Summary of Thrombolytics
Transcript for Thrombolytics
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.
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.
Now, during an injury, more coagulation factors get activated, which causes more tPA to get released by the endothelial cells, and more plasminogen gets converted to plasmin.
Plasmin then acts as a protease and cuts the fibrin into smaller pieces--allowing the trapped red blood cells and platelets to float away, letting the clot dissolve.
Now - although tPA is the main activator of plasmin - a few other proteins activate plasmin as well, including coagulation factors IXa, XIIa, kallikrein, and protein C.
Medicine has taken advantage of tPA, using it clinically as a “clot buster” because it’s used to dissolve pathological blood clots.
Streptokinase is derived from beta hemolytic bacteria proteins with a similar mechanism of action.
All thrombolytics are given via IV.
Alteplase, reteplase, and tenecteplase work by binding directly to fibrin proteins on the clot.
Next, they bind to nearby fibrin bound plasminogen, convert it to plasmin, which then cuts up the fibrin mesh.
Of these medications, tenecteplase has the highest affinity for fibrin, is resistant to plasminogen activator inhibitor 1 and has a longer half life.
In contrast, streptokinase works by binding to either circulating or fibrin bound plasminogen.
This creates a plasminogen-streptokinase complex that converts other plasminogen to plasmin, which then degrades the fibrin mesh.
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