Chodirker: Reactions to alteplase in patients with acute thrombotic stroke [CMAJ

Reactions to alteplase in patients with acute thrombotic stroke

CMAJ 2000;163(4):387-8

See response from: M.D. Hill, et al

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Michael Hill and colleagues have made an important contribution by documenting the occurrence of serious adverse reactions to alteplase in patients treated for acute thrombotic stroke [Research].¹ I am concerned, however, by some of their comments.

Anaphylactic reactions and anaphylactoid reactions are distinct, and these terms should not be used interchangeably. Both are acute generalized reactions mediated by mast cell mediators such as histamine. With anaphylactic reactions, mast cell mediator release is triggered by IgE antibody to the causal agent (e.g., penicillin). With anaphylactoid reactions, mast cell mediator release is not mediated by IgE. This distinction has important diagnostic and management implications.

The authors suggest that their first patient "may have had an undiagnosed hereditary or acquired C1 esterase inhibitor deficiency." Angioedema due to this deficiency is not characteristically associated with urticaria, which this patient exhibited. C2 and C4 are the natural substrates for C1 esterase activity and are typically depleted during acute angioedema provoked by CI esterase inhibitor deficiency. Levels of C4 were reported to be normal in this patient, arguing strongly against CI esterase inhibitor deficiency.

The authors comment that their "treatment with antihistamines and corticosteroids has been empirical and is based on the treatment of angioedema associated with hereditary or acquired deficiency in C1 esterase inhibitor." Angioedema associated with this deficiency is notoriously resistant to treatment with antihistamines, corticosteroids and epinephrine. This refrac- toriness to conventional therapy is an important clue to the possibility of a deficiency in C1 esterase inhibitor. The only effective treatment of angioedema in this situation is perfusion with purified C1 esterase inhibitor, available from Canadian Blood Services. The most effective preventive measure is regular use of an attenuated androgen such as danazol.

The authors recommend caution treating patients receiving angiotensin-converting-enzyme inhibitors with alteplase because of the risk of angioedema. Angiotensin-converting-enzyme inhibitors are a well-documented cause of angioedema. Although published anecdotes have suggested that the risk of anaphylaxis or angioedema attributed to other agents is higher in patients taking an angiotensin-converting-enzyme inhibitor, this has not been firmly established. It is important to remember that the patient population most likely to suffer a stroke is also most likely to be taking an angiotensin-converting-enzyme inhibitor.

William B. Chodirker
Allergist and clinical immunologist
London Health Sciences Centre, University Campus
London, Ont.

Reference

1. Hill MD, Barber PA, Takahashi J, Demchuk AM, Feasby TE, Buchan AM. Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. CMAJ 2000;162(9):1281-4.