| Catalog Number |
12220 |
| Medical Device Problem Codes |
Adverse Event Without Identified Device or Use Problem (2993); Insufficient Device Problem Information (3190)
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| Health Effect - Clinical Code |
Hemolysis (1886)
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| Date of Event |
03/22/2024
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Type of Reportable Event
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Serious Injury
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Additional Manufacturer Narrative
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Lot number, manufacture date and expiry date are not available at this time.Investigation is in process, a follow-up report will be provided.Citation: hilberath, j., camelli, v., hofer, c., hartleif, s., nadalin, s., peters, m., kumpf, m., bevot, a., zirngibl, m., weitz, m., & sturm, e.(2024).Role of high-volume plasmapheresis in the management of paediatric acute liver failure.Journal of pediatric gastroenterology and nutrition, 78(6), 1364¿1373.Https://doi.Org/10.1002/jpn3.12211.
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Event or Problem Description
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Per journal article "role of high-volume plasmapheresis in the management of pediatric acute liver failure " by johannes hilberath | vittoria camelli | christiane hofer |steffen hartleif | silvio nadalin | maren peters | matthias kumpf | andrea bevot | matthias zirngibl | marcus weitz | ekkehard sturm objectives: paediatric acute liver failure (palf) is a life-threatening disease.Management aims to support hepatic regeneration or to bridge to liver transplantation.High-volume plasmapheresis (hvp) removes protein-bound substances, alleviates inflammation, and improves survival in adult acute liver failure.However, experience with hvp in palf is limited.Aim of this study is to report on feasibility, safety, efficacy and outcomes of hvp in palf.Methods: retrospective observational study in children with palf.Hvp was performed upon identification of negative prognostic indicators, in toxic aetiology or multiorgan failure (mof).Exchanged volume with fresh-frozen plasma corresponded to 1.5¿2.0 times the patient's estimated plasma volume.One daily cycle was performed until the patient met criteria for discontinuation, that is, liver regeneration, liver transplantation, or death.Results: twenty-two children with palf (body weight 2.5¿106 kg) received 1¿7 hvp cycles.No bleeding or procedure-related mortality occurred.Alkalosis, hypothermia and reduction in platelets were observed.Haemolysis led to hvp termination in one infant.Seven children (32%) survived with their native livers, 13 patients (59%) underwent liver transplantation.Two infants died due to mof.Overall survival was 86%.International normalization ratio (inr), alanine aminotransaminases (alt), bilirubin and inotropic support were reduced significantly (p < 0.05) after the first hvp-cycle (median): inr 2.85 versus 1.5; alt 1280 versus 434 u/l; bilirubin 12.7 versus 6.7 mg/dl; norepinephrine dosage 0.083 versus 0.009 g/kg/min.Median solubleinterleukin- 2-receptor dropped significantly following hvp (n = 7): 2407 versus 950 u/ml (p < 0.02).Conclusions: hvp in palf is feasible, safe, improves markers of liver failure and inflammation and is associated with lowering inotropic support.Prospective and controlled studies are required to confirm efficacy of hvp in palf.The collection set is not available for return because it was discarded by the customer.Specific details, such as patient outcome, was not included in the article for this events, therefore this report is being provided as a summary of the event.It is unknown at this time if medical intervention was required for this events.
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Event or Problem Description
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Per journal article "role of high-volume plasmapheresis in the management of pediatric acute liver failure " by johannes hilberath | vittoria camelli | christiane hofer |steffen hartleif | silvio nadalin | maren peters | matthias kumpf | andrea bevot | matthias zirngibl | marcus weitz | ekkehard sturm objectives: paediatric acute liver failure (palf) is a life-threatening disease.Management aims to support hepatic regeneration or to bridge to liver transplantation.High-volume plasmapheresis (hvp) removes protein-bound substances, alleviates inflammation, and improves survival in adult acute liver failure.However, experience with hvp in palf is limited.Aim of this study is to report on feasibility, safety, efficacy and outcomes of hvp in palf.Methods: retrospective observational study in children with palf.Hvp was performed upon identification of negative prognostic indicators, in toxic aetiology or multiorgan failure (mof).Exchanged volume with fresh-frozen plasma corresponded to 1.5¿2.0 times the patient's estimated plasma volume.One daily cycle was performed until the patient met criteria for discontinuation, that is, liver regeneration, liver transplantation, or death.Results: twenty-two children with palf (body weight 2.5¿106 kg) received 1¿7 hvp cycles.No bleeding or procedure-related mortality occurred.Alkalosis, hypothermia and reduction in platelets were observed.Haemolysis led to hvp termination in one infant.Seven children (32%) survived with their native livers, 13 patients (59%) underwent liver transplantation.Two infants died due to mof.Overall survival was 86%.International normalization ratio (inr), alanine aminotransaminases (alt), bilirubin and inotropic support were reduced significantly (p < 0.05) after the first hvp-cycle (median): inr 2.85 versus 1.5; alt 1280 versus 434 u/l; bilirubin 12.7 versus 6.7 mg/dl; norepinephrine dosage 0.083 versus 0.009 g/kg/min.Median solubleinterleukin- 2-receptor dropped significantly following hvp (n = 7): 2407 versus 950 u/ml (p < 0.02).Conclusions: hvp in palf is feasible, safe, improves markers of liver failure and inflammation and is associated with lowering inotropic support.Prospective and controlled studies are required to confirm efficacy of hvp in palf.The collection set is not available for return because it was discarded by the customer.Specific details, such as patient outcome, was not included in the article for this events, therefore this report is being provided as a summary of the event.It is unknown at this time if medical intervention was required for this events.
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Additional Manufacturer Narrative
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This report is being filed to provide additional information in b.7, h.6 and h.11.Investigation: paediatric acute liver failure (palf) is a rare, lifethreatening disease of heterogeneous aetiology.Disease progression is driven by the effects of liver necrosis and inflammation, vitally affecting hepatic and extrahepatic organ function which ultimately can lead to multiorgan failure (mof) and death.The chances of spontaneous recovery without liver transplantation are only 10%¿40%.Nontransplant treatment options are limited.Therapy aims at stabilizing vital organ functions, preventing complications and promoting hepatic regeneration.Extracorporeal liver support (els) with high-volume plasmapheresis (hvp) offers the potential to remove hepatotoxic substances, pro-inflammatory cytokines, and damage-associated molecular patterns.Els systems with or without renal replacement therapy (rrt) can potentially mitigate coagulopathy, stabilize cardiovascular function, and serve as a bridge to liver transplantation or liver regeneration.The aim of this single-centre study was to analyse all hvp procedures in palf between 2010 and 2023 with regard to feasibility, efficacy, safety, and outcome.In children ages 0¿17 years, palf was diagnosed according to palf study group criteria.Clinical, biochemical, diagnostic, and management data were collected from medical records and analysed (t-test, mann¿whitney u-test).All patients were managed according to a local protocol in the paediatric intensive care unit, including inotropic support to address hemodynamic instability.Rrt was established in patients with significantly elevated plasma ammonia levels (i.E., 200 mol/l), renal insufficiency, electrolyte imbalance, fluid overload, metabolic disturbances, or high-grade hepatic encephalopathy (he = 3).Neuroprotective measures were provided throughout the course.Aetiology-specific treatment of palf was provided as soon as a diagnosis was made.Each patient was evaluated by a multidisciplinary team comprising representatives of paediatric hepatology, transplant surgery, intensive care, nephrology, and neurology.The team made therapeutic management decisions including the time point to employ hvp and rrt and whether to proceed with liver transplantation.Palf patients meeting one or more of the following criteria were considered for hvp: haemodynamic instability; he grades = 3; severe hyperbilirubinemia (total bilirubin > 12 mg/dl); suspected aetiology of wilson disease (wd) with the new wilson index = 11; and autoimmune/hyperinflammatory or druginduced liver disease.Hvp was performed using spectra optia (terumo bct) based on centrifugal apheresis technique by a high-flow double lumen central venous catheter with body-weight-dependent size.Citrate was used for nonsystemic anticoagulation.The volume of centrifugation plasma exchange with fresh-frozen plasma corresponded to 1.5¿2.0 times the estimated patient's plasma volume, up to a maximum of 6 l.Below a threshold of 0.9 mmol/l calcium was substituted intravenously.Hvp consisted of one daily cycle over 2¿6 h.Hvp was discontinued in case of suspected and noncorrectable complications including bleeding and haemolysis, metabolic alkalosis, electrolyte disorders, and hemodynamic instability.Otherwise, hvp was performed until the child improved or was liver-transplanted.If necessary, rrt was performed in between hvp cycles.Between 2010 and 2023, of 76 children with acute liver failure treated at our centre, 22 children (29%; 12 male) with a mean age of 11 years and a mean body weight of 34 kg underwent hvp.Four children were younger than 3 months.Body weight ranged from 2.5 to 106 kg (including three infants with body weight < 3.5 kg).In six cases (27%), aetiology could not be determined; one recent case was associated with a severe covid-19 infection (adenovirus negative) in a chronically ill child (dravet syndrome).Eight patients were affected by he grade = iii.Six of them were mechanically ventilated, needed inotropic support and underwent rrt while one patient was on the ventilator but did not require inotropic support.One patient was not on the ventilator and did not need inotropes; he recovered rapidly after the first hvp cycle.Median number of applied hvp cycles was 2 (range 1¿7) and 4 (range 1¿7) for children with native liver survival.The median time from establishing a diagnosis of palf to beginning hvp was 9.5 h (interquartile range [iqr]: 21.25 h).The mean duration of follow-up was 50 months (range of follow-up 1¿154 months).The overall survival rate in this cohort was 86%, three patients died.All 22 patients met criteria for liver transplantation eligibility, 20 children were granted the highly urgent status on the waiting list and two had contraindications.Seven children (32%) showed sustained regeneration, could be removed from waiting list and survived with native liver.13 patients (59%) underwent liver transplantation after a median waiting period of 4 days.Four newborns were included in the study.At time of hvp, their individual ages were 4, 17, 19 and 24 days old at time of diagnosis.The two youngest were too sick to be considered for liver transplantation and died due to mof: only one full hvp cycle in each could be completed, however, this intervention was not able to permanently stabilize these two infants.The first cycle of hvp led to a reduction of vasoactive support in the 4-day-old patient with familial hemophagocytic lymphohistiocytosis, however, the second and third plasmapheresis cycles had to be suspended due to haemolysis.The other infant showed a very rapid deterioration and decompensated due to sepsis.The two infants with gald including the smallest patient in our cohort with 2.5 kg of body weight completed 1¿4 hvp cycles and survived¿one with its native liver.An 11-year-old girl died due to sepsis 4 weeks after a primarily successful liver transplantation.Regarding terumo bct product, spectra optia, the authors concluded that no hvp-related mortality or sepsis was observed.The use of citrate for regional anticoagulation was attributed to two cases of mild and correctable alkalosis (ph 7.5 and 7.52) and hypocalcaemia in two patients (ionized calcium 0.77 and 0.8 mmol/l).No citrate-related cardiovascular instability was observed.There were no cases of hvp discontinuation because of hemodynamic instability or electrolyte or acid¿base disbalance.In one 4-day-old newborn, two out of three cycles had to be suspended due to haemolysis.Transient hypothermia below the targeted core body temperature of 36°c occurred in four out of five infants.A significant reduction of platelet count was observed (p < 0.005).However, neither patient had a bleeding episode.Two patients without platelet drop did develop a bleeding episode that was not attributed to hvp: one case was an abdominal bleed following liver biopsy requiring transfusion, and the other a mild nosebleed.There were no instances of bleeding associated with placement of the central venous catheter for hvp.The authors concluded that hvp in palf is safe and feasible even in infants with a body weight under 3 kg.No bleeding episode, sepsis, or death could be attributed to hvp.However, hypothermia and haemolysis, in particular in young infants, and a reduction in platelets, can occur when performing an extracorporeal treatment like hvp.Therefore, adequate monitoring is recommended.Since this was a retrospective study reviewing pediatric patients between 2010 and 2023; the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.According to the therapeutic apheresis: a physician¿s handbook; the rate of adverse events during therapeutic apheresis is 4% to 5%, with the risk being slightly higher during the first procedure, and varying considerably with the type of procedure.Among the most commonly performed procedures, the risk was higher for those involving allogeneic red cell or plasma transfusion and lower for peripheral blood progenitor cell collection.When complications are aggressively monitored and expected physiologic responses and minor reactions are included, one-third of treatments may be noted to involve side effects.The number of complications and rate of complications were significantly greater in patients receiving plasma as the replacement fluid rather than 3.3% albumin.Since the root cause for hemolysis is due to patient/donor physiology and/or disease state, and not a device malfunction, risk related to a specific failure mode could not be evaluated.According to the therapeutic apheresis: a physician¿s handbook; as large volumes of donor or patient blood circulate through an apheresis device, blood cells are intentionally or incidentally removed.The effects of single apheresis procedures have been studied extensively, especially in the setting of platelet donation.The thrust of these studies is that individual apheresis procedures produce only modest decreases in circulating blood cell counts, which are not associated with any immediate side effects.With some early apheresis equipment, significant platelet loss was reported during plasma exchange.With current centrifugal technology, reductions in platelet count are usually modest, and levels quickly return to baseline.In a severely thrombocytopenic patient, however, such a loss may mask the beginning of platelet recovery.Since this was a retrospective study reviewing pediatric patients between 2010 and 2023; the lot numbers were not requested; therefore, a dhr search could not be conducted for this specific incident.All lots must meet acceptance criteria for release.Root cause: the authors confirmed that no high-volume plasmapheresis related mortality or sepsis was observed.A root cause investigation was therefore performed for the reported hypothermia, haemolysis and for a reduction in platelets hypothermia: based on the clinical findings, a definitive root cause for hypothermia could not be determined.Hypothermia during therapeutic apheresis is primarily caused by the infusion of large volumes of unwarmed or room-temperature fluids and blood products, and the patient's exposure to a cool environment.Extremes of age and low body weights can pre-dispose or increase the likelihood of hypothermia.Very young children; like those in this study, and those with low body weights, are more prone to heat loss and less efficient at thermoregulation.An exposure to a cool environment, such as a room with air-conditioning can exacerbate this as it can lead to heat loss through a patient¿s exposed skin through radiation and convection.Other possible contributors to the reported hypothermia include but are not limited to: ¿ patient-specific factors ¿ underlying medical conditions ¿ procedural factors: a higher rate of blood flow through the machine and a longer procedure duration can increase the amount of heat lost.Haemolysis: based on the clinical findings, a definitive root cause for haemolysis could not be determined but it is likely due to one or a combination of the possible causes listed below: ¿ patient's blood physiology ¿ patient's medication and/or medical treatment thrombocytopenia: a root cause assessment was performed for the thrombocytopenia.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 underlying disease state ¿ inlet flow rate was set too high ¿ clumping in the extracorporeal system ¿ running a lengthy procedure ¿ collect flow rate was set too high ¿ a dilutional effect on the post procedure sample due to the volume of infused acda citation: hilberath, j., camelli, v., hofer, c., hartleif, s., nadalin, s., peters, m., kumpf, m., bevot, a., zirngibl, m., weitz, m., & sturm, e.(2024).Role of high-volume plasmapheresis in the management of paediatric acute liver failure.Journal of pediatric gastroenterology and nutrition, 78(6), 1364¿1373.Https://doi.Org/10.1002/jpn3.12211.
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