C4A and intracranial hemorrhage: Plasmin also activates the complement system and leads to the production of the anaphyloxins C3a, C4a, and C5a, which also cause mast cell degranulation and histamine release.4 Patient assessment should be done every 15 minutes during tPA infusion for signs of clinical deterioration indicating a possible intracranial hemorrhage, or for signs of angioedema.