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Investigation: see attached word file for full investigation information concerning the summary of the terumo bct product in relation to the journal article.Since this was a journal publication involving a retrospective study which investigates and delves into the efficacy and safety of tpe in the management of severe gbs in pediatric patients between march 2015 and march 2017, 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.Since this was a journal publication involving a retrospective study which investigates and delves into the efficacy and safety of tpe in the management of severe gbs in pediatric patients between march 2015 and march 2017, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.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.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%.Symptoms of these 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 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.Vasovagal incidents occur around 0.5% of procedures.The reactions generally manifest as pallor and diaphoresis.In a full blown attack, the reaction progresses from pallor and sweating to pulse slowing and blood pressure decreasing.More severe vasovagal reactions may include nausea, vomiting, and/or convulsions according to therapeutic apheresis: a physician's handbook, when plasma is exchanged with a non plasma replacement solution, coagulopathy caused by dilution of coagulation factors is a potential problem.The prothrombin time and activated partial thromboplastin time rise and fibrinogen falls to an extent related to the intensity of the exchange.Despite these hemostatic alterations, hemorrhagic complications of dilutional coagulopathy are seldom encountered unless a patient is hemostatically compromised before treatment.Routine supplementation of replacement fluids with plasma or other sources of clotting factors is not recommended for nonbleeding patients whose baseline coagulation is normal.Redistribution and ongoing synthesis raise levels of most coagulation factors rapidly in the hours following an exchange.Fibrinogen is usually replaced more slowly and might be considered the rate-limiting factor determining the frequency of procedures performed without replacement of coagulation factors.However, the production of this acute-phase protein varies greatly among patients.Fibrinogen levels may decrease somewhat below 100 mg/dl if several procedures are performed on consecutive days.A level near 100 mg/ml is generally sufficient for hemostasis unless the individual has another hemostatic challenge.If fibrinogen decreases a great deal below 100 mg/dl, some physicians will then increase the interval between procedures or will use plasma replacement during the last part of the procedure to avoid a potential bleeding diathesis.Fresh frozen plasma (ffp) is the preferred source of fibrinogen, and it supplies other coagulation factors as well.Ffp is seldom required, though, if tpe is performed at intervals of 72 hours or greater.Hemorrhage is rarely reported in patients undergoing a tpe series without plasma replacement if there is no underlying predisposition to bleeding.According to therapeutic apheresis: a physician's handbook, apheresis procedure itself leads to both hemodynamic and dilutional changes.Those physiologic consequences may also result in adverse events for the patient.Another major category of physiologic responses to therapeutic apheresis is fluid shifts that occur as whole blood is removed, as one or another component is retained, and as the remaining components are returned with or without replacement solution.Resultant changes in intravascular volume can induce hemodynamic alterations.Fluid overload (hypervolemia) may be a problem for patients with cardiac or renal impairment.In other situations, hypovolemia may be a concern.There is general sense that hemodynamic changes are more common with intermittent flow centrifugation than with continuous flow procedures.This situation probably relates to the greater extracorporeal volume associated with earlier models of intermittent flow machines (see table 1).Therapeutic apheresis procedures may lead to major physiologic changes, including hypocalcemia caused by citrate infusion, hemodynamic changes associated with fluid shifts, and depletion of cellular and plasma constituents.As greater understanding of the physiology of apheresis has guided continued improvements in technology, the potential for untoward effects has been minimized so that procedures may usually be performed without adverse events.According to anticoagulation techniques in apheresis: from heparin to citrate and beyond (lee, et al), several metabolic complications other than hypocalcemia have been described with citrate administration including hypomagnesemia, metabolic alkalosis, hypokalemia, and changes in parathyroid hormone levels (pth).These metabolic complications are citrate mediated and often related to citrate infusion rates or donor characteristics.The generation of a metabolic alkalosis contributes to the development of hypokalemia.For example, the simultaneous development of metabolic alkalosis and hypokalemia, with serum potassium levels less than 3.0 meq/l, has been found to occur frequently in patients with ttp after plasma exchange.Metabolic alkalosis directly induces hypokalemia, as high serum bicarbonate levels cause a compensatory shift of hydrogen ions out of the intracellular compartment in exchange for potassium.The concurrent presence of hypocalcemia and hypomagnesemia also contributes to the development of hypokalemia, as the development of citrate-induced hypocalcemia has been found to be strongly associated with the subsequent development of citrate-induced hypokalemia.According to therapeutic apheresis: a physician's handbook, 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.Similarly, the small amount of red cells lost in the apheresis circuit may be more apparent in an anemic patient who has meager production capacity and who is receiving multiple procedures.Although generally well tolerated, the large-volume leukocytapheresis for stem cell collections in patients often results in a decline in hematocrit and platelet count, particularly because some red cells and platelets are incidentally removed with the stem cells.Root cause: a root cause assessment was performed for the reported adverse reactions listed in fig.6 including tachycardia, hypotension, hypoxia, bradycardia, allergic reactions, seizures, nausea, vomiting, hypocalcemia, hypokalemia, hypercalcemia, siahlorrhea and tachypnea.These adverse reactions are common side effects of therapeutic apheresis procedures.They are typically caused by the patient's disease state, the rate of ac infusion, the length of the procedure, the patient's sensitivity to the procedure and/or the hemodynamic stress of the procedure.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.Other root causes root causes include but are not limited to: hypersensitivity to the ethylene oxide used to sterilize the disposable set.Hypersensitivity to the components inside the disposable set.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.Therapeutic apheresis procedures may lead to major physiologic changes, including hypocalcemia caused by citrate infusion, hemodynamic changes associated with fluid shifts, and depletion of cellular and plasma constituents.Citrate reactions occur due to decreased ionized calcium in circulation as a result of exogenous citrate administered during the apheresis procedure and are influenced by donor physiology, the rate of ac infusion, and/or the length of the procedure.These symptoms may be treated with oral or intravenous calcium supplements or by adjusting the ac infusion rate.Another major category of physiologic responses to therapeutic apheresis is fluid shifts that occur as whole blood is removed, as one or another component is retained, and as the remaining components are returned with or without replacement solution.Resultant changes in intravascular volume can induce hemodynamic alterations.Fluid overload (hypervolemia) may be a problem for patients with cardiac or renal impairment.In other situations, hypovolemia may be a concern.There is general sense that hemodynamic changes are more common with intermittent flow centrifugation than with continuous flow procedures.A root cause assessment was performed for the anemia.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 patient's blood physiology interferes with separation of cellular components (i.E.Abnormal rbcs, hyperviscous plasma) improper or inadequate custom blood prime a root cause assessment was performed for the coagulopathy.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: exchanged with a non-plasma replacement solution resulting in coagulopathy caused by dilution of coagulation factors.Large volume exchange conducted over a relatively short period treatment.Large volume depletion resulting in coagulopathy caused by removal of clotting factors and dilution of coagulation factors due to large volume of infused acda.Patient was hemostatically compromised before treatment.A root cause assessment was performed for the hypokalemia.These metabolic complications are citrate mediated and often related to citrate infusion rates or patient characteristics.The generation of a metabolic alkalosis contributes to the development of hypokalemia.For example, the simultaneous development of metabolic alkalosis and hypokalemia, with serum potassium levels less than 3.0 meq/l, has been found to occur frequently in patients with ttp after plasma exchange.Metabolic alkalosis directly induces hypokalemia, as high serum bicarbonate levels cause a compensatory shift of hydrogen ions out of the intracellular compartment in exchange for potassium.The concurrent presence of hypocalcemia and hypomagnesemia also contributes to the development of hypokalemia, as the development of citrate-induced hypocalcemia has been found to be strongly associated with the subsequent development of citrate-induced hypokalemia.Citation: ali, t., hkima abou fakher, f., alawir, m., allababidi, a., & sheikh hasan, a.(2024).Management of severe pediatric guillain-barre syndrome in a low-income country: efficacy and safety of therapeutic plasma exchange in pediatric patients: a retrospective study.Bmc pediatrics, 24(1).Https://doi.Org/10.1186/s12887-024-05298-6.
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Per journal article "management of severe pediatric guillain-barré syndrome in a low-income country: efficacy and safety of therapeutic plasma exchange in pediatric patients: a retrospective study" by ali, t., hkima abou fakher, f., alawir, m., allababidi, a., & sheikh hasan, a.¿plasmapheresis was initiated on an average of 6.1 ± 2.5 days after the onset of symptoms (range: 1 to 11 days, median: 6 days).Tpe was the sole treatment for 29 patients; three patients received ivig before tpe, with one patient dying from septic shock; and four patients received ivig after tpe, with two transitioning from tpe to ivig after two tpe sessions due to complications associated with plasmapheresis.¿ ¿tpe was found to be generally safe when applied in this cohort of pediatric patients, and it is routinely performed in our hospital, despite the challenges associated with its application.However, some adverse events occurred during or after plasmapheresis sessions, including a few that were serious and life-threatening.We will describe the details of these complications next.¿ ¿throughout the course of 122 tpe sessions, complications were observed in 47 sessions (39%) involving 29 patients (81%).Tachycardia emerged as the most prevalent complication, occurring in 24% of sessions, followed by hypotension at 13%.Other observed complications included hypoxia (6%), and other less frequent complications, which are illustrated in (fig.6).Notably, these complications were severe in two patients during their second session, prompting the discontinuation of plasmapheresis and a transition to ivig.The first patient experienced complications such as hypertension, tachycardia, hypoxia, acidosis and hypercalcemia, while the second patient encountered hypotension with hemodynamic instability, along with tachycardia, seizures, hypoxia, acidosis, and hypercalcemia.¿ ¿complications were evident after a total of 70 tpe sessions (57%), impacting 31 patients.Anemia was the most common complication, observed in 31 sessions (25%).This was managed by the transfusion of packed red blood cell units as deemed necessary.Moreover, prolonged pt and aptt were observed following 30 sessions (25%) and 10 sessions (8%), respectively.Anomalous coagulation test results prompted the transfusion of ffp units.A total of 16 ffp units were transfused after 11 different tpe sessions, including one ffp unit administered during a patient¿s final plasmapheresis session.Furthermore, hypokalemia occurred after 13 sessions (11%), hypocalcemia after 10 sessions (8%), and hypotension after six sessions (5%).Hypocalcemia was managed through oral calcium administration.Additional, albeit milder, complications are detailed in (fig.7).In a specific case, a patient developed pulmonary edema accompanied by hypoxia and periorbital edema shortly after their second plasmapheresis session.Arterial blood oxygen saturation dropped to 60%, classifying manual ventilation using an ambo bag.Subcutaneous adrenaline administration and intravenous furosemide were used to treat the patient, along with the transfusion of one unit of ffp.In a separate incident, a central venous catheter was erroneously inserted into the right femoral artery instead of the intended vein, resulting in subsequent cellulitis in the affected area.One patient passed away 65 days after admission to the hospital, and after receiving four tpe sessions.There was a 48-day time lapse between the patient¿s last plasmapheresis session and date of death; thus, the cause of death could not be attributed to plasmapheresis.The determined cause of death was septic shock arising from severe vap.¿ the collection set is not available for return because it was discarded by the customer.Specific details, such as patient information and outcome, were not included in the article for these events, therefore this report is being provided as a summary of the events.It is unknown at this time if medical intervention was required for these events.This was a journal publication involving a retrospective study which investigates and delves into the efficacy and safety of tpe in the management of severe gbs in pediatric patients between march 2015 and march 2017.A request for specific patient information is not feasible because there are many months between collection of data, to peer review, to final publication.The article mentions a patient death and per the article the determined cause of death was "septic shock arising from severe vap" and there was no detectable malfunction with the terumo bct device or allegation of a malfunction.
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