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Cerus is reporting this case of a non-serious adverse event because of similar cases involving environmental bacterial contamination of platelet components that had been successfully treated with the intercept blood system for platelets.Febrile episode [pt: febrile non-haemolytic transfusion reaction]; suspected transfusion transmitted bacterial infection [pt: transmission of infectious agent via product] date cerus received: (b)(6) 2021 (in).The patient is a (b)(6), male.Product complaint #: (b)(4).Product code #: int2230b.Set lot #: ce21d02l71 (amicus lot #fa21f14169 / pas intersol lot # fm21f11033) illuminator serial #: (b)(4).On (b)(6) 2021, cerus received a spontaneous report of a patient with non-serious transfusion reactions ((b)(4)) of a suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] and of a febrile episode [pt: febrile non-haemolytic transfusion reaction] during transfusion from (b)(6), a capa quality engineer/capa systems from the (b)(6) - biomedical headquarters quality, safety and regulatory affairs in (b)(6).(b)(6) received this information via a phone call with the primary reporter at (b)(6) hospital in (b)(6) on (b)(6) 2021.The initial report was to notify cerus of a possible transfusion reaction in a patient, involving an intercept treated platelet concentrate (pc) transfusion, in which the patient experienced a febrile episode during intercept pc transfusion and, acinetobacter baumannii/calcoaceticus complex and a bacillus sp.(not anthracis) isolation from a pathogen reduced (pr) platelet product (din #: (b)(4); arc's product code: e8342v00), at (b)(6) hospital.Further information on the initial report was received from the initial reporter (b)(6), arc - senior director, transfusion innovation, and (b)(6), (b)(4) customer, supplier & physical controls quality manager on (b)(6) 2021.Platelet collection: on (b)(6) 2021 10:11h, a double apheresis leukoreduced platelet collection was performed at the (b)(6) blood donation center - (b)(6) region in (b)(6).The type of platelet collection was reported as allogeneic platelets and the collection instrument was fenwal amicus apheresis machine.The platelets were collected from an a positive, (b)(6) male, did: 30ymdt2.There was no bacterial detection test performed on the donor's blood pre- or post- donation.The platelet collection was divided into 2 bags.On (b)(6) 2021, each of the two bags resulting from the double apheresis leukoreduced platelet collection was treated at the (b)(6) facility with an intercept blood system large volume storage (lv) processing set (processing set product code/set lot number: int2230b/ ce21d02l71) and illuminated simultaneously with intercept illuminator serial number (b)(4) from 09:56h -10:03h.Intercept treatment resulted in two pathogen reduced platelet components: din: (b)(4); implicated unit blood product code e8342v00; co-component unit blood product code e8341v00.The treatment reports of the implicated unit and the co-component showed successful illumination with no indication of illuminator malfunction or irregularities.On (b)(6) 2021, the two pathogen-reduced platelet (implicated unit and co-component expiration date: 19-aug-2021), manufactured by (b)(4) region were distributed by (b)(4) region to (b)(6) hospital.It was reported the non-implicated co-component pc (arc's product code e8341v00) from this collection was transfused at the same facility on an unknown date to a different patient, with no adverse reaction noted.Patient's clinical course: this report involves a (b)(6) a positive male patient, who experienced a non-serious event of febrile episode [pt: febrile non-haemolytic transfusion reaction] and the event of suspected transfusion-transmitted bacterial infection (ttbi) [pt: transmission of an infectious agent via product] following a transfusion of an intercept pc.The patient's concurrent condition included acute myelomonocytic leukemia (treatment with chemotherapy) and neutropenic fevers.The patient's concomitant medication included unspecified broad-spectrum antibiotics.The patient did not have a documented history of transfusion reaction prior to the reported event.On an unspecified date, the patient completed chemotherapy for acute myelomonocytic leukemia.He presented with neutropenia and a fever attributed to sepsis of an unknown etiology.Subsequently, the patient was admitted to the hospital for neutropenic fevers.Prior to the patient's pc transfusion, a bacterial culture (date and time pending) was performed on the patient's peripheral blood sample, which showed no growth, and the source of presumed infection was unknown.On (b)(6) 2021 14:41h, the patient started to receive the implicated unit of intercept treated platelet concentrate (pc) (leukoreduced) after 3 days of storage for thrombocytopenia.At 15:05h, after receiving 200 milliliters (ml) of intercept pc, the patient experienced the suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] and a febrile episode [pt: febrile nonhaemolytic transfusion reaction].The patient's temperature increased from 99.0°f (pre-transfusion) to 101.0°f.The transfusion was discontinued due to the transfusion reaction.The treatment for this event is being queried at this time.At 16:31h, (post transfusion) the primary residual component bag was sampled for bacterial culture through a bag port, however, the volume cultured was unknown.At 18:49h, after the transfusion was stopped, the patient's temperature decreased to 98.4°f.No other symptoms or changes in vital signs were noted.Per the reporter, the transfusion bag was connected and disconnected through a peripheral vein, not central venous catheter.On the same day, the patient's post-transfusion peripheral blood culture was drawn and showed no growth on (b)(6) 2021.The patient's clinical outcome within 24 hours of the reactions was reported as "unchanged".On an unreported date and time (query pending), a gram stain was performed on a sample from the primary residual platelet transfusion bag with a negative result.On (b)(6) 2021 14:36h, the bacterial culture of the primary residual bag collected on (b)(6)-2021 became positive.On(b)(6) 2021, the sample from the platelet transfusion bag showed growth of acinetobacter baumannii/calcoaceticus complex and bacillus sp.(not anthracis).There was not an attribution of the contamination to retrograde contamination.The attribution was indeterminate.Per the reporter, a contamination of the product bag during patient phlebotomy seemed very unlikely.The patient's vital signs pre-transfusion and during the event of suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] included: the patient's pre-transfusion vital signs: body temperature: 99.0°f blood pressure: unknown pulse rate: unknown respiratory rate: not reported.The patient's vital signs during the transfusion reaction: body temperature: 101.0°f blood pressure: unknown pulse rate: unknown respiratory rate: not reported.The patient's transfusion of intercept pc was not resumed.The outcome of the event of the suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] and the event of febrile episode [pt: febrile non-haemolytic transfusion reaction] were not reported, however, the febrile episode resolved shortly after the transfusion was stopped.The patient continued to have intermittent (neutropenic) fevers in the days after this transfusion episode.The treatment for neutropenic fevers and a blood culture (if obtained) results are pending.As of (b)(6) 2021, the patient remained hospitalized.Cerus investigation: a batch record review for int2230b set lot number ce21d02l71 (manufacture date 02-apr-2021, expiration date: 30-sep-2021) was performed.The released product met all functional and quality requirements.A review of the batch history indicated that there have been no other complaints reported for this product.On (b)(6) 2021, cerus qa received photographs of the residual platelet bag, taken by (b)(6) at (b)(6) laboratory, from (b)(6) (arc).(b)(6) hospital investigation: a routine transfusion reaction workup was performed to include clerical check of the transfusion, appearance of returned blood bag and contents and the appearance of returned solutions, tubing and filters were correct and normal.Arc investigation: on an unspecified date, the implicated intercept pc was returned by the hospital to the blood blank in a sealed biohazard bag after the transfusion reaction.On (b)(6) 2021, (b)(6) at the (b)(6) laboratory received the implicated intercept pc transfusion bag.Visual inspection of bag damage was conducted and the damage to the transfusion bag was described as a microscopic leak on the front of the bag at the bottom port (indicated by the platelets on the brown paper towel after being manually pressure tested).It was reported that the bag, the platelet sample and slants would be sent to cerus once the bacteria are isolated and confirmed.The unit was inspected for clerical errors and discoloration.No clerical errors were found, and the unit appeared to be a normal platelet product.Environmental testing: on (b)(6) 2021, sampling was scheduled to occur at the (b)(4) main site (manufacturing).(b)(4) investigation: on 10-sep-2021, the implicated unit was sent from the hospital to (b)(4) for further investigation and received on 13-sep-2021.On 14-sep-2021, cerus received the completed investigation on int2230b batch: ce21d02l71 from (b)(4).An emptied and cleaned platelets storage container was received and examined.A green plug with luer lock connection was inserted in the central outlet port that was used for the transfusion.The container was filled with 300ml of water and the test confirmed the leak reported by the (b)(6) lab.The leak could be described as a one millimeter slit neatly cut parallel to and one millimeter below the outlet port used for the transfusion.The morphology of the cut was consistent with a mechanical damage having a direction from the inside of the container to the outside.Thorough examination confirmed that the sheeting was pierced from inside to outside by a sharp object (extremity of the spike of the transfusion set) causing a tiny slit.There was no other damage altering the integrity of the container.The review of the batch records indicates no exception report, and no similar defect reported during production or at in-process and final physical controls in 2021 (all intercept products).There was no manufacturing cause identified either.Reporter assessment: reporter assessment: the reporter assessed the events of suspected transfusion-transmitted bacterial infection (ttbi) [pt: transmission of an infectious agent via product] and a febrile episode [pt: febrile non-haemolytic transfusion reaction, fnhtr] as mild in severity and non-serious.The reporter considered the fnhtr to be an expected transfusion reaction with any blood product transfusion.The relationship of this event and the suspected transfusion transmitted bacterial infection were both reported as possibly related to the intercept-treated platelet concentrate and the intercept blood system for platelets device.However, the reporter noted that "fever is a known sign of a transfusion reaction but can have another causes." in further communication, the reporter stated that an fnhtr is likely to be the reason for a fever spike during transfusion but also that the patient continued to have intermittent neutropenic fever episodes following this event, and this fever increase during transfusion may also have been one of the neutropenic fever episodes.Cerus medical review assessment: from the clinical presentation (one-time temperature increase with no further signs or symptoms of infection) and the microbiology findings (patient's pre- and post-transfusion negative blood cultures), cerus medical reviewer considers the above-described event to be a mild and non-serious febrile non-hemolytic transfusion reaction (fnhtr) in a neutropenic patient after chemotherapy treatment, with underlying ongoing neutropenic fevers, and not a ttbi.The cerus medical reviewer considers the causality of the event of fnhtr to be possible in relation to intercept pc, however, not related to intercept blood system for platelets device, which, based on the treatment records, performed as designed.A lack of patient blood culture positivity and lack of clinical manifestation of a septic episode, together with an intercept co-component transfusion to another patient without a transfusion reaction, does not support an intercept blood system for platelets device-related ttbi.The gram stain of the product post transfusion was negative, implying a low or non-existent concentration of bacteria.A contamination post intercept treatment of the pc is suspected.A breach in integrity of the pc bag most likely occurred at the time of transfusion during preparation of the transfusion set by excessive force from a cannula spike through the port, that contaminated the pc but did not cause a ttbi.Proliferation of the bacteria in the few hours after spiking until the time of sampling probably gave rise to the positive bag cultures.This hypothesis is in keeping with other reported septic transfusion cases that implicated post intercept contamination of pcs from the surface of the platelet bag into the container through breeches in the integrity of the container.Given the above, it is the medical reviewer opinion that the event was an fnhtr episode.
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Cerus received additional follow-up information on this non-serious adverse event case on 11-oct-2021, 12-oct-2021, and 21-oct-2021.Platelet collection (updated information): it was reported that the non-implicated co-component pc (arc's product code e8341v00) from this collection was transfused to a different patient at the same facility three days after the collection ((b)(6) 2021) with no adverse reaction noted.Patient clinical course (new information): on (b)(6) 2021, the patient was admitted to the hospital for neutropenic fevers.At the time, imaging studies showed no hepatic lesions.On (b)(6) 2021, an imaging study showed intrahepatic hematoma.On (b)(6) 2021, at 06:26h, a final blood culture was taken before transfusion and like all the other blood cultures, the result was negative.At 16:15h [after transfusion], a sample from the intercept pc bag was collected for gram stain which showed no organisms.At 20:53h, the patient's blood was drawn for culture which showed no growth.In addition to the patient's blood culture on (b)(6) 2021, the patient had seven blood cultures performed from (b)(6) 2021 which were all negative for growth.During the patient's hospital stay, he was treated with antibiotics.First vancomycin and cefepime.Later, he was treated with vancomycin, cefepime, acyclovir, and micafungin.It was noted the patient's antibiotics were unchanged after the transfusion reaction.On (b)(6) 2021, an abdomen imaging study showed "thickening and complexity" of the intrahepatic lesion, and the interpretation stated was that "superimposed infection was difficult to exclude".On (b)(6) 2021, the patient was discharged to hospice and died during hospice care on (b)(6) 2021.It was noted the patient's neutropenic fever and sepsis were felt to have been due to a hepatic abscess which was present at admission.A "final case assessment" was pending from the reporter at the time of this report.American red cross investigation (new information): on (b)(6) 2021, video footage (following staff and tasks performed on (b)(6) 2021), collection staff, and manufacturing staff were observed.Observations resulted in no irregularities.Collection records were reviewed and found to be acceptable.On (b)(6) 2021, an additional collection staff observation was completed and no irregularities were noted.Reporter assessment: (updated information) the reporter assessed the events of febrile episode [pt: febrile non-haemolytic transfusion reaction, fnhtr] and possible suspected transfusion-transmitted bacterial infection (ttbi) [pt: transmission of an infectious agent via product] and a febrile episode [pt: febrile non-haemolytic transfusion reaction, fnhtr] as mild in severity and non-serious.(new information) it was noted from the reporter that the underlying hepatic abscess may have been the source of the patient's sepsis.Cerus medical review assessment (updated information): from the clinical presentation (one-time temperature increase with no further signs or symptoms of infection) and the microbiology findings (patient's pre- and post-transfusion negative blood cultures), cerus medical reviewer considers the above-described event to be a mild and non-serious febrile non-hemolytic transfusion reaction (fnhtr) in a neutropenic patient after chemotherapy treatment, with underlying ongoing neutropenic fevers, and sepsis from a hepatic abscess, and not a ttbi.A lack of patient blood culture positivity and lack of clinical manifestation of an acute septic episode, together with an intercept co-component transfusion to another patient without a transfusion reaction, does not support an intercept blood system for platelets device-related ttbi.Given the above, it is the medical reviewer opinion that the event was an fnhtr episode in a neutropenic patient, with underlying neutropenic fevers and sepsis from a hepatic abscess, and not a ttbi.
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