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This report is being filed to provide additional information in h.6 and h.10.Investigation: the authors concluded ¿the tpe sessions were generally well tolerated; most of the aes observed in our pediatric patients were not unexpected and could perhaps be avoided in the future.¿ the tpe was performed on cobe spectra throughout the study (cobe bct inc., lakewood, colorado).The blood flow was set to 20 to 60 ml/min for all patients with vascular access.A combination of 5% albumin and fresh-frozen plasma (quarantine secured, viral inactivation via tri nbutyl phosphate/triton, methylene blue) have been used as replacement fluid.The proportion of fresh frozen plasma prescribed was different depending on indications and the hemorrhage risk.Anticoagulation was based o citrate infusion, and patients received a recommended anticoagulant to whole blood ratio of 1:14 on the reinfusion line.The patients' heart rate, blood pressure, and blood oxygen saturation level were monitored throughout each tpe procedure.The tpe was performed on cobe spectra throughout the study (cobe bct inc., lakewood, colorado).The blood flow was set to 20 to 60 ml/min for all patients with vascular access.A combination of 5% albumin and fresh-frozen plasma (quarantine secured, viral inactivation via tri n-butyl phosphate/triton, methylene blue) have been used as replacement fluid.The proportion of fresh frozen plasma prescribed was different depending on indications and the hemorrhage risk.Anticoagulation was based on citrate infusion, and patients received a recommended anticoagulant to whole blood ratio of 1:14 on the reinfusion line.The patients' heart rate, blood pressure, and blood oxygen saturation level were monitored throughout each tpe procedure.All data were collected via an ecrf and database (cleanweb, telemedicine technologies boulogne billancourt, france; https://www.Tentelemed.Com/la-solution-cleanweb/?lang=en).The collected data included demographic parameters (age, sex, and body weight), disease characteristics (supplementary data), number of tpe sessions, and parameters for the first procedure (vascular access, volume exchanged, anticoagulation, and treatment during a procedure).In addition, any untoward medical occurrence in patients during all procedures or within 2 weeks were recorded as aes (supplementary data, sd1).Aes included any complications related to vascular access (obstruction, bleeding, or infections), allergic reactions, hypocalcemia, and potentially life threatening complications (respiratory or hemodynamic decompensation), investigators have used common terminology criteria for adverse events (ctcae) to grade ae.12 grade 1 or mild referred to asymptomatic or mild symptoms, and intervention was not indicated.Grade 2 or moderate referred to minimal signs, and noninvasive intervention was indicated.Grade 3 or severe were medically significant but not immediately life-threatening.Grade 4 or life-threatening, consequences were urgent, and intervention was assessed in an emergency.Finally, grade 5, ae induced the death.We also noted specific concomitant treatments and the number of tpe procedures and series per patient.Clinical outcome was assessed for each indication concerning relapses, exchange resumption, and specific clinical and biomarker evaluation at 1 year (graft function, plasma creatinine, proteinuria, steroid-sparing, or reduced immunosuppressant dose levels, and the schistocyte count).Investigators classified the resulting patient outcomes into four levels: clinical worsening with severe persistent disease (treatment failure, graft removal, or relapse), clinical stability with no active disease, clinical improvement, and recovery without sequelae (supplementary data, sd3).The first tpe series of sessions covered 549 of the 731 procedures.Each patient underwent a median of 6 procedures [1-19], with a median volume of 1834 ml [500-5000 ml]; this corresponded to a median total plasma volume equivalent of 1.4 l/m2 [0.6-2.1 l/m2] (table 2).The first procedures were performed with peripheral vascular access in only six cases (8%).Central venous access was selected in 57 cases (73%), whereas arteriovenous fistulas had been used in 15 cases (19%).The proportion of crystalloid or plasma substitute depended on the indication and the patient's status.The median volume of plasma used per patient was 900 ml [0-5000 ml], which corresponded to 42% of the exchange volume.Patients with tma accounted for most of plasma (88%) with a median volume of 1100 ml [400-5000 ml]; this corresponded to 1.12 l/kg body mass [0.26-1.76 l/kg].All procedures were performed with acid-citrate-dextrose anticoagulation, and the citrate ratio did not decrease during the procedure.Ten patients received fibrinogen replacement therapy: three patients with a pre-tpe fibrinogen level below 1.0 g/l, and seven were treated to prevent postoperative hemorrhage.In the 2 weeks following tpe initiation, 72 patients (92%) present a total of 311 aes potentially related to this procedure.They also presented 94 aes not related to the tpe procedure.Each patient experienced a median of 5 aes [0-24] (table 3).Twenty-three aes (4%) were medically relevant, with a 3 or higher grade on the ctcae scale.The most frequently recurrent aes were related to citrate intolerance (n = 115; 37%) and line obstruction (n = 133; 43%).Only five (6%) patients developed documented line infections.Twenty of the aes were allergic reactions (grade i: n = 18; grade ii: n = 1; grade iii: n = 1), and occurred in 14 patients.Tma group was related to many patients with grade 1 allergic events (p =.0145).Nine (12%) patients received dexchlorpheniramine, and only one (1%) received intravenous methylprednisolone.None of the patients received hydrocortisone, ¿-2 agonist aerosols, or adrenalin.Allergic events were not linked to the type of plasma (fresh-frozen plasma or plasma with viral inactivation via solvent/detergent or methylene blue).Fifteen aes were due to facility or kit problems (plasma interface problems: n = 2; fluid balance and restitution: n = 7; kit defects or thrombosis: n = 6).A total of 55 procedures terminated prematurely because of a lack of clinical tolerance (citrate intolerance: n = 15; hemodynamics: n = 2, anaphylaxis: n = 1; fever: n = 1, agitation: n = 2; other: n = 4), kit problems (n = 5), or venous access problems (n = 25).Despite premature stoppage, volume treatment was effective for the majority of the procedure.At the 12-month endpoint, 10 patients (13%) were lost to follow-up, and 14 patients (18%) had died (supplementary data, sd2).Among patients with clinical evaluation at m12 (n = 54), 11 patients (20%) had severe persistent disease (supplementary data, sd3).Nine patients underwent a second or a third session of tpe procedures.None of ae declared during the procedures had consequences on midterm disease outcomes, and none of the death was related to the tpe procedures.The authors reported 6 occurrences of hemodynamic decompensation (grade iv), an allergy (grade iii), 3 respiratory decompensation (grade iii), 2 arteriovenous fistula (avf) obstruction (grade iii), 4 line infections (grade iii) and 1 line infections (grade iv).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.According to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Symptoms of allergic reactions may include hives, dyspnea, wheezing, burning eyes, tachycardia, hypotension, and or facial swelling and flushing.Mild reactions can be treated with diphenhydramine administered through an iv.According to surgical treatment for occlusion of graft arteriovenous fistula in patients undergoing hemodialysis published by noh, et al, a graft arteriovenous fistula (avf) has a lower patency rate than native avf because of the stenosis caused by excessive neointimal proliferation at the venous anastomosis site.In general, graft avf has a lower long-term patency rate than native avf, so it is very important to conduct studies for assessing the improvement of the patency rate of graft avf and for determining the rescue therapy which treats thrombotic occlusion appropriately.According to therapeutic apheresis: a physician's handbook, adverse effects related to vascular access are a frequent concern.Hemorrhage or pneumothorax or both may complicate cvc insertion, while thrombosis and infection are the most frequently observed complications of prolonged central venous access.During a dressing change, the site should be cleaned and observed for signs of infection such as redness, swelling, drainage, and foul odor.If an infection is suspected, cvc removal should be considered, and the patient should be treated for infection as appropriate.The placement of a cvc is considered by some to be the greatest risk related to the apheresis procedures, and it should be avoided if the procedure can be performed using peripheral iv.Since this is a retrospective cohort study via a web-based electronic case report form including pediatric patients referred for tpe using cobe spectra between january 2005 and december 2014, the lot numbers were not provided; therefore, a disposable lot history search could not be conducted.Citation: diana j-s, manceau s, rabeony t, et al.Therapeutic plasma exchange for life-threatening pediatric disorders.J clin apher.2021;36(6):823-830.Doi:10.1002/jca.21934 root cause: the authors reported 6 occurrences of hemodynamic decompensation (grade iv), an allergy (grade iii), 3 respiratory decompensation (grade iii), 2 arteriovenous fistula (avf) obstruction (grade iii), 4 line infections (grade iii) and 1 line infections (grade iv).A root cause assessment was performed for the respiratory and hemodynamic decompensation (grade iv).The reported adverse reactions are common side effect of therapeutic apheresis procedures.It is typically caused by 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: * patient's sensitivity to the replacement fluids * patient's sensitivity to the ethylene oxide used to sterilize the disposable set a root cause assessment was performed for the arteriovenous fistula (avf) obstruction.Based on the available information a definitive root cause could not be determined but it is likely due to the fact that a graft arteriovenous fistula has a lower patency rate than native avf because of the stenosis caused by excessive neointimal proliferation at the venous anastomosis site.A root cause assessment was performed for the line infections.Based on the available information a definitive root cause could not be determined but it is likely due to improper maintenance of the cvc.
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