIESH R
22PO04
II MSc BIOTECHNOLOGY

2. • Blood blots are clumps of blood that form when the body
is trying to repair a damged blood vessel.While they are
important for healinng, they can also be dangerous if they
form in the wrong place. Clots thatform in the deep veinsof the
legs,forexample,can breakoff and travelto the lungs,causing a
pulmonary embolism(arteries in lungs gets blocked).
HEMOSTASIS THROMBOSIS
If any damage to
blood vessel
(accident
/injury).
Stimulated by inappropriate
pathways and many risk factors can
increase the formation of abnormal
clot.
Abnormal Clotting Mechanism
Normal Clotting
Mechanism
BLOOD CLOTS

3. Risk Factors
The Major Risk factors that causes thrombosis includes,
• Myocardial infarction
• Diabetes
• Hypertension
• Artherosclerosis
• Other Major risk factor is the excessively increase in the level of
cholestrol which causes atheroma( fatty substance deposition in
blood) and when it ruptures, it activates coagulation factors as well as
clotting.

4. TissuePlasminogen Activator
• TissuePlasminogen Activator (TPA)is a protein that is naturally produced bythe
body.
• I t is a Serine Protease found on the endothelial cells(cell that lines the blood vessel).
• It helpsto break down blood clots by converting plasminogen into plasmin,which
dissolves fibrin.
• TPA is also used as a medication to treat blood clots.
• Its primary function includes catalyzing the conversion of plasminogen to plasmin,
the primary enzyme involved in dissolving blood clots.
• Recombinant biotechnology has allowed tPA to be manufactured in labs, and these
synthetic products are called recombinant tissue plasminogen activators (rtPA).
• Tissue plasminogen activator is a thrombolytic protease that converts inactive
plasminogen into active plasmin, which then degrades fibrin complexes, a
major component of a thrombus.

5. • A tPA is a drug used to break up a blood clot and restore blood flow to
the brain. A tPA can only be administered within a few hours after
stroke symptoms appear.
• It’s used in medicine as a thrombolytic agent to dissolve blood clots
that can cause conditions like heart attacks, strokes, and deep vein
thrombosis.
• Mechanism of Action:
When there’s an injury or damage to blood vessels, the body initiates
the clotting process to prevent excessive bleeding. However, in some
cases, these clots can become problematic. tPA plays a crucial role in
regulating this process. It converts the inactive form of plasminogen
into active plasmin, which is an enzyme responsible for breaking
down fibrin, a protein that forms the structure of blood clots.
• Administration:
tPA is typically administered intravenously by healthcare
professionals in controlled settings such as hospitals. The dosage and
timing are carefully monitored based on the patient’s condition and
medical history.

6. • The central enzyme component in this system is the glycoprotein plasminogen
present in plasma and most extravascular fluids.
• Plasminogen is a zymogen of a serine protease which, following partial cleavage by
a plasminogen activator, is converted into its active form plasmin.
• Plasmin is involved in a variety of biological processes, including cell migration,
growth, inflammation and tumour invasion, although its primary function is assumed
to be lysis of fibrin in the vasculature.
• Two plasminogen activators have been found in the human body, the tissue-type
plasminogen activator (t-PA) and the urinary-type activator (u-PA).
• t-PA is the principle activator of plasminogen in blood, whereas u-PA has its major
function in tissue-related proteolysis and is believed to only be secondary to t-PA in
the removal of intravascular fibrin.
Plasminogen activator inhibitors:
A number of inhibitors have been identified in plasma and other body fluids with
the capacity to inhibit t-PA, including PAI-1, PAI-2 (placenta plasminogen
activator inhibitor), PAI-3 (protein C inhibitor), protease nexin, α2-
macroglobulin, trypsin inhibitor and CI-inhibitor.

7. .
Plasminogen is the proenzyme of plasmin, whose primary target is the degradation of fibrin.
The activation of plasminogen to plasmin in blood is catalyzed by t-PA secreted from
endothelial cells. Fibrin provides binding sites for both plasminogen and t-PA, thereby
optimizing contact between them. This mechanism ensures a high concentration of
plasminogen and t-PA at the site of fibrin formation and localizes the action of plasmin. Further
regulation of the system is provided by PAI-1 and plasmin inhibitor. Free t-PA, as well as
complexed t-PA/PAI-1, is cleared from the circulation by receptors in the liver.
The fibrinolytic system in vivo

9. Medical Use
The tPA is used as a thrombolytic agent in medicine to treat conditions where
blood clots obstruct blood flow. The most common applications include:
• Heart Attacks (Myocardial Infarctions): tPA can be administered to dissolve
blood clots in the coronary arteries, helping to restore blood flow to the heart
muscle. In this case the drug should be given within 12 hours after attack.
• In case of Acute thrombotic stroke the drug should be given within 3 hours if
not the drug is ineffective.
• Ischemic Strokes: It’s used to treat strokes caused by blood clots in the brain,
aiming to restore normal blood flow and minimize brain damage.
• Deep Vein Thrombosis (DVT): tPA can be used to dissolve blood clots in deep
veins, reducing the risk of complications like pulmonary embolism.

10. • Considerations:
While tPA can be lifesaving in certain situations, it’s essential to be
cautious as it carries potential risks and side effects, including
bleeding complications. Therefore, its use requires careful evaluation
by medical experts to balance the benefits and risks for each patient,
The side effects are.,
 Haemorrhage(Bleeding)
It can be controlled and prevented by antifibrinolytic agent like
Tranexamic acid
 Skin Rashes
 Itching
 Fever
 Headache
 Dizziness
 Hypotension

11. Contraindications
This drug is used as a lifesaver medicine even though it should be avoided
to person’s like
• High Blood Pressure >175/110 mm Hg
• Pregnancy
• Diabetic retinopathy
• After any major surgeries
• Gastric bleeding
• Acute pericarditis
• Cerebrovascular disease
• Elders of >75 age
tPA Medication used
• Alteplase
• Reteplase
• Tenecteplase
• Streptokinase.
• Urokinase
• Anistreplase

12. Conclusion
In summary, tissue plasminogen activator (tPA) is a critical enzyme that plays a
key role in dissolving blood clots.
Its medical use is vital in treating conditions involving abnormal clot formation,
but its administration should always be carried out by trained healthcare
professionals in a controlled environment due to the potential for serious side
effects.
Time is of the essence in many cases where tPA is used, as early intervention
can greatly improve outcomes.
Tissue plasminogen activator (tPA) primarily plays a role in the physiological
process of fibrinolysis, which is the breakdown of blood clots in the body.
While it is not directly involved in biotransformation, which typically refers to
the chemical modification of substances in the body,

13. References
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• Intra-Arterial Alteplase Thrombolysis during Mechanical Thrombectomy
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Smolenski AM, Tsimpas A, Ashley WW.
• Tissue plasminogen activator: an evaluation of clinical efficacy in acute
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Riemersma LB, Clements SD.
• Thrombolytic therapy in pulmonary embolism. Indications and therapeutic
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Niedermeyer J, Meissner E, Fabel H.
• Textbook on Pharmaceutical Biotechnology Fundamentals and
Applications written by Daan J. A. Crommelin, Robert D. Sindelar, Bernd
Meibohm.