Biochemical basis of angioedema associated with recombinant tissue plasminogen activator treatment: an in vitro experimental approach.

Abstract

Angioedema has been reported during recombinant tissue plasminogen activator (rtPA) treatment of acute ischemic stroke, often with concomitant use of angiotensin I-converting enzyme inhibitor treatment. Angioedema has been partly attributed to the nonapeptide bradykinin (BK), although its precise role has been poorly documented until now. The purposes of this report are 2-fold. First, we sought to define and characterize the in vitro kinin-forming capacity of rtPA when incubated with human plasma at a concentration within the therapeutic concentration range of rtPA attained in blood in vivo during fibrinolysis. Second, we sought to define the mechanism by which rtPA liberates BK from purified human single-chain high-molecular-weight kininogen, a key constituent of the contact system of plasma and the precursor of BK.