MAUDE Adverse Event Report: CRYOLIFE, INC. ¿ KENNESAW BIOGLUE - UNKNOWN CONFIGURATION; GLUE,SURGICAL,ARTERIES

Model Number BG3510-5-G

Device Problem Biocompatibility (2886)

Patient Problems Atherosclerosis (1728); Calcium Deposits/Calcification (1758); Reaction (2414)

Event Type  Injury  

Manufacturer Narrative

This investigation is currently ongoing.Any additional information will be provided in the follow-up report.

Event Description

According to article, "anaphylaxis to bovine serum albumin tissue adhesive in a patient without meat allergy", a (b)(6)-year-old atopic man, was admitted to the hospital for an aortic aneurysm.A bentall operation was performed using a bioglue.He experienced an anaphylactic shock with bronchospasm and hypotension shortly after this application, requiring crystalloids, norepinephrine, epinephrin and salbutamol.A blood sample taken during this even showed an elevated serum tryptase level (18.5g/l).The patient was referred to our allergology department for evaluation.He had a history of allergic rhinitis to cat, but no food allergies.Skin prick test with cat, dog, hamster, guinea-pig and rabbit were positive.Specific ige (sige) were positive for fel d 1 (21.6 ku/l); fel d 2 (3.7 ku/l) and fel d 4 (10.7 ku/l) (immunocap, thermo fisher scientific, uppsala, sweden), but negative for bos d 6.Skin prick tests were performed using both components of bioglue, native bovine serum albumin (bsa) and glutaraldehyde.The test was positive for bsa (5 mm), negative for glutaraldehyde and the mix of both.In order to further elucidate the target of the patient¿s ige antibodies, we performed immunoblot inhibition assays on the bsa component of bioglue and commercial bsa (sigma-aldrich, diegem, belgium).Proteins were separated by coomassie stained sds-page or immunoblotted as reported (fig 1a) [3].Ige-reactivity was directed mostly to high (>100 kda) and low (35-40 kda) molecular weight components in bioglue and bsa samples.Reactivity could be completely abolished by inhibition with bsa (100 ¿g/ml), confirming that all reactivity was directed to the bsa component of bioglue.In order to further understand the discrepancy between a positive immunoblot to bsa and a negative ige test by immunocap, we assayed ige-binding to bsa in a native and denatured form (fig.1b).Bsa was denatured using 1% sds and 0.35 m ¿-mercaptoethanol and spotted onto a nitrocellulose membrane.Ige-reactivity to denatured cat serum albumin (csa), the bsa component of bioglue and bsa is much stronger than that to native albumin, suggesting that ige-binding is predominantly directed against non-conformational epitopes.This would explain a negative immunocap test with bos d 6.A similar case of anaphylactic shock to bioglue was reported in a patient who presented with pork-cat syndrome, but negative for bos d 6 [4].Our patient did not report any symptoms upon ingestion of meat but he owns a cat since several years and has a history of allergic rhinitis in the presence of cats.We hypothesize that fel d 2 cross-reactive epitopes on bsa would be exposed briefly to ige-antibodies during denaturation when mixing the two components, bsa and glutaraldehyde.Solidification of the mix and strong protein cross-linking would then preclude any further ige-binding and lead to asymptomatic further outcome.The severity of the reaction is probably due to the high concentration of bsa used in the product.A recent report on human serum albumin (hsa) induced anaphylaxis due to intravenous administration supports the idea that treated albumin could present structural changes capable of inducing sensitization and subsequent allergic responses upon administration.The patient was tolerant to human blood and plasma derivatives and did not present sige to animal serum albumins [5] the present case shows that patients with sige to fel d 2, even at low levels, may have a high risk of perioperative anaphylaxis upon using bioglue as tissue adhesive.Cat-allergic patients should be screened for sige to fel d 2 before undergoing thoracic surgery.Up to 14-23% of cat-allergic patients have been reported to be sensitized to fel d 2 and about 1-3% are likely to present a pork-cat syndrome [6].Despite the fact that surgical sealants composed of purified bovine serum albumin are widely used, this is only the second case reported in the literature.In addition to sige against fel d 2, other yet unidentified co-factors might lead to the severe reactions described in our case and by dewachter et al[4].The risk-benefit balance should be carefully assessed for each patient and alternative sealants considered.In conclusion, we report another case of perioperative anaphylaxis to bioglue.We confirm the importance of ige-screening for sensitization to fel d 2 in cat-allergic patients, but we also want to caution clinicians against the fact that a negative ige-test to bos d 6 and tolerance of bovine or porcine meat does not exclude a potential risk of reactivity to bsa tissue adhesives.".

Manufacturer Narrative

According to article, "anaphylaxis to bovine serum albumin tissue adhesive in a patient without meat allergy", a 67-year-old man underwent bentall procedure for aortic aneurysm.Went into anaphylactive shock shortly after application of bioglue.Allergy blood test for sensitization to fel d 2 allergen (cat sa serum) important in cat-allergic patients.1-3% of patients sensitized for fel d 2 allergen are likely to present this ¿pork-cat syndrome¿.A review of manufacturing records could not be performed as a definitive lot number was not provided by the complainant.No product was returned.If information is provided in the future, a supplemental report will be issued.A review of the available information was performed.According to article, "anaphylaxis to bovine serum albumin tissue adhesive in a patient without meat allergy" (hilger et al), 67-year-old man underwent bentall procedure for aortic aneurysm.Shortly after the application of bioglue the patient experience anaphylactic shock.Per the article, the patient had a history of allergic rhinitis to cat, but no food allergies.A skin prick test found the patient was allergic to bovine serum albumin (bsa) but not to glutaraldehyde or the mix of both components.An allergy blood test also found the patient had sensitization to fel d 2 allergen (cat sa serum).Given the information provided, anaphylactic shock due to the exposure of bioglue cannot be excluded.The patient was found to be allergic to bsa after further testing.The following is provided in the applicable bioglue instructions for use: "bioglue is not for patients with known sensitivity to materials of bovine origin." the patient was found to have an allergy to bsa, so an anaphylactic reaction to bioglue cannot be excluded.A review of the ifu shows adequate precautions and warnings provided about the potential for allergic reaction to materials of bovine origin.Root cause for this event is allergy to bsa.The patient was found to have an allergy to bsa, so an anaphylactic reaction to bioglue cannot be excluded.A review of the ifu shows adequate precautions and warning provided about the potential for allergic reaction to materials of bovine origin.Based on the available information, root cause for this event is allergy to bsa.This event does not identify additional hazards or modify the probability and severity of existing hazards.No further action required.This report is being submitted as required by federal regulations and does not constitute an admission that the device caused or contributed to the reported event.Furthermore, this report reflects the event as alleged by the complainant and does not imply that the information reported to cryolife is accurate or has been confirmed by cryolife.

Manufacturer Narrative

The following additional information was received january 19, 2021.The bentall procedure took place on (b)(6) 2018.The amount of product applied is unknown application did not occur in an infected area.According to the operative report; "placement after drying of bioglue on the coronary buttons and the base of the root.Arteriosclerosis was present as well as aortic calcifications.The patient had never been previously exposed to bioglue and has been doing well since." a search for previously distributed bioglue from the date of surgery back six months returned lot number 17egx001.A review of the new information was performed and does not alter or impact the original findings in any way.Additionally, manufacturing records for the bg3510-5-g lot number 17egx001 were reviewed and it was confirmed that all records were controlled, available for review, and met all specifications per the device master record.All lots passed functional testing and met release specifications.This report is being submitted as required by federal regulations and does not constitute an admission that the device caused or contributed to the reported event.Furthermore, this report reflects the event as alleged by the complainant and does not imply that the information reported to cryolife is accurate or has been confirmed by cryolife.

• Brand Name: BIOGLUE - UNKNOWN CONFIGURATION
• Type of Device: GLUE,SURGICAL,ARTERIES
• Manufacturer (Section D): CRYOLIFE, INC. ¿ KENNESAW; 1655 roberts blvd. nw; kennesaw GA 30144
• MDR Report Key: 10379026
• MDR Text Key: 202524888
• Report Number: 1063481-2020-00010
• Device Sequence Number: 1
• Product Code: MUQ
• Combination Product (y/n): N
• PMA/PMN Number: P010003
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,literature
• Type of Report: Initial,Followup,Followup
• Report Date: 02/19/2021

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: No Information
• Device Expiration Date: 10/21/2019
• Device Model Number: BG3510-5-G
• Device Lot Number: 17EGX001
• Was Device Available for Evaluation?: No
• Distributor Facility Aware Date: 07/27/2020
• Initial Date Manufacturer Received: 07/27/2020
• Initial Date FDA Received: 08/07/2020
• Supplement Dates Manufacturer Received: 07/27/2020; 07/27/2020
• Supplement Dates FDA Received: 10/08/2020; 02/19/2021
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Patient Outcome(s): Required Intervention
• Patient Age: 67 YR