Thrombolytic Agents

Question 1

What is the main endogenous enzyme for lysing clots? What is its zymogenic form?

Answer 1

Plasmin

Plasminogen is the inactive form.

Question 2

What are the two general types of activators for the conversion of plasminogen to plasmin?

Answer 2

tPA (tissue Plasminogen activator)

Streptokinase

Question 3

What drug inhibits the conversion of plasminogen to plasmin?

Answer 3

Aminocaproic Acid

Question 4

What are two chronic conditions that can cause defective fibrinolysis?

Answer 4

Diabetes and HTN

Question 5

Physiological activators of plasminogen conversion to plasmin

Answer 5

tPA
Urokinase
Factor 12a

Question 6

Physiological Inhibitors of plasminogen conversion to plasmin

Answer 6

PAI-1 (rapid acting plasminogen activator inhibitor)

TAFI (thrombin activatable fibrinolytic inhibitor)

Alpha-2-antiplasmin

Question 7

Why is time an important factor for the use of thrombolytic agents?

Answer 7

Waiting longer to administer thrombolytic agents allows Factor 13a (transamidase) to cross link and stabilize the fibrin clot, making it much more difficult to digest with plasmin

Question 8

What is a positive D dimer result indicative of?

Answer 8

DIC (disseminated intravascular coagulation) will have high D dimer

Could also diagnose DVT (small increase in D dimers)

Question 9

What does the D dimer test actually measure?

Answer 9

Fragments of fibrin formed by the action of plasmin on the polymerized fibrin monomers

Question 10

List some factors that PROMOTE fibrinolysis

Answer 10

Plasminogen incorporation into the thrombus via fibrin binding

Binding of tPA to fibrin

Local release of tPA
Enhanced tPA or urokinase activity in presence of fibrin
Protection of bound plasmin from antiplasmin

Question 11

List some factors that INHIBIT fibrinolysis

Answer 11

Fibrin crosslinking by Factor 13a

Binding of alpha-2-antiplasmin to fibrin

PAI-1 increase (plasminogen activator inhibitor)

Question 12

Degradation of the clot by thrombolytic agents will lead to….

Answer 12

• Reduction in thrombus size
• Reduction of fibrinogen levels
• Increase in fibrinogen and fibrin degradation products
• Antiplatelet activators

Question 13

What is the mechanism of streptokinase? (Very general)

Answer 13

Activates plasminogen to plasmin

Question 14

What are the recombinant tissue plasminogen activators?

Answer 14

Alteplase
Reteplase
Tenecteplase

Question 15

What is alteplase?

Answer 15

Recombinant form of Human t-PA

Question 16

What is reteplase?

Answer 16

Mutant form of human t-PA with a longer half life

Question 17

What is tenecteplase?

Answer 17

Mutant form of human t-PA with a long half life and high fibrin specificity

Question 18

What is the main difference in functionality with a streptokinase and a recombinant tissue plasminogen activator?

Answer 18

Less bleeding with t-PA

More bleeding with streptokinase

Question 19

Side effects and complications of Thrombolytic agents

Answer 19

Systemic lytic state
Bleeding is most likely

Re-occlusion
Stroke –> improper lysis of a clot may embolize

Question 20

Clinical Uses of Thrombolytic Agents

Answer 20

Acute MI (thrombus in coronary vessels)
Peripheral Arterial Occlusion (like a DVT)
Pulmonary Embolism
Thrombotic Stroke
Ischemic Stroke
Catheter Clearance

Question 21

When should thrombolytic agents NEVER be given?

Answer 21

Intracranial bleeding
Massive hemorrhage

The drugs will just cause more bleeding!

Question 22

What are the pharmacologic antagonists of thrombolytic agents?

Answer 22

• EACA (epsilon-aminocaproic acid)

- Tranexemic Acid

Question 23

Snake venoms have what kind of effect on coagulation?

Answer 23

Anticoagulant effects

Many venoms contain enzymes that digest fibrinogen

Question 24

When are thrombolytic antagonists used clinically?

Answer 24

Overdose of a thrombolytic drug