title: Controlled insect-sting challenge in 55 patients: correlation between activation of plasminogen and the development of anaphylactic shock.
abstract: The pathogenesis of anaphylactic shock is not completely understood. Mast cell degranulation products may stimulate endothelial cells, leading to activation of fibrinolytic and coagulation systems. We investigated the activation of these systems in insect-sting anaphylaxis. Fifty-five patients with a previous insect-sting anaphylactic reaction and 8 volunteers were challenged with an in-hospital sting. Plasma levels of von Willebrand factor (vWF), coagulation, and fibrinolytic parameters were assessed. After the sting challenge, 20 patients developed anaphylactic symptoms, 7 of whom developed hypotension. In only these 7 patients, but not in the volunteers or in the other patients with no or mild anaphylactic symptoms, vWF levels increased from 107% +/- 33% (mean +/- SD) before, to 235% +/- 134% 60 minutes after the onset of clinical symptoms. This increase of vWF was accompanied by an increase of circulating tissue-type plasminogen-activator (tPA) levels from 5 +/- 3 micrograms/L to 50 +/- 59 micrograms/L and of plasminogen-alpha 2-antiplasmin complex (PAP-c) levels from 6 +/- 3 nmol/L to 297 +/- 225 nmol/L. Both tPA and PAP-c levels peaked 5 minutes after the onset of clinical symptoms. Such increases of tPA and PAP-c were not observed in the volunteers or in the patients who did not develop shock. The increase of tPA and PAP-c levels in the hypotensive patients correlated positively with the degree of mast cell degranulation and inversely with the mean arterial pressure. We conclude that activation of plasminogen may be involved in the pathogenesis of anaphylactic shock induced by insect venom.
authors.affiliation: Department of Internal Medicine, Eemland Hospital, Amersfoort, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: van der Linden
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: A
authors.initials: A
authors.lastname: Struyvenberg
authors.forename: D
authors.initials: D
authors.lastname: Roem
authors.forename: M C
authors.initials: MC
authors.lastname: Brouwer
authors.forename: J P
authors.initials: JP
authors.lastname: de Boer
authors.forename: J K
authors.initials: JK
authors.lastname: van der Zwan
mesh_terms: D000328:Adult; D000707:Anaphylaxis / Q000097:blood* / Q000276:immunology; D000818:Animals; D000933:Antifibrinolytic Agents; D001516:Bees; D001733:Bites and Stings / Q000097:blood* / Q000276:immunology; D005260:Female; D005341:Fibrinolysin / Q000032:analysis; D005342:Fibrinolysis; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D010958:Plasminogen / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D014863:Wasps; D000979:alpha-2-Antiplasmin / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000933:Antifibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D014841:von Willebrand Factor; D007073:Immunoglobulin E; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator