How Does Tissue Plasminogen Activator Work

Tissue plasminogen activator (tPA) is a widely used drug for thrombolytic therapy. It is given when a patient experience a heart attack caused by a blood clot. The blood clot is dissolved/broken down by the action of tissue plasminogen activator. The tissue plasminogen activator is administrated intravenously (IV) within 3-4.5 hours after a shock. They activate plasminogen to become plasmin that breaks down cross-links in fibrin. The mechanism of action of tissue plasminogen activator in dissolving blood clots is described in this article. 

Key Areas Covered

1. What is Tissue Plasminogen Activator
     – Definition, Structure, Function
2. How Does Tissue Plasminogen Activator Work
    – Mechanism of Action of Tissue Plasminogen Activator

Key Terms: Blood Clot, Fibrin, Fibrinolytic Drugs,  Plasmin, Plasminogen, Tissue Plasminogen Activator (tPA)

How Does Tissue Plasminogen Activator Work - Infographics

What is Tissue Plasminogen Activator

Tissue plasminogen activator is one of the three main classes of fibrinolytic drugs that activate plasminogen. It is used to treat cerebrovascular thrombotic stroke, acute myocardial infarction, and pulmonary embolism. Tissue plasminogen activator can also be found in the endothelial cells. It is a type of serine protease that catalyzes the conversion of plasminogen into plasmin. It is produced in vitro by recombinant DNA technology and is used in clinical medicine as a drug. The structure of tissue plasminogen activator is shown in figure 1.

How Does Tissue Plasminogen Activator Work

Figure 1: Tissue Plasminogen Activator

How Does Tissue Plasminogen Activator Work

Blood clots may occur in any vascular bed due to the activation of platelets. Blood clots in cerebral, coronary or pulmonary vessels can block blood supply to the important parts of the brain and heart. This could be life-threatening and should be treated soon. If not, corresponding tissues may die due to lack of oxygen.

Tissue plasminogen activator dissolves blood clots by activating plasminogen. It binds to the fibrin on the surface of the blood clot, activating the fibrin-bound plasminogen. Plasminogen is cleaved into plasmin, the active form of the proteolytic enzyme. Plasmin cleaves the cross-links between fibrin molecules. Since fibrin is cleaved off into individual fibrin molecules, the blood clot also dissolves. The mechanism of action of tissue plasminogen activator is shown in figure 2.

How Does Tissue Plasminogen Activator Work_Figure 2

Figure 2: Mechanism of Action of Tissue Plasminogen Activator

However, tissue plasminogen activator should not be administrated under the conditions listed below.

  1. Head injury
  2. A history of bleeding problems
  3. Bleeding ulcers
  4. Pregnancy
  5. Recent surgery
  6. Taking blood thinning medications
  7. Recent trauma
  8. Uncontrolled high blood pressure

Conclusion

Tissue plasminogen activator is a fibrinolytic drug used to dissolve blood clots inside vessels. It binds to the plasminogen associated with fibrin on the surface of the blood clot, activating it. Plasmin is the active form of plasminogen that cleaves the cross-links between fibrin molecules. This leads the blood clot to dissolve. 

Reference:

1.Klabunde E. R., “Thrombolytic (Fibrinolytic) Drugs.” Cardiovascular Pharmacology Concepts,  .

Image Courtesy:

1. “T-PA” By MedicineFTWq – Own work via
2. “Tpa pathways” By Djain2 – Own work via

About the Author: Lakna

Lakna, a graduate in Molecular Biology & Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things

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