We report here a case of anaphylaxis caused by aprotinin-containing fibrin sealant that was locally applied in the surgical field during pulmonary surgery. Skin tests and BATs showed that the causative agent of anaphylaxis was aprotinin.
Fibrin sealants have many different uses across a broad range of surgeries, where they have proved successful in controlling bleeding, providing suture support, and for tissue sealing. The common components of fibrin sealants are fibrinogen, thrombin, aprotinin, and calcium chloride [7]. Aprotinin has been identified as a causative agent of anaphylaxis, and many cases of aprotinin-induced anaphylaxis have been reported [2, 4]. Indeed, the incidence of hypersensitivity reactions was previously reported to be 2.8% on re-exposure to aprotinin, although the observed rate of hypersensitivity reactions on primary exposure is less than 0.1% [8]. However, there have been only a limited number of reports on anaphylaxis following the topical use of fibrin sealant [2, 4, 9,10,11]. This could be related to the fact that fibrin sealant is a substance used by surgeons in the surgical field and is difficult for anesthesiologists to recognize as a cause of anaphylaxis.
A recently developed clinical scoring system can be helpful to determine whether symptoms are due to anaphylaxis [5]. After the diagnosis of anaphylaxis, allergological assessment is essential to identify the causative agent and prevent recurrences. Skin tests remain the gold standard for detection of the culprit drug [6, 12, 13]. However, skin tests carry the risk of recurrence of anaphylaxis, and the positive predictive value of skin tests is not 100%. Hence, there seems to be room for other in vitro tests, including BATs, to diagnose anaphylaxis [14]. BATs recently became generally accepted as an additional and reliable tool with high sensitivity and specificity to identify the causative agent of perioperative anaphylaxis [14,15,16]. BATs have been used for testing for allergic reactions to a wide variety of drugs, including neuromuscular blocking agents, antibiotics, iodinated radiocontrast media, opiates, and sugammadex [17,18,19,20]. However, only few cases of aprotinin-induced anaphylaxis have been validated by BATs. Indeed, aprotinin-specific IgE and/or IgG were used for the diagnoses in the previous reports of aprotinin-induced anaphylaxis [2, 4]. In this case, we performed BATs in addition to skin tests to identify the causative agent, and similar results were obtained with both tests. These results suggest that both mast cells and basophils were likely involved in the underlying mechanism of anaphylaxis. BATs are probably helpful for the diagnosis of aprotinin-induced anaphylaxis. Further, the combination of BATs and skin tests allows for the diagnosis of anaphylaxis with high accuracy.
In conclusion, we diagnosed aprotinin-induced anaphylaxis using both skin tests and BATs. The occurrence of anaphylaxis should be considered when changes in vital signs are observed after the use of fibrin sealant in the surgical field during anesthesia.