Anaphylactoid reaction after injection of alteplase

Purvis, J. G.; Booth, NualaA.; Wilson, CarolM.; Adgey, A. A. J.; Mccluskey, D.R.

doi:10.1016/0140-6736(93)91263-l

Cited by 25 publications

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“…The observation that orolingual angioedema, an uncommon but potentially serious adverse event, was more frequent among CASES patients (1.3%) than among patients receiving thrombolysis for myocardial infarction (0.02%) 43 is an important feature of this treatment surveillance study. The mechanisms of orolingual angioedema may be related to angiotensin-converting-enzyme inhibitors and the location of the infarction.…”

Section: Discussionmentioning

confidence: 99%

Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study

Hill¹

2005

Canadian Medical Association Journal

421

284

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Section: Discussionmentioning

confidence: 99%

Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study

Hill¹

2005

Canadian Medical Association Journal

421

284

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“…[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%.…”

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Biochemical Basis of Angioedema Associated With Recombinant Tissue Plasminogen Activator Treatment

Molinaro

Gervais

Adam

2002

Stroke

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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-Arg 9 -BK. The quantity of kinins generated by rtPA is similar to that observed during the activation of the contact system of plasma with a negatively charged surface, suggesting that it is physiologically relevant. The total amount of des-Arg 9 -BK liberated during the incubation period depends on the aminopeptidase P activity, its main degrading peptidase. Additionally, incubations using purified proteins of the fibrinolytic and the contact system pathways show that the rtPA kinin-forming capacity is mediated by plasmin. Conclusions-We conclude that rtPA used in vitro at a therapeutic concentration has the capacity to generate significant quantities of kinins from human plasma. This kinin-forming activity depends on the activation of the fibrinolytic pathway. These data suggest that angioedema associated with rtPA treatment of ischemic stroke results directly from plasmin-mediated release of BK. Key Words: angioneurotic edema Ⅲ kinins Ⅲ stroke Ⅲ tissue plasminogen activator S erious allergic reactions (anaphylactoid reactions or angioedema) have been observed during thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) (alteplase) used for the treatment of acute ischemic stroke, myocardial infarction, and deep vein thrombosis. 1-8 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%. This frequency is higher than that observed in patients treated with an ACE inhibitor for hypertension or heart failure (0.1% to 0.2%). 1,4,9 In these different clinical situations, angioedema has been attributed, at least in part, to bradykinin (BK).BK is the prototype of a family of powerful vasodilatory peptides, the kinins. BK is released from high-molecularweight kininogen (HK) when hydrolyzed by plasma kallikrein. This hydrolysis occurs, at least in vitro, when plasm...

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“…[1][2][3] Until now, specific antibodies against alteplase were not detected in blood samples obtained in these patients. [1][2][3] We report an anaphylactic reaction in a 70-year-old caucasian female who was treated with intravenous alteplase (Thomae) for thrombolysis of acute ischemic stroke 160 minutes after onset of a right-sided hemiparesis. There was no history of atopia, and except for untreated arterial hypertension, no relevant preexisting disease.…”

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confidence: 99%

“…Elevated total serum IgE levels were reported from patients with history of atopia and anaphylactoid reaction to alteplase, but specific antibodies to alteplase were not detected. 1,3 Therefore, the allergic etiology of anaphylactoid reactions following alteplase infusion was questioned, and a complement-mediated reaction was assumed. 1,3 Elevated levels of serum IgE are observed as a response to myocardial infarction and stroke and do not necessarily reflect an allergic reaction.…”

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confidence: 99%

“…1,3 Therefore, the allergic etiology of anaphylactoid reactions following alteplase infusion was questioned, and a complement-mediated reaction was assumed. 1,3 Elevated levels of serum IgE are observed as a response to myocardial infarction and stroke and do not necessarily reflect an allergic reaction. 4 However, the detection of specific IgE antibodies reactive with alteplase (anti-tPA IgE) in this patient could provide the first evidence of an anaphylactic-type reaction to alteplase in man.…”

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Evidence of Anaphylaxy After Alteplase Infusion

Rudolf

Grond

Prince

et al. 1999

Stroke

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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.

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Anaphylactoid reaction after injection of alteplase

Cited by 25 publications

References 0 publications

Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study

Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study

Biochemical Basis of Angioedema Associated With Recombinant Tissue Plasminogen Activator Treatment

Evidence of Anaphylaxy After Alteplase Infusion

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