An Expert Report on Alteplase (rt-PA)

I. Executive Summary

Alteplase is a biosynthetic form of human tissue-type plasminogen activator (t-PA), a cornerstone thrombolytic agent used in the emergency management of acute thromboembolic events.[1] As a recombinant protein, it represents a significant achievement in biotechnology, providing a potent therapy for life-threatening conditions. Its primary, FDA-approved indications include the treatment of Acute Ischemic Stroke (AIS), Acute Myocardial Infarction (AMI) with ST-segment elevation, and Acute Massive Pulmonary Embolism (PE). A lower-dose formulation is also approved for restoring patency to occluded central venous access devices (CVADs).[2]

The therapeutic action of Alteplase is derived from its function as a serine protease. It exhibits relative fibrin-specificity, preferentially binding to fibrin within a thrombus and catalytically converting entrapped plasminogen into plasmin. Plasmin, in turn, degrades the fibrin matrix, leading to clot dissolution and restoration of blood flow.[1] The clinical utility of Alteplase is defined by a critical balance between this efficacy and a significant, inherent risk of hemorrhage, most notably life-threatening intracranial hemorrhage (ICH). This risk necessitates strict adherence to a narrow therapeutic window, rigorous patient selection criteria, and meticulous periprocedural monitoring.[1]