Evidence of Anaphylaxy After Alteplase Infusion

Abstract

Background and Purpose-Although alteplase, a recombinant tissue plasminogen activator (tPA), is structurally identical to endogenous tPA and therefore should not induce allergy, single cases of acute hypersensitivity reactions have been reported. Until now, specific antibodies against alteplase were not detected in blood samples obtained in these patients. Case Description-We report an anaphylactic reaction in a 70-year-old white female who was treated with intravenous alteplase for thrombolysis of acute ischemic stroke 160 minutes after onset of a right-sided hemiparesis. Thirty minutes after infusion of alteplase had been started, the patient suffered acute severe sinus tachycardia and hypotension, followed by cyanosis and loss of consciousness. The alteplase infusion was stopped, and following antiallergic therapy, tachycardia and hypotension resolved within 1 hour. The hemiparesis remained unaltered, but additional harm resulting from the hemodynamic complication was not observed. Serum samples analyzed with a radioimmunoprecipitation assay were negative for total antibodies to alteplase, but in a subsequent ELISA, both samples were positive for IgE antibodies to alteplase. Conclusions-The detection of specific IgE antibodies reactive with alteplase in this patient could provide the first evidence of an anaphylactic-type reaction to alteplase in man. Because previous exposure to alteplase can be excluded, the results suggest that this patient had preexisting antibodies that were cross-reactive with one or more epitopes of alteplase and therefore precipitated the anaphylactic-type reaction.

Guidelines for the Early Management of Patients With Ischemic Stroke

“…[17][18][19] Although the previous use of angiotensin-converting enzyme inhibitors is not a contraindication for the administration of rtPA, physicians should be aware of this potential complication. Presumably, medications used to treat angioedema would be indicated to treat a severely affected patient.…”

Repeated Mechanical Thrombectomy in Recurrent Large Vessel Occlusion Acute Ischemic Stroke

“…Although repeated systemic thrombolysis has been reported to be safe and efficient for patients presenting with a recurrent AIS [3,4,5,6], its use carries the limitations inherent to tissue plasminogen activator (t-PA) including bleeding risk mostly if the recurrence is relatively early on [15]. Intravenous t-PA re-administration has also been associated with severe immune reactions [16,17]. The majority of our patients had a cardioembolic etiology, which has been described in the literature to be more prone to stroke recurrence with a risk varying between 1 and 22% and a mean time between the 2 events of 12 days [18].…”

Biochemical Basis of Angioedema Associated With Recombinant Tissue Plasminogen Activator Treatment

“…Moreover, the equivalent kinin-forming capacity of both forms of rtPA constitutes an experimental argument against the fact that angioedema observed in stroke during fibrinolysis could be attributed to the arginine content of the injectable form, as previously suggested. [1][2][3][4][5][6][7][8] Our in vitro observations suggest that further characterization of the metabolic pathways (protease-antiprotease balance, metallopeptidases) controlling the release and the inactivation of BK and its active metabolite des-Arg 9 -BK in stroke patients who presented an rtPA-related angioedema is warranted. In conclusion, our data strongly suggest that, similar to other acute side effects of ACE inhibitor, such as angioedema, rtPA-associated angioedema seen in stroke patients may also result from BK release.…”

“…[1][2][3][4][5][6][7][8] A substantial number of these patients were simultaneously treated with an angiotensin I-converting enzyme (ACE) inhibitor. Angioedema, a local acute, potentially life-threatening inflammatory reaction, has been reported in patients with acute ischemic stroke treated with rtPA with a frequency of 1.9%.…”