Thrombolytic Agents

Thrombolytics: MOA - Clot Demolition Crew

• Primary Goal: Rapid dissolution of existing intravascular thrombi by initiating fibrinolysis.
• Core Action: Convert plasminogen (inactive proenzyme) to plasmin (active enzyme). 📌 Plasmin Pulverizes Pathologic clots!
• Plasmin's Role: A serine protease that degrades the fibrin mesh of the clot into soluble fibrin degradation products (FDPs).

• Activators:
  • Endogenous: e.g., tissue Plasminogen Activator (t-PA).
  • Exogenous (Drugs): Directly/indirectly activate plasminogen.

⭐ Thrombolytics achieve their effect by converting plasminogen to plasmin, which then degrades fibrin clots.

Thrombolytics: Agents - Fibrin's Nightmare

Key agents used to dissolve intravascular clots by converting plasminogen to plasmin, which degrades fibrin.

📌 Mnemonic (Generations): Silly Unicorns Always Race Turtles. (1st: SK, UK; 2nd: Alteplase; 3rd: Reteplase, Tenecteplase).

Thrombolytics: Uses - Clots: Time to Go!

These drugs dissolve existing fibrin clots by converting plasminogen to plasmin. Administered IV.

Key Indications & Therapeutic Windows:

• Acute MI (STEMI):
  • Within <12 hours of onset (ideal <6 hours).
  • Door-to-needle time goal: <30 minutes.
  • PCI preferred if available timely (<90-120 min from first medical contact).
• Acute Ischemic Stroke:
  • IV Alteplase within <4.5 hours of symptom onset.

  ⭐ For acute ischemic stroke, IV thrombolysis (e.g., with alteplase) is indicated within 3 to 4.5 hours of symptom onset in eligible patients.

• Massive Pulmonary Embolism (PE):
  • If hemodynamically unstable.
• Extensive Deep Vein Thrombosis (DVT):
  • E.g., phlegmasia cerulea dolens, iliofemoral DVT.

📌 Mnemonic: "Time is Tissue!" Critical windows save lives.

• Stroke: <4.5h
• STEMI: <12h

Monitoring:

• Primary risk: Bleeding (intracranial, GI).
• Neuro status, vital signs, signs of reperfusion (e.g., arrhythmia resolution in MI).

Thrombolytics: Risks - Handle With Care!

• Adverse Effects:
  • Bleeding: Major risk (ICH, GI).
  • Allergy/Anaphylaxis (esp. Streptokinase).
  • Hypotension.

⭐ The most devastating adverse effect of thrombolytic therapy is intracranial hemorrhage (ICH); meticulous patient selection is crucial.

• Contraindications:

  Absolute	Relative
  Active bleed, Prior ICH	Severe HTN (>185/110 mmHg)
  Recent surgery/trauma (<3 wks)	Recent internal bleed (<2-4 wks)
  Intracranial neoplasm/AVM, Aortic dissection	Pregnancy, Active PUD, Anticoagulants (INR >1.7)

• Bleeding Management:
  • Stop thrombolytic.
  • Supportive care.
  • Reversal: Aminocaproic acid, Tranexamic acid, FFP, Cryoprecipitate.

High‑Yield Points - ⚡ Biggest Takeaways

• Mechanism: Convert plasminogen to plasmin for fibrinolysis.
• Examples: Streptokinase (antigenic), Alteplase (t-PA, fibrin-selective), Tenecteplase.
• Major adverse effect: Bleeding (e.g., intracranial hemorrhage).
• Antidotes: Aminocaproic acid or Tranexamic acid.
• Key indications: Acute MI, ischemic stroke (window period), PE.
• Contraindications: Active bleeding, recent surgery/trauma, hemorrhagic stroke history, severe uncontrolled HTN.