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 that form in the deep veins of the legs, for example, can break off and travel to 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. Tissue Plasminogen Activator Tissue Plasminogen Activator (TPA) is a protein that is naturally produced by the body. I t is a Serine Protease found on the endothelial cells(cell that lines the blood vessel). It helps to 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,

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