| Model Number INT2230B |
| Device Problem
Adverse Event Without Identified Device or Use Problem (2993)
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| Patient Problem
Insufficient Information (4580)
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| Event Date 07/24/2021 |
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Event Type
Death
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Event Description
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Transfusion-transmitted bacterial infection [pt: transfusion of an infectious agent via product].Date cerus received: (b)(6) 2021 (in).The patient involved in this report is a (b)(6), black female product complaint #: (b)(4).Product code #: int2230b.Set lot #: ce21c08l71 (fenway amicus apheresis kit lot fa21e24129, pas lot fm21e04048) illuminator serial #: (b)(4).Din #: (b)(4).On 02-aug-2021, cerus received a spontaneous serious adverse event report (b)(4) of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] from (b)(6), a capa quality engineer at the (b)(6).The initial report was to notify cerus quality assurance (qa) of a transfusion reaction in a patient involving an intercept-treated platelet concentrate (pc) transfused at (b)(6) clinic and to report bacterial contamination in the intercept pc transfusion bag.The initial reporter received this information from dr.(b)(6), the regional medical director at the (b)(6) region on (b)(6) 2021 involving a patient in (b)(6) clinic.Further information on the initial report was received from the reporter (b)(6) subsequently on (b)(6) 2021.Platelet collection: on (b)(6) 2021, double platelet apheresis was initiated on the amicus apheresis separator at toledo blood donation center.The bacterial testing was not performed.Of note, there were four co-components from the same donor involved in this case.Two platelets, and two plasma units (under quarantine).The donor of the implicated unit was a (b)(6) b positive female with a history of two hundred and forty-nine donations (both rbc and platelets).On (b)(6) 2021, the implicated platelet unit (din: (b)(4)) was treated with an intercept blood system large volume (lv) processing set (product code : int2230b, set lot number: ce21c08l71, din#: (b)(4), manufacturer date: 08-mar-2021, expiration date: 31-aug-2022) and illuminated with the intercept blood system for platelets from 08:58h - 09:04h at the central (b)(6).The treatment report showed successful illumination with no indication of illuminator malfunction or irregularities.The implicated platelet unit was partially infused to the patient on (b)(6) 2021 as described in the clinical course below.On (b)(6) 2021 10:00h, two pathogen reduction platelet units manufactured by (b)(4) (expiration date: 24-jul-2021) were distributed to (b)(6) clinic by (b)(6).There were a total of five pathogen-reduced platelet productions in that shipment.Additional follow up was done with the consignee ((b)(6) clinic) to confirm if the other products in the shipment were transfused without incident, awaiting confirmation.Platelet bag was inspected before release to the patients and was documented to be "ok" in the ehr (electronic health record).Platelet shakers were sterilized subsequently but not cultured.On (b)(6) 2021, the other non-implicated unit was transfused fully to another patient at the same hospital ((b)(6) clinic) without any incident.The patient's blood was later cultured, and the result was negative.Patient's clinical course: this report involves a (b)(6), (b)(6) female patient who experienced a fatal serious adverse event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] following transfusion of intercept pc.The patient's medical history included hepatic cirrhosis, obesity, alcohol abuse, alcohol hepatitis, renal failure, liver failure and vaginal bleeding.Surgical history included trans-jugular liver biopsy ((b)(6) 2021).The patient's concomitant medications included ceftriaxone [ceftriaxone], vancomycin [vancomycin] and zosyn [piperacillin sodium, tazobactam sodium].On (b)(6) 2021, the patient presented to the (b)(6) clinic due to neck pain at the site of a recent trans-jugular liver biopsy performed on (b)(6) 2021, nausea, vomiting, increased jaundice, generalized weakness, shortness of breath on exertion, and bilateral lower extremity swelling.The patient was found to have acute kidney injury and developed acute generalized abdominal pain and was subsequently admitted to the hospital.During the initial workup for abdominal pain, the patient was found to have hematuria and oliguria.Menorrhagia was also noted, and the patient was transfused with a total of 8 units of red blood cells (rbc) from (b)(6) 2021 through (b)(6) 2021, without incident.The patient developed coagulopathy due to cirrhosis with thrombocytopenia and leukocytosis.On (b)(6) 2021, the patient was treated for suspicion of "spontaneous bacterial peritonitis" with a one- time dose of 2g of ceftriaxone.Blood cultures were collected from the patient, which showed no growth.On (b)(6) 2021, the patient was started on empiric antibiotics for a concern for sepsis.Vancomycin and zosyn were started due to rising white blood cell (wbc) count and declining clinical status.Blood cultures were collected from the patient, which showed no growth.On (b)(6) 2021, the patient's kidney function continued to decline, and she experienced episodes of hypotension related to vaginal bleeding and developed slowed mentation and drowsiness with asterixis.The patient was transferred to the medical intensive care unit (micu).A computed tomography (ct) scan revealed pneumonia and the urinalysis showed pyuria, however there was no clear evidence of urinary tract infection.Susceptibilities were provided with the organism ids.The patient began hemodialysis and was not deemed a candidate for a liver transplant.The patient's liver function continued to decline despite aggressive therapy.From (b)(6) 2021 through (b)(6) 2021, the patient was transfused with three units (confirmation of the number of units is pending) of intercept pc (din: (b)(4), issued on (b)(6) 2021) and (din: (b)(4), issued on (b)(6) 2021), seven units of rbcs, four units of plasma, and two pools of cryoprecipitate, without incident.On (b)(6) 2021, the patient was started on pressor support due to the progression of hypotension.Attempts were made to control vaginal bleeding, which were unsuccessful and pressor support requirements increased.On (b)(6) 2021, a feeding tube was placed.Vaginal bleeding continued despite attempts at medical management.Blood cultures were collected from the patient, which showed no growth.At 01:33h, the patient's lactate level was 2.6 mmol/l.On (b)(6) 2021, from 12:30h - 13:00h, the patient was transfused with 141 ml (out of 337ml) of the implicated intercept pc (din: (b)(4)), due to persistent thrombocytopenia and coagulopathy.At 13:00h, after receiving 141 ml of intercept pc, the patient experienced a serious adverse event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product].She became bradycardic, was treated with atropine, which was followed by a "pulseless electrical activity cardiac arrest." at 13:10h, the intercept pc transfusion was discontinued.At 13:25h, the patient became severely acidotic with a ph level of 7.14 and a lactate level of 10.6 mmol/l, which increased "sharply" following transfusion.Spontaneous circulation returned after two cycles of cardiopulmonary resuscitation (cpr), and the patient was given "various pressors" and was emergently intubated.Pressor support was continued, however, the patient's blood pressure remained labile.The patient was declared a do not resuscitate (dnr) by her family and died at 17:10h.According to the patient's death certificate, thrombocytopenia and alcohol-related liver disease were also listed as contributing factors to the fatal outcome.An autopsy was not performed.The intercept pc unit was returned to the blood bank with all tubing clamped and sealed on (b)(6) 2021.Clinicians did not expect the patient to have experienced a septic reaction, therefore, blood cultures post transfusion were not obtained, however, a culture was performed on her post-transfusion "type and screen" blood sample, which was "positive on 5 bottles for acinetobacter baumannii and leclercia adecarboxylata." the implicated unit was sampled at the cleveland clinic.The microbiology lab reported that the intercept pc was gram-stained, which identified gram-positive and gram-negative organisms, no polymorphonuclear leukocytes and no mononuclear cells.The culture report provided on (b)(6) 2021 also identified bacillus species, acinetobacter baumannii complex, leclercia adecarboxylata, and staphylococcus saprophyticus.Quantitative culture identified bacillus species (not bacillus anthracis) (2.05 x 10^7/ml count), staphylococcus saprophyticus (6.7 x10^6/ml count), acinetobacter baumannii complex and leclercia adecarboxylata.(all gram negatives 2.13 x 10^7/ml count).A clerical check performed in the blood bank revealed no discrepancies.The patient's pre-transfusion plasma was described as "yellow and clear" and post-transfusion plasma was described as "orange and clear".The patient's pre-transfusion and post-transfusion dat was weak positive for igg.The outcome of the event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] was reported as fatal.Investigations: cerus investigation: on 03-aug-2021, a review of the product release records for int2230b lot ce21c08l71 was performed.The released product met all functional and quality requirements.A review of the batch history indicated that there were no other product complaints reported for this lot.On 04-aug-2021, cerus qa received photographs of a residual plt bag, taken by (b)(6) at (b)(6) laboratory, from (b)(6) (arc).On 10-aug-2021, the residual bag, refrigerated residual platelets in sterile tube, frozen platelet sample and bacterial slants were shipped to cerus from (b)(6) at (b)(6)laboratory.On 16-aug-2021, cerus qa received the residual bag, storage container, bacterial slants, and samples for residual amotosalen analysis.The investigation results from the residual pc amotosalen level and storage container macroscopic inspection are summarized below: all residual platelets were drained from the transfusion bag and were taken up by absorbent material.Damage was observed on the front of the bag, the back of the container sheeting, the port, and on the inlet and sampling ports on the rear side of the container.Cerus qa was unable to identify the exact location of the leak, near the top of the seal and port of the container, as described by holland laboratory (below).This was due to the liquid having escaped the container during transport.On 19-aug-2021, cerus performed an analysis by hplc for residual amotosalen in the pc sample.The amotosalen concentration was 0.31 um, which is consistent with successful addition of amotosalen and illumination of the implicated unit.On 27-aug-2021, it was confirmed cerus sent four bacteria (leclercia adecarboxylata, staphylococcus saprophyticus, acinetobacter baumannii complex, and bacillus species) isolates from pc bag to charles river and midi labs for sequencing to confirm the initial species identification.At the time of this report, preliminary results were pending.Additional pathogen inactivation (pi) studies may be performed based on the sequencing results.(b)(6) clinic investigation: (b)(6) clinic performed a record review and confirmed that the patient did not have previous history of transfusion reaction and they sent the isolates from the patient's blood to (b)(6) clinic for dna sequencing (genotyping).The (b)(6) clinic also received isolates from (b)(6), to use as a comparison.The result is pending.Arc investigation: on 30-jul-2021, (b)(6) at the (b)(6) laboratory received the implicated intercept pc transfusion container and aliquots.Visual inspection of bag damage was conducted and the damage to the transfusion bag and container was described as two bag punctures on the front of the bag, one on a port and one at the top of the bag.Per (b)(6), a damage (a hole) to the port was caused by sampling by the (b)(6) clinic microbiology lab and they were informed of the punctures by arc.Additionally, she planned to send a sample of the leclercia adecarboxylata bacteria identified in this report and a sample from the (b)(6) case (from june 2020), to the university of (b)(6) for whole genome sequencing and to confirm if the leclercia spp.In both cases matched.Results are pending.On 02-aug-2021, (b)(6) notified fresenius kabi of the transfusion-transmitted bacterial infection.They responded indicating that they did not have any complaints about the apheresis collection set and platelet additive solution lots involved and zero remaining inventory in stock.On 06-aug-2021, microbiology testing was completed by (b)(6) laboratory (arc), which confirmed the results from the hospital microbiology laboratory with "100% accuracy".On 09-aug-2021, cerus received a copy of the arc fatality report sent to fda (arc case# (b)(4)).Arc's investigation from that report are summarized below: upon becoming aware of this case on 26-jul-2021, arc was able to procure the implicated bag from (b)(6) clinic, which was received on 29-jul-2021 and was transported to arc (b)(6) labs for additional bacterial testing.Two plasma products from the same donor were quarantined.Plasma unit (e7648v00/apf24rt2) was quarantined on (b)(6) 2021 at (b)(6) regional medical center.The other plasma unit (e7646v00/apf24rt1) was also quarantined in-house.Donor look back screening was also initiated.The donor has had 16 deferrals between 11-sep-2013 to 24-mar-2021 for various reasons such as medications, physical findings such as hemoglobin/hematocrit, and donation interval.She was also under surveillance 120 times from 07-mar-2012 to 19-jul-2021 for yes to transfusion related acute lung injury (trali) risk question and five times since 2014-2019 for hla antibodies non-reactive.The donor was contacted by the donor and client support center (dcsc) to perform a sepsis risk assessment, she denied any risk factors for sepsis.Bacterial slants were sent to the centers for disease control and prevention (cdc) for whole genome sequencing and local public health notifications.Results are pending from this lab.Dr.(b)(6) at the hospital also indicated they have reached out to arc regarding the (b)(6) case that happened previously (published in transfusion 2021;61(2): 641-648).The (b)(6) case included 3 similar bacteria: acinetobacter baumannii complex, leclercia adecarboxylata and (b)(6).A microscopic leak was also found near the port of the transfusion bag by fresenius kabi and confirmed by fenwal.Arc environmental testing: central (b)(4) facilities were scheduled to perform sampling on (b)(6) 2021.Results are pending.Fenwal investigation: on 16-aug-2021, cerus qa shipped the implicated intercept pc transfusion bag to fenwal for investigation.On 19-aug-2021, fenwal received an implicated storage container.The bag was visually inspected and underwater leak tested.On 27-aug-2021, cerus received a preliminary investigation report from fenwal.The implicated container was visually inspected, and a leak confirmed in the container sheeting on the label side of the container after the addition of water.A pressure test under water identified three additional leaks on the back side of the container.All leaks were in the sheeting: one was located below an outlet port that had a transfusion set spiked into the port; the other leaks were closer to the middle of the container.In addition, white marks and scratches were visible in the container sheeting, most prominently seen near the largest leak.Although the exact cause of the damage that caused these leaks could not be identified; these observations are not consistent with any identified manufacturing defect.Assessments: reporter assessment: the reporter assessed the event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] as fatal in severity and serious due to death.The causality was not reported.Cerus medical reviewer assessment: cerus medical reviewer concurs with the reporter's assessment of the event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product].The event was severe and serious due to being fatal.The cerus medical reviewer considers the causality for the event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] to be probable in relation to the transfused intercept-treated platelet concentrate but not related to a failure of the intercept blood system for platelets device.The cerus medical reviewer considered the expectedness for the event of transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] to be listed based on applicable cerus safety reference information for intercept-treated platelet concentrate.Previous studies at cerus have demonstrated that log reduction following pathogen inactivation by intercept is > 7 for acinetobacter baumannii, (b)(6) and leclercia adecarboxylata, combined.The intercept process was performed according to manufacturer's instructions.A split unit was transfused without incident.The report from fenwal investigation of the bag indicates significant breaches of integrity of the storage bag at multiple sites, most compatible with post manufacture damage to the bag, although the reviewer cannot rule out that some of these injuries occurred during transport and storage of the bag after the septic transfusion event.Investigations are underway to confirm that the bacterial strains involved are the same as those that have previously been implicated in prior similar cases (fridey et al.2020, transfusion 60(9):1960-1969; fadeyi et al.2021, transfusion 61(2):641-648).Overall, the data are most in keeping with post manufacture contamination of the intercept treated platelet component by environmental bacteria by means of holes in the bag.The holes in the bag were most likely caused by trauma to the bag during transport and storage after the intercept process.
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Event Description
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Cerus received additional follow up information on this event on 03-sep-2021, 08-sep-2021, 22-sep-2021 , 07-oct-2021, 20-jan-2022.Updates to product code : the patient involved in this report is a 39-years-old, black female.·product complaint #: (b)(4).·product code #: int2230b.·set lot #: ce21c08l71 (fenway amicus apheresis kit lot fa21e24129, pas lot fm21e04048).·illuminator serial #: (b)(6).·din #: (b)(4); arc product code: e8342v00.Further information on the initial report was received from the reporter (b)(6) (arc), dr.(b)(6) (arc), dr.(b)(6), head of transfusion medicine at (b)(6) clinic, dr.(b)(6), senior director, (b)(6), (b)(6), arc , (b)(6) laboratories ((b)(6)), and (b)(6) labs (b)(6).Updates to platelet collection : (new information) on (b)(6) 2021, 10.27h double platelet apheresis was initiated on the amicus apheresis separator at toledo blood donation center.The bacterial testing was not performed.Of note, there were four co-components from the same donor involved in this case.Two platelets, and two plasma units (under quarantine).The donor of the implicated unit (din: (b)(4); arc product code: e8342v00) was a 72-year-old b positive female with a history of two hundred and forty-nine donations (both rbc and platelets).(revised information) on (b)(6) 2021, the implicated platelet unit (din: (b)(4), arc product code: e8342v00 ) was split and treated with an intercept blood system large volume (lv) processing set (product code : int2230b, set lot number: ce21c08l71, din#: (b)(4), manufacturer date: 08-mar-2021, expiration date: 31-aug-2022) and illuminated with the intercept blood system for platelets.(new information) on (b)(6) 2021 10:00h, two pathogen reduction platelet units (din# (b)(4)) manufactured by central ohio region-columbus (expiration date: 24-jul-2021), were distributed to (b)(6).There were a total of five pathogen-reduced platelet productions in that shipment (dins: (b)(4) (implicated unit, and the co-(component ) two dins), (b)(4); collected on (b)(6) 2021 and treated with the intercept blood system on (b)(6) 2021).(revised information) on (b)(6) 2021, the non-implicated co-component #1.Updates to patients clinical course: (revised information) from (b)(6) 2021 through (b)(6) 2021, the patient was transfused with two units of intercept pc (din: (b)(4), issued on (b)(6) 2021) and (din: (b)(4), issued on (b)(6) 2021), seven units of rbcs, four units of plasma, and two pools of cryoprecipitate, without incident.Updates to cerus investigations : (new information) on (b)(6) 2021, a cerus representative evaluated the illuminator at the arc columbus.No issues or concerns were noted.(new information) on (b)(6) 2021, the residual bag (din: (b)(4); arc product code: e8342v00), refrigerated residual platelets in sterile tube, frozen platelet sample and bacterial slants were shipped to cerus from (b)(6).(revised information) on (b)(6) 2021, cerus received the residual bag, storage container, bacterial slants, and samples for residual amotosalen analysis.(new information) on (b)(6) 2022, cerus received final sequencing results from (b)(6): per cerus bacteriology, "additional sequencing data was received from (b)(6) confirming the identity of leclercia adecarboxylata, staphylococcus saprophyticus, acinetobacter baumannii complex (acinetobacter seifertii).Analysis of multi-locus sequence typing (mlst) compared these strains to the strains identified from (b)(6).(b)(6) clinic strain was indistinguishable from (b)(6) strain.S.Saprophyticus (b)(6) clinic strain had a different sequence type compared to s.Saprophyticus wake forest strain.L.Adecarboxylata cleveland clinic strain was indistinguishable from l.Adecarboxylata (b)(6) strain." this result confirmed a possible common source for two of the three pathogens (a.Seifertii and l.Adecarboxylata).Updates to cleveland clinic investigation: (b)(6) clinic performed a record review and confirmed that the patient did not have previous history of transfusion reaction and they sent the isolates from the patient's blood to (b)(6) clinic for dna sequencing (genotyping).The (b)(6) clinic also received isolates from (b)(6), to use as a comparison.The result were not reported.Updates to arc investigation: on (b)(6) 2021, (b)(6) laboratory received the implicated intercept pc transfusion container and aliquots.Visual inspection of bag damage was conducted and the damage to the transfusion bag and container was described as two bag punctures on the front of the bag, one below the port entry and one on lower quadrant.A microscopic assessment of the bag and formal leak testing was not conducted.Per (b)(6), a damage (a hole) to the port was caused by sampling by the (b)(6) clinic microbiology lab and they were informed of the punctures by arc.Additionally, she sent a sample of the leclercia adecarboxylata bacteria identified in this report and a sample from the (b)(6) case (from (b)(6) 2020) to the university of (b)(6) for whole genome sequencing and to confirm if the leclercia spp.In both cases matched.The results are were not reported.(new information) from (b)(6) 2021 to (b)(6) 2021 observation of the collection staff, manufacturing staff, and the quality associate at arc observed the collection staff perform an apheresis of the pc per procedure.The only concern noted was (bb) aseptic techniques."the staff kept putting his gloved hand with a first made up to his face as if he was going to sneeze covering his mouth." (new information) on (b)(6) 2021, microbiology testing was completed by (b)(6) laboratory (arc), which confirmed the results from the hospital microbiology laboratory with "(b)(4) accuracy".The microbiology testing identified staphylococcus saprophyticus, bacillus species (not anthracis), leclercia adecarboxylata (saccharose utilization negative), leclercia adecarboxylata (saccharose utilization positive), acinetobacter baumannii/calcoaceticus (phenylacetic acid assimilation positive) and acinetobacter baumannii/calcoaceticus (phenylacetic acid assimilation negative).(new information) on (b)(6) 2021, cerus received a copy of the arc fatality report sent to fda (arc case# (b)(4)).Arc's investigation from that report are summarized below: upon becoming aware of this case on (b)(6) 2021, arc was able to procure the implicated bag from (b)(6) clinic, which was received on (b)(6) 2021 and was transported to arc holland labs for additional bacterial testing.Two plasma products from the same donor were quarantined.Plasma unit ((b)(4)) was quarantined on (b)(6) 2021 at (b)(6) medical center.The other plasma unit ((b)(4)) was also quarantined in-house.Per dr.(b)(6), the plasma products were not transfused, and no further testing was conducted.As of (b)(6)2021, the two plasma products were quarantined in-house at the columbus manufacturing location.Bacterial slants were sent to the centers for disease control and prevention (cdc) for whole genome sequencing and local public health notifications.The results from this lab were not reported.(revised information) arc external regulatory correspondences are summarized below: on (b)(6) 2021, arc sent a preliminary investigation summary to the fda.Arc environmental testing: central ohio region-columbus manufacturing site- east board street facility and western lake erie collection site -- toledo facilities were sampled on (b)(6) 2021 and (b)(6)2021.On (b)(6) 2021, arc sent responses to information requested by the fda in regard to the septic transfusion reactions and included the preliminary investigation summaries for the non-fatal septic transfusion reactions from mid-atlantic region and great lakes-central ohio region.
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