IC3 Fibrinolytics

Question 1

Which stage of hemostasis and thrombosis do fibrinolytic work on?

Answer 1

Clot stabilization
- they break down fibrin meshwork

Question 2

What is the role of tissue-type plasminogen activator (tPA)?

Answer 2

tPA is involved in endogenous thrombolysis

It activates the conversion of plasminogen to plasmin

Plasmin is an enzyme that mediates fibrinolysis via depolymerizing and breaking down the fibrin meshwork that stabilizes the thrombus

Question 3

How is tPA inactivated?

Answer 3

Inactivated via liver uptake of tPA-PAI-1

PAI-1: plasminogen activator inhibitor-1

Question 4

Alteplase MOA

Answer 4

Recombinant tPA, therefore able to accelerate the breakdown of clot by activating conversion of plasminogen to plasmin

Question 5

Advantage of Alteplase over endogenous tPA?

Answer 5

• longer plasma half-life
• bind preferentially to clot-associated plasminogen (compared to kinases)

Question 6

Adverse effects of Alteplase

Answer 6

• hypersensitivity and anaphylaxis
• bleeding
• ventricular arrhythmias, hypotension, edema (to monitor)
• cholesterol embolization, venous thromboembolism (VTE)

Question 7

Why might fibrinolytic cause VTE?

Answer 7

Mobilized fragments of the clot can embolize and form another clot

Question 8

Anti-fibrinolytic agents include:

Answer 8

• Tranexamic acid (e.g., used in menorrhagia)
• Aminocaproic acid

MOA: compete for lysine binding sites on plasminogen and plasmin, therefore blocking their interaction with fibrin

Question 9

Contraindications with fibrinolytic

Answer 9

• Active bleeding
• Prior intracranial hemorrhage
• Recent (within last 3m) intracranial or intraspinal surgery, serious head injury, stroke

Question 10

Caution with fibrinolytic

Answer 10

• Major surgery within 10d
• Risk of bleeding
• Cerebrovascular disease
• Mitral stenosis
• AFib
• Acute pericarditis
• Subacute endocarditis
• Presence of stable clot that could risk embolism
• History of conditions that may have clot

Question 11

DDIs with -teplases

Answer 11

• Incr risk of bleeding (antiplatelets, anticoagulants)
• Nitroglycerin may decrease alteplase levels

Question 12

In what situations may fibrinolytics be used?

Answer 12

In general fibrinolytic only used in situations whereby preexisting clots may cause high mortality (e.g., high risk PE, ACS, AIS)