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Septic transfusion reaction initial information received: 31-jul-2023, 09-aug-2023, 17-aug-2023, 18-aug-2023, 23-aug-2023 (in).Executive summary: the patient involved in this report is an 84-year-old female product complaint #: (b)(4); manufacturing blood center: (b)(6); intercept product code #: int2504b; collection instrument: trima; suspension medium: acda/terumo bct; apheresis kit lot #: not reported; pas intersol lot #: 22111701f1; product type: platelets; implicated component product code #: not reported; illuminator serial #: (b)(6); implicated unit donation id # (din#): (b)(6); intercept blood system for platelets processing set lot#: ce23a19l71.On 31-jul-2023, cerus received a spontaneous report of suspected bacillus cereus (b.Cereus) septic transfusion reaction with an intercept pc [pt: transmission of an infectious agent via product] from the cerus vp of global scientific and medical affairs.He was in communication with the chief medical officer (cmo) of haema ag in germany and relayed the information to cerus customer care team.The event of suspected b.Cereus septic transfusion reaction was associated with one of the two units of intercept platelet concentrate (pc) (din# (b)(6); implicated unit blood component processing set lot #: ce23a19l71) manufactured from a double apheresis platelet collection transfused to two patients.The other patient who received the implicated co-component intercept pc (din# (b)(6)) was reported to cerus at the same time (refer to (b)(4) for details about this patient's investigation).Additional information on the initial report was received on 09-aug-2023 from haema ag that indicated this incident has evolved into a serious fatal adverse event due to the outcome of death for this patient.Donor information: the donor of the implicated unit (din#: (b)(6)) was a 61-year-old, male with no history of positive bacterial detection with platelet donation.He donated a double apheresis platelet and a single apheresis plasma component on (b)(6) 2023.No further information about the donor was reported.Apheresis platelet and plasma samples from a subsequent donation on (b)(6) 2023 were cultured on (b)(6) 2023 with negative results on (b)(6) 2023.Gram stain was not performed.Haema ag uses descoderm, a 70% propanol skin disinfectant for blood donations.Implicated unit collection and manufacturing information: on (b)(6) 2023 from 13:02h to 14:09h, a double apheresis platelet and single apheresis plasma collection was performed on a trima (apheresis collection kit lot # was not reported) at (b)(6), germany.The apheresis platelets were suspended in acda/terumo bct platelet container (lot#: 23063010 expiration date: 01-mar-2025).On the same day, the implicated unit was treated with an intercept blood system dual storage (ds) processing set (product code #: int2504 b, processing set lot#: ce23a19l71, set expiration date: 31-dec-2024) and illuminated with the intercept illuminator serial number (b)(6) from 17:27h - 17:33h (3.5 hours after the end of collection) at (b)(6), germany.There were no device malfunctions of irregularities associated with the intercept treatment process reported by (b)(6), germany.On (b)(6) 2023, haema ag provided a summary of microbiological investigation that did not identify any environmental source of the b.Cereus.As part of the investigation, they performed skin swabs from the antecubital area of the donor arm, swab samples of external storage location, manufacturing site and have ongoing hygiene monitoring of blood donation center, manufacturing site and laboratory.There were no reports of b.Cereus contamination at haema ag in the last 3 years.Blood component(s) information: intercept pcs transfused to the patient on (b)(6) 2023 on (b)(6)2023 the residual bag of the implicated intercept pc (din# (b)(6)) was received at laboratory of haema ag unsealed along with the transfusion kit.On the same day, the residual bag was rinsed with sterile saline and the rinse solution was cultured and grew b.Cereus var.Cereus under aerobic and anaerobic conditions.The hours to positive blood culture results were reported as aerobic: 17:58h (6 h 40 min) and anaerobic: 17:16h (5 h 58 min), determined by the reporter as rapid growth.Antigram of the b.Cereus var.Cereus indicated sensitivity at standard dose against imipenem, meropenem, clindamycin, vancomycin linezolid and sensitivity at higher dose against levofloxacin.On (b)(6) 2023, the residual bag of a second unit of intercept pc (din# (b)(6)), collected from a different donor, also transfused to this patient during the same transfusion episode on (b)(6) 2023 was received at haema ag unsealed along with the transfusion kit.On the same day, the residual bag was rinsed with the same sterile saline and the rinse solution was cultured with negative result.Co-components of the implicated intercept pc on (b)(6) 2023 (day 5 of storage), the implicated co-component of intercept pc (din# (b)(6)) was transfused to another patient who subsequently experienced a suspected transfusion transmitted bacterial infection.Refer to (b)(6) for full details about this patient's investigation.The apheresis plasma co-component was quarantined, not transfused and cultured with negative result.Patient clinical course: this report involved an 84-year-old female patient with a history of multiple myeloma and pancytopenia, who experienced a serious fatal adverse event of suspected b.Cereus septic transfusion reaction following the transfusion of an intercept pc.The patient's pre-transfusion vitals were reported as unknown.The reporter indicated there was no evidence of infection or sepsis in the patient prior to the transfusion reaction.On (b)(6) 2023 at an unknown time the patient received the implicated intercept pc (din# (b)(6)) for pancytopenia, out-of-treatment myeloma.This transfusion episode took place at an outpatient transfusion center, thus limited clinical and laboratory information were obtainable for evaluation.The full unit of 199 milliliters (ml) was transfused and sometime either during or immediately after the transfusion, the patient developed symptoms suspected to be an allergic transfusion reaction and prednisolone was administered.On the same day at an unknown time, the patient received a second unit of intercept pc transfusion (din# (b)(6)), collected from a different donor, for the same indication.Reported indicated both transfusions were given through a central line.On (b)(6) 2023, the patient was hospitalized due to concerns for sepsis because of chills/rigors, tachycardia (~110/min) and elevated temperature (38.2 °c).Tazobactam/piperacillin were administered empirically.On the same day, two blood culture samples were collected from the patient at a venipuncture site and at the port.On (b)(6) 2023, the patient's blood culture results were reported as inconclusive due to discrepant results from venipuncture site (no organisms) versus the port (positive for b.Cereus).The patient's antibiotic regiment was changed to vancomycin after receiving the positive b.Cereus result from the port and she was diagnosed with sepsis.On (b)(6) 2023, the patient continued to be tachycardic with heart rate ranging between 100-150 bpm and high-grade fever above 39°c.On (b)(6) 2023 at an unknown time, the subject died due to sepsis associated with pancytopenia.On the same day, a saline rinse sample from the residual bag of the implicated intercept pc (din# (b)(6)) was collected and grew b.Cereus var.Cereus under aerobic and anaerobic conditions.Investigations: cerus investigation: on 01-aug-2023, cerus sent the transfusion reaction form ((b)(4)) to the representative at haema ag in germany to provide additional information.On 09-aug-2023, cerus received the completed transfusion reaction form ((b)(4)) from the representative at haema ag in germany.On 09-aug-2023, cerus completed a batch record review for (intercept product code #: int2504b, processing set lot#: ce23a19l71).The review of the batch records for the finished goods did not indicate any out-of-limit results during testing and controls.The product met all quality requirements and specifications at the time of release.(b)(4).There were no other complaints for lot ce23a19l71.(b)(4).On 17-aug-2023 and 18-aug-2023, cerus held two conference calls with dr.(b)(6), cmo and dr.(b)(6), senior manager hemovigilance at haema ag in germany.Additional clinical information and clarifications were obtained from haema ag regarding this adverse event report which have been incorporated in this narrative.Assessments: reporter assessment: 1.B.Cereus septic transfusion reaction with intercept pc [pt: transmission of an infectious agent via product]: the reporter assessed the event as fatal in severity, serious due to hospitalization and death.Causality was assessed as possible in relation to the intercept blood system for platelets device and possible in relation to the transfused intercept pc.Cerus medical reviewer (mr) assessment: 1.B.Cereus septic transfusion reaction with intercept pc [pt: transmission of an infectious agent via product]: the cerus mr assessed the event as serious due to hospitalization and death.The causality was assessed as unlikely in relation to a defect in the intercept blood system for platelets device since there were no indication of device malfunction, compromise of the platelet processing set or the pathogen inactivation process from haema ag and cerus.Bacillus cereus is a common environmental spore-forming organism that may be found on the skin.Bacillus cereus is effectively inactivated in the vegetative state but the spore form is known to be relatively resistant to the intercept process.This is stated in the manufacturers' technical data sheet.Transmission of bacillus cereus contaminated platelets is a rare but known complication, even when the intercept process is performed appropriately.The causality was assessed as possible in relation to the transfused intercept pc, although other causes cannot be definitively ruled out.The implicated intercept pc was transfused to the patient who developed clinical signs and symptoms concerning of an allergic transfusion reaction either during or immediately after transfusion.She was administered prednisolone empirically for the suspected allergic transfusion reaction, this may have contributed to attenuation of worsening symptoms in the immediate period after the initial recognition of a transfusion reaction.This may have also contributed to the delayed hospitalization and administration of antibiotics for the suspected septic transfusion reaction.Of note is the discrepant blood culture results from the patient's peripheral blood taken from a venipuncture site (negative for bacteria) vs.Blood taken from the port (positive for b.Cereus).Since the transfusion of the implicated intercept pc was administered through the port, it is possible that the patient's port was already colonized/contaminated by b.Cereus which then caused retrograde contamination of the platelet bag.Furthermore, the positive b.Cereus culture result from the residual platelet bag was from a sample taken 8 days after the transfusion because culture of residual blood bag is not routinely done at the transfusion center and there was no clinical suspicion of a septic transfusion reaction at the time of the transfusion episode.Since it was reported that the residual bag was left unsealed and had protracted storage time under unknown storage conditions, it is entirely possible the positive bag culture result is due to environmental contamination after the transfusion episode.Although the antigram for this implicated intercept pc demonstrated similar sensitivities as the implicated co-component intercept pc transfused to another patient (please reference (b)(4)), b.Cereus is a common environmental contaminant and genotyping of the strain isolated from the patient and the bags would be required to formally implicate the platelet product in a septic reaction.However, the patient's central line culture strain is not available for further analysis.The co-component apheresis plasma was cultured with negative result, arguing against gross contamination at the time of collection.Finally, propanol-based skin disinfectant is not a robust bactericidal agent against bacillus sp.Spores, thus the possibility of a true contamination event due to ineffective skin prep still exist but cannot be corroborated given the limited clinical information and lack of adequate residual platelet and patient positive culture samples for further analysis.The cerus medical reviewer considered the listedness for the event to be listed for transfused intercept blood system for platelets device and intercept pc based on applicable cerus safety reference information.
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