The present invention provides a fusion protein suitable for dissolving a fibrin clot and a pharmaceutical composition containing the fusion protein. According to the present invention, there is provided a fusion protein of an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a prourokinase mutant, in which amino acid sequence of a plasmin in a kringle domain is modified so as to be less cleavable with a plasmin, and a pharmaceutical composition containing the fusion protein.

Provided herein are methods for safe and effective thrombolysis in therapy for human subjects with symptoms of a potential stroke or acute myocardial infarction (AMI) using a sequential administration of a low dose bolus of human tissue plasminogen activator (tPA) followed by an infusion of a mutant form of human pro-urokinase (proUK).

The present invention provides means and methods for treating MVT and associated and/or similar conditions. The invention therefore provides hybrid proteins for targeted delivery of plasminogen activators to platelet-VWF complexes, or alternatively to the site where these are located, in a fibrin-independent manner. The invention further provides therapeutic methods for conditions that can be prevented or treated by local delivery/stimulation of plasminogen activation to sites of microvascular occlusion.