Thrombolytic Agents

Thrombolytic Agents: Intro & MOA - Clot Busters 101

• Thrombolytics ("Clot Busters"): Drugs dissolving existing blood clots (thrombi).
• Primary Goal: Restore blood flow (reperfusion) in occluded vessels.
• Mechanism of Action (MOA):
  • Convert inactive plasminogen to active plasmin.
  • Plasmin (serine protease) degrades fibrin, the main structural component of a thrombus.
  • Leads to clot dissolution (thrombolysis).

⭐ Thrombolytics are time-sensitive; efficacy ↓ significantly with delay. E.g., for acute ischemic stroke, ideal window is within 3-4.5 hours of symptom onset.

Thrombolytic Agents: Classification & Drugs - The Clot‑Dissolving Crew

• Mechanism: Convert plasminogen to plasmin, dissolving existing thrombi.
• Classification & Key Drugs:
  • First Generation (Non-Fibrin Specific):
    • Streptokinase (SK): Bacterial origin; antigenic; systemic lytic state.
    • Urokinase (UK): Human enzyme; non-antigenic; systemic lytic state.
  • Second Generation (Fibrin Specific - "Clot Busters"):
    • Alteplase (rt-PA): Recombinant t-PA; short half-life (~5 min); IV infusion.
    • Reteplase (r-PA): Modified rt-PA; longer half-life; bolus dosing possible.
    • Tenecteplase (TNK-tPA): Engineered variant; longest half-life; single IV bolus; highest fibrin specificity.

    ⭐ Tenecteplase (TNK-tPA) boasts the highest fibrin specificity and longest half-life, allowing single IV bolus administration and resistance to PAI-1 (Plasminogen Activator Inhibitor-1).

Thrombolytic Agents: Indications & Regimens - When to Unleash Busters

• Goal: Rapid reperfusion.

• Indications:

  • STEMI: <12h onset (ideal <3h), ST ↑, no immediate PCI (<90-120min access).
  • Acute Ischemic Stroke (AIS): <4.5h onset (selected patients up to 6h); CT excludes bleed.
  • Massive PE: Hemodynamic instability (e.g., SBP <90mmHg).
  • Severe DVT/Acute limb ischemia (catheter-directed options).

• Regimens (Examples):

  • Alteplase (tPA): STEMI: accelerated IV (total 100mg). AIS: 0.9mg/kg (max 90mg).
  • Tenecteplase (TNK): Single IV bolus (weight-adjusted for STEMI).
  • Streptokinase: IV infusion (antigenic).

⭐ STEMI "door-to-needle" time target: < 30 minutes.

Thrombolytic Agents: Contraindications & Adverse Effects - Danger Zones & Bleed Risks

• Absolute Contraindications (STOP!):
  • Active internal bleeding; Significant closed-head/facial trauma (<3 mo)
  • Prior hemorrhagic stroke; Known intracranial AVM/neoplasm/aneurysm
  • Suspected aortic dissection; Uncontrolled HTN (>185/110 mmHg)
  • Ischemic stroke <3 mo (excl. current AIS <4.5h); Bleeding diathesis
• Relative Contraindications (CAUTION!):
  • Recent major surgery (<3 wks); Internal bleed (<2-4 wks)
  • Pregnancy; Current anticoagulant use (INR >1.7); Active PUD
  • Traumatic CPR (>10 min); Severe chronic HTN
• Adverse Effects (DANGER!):
  • Bleeding (intracranial, GI, GU) - most common & serious

  ⭐ Intracranial hemorrhage (ICH) is the most feared complication (~1% risk).

  • Allergic reactions (esp. streptokinase); Hypotension
  • Reperfusion arrhythmias; Cholesterol emboli (rare)

Thrombolytic Agents: Management of Bleeding - SOS for Oozes

📌 Mnemonic: SOS

• Stop thrombolytic agent immediately.
• Oozing control: Apply local pressure; maintain IV access.
• Supportive therapy for significant bleeding:
  • Blood products:
    • Fresh Frozen Plasma (FFP): Replaces clotting factors.
    • Cryoprecipitate: For fibrinogen, Factor VIII.
    • Platelet concentrates: If severe thrombocytopenia.
  • Antifibrinolytic agents:
    • Tranexamic acid (TXA): 10-15 mg/kg IV.
    • Epsilon Aminocaproic Acid (EACA).
• Monitor vitals, Hb, Hct, coagulation studies.

⭐ Tranexamic acid is generally preferred over EACA due to greater potency and longer half-life.

High‑Yield Points - ⚡ Biggest Takeaways

• Thrombolytics convert plasminogen to plasmin, causing fibrinolysis and clot breakdown.
• Indicated for acute MI, ischemic stroke (time-sensitive), and massive PE.
• Bleeding is the primary, most serious complication; monitor vigilantly.
• Contraindicated with active bleeding, recent major surgery, or hemorrhagic stroke history.
• Alteplase (t-PA) is fibrin-specific; Streptokinase is antigenic, may cause allergic reactions.
• Tenecteplase allows single bolus, has a longer half-life.
• Reversal agents include tranexamic acid or aminocaproic acid.