title: Hypersensitivity reactions associated with recombinant tissue-type plasminogen activator and urokinase.
abstract: Anaphylaxis or angioedema in response to recombinant tissue-type plasminogen activator or urokinase have been reported in only a few isolated cases. Both agents are endogenous proteins and thus considered non-antigenic. Activation of fibrinolysis may per se facilitate anaphylactoid reactions by pathophysiologic pathways that are not well understood. We report a unique case, review the literature and discuss implication for the clinician. The 25-year-old patient underwent thrombolytic treatment for extensive thrombosis of pelvic and deep lower extremity veins. The patient developed protracted anaphylactoid reactions during recombinant tissue-type plasminogen activator continuous intravenous infusion. After changing treatment to urokinase, the same symptoms recurred with more severe intensity, despite corticosteroid premedication. Symptoms resolved within hours after treatment with histamine receptor blockers. This unique observation, i.e. sequential occurrence of anaphylactoid reactions during recombinant tissue plasminogen activator and urokinase treatments, adds to existing evidence for an unspecific non-antigenic pathomechanism, and for a class effect of thrombolytics. Steroids do not prevent, but histamine receptor blockers seem to be an effective treatment of this unusual complication of thrombolytic therapy.
authors.affiliation: Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria. christoph.pechlaner@uibk.ac.at
authors.forename: C
authors.initials: C
authors.lastname: Pechlaner
authors.forename: E
authors.initials: E
authors.lastname: Knapp
authors.forename: C J
authors.initials: CJ
authors.lastname: Wiedermann
mesh_terms: D015746:Abdominal Pain; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D000925:Anticoagulants / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D014581:Urticaria; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D000305:Adrenal Cortex Hormones; D000925:Anticoagulants; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator