Alteplase (tPA) is used in ischemic stroke within 4.5 hours of symptom onset. Which pharmacokinetic property distinguishes alteplase from streptokinase in terms of fibrin selectivity?

• A Alteplase is larger than streptokinase and cannot penetrate the thrombus; it acts on the thrombus surface only
• B Alteplase is fibrin-selective because it requires binding to fibrin-bound plasminogen to achieve high catalytic activity; in the absence of fibrin it has low activity and does not cause systemic fibrinolysis to the same degree as streptokinase ✓
• C Alteplase is not antigenic, unlike streptokinase, which means it can be re-administered for multiple episodes
• D Alteplase has a longer half-life than streptokinase, allowing single-bolus dosing with sustained lytic activity

Explanation

Alteplase (recombinant tPA) has a fibrin-binding domain (finger and kringle 2 domains) that allows it to bind fibrin within a thrombus. Upon binding fibrin-bound plasminogen, the catalytic efficiency (kcat/Km) of alteplase increases approximately 400-fold compared to acting on circulating free plasminogen. This fibrin selectivity means alteplase preferentially generates plasmin at the thrombus site, with minimal systemic plasminogen activation and less systemic fibrinogenolysis than streptokinase. However, alteplase is not completely fibrin-selective (systemic bleeding still occurs). Its half-life is very short (~4 minutes), requiring a bolus plus infusion protocol for stroke (0.9 mg/kg, max 90 mg, 10% as bolus).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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