264 Basophil-Mediated Anaphylaxis Triggered by Drug-Activated Complement Alternative Pathway Without Mastocyte's nor Immunoglobulins Involvement

BACKGROUND: It's well known that drugs may induce complement alternative pathway's activation. On the other hand there is evidence that anaphylaxis may occur in absence of IgE and IgG antibodies (so-called non-immune anaphylaxis). We determined the tryptase, complement and circulating immune complexes (CIC) levels to understand the nature of anaphylaxis occurred in a woman during high rate infusion of high concentrated iron. METHODS: A 46 years-old woman was admitted to our department because of mixed anemia, iron and cobalamin deficiency-related, started after a surgical intervention (bilio-pancreatic derivation) for heavy obesity occurred 7 years ago (starting Hgb = 7g/dl). Ev. hydroxicobalamin and iron infusions were planned, but during high rate (100 gtt/m’) infusion of high concentrated (0,5 mg/mL) iron, the patient suffered from discomfort, sweat and drop in blood pressure (BP 60/30). Blood samples were taken to evaluate tryptase, complement and CIC levels; standard treatment of anaphylaxis was started (im. epinephrine, inhaled O2 with steroids and beta-agonists, ev. electrolyte solution and vital parameters continuous evaluation). The shock resolution was gained in 3 hours. RESULTS: The level of tryptase was normal (4 mcg/mL; N.R.-Normal Range-= 1–20), while C3 and C4 were impaired (C3 = 65 mg/dl; N.R. = 75–165; C4 = 12 mg/dl; N.R. = 20–55). The search for CIC IgG, IgA, IgM was negative. Six months later the low rate (30 gtt/m’) low concentration (0,25 mg/mL) iron infusion was well tolerated by the patient, so excluding any IgE sensitization. CONCLUSIONS: We describe here for the first time a case of human anaphylaxis without mastocyte nor IgE involvement. The high infusion rate and hyperosmolality of hyperconcentrated drug caused complement alternative pathway's activation. The only cell type able to release anaphylaxis mediators other than mastocytes are the basophils, having anaphylotoxins receptors. So, we conclude that drug-induced complement alternative pathway's activation with consequent basophil's involvement was responsible for the patient's “non-immune” anaphylaxis.