Biochemical Basis of Angioedema Associated With Recombinant Tissue Plasminogen Activator Treatment

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Abstract
Background— 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. Summary of Report— When incubated with human plasma, in the presence of an angiotensin I–converting enzyme inhibitor, rtPA generates BK, which is further metabolized to des-Arg9-B...

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