Chapter 39  ·  Module 6

Thrombolytic Therapy and Procoagulant Agents

Thrombolytics, reversal agents, and hemostatic pharmacology at a glance

Abbreviations: tPA = tissue-type plasminogen activator  ·  PAI-1 = plasminogen activator inhibitor-1  ·  STEMI = ST-elevation myocardial infarction  ·  AIS = acute ischemic stroke  ·  PE = pulmonary embolism  ·  TXA = tranexamic acid  ·  EACA = epsilon-aminocaproic acid  ·  4F-PCC = four-factor prothrombin complex concentrate  ·  INR = international normalized ratio  ·  ICH = intracranial hemorrhage

Thrombolytic Agents

Agent Fibrin Specificity Half-Life Dosing Approved Indications
Alteplase High (fibrin-dependent) 3–5 min Weight-based infusion over 60–90 min STEMI, AIS (0–4.5 h), massive PE — universal coverage
Tenecteplase Highest; 80× PAI-1 resistant 20–24 min Single weight-based IV bolus STEMI (preferred); less non-cerebral bleeding vs alteplase
Reteplase Moderate 13–16 min Two fixed 10-unit boluses 30 min apart; no weight adjustment STEMI and AMI only; not for stroke or PE
Streptokinase None — systemic lytic state Variable 1.5 million units over 60 min STEMI only; antigenic; no repeat within 6–12 months; not for stroke

Anticoagulant Reversal Agents

Thrombolytic Reversal

Antifibrinolytics + Cryoprecipitate

  • Stop infusion immediately on suspected ICH
  • Cryoprecipitate 10 units IV: fibrinogen target ≥150 mg/dL
  • TXA 10–15 mg/kg IV over 10 min OR EACA 5 g load then 1 g/hr
  • TXA mechanism: blocks plasminogen lysine-binding sites on fibrin
  • TXA also reduces mortality in trauma (within 3 hours) and surgical blood loss

Heparin / Warfarin Reversal

Protamine & Vitamin K / 4F-PCC

  • UFH: protamine 1 mg per 100 units (last 2–3 h)
  • LMWH: protamine 1 mg per 1 mg enoxaparin; partial anti-Xa reversal only
  • Fondaparinux: no specific agent; 4F-PCC off-label
  • Warfarin life-threatening: 4F-PCC (INR-dosed) + IV vitamin K 10 mg
  • Warfarin non-urgent: oral vitamin K 2.5–5 mg

DOAC Reversal

Idarucizumab & Andexanet Alfa

  • Dabigatran: idarucizumab 5 g IV (two 2.5 g boluses); complete reversal in minutes
  • Apixaban / rivaroxaban: andexanet alfa (low or high dose per timing)
  • Edoxaban: 4F-PCC 50 units/kg (no approved specific agent)
  • All: 4F-PCC 50 units/kg is best non-specific alternative if specific agent unavailable
  • Resume anticoagulation when hemostasis achieved

Thrombolysis Time Windows and Selection Rules

STEMI: fibrinolysis if PCI not available within 120 min of first medical contact; benefit greatest within 3 hours; tenecteplase single bolus preferred; pharmacoinvasive strategy (coronary angiography 3 to 24 hours after) if successful lysis; rescue PCI if less than 50% ST resolution at 90 minutes. AIS: alteplase 0.9 mg/kg within 4.5 hours; confirm ischemic stroke by CT; blood pressure below 185/110 before treatment; mechanical thrombectomy for large vessel occlusion. Massive PE: alteplase 100 mg over 2 hours for hemodynamic instability; catheter-directed thrombolysis for intermediate-high risk with right ventricular dysfunction.