Thrombolytics

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Thrombolytics

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USMLE® Step 2 style questions USMLE

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A 57-year-old man presents to the emergency department with his spouse due to right-sided weakness that began 30 minutes ago. According to the patient’s spouse, he had just returned home from work when he suddenly could not move his right arm or leg. Past medical and surgical history are unremarkable. Temperature is 37.2°C (99.0°F), pulse is 101/min, respirations are 21/min, and blood pressure is 172/95 mmHg. On physical examination, he has 0/5 strength in the right upper and right lower extremity with a left gaze preference. A CT-brain without contrast and chest x-ray are unremarkable. Which of the following is the most appropriate next step in managing this patient?  

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External References

First Aid

2024

2023

2022

2021

Alteplase (tPA) p. 418, 442

Tenecteplase (TNK-tPA) p. 418, 442

Tissue plasminogen activator (tPA)

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Thrombolytics, also called fibrinolytics, are medications that break up blood clots formed during hemostasis, where hemo means blood, and stasis means to halt or stop.

Hemostasis is divided into primary hemostasis, which involves the formation of a platelet plug at the site of an injured blood vessel, and secondary hemostasis, which involves multiple coagulation factors working together to form a fibrin mesh to stabilize the platelet plug.

Together, these two processes create a blood clot which stops the bleeding.

Sometimes blood clots could cause problems, like when they form in a coronary artery to cause a heart attack, or when they break off and travel to the brain and cause a stroke.

In these instances we can use thrombolytics to break up the clot and restore blood flow.

Thrombolytic medications were actually derived physiologically--from what is known as the fibrinolytic system.

Approximately two days after an injury occurs to a blood vessel and the blood clot forms, it’s time for the body to dissolve the blood clot through a process called fibrinolysis, which is the gradual degradation of the fibrin mesh.

To do this, a circulating protein produced by the liver called plasminogen, gets converted by an enzyme called tissue plasminogen activator, or tPA, into its active form called plasmin.

Normally, healthy endothelial cells release only tiny amounts of tPA, but when they’re exposed to coagulation factors produced during 2ndary hemostasis, Factor Xa and thrombin in particular, they start making lots of tPA.

But it’s important that plasmin activity doesn’t get out of hand, either.

So the endothelial cells also release plasminogen activator inhibitor 1 and antiplasmin which are proteins that bind and sequester tPA and plasmin respectively.

It’s all about always reaching that zen balance of coagulation and anticoagulation.

Summary

Thrombolytics, also known as clot-busting drugs, are a class of medications that are used to dissolve blood clots. These drugs work by converting plasminogen to plasmin, an enzyme that breaks down fibrin, a protein that forms the backbone of blood clots. By breaking down fibrin, thrombolytics can dissolve blood clots and restore blood flow to the affected area.

Thrombolytics include drugs like alteplase, reteplase, and tenecteplase, typically given for the acute management of pathological blood clots like in embolic or thrombotic strokes. The main side effect of thrombolytics is undue bleeding from other sites, including the injection sites, gastrointestinal bleeds, and hemorrhagic stroke. This is why they are contraindicated in hemorrhagic strokes and head trauma.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Nomograms" D. Nicoll , C. Mark Lu, S.J. McPhee (Eds.), Guide to Diagnostic Tests, 7e. McGraw-Hill (2017)
  5. "Overview of hemostasis" J.C. Aster, H. Bunn (Eds.), Pathophysiology of Blood Disorders, 2e. McGraw-Hill. (2016)
  6. "Fibrinolytics and Intraventricular Hemorrhage: A Systematic Review and Meta-analysis" Neurocritical Care (2019)
  7. "Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis" The Lancet Neurology (2019)
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