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This report is being filed to provide additional information in h.6 and h.11.Investigation: per the article, the replacement fluid was either fresh frozen plasma (ffp) and 0.9% normal saline.An investigation was conducted for journal article that references terumo bct product.Journal article, titled ¿variable response to therapeutic plasma exchange in pediatric anti-nmda receptor encephalitis¿ by mukherjee et al.Apr 2021, was reviewed with primary purpose of screening for allegations of terumo bct device causing or contributing to death/injury or device malfunctions.Part evaluation is not feasible for this journal article investigation because there are many months between collection of data, to peer review, to final publication.Anti-nmdar encephalitis, first described in 2005 by vitaliani et al., is characterized by psychiatric symptoms, memory loss, and reduced level of consciousness.Common treatment protocols in an adults include tumor removal (when present) and first-line immunotherapy, such as steroids, intravenous immunoglobulin (ivig).When the patient fails to respond to first-line treatment, therapeutic plasma exchange (tpe) is considered as it may, in turn, reduce hospitalization time, drug needs, and possibly short-term morbidity.This is a retrospective analysis of the effect of tpe in four cases of anti-nmdar encephalitis who were presented to the department of paediatric and then referred to the department of transfusion medicine and blood bank for plasma exchange.The diagnosis was confirmed by the presence of anti-nmdar in csf or plasma.All cases were evaluated, referring to a clinical condition, laboratory parameters, risk-benefit analysis, asfa category, venous status(central/peripheral) before tpe.Regarding terumo bct product, cobe spectra, the authors reported a tx reaction (rash) and hypotension.A patient died a month after discharge from the hospital.See case 3 in table 1 below.These anti-nmdar encephalitis patients' may present with hypotension during the procedure due to accompanying autonomic dysfunction.Hence, tpe in these cases should be done meticulously under comprehensive monitoring.Only one episode of allergic reaction and hypotension was observed in the third case due to ffp transfusion, which the authors stated was manageable.The time between 1st symptoms and 1st tpe was 44 days, significantly longer than any of the other cases treated.All patients had variable neurological manifestations during presentation at our hospital, like abnormal movements, focal or generalized seizure, psychiatric symptoms, and/or autonomic instability.The duration from onset of symptom to presentation in our hospital is an average of 12 to 24 days.Initially, patients were started with antiepileptic like lorazepam 4 mg by slow intravenous route (i.V), then oral valproate 50 mg/kg/day, phenytoin 5 mg/kg/day, levetiracetam 50 mg/kg/day, carbamazepine 20 mg/kg/day, phenobarbital3 mg/kg/day, and risperidone 0.5 mg/day were started to control the seizure and psychotic features and movement disorder.The csf testing for anti-nmdar antibody and the viral marker was sent suspecting autoimmune encephalitis and viral encephalitis.The absence of a viral marker and the presence of nmda anti-body in csf confirms the diagnosis of anti-nmdar encephalitis.Patients were initially managed with first-line immunotherapy like i.V methylprednisolone 1 g/day for 3¿5 days and ivig 0.4 g/kg/dayfor five days.Tpe was started when patients were failed to respond to primary therapy like corticosteroid and ivig.Tpe was performed on an alternate day using the cobe spectra (caridianbct, lakewood, co, usa) (table 1).The replacement fluid was either fresh frozen plasma (ffp) and 0.9% normal saline.Ffp was used as replacement fluid as patients were unable to afford the cost of albumin.Albumin (5%) was used in only one case after 2nd procedure when the patient developed an allergic transfusion reaction to ffp transfusion.Before tpe, laboratory parameters like complete blood count (cbc), coagulation profile, liver function test (lft), renal function test (rft), ionized calcium were evaluated.Vascular access was established by inserting an indwelling double lumen catheter into the femoral vein.Total blood volume was calculated using glicher¿s rule of five according to their body built [8].Approximately one plasma volume was exchanged in each procedure.Acid-citrate-dextrose-a (acd-a) was used as an anticoagulant for the tpe procedure.Inj.Calcium gluconate (10% w/v) was dissolved in 100 ml normal saline and infused slowly for every 1000 ml of plasma exchanged to prevent hypocalcemia.At the tpe procedure initiation, the tubing sets were primed with group-specific coomb¿s crossmatched red blood cell unit if the extracorporeal volume is more than 10% of total blood volume (tvb) to prevent hypotension.The heart rate, pulse rate, blood pressure, spo2, and temperature were constantly monitored during the procedure.If any adverse transfusion reaction occurred, injection pheniramine maleate 22.75 mg i.M, i.V hydrocortisone 50-100 mg was used as per bodyweight whenever indicated.The central line was taken care of properly to prevent any complications like hemorrhage, infection, or signs of venous thrombosis and so also flushed with heparin twice daily.Cbc, lft, serum electrolytes, pt, aptt, were repeated after each tpe procedure.Informed written consent was taken from thelegal guardians of the patients for the tpe procedure.A total of 20 procedures were performed, and the first case itself was undergone 8 tpe.According to the aabb circular of information for the use of human blood components (revised 2017), allergic reactions frequently occur (ie, 1-3% of plasma-containing components) as mild or self-limiting urticaria or wheezing that usually respond to antihistamines.More severe manifestations, including respiratory and cardiovascular symptoms, are more consistent with anaphylactoid/anaphylactic reactions and may require more aggressive therapy (see below).No laboratory procedures are available to predict these reactions.Anaphylactic reactions, characterized by hypotension, tachycardia, nausea, vomiting and/or diarrhea, abdominal pain, severe dyspnea, pulmonary and/or laryngeal edema, and bronchospasm and/or laryngospasm, are rare (<10/100,000 transfused units) but dangerous complications requiring immediate treatment with epinephrine.While these reactions have been reported in iga-deficient patients with anti-iga antibodies and patients with haptoglobin deficiency, most reactions are idiosyncratic and not associated with a specific serum protein deficiency, polymorphism, or identifiable cause according to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Some of the most common reactions include fever, urticaria, hypocalcemic symptoms, pruritus, dyspnea, tachycardia, and mild hypotension transient hypocalcemia associated with apheresis is usually well tolerated.Symptoms often show as paresthesia (tingling) but patients may also experience unusual taste, nausea, lightheadedness, shivering, and tremors.Severe hypocalcemia may also cause muscle contractions and can progress to tetany and seizures if hypocalcemia escalates and is not corrected.Since this was a retrospective analysis of the effect of tpe in four cases of anti-nmdar encephalitis, published in 2021, the disposable lot numbers were not requested; therefore, a disposable lot history search could not be conducted.Root cause: the reported hypotension is a common side effects of therapeutic apheresis procedures.They are typically caused by the patient's disease state, the rate of ac infusion, fluid shift, blood loss, length of the procedure, patient's sensitivity to the procedure and/or hemodynamic stress of the procedure.A root cause assessment was performed for the allergic reactions.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: * hypersensitivity to the ethylene oxide used to sterilize the disposable set.* hypersensitivity to the components inside the disposable set.* anaphylactic reactions have been reported in iga-deficient patients with anti-iga antibodies and patients with haptoglobin deficiency, most reactions are idiosyncratic and not associated with a specific serum protein deficiency, polymorphism, or identifiable cause.* immediate hypersensitivity reaction (production of ige antibodies in response to allergens (plasma proteins in fresh frozen plasma).* passive sensitization (passive transfer of donor allergens or donor antibodies (e.G.Allergen-specific ige); transient allergic sensitivity to allergens.Naik, a., prakash, s., ray, g.K., & mukherjee, s.(2021).Variable response to therapeutic plasma exchange in pediatric anti-nmda receptor encephalitis.Transfusion clinique et biologique, 28(3), 287¿290.Https://doi.Org/10.1016/j.Tracli.2021.03.006.
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