| Model Number 70700 |
| Device Problems
Adverse Event Without Identified Device or Use Problem (2993); Insufficient Information (3190)
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| Patient Problems
Anemia (1706); Hemorrhage/Bleeding (1888)
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| Event Date 02/29/2020 |
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Event Type
Death
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Event Description
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The journal, 'effectiveness and safety of leukapheresis in hyperleukocytic leukemias: a retrospective multicenter study' describes a retrospective study on leukapheresis among 420 patients with acute myeloid leukemia (aml), acute lymphoblastic leukemia (all) and chronic myeloid leukemia (cml).Per the article there were adverse events (aes) seen during the study period.Anemia was most frequent in aml patients, which was significantly higher than that in all and cml patients.Thrombocytopenia was less frequent in cml patients than in aml patients and all patients.Thrombocytopenia might deteriorate with increasing cycles of apheresis, but statistical significance was observed only in the aml cohort.Regarding the nonhematological aes, 49.76% of aes were related to serum biochemical changes after leukapheresis, of which the most common aes included hypoalbuminemia, increased creatinine and hypocalcemia.All and aml patients had a higher risk of coagulation dysfunction, presenting as decreased fibrinogen levels.There was also a risk of aptt prolongation, but there was no difference among the three cohorts.The incidences of bleeding events were 23.58% in the aml cohort (5 cases of severe organ bleeding, 21 cases of skin ecchymosis, 17 cases of gingival, oral and nasal bleeding, 4 cases of gastrointestinal bleeding, 6 cases of bloody expectoration and 1 case of hematuria), 20.00% in the all cohort (3 cases of organ bleeding, 9 cases of skin ecchymosis, 13 cases of gingival, oral and nasal bleeding), and 15.15% in cml (1 case of organ bleeding, 5 cases of epistaxis and 4 cases of skin ecchymosis).A total of 25.33% had infections in the aml cohort, 13.60% in all, and 10.61% in cml.Most of these aes were caused by the leukemia rather than the leukapheresis procedure.Within 30 days postprocedure, 7 patients (5.6%) died in the all cohort, compared to 15 patients (6.6%) in the aml cohort (p¼0.723).Deaths in the first week were 10 cases (4.4%) in aml and 1 case in all (0.8%) (p¼0.065).The main causes of death were infection (14/22 cases, 63.6%), bleeding (5/22, 22.7%), leukostasis (1/22, 4.54%), tls (1/22, 4.54%) and respiratory failure (1/22, 4.54%).Specific details regarding patient information, were not included in the article for these events, therefore this report is being provided as a summary of the events.The apheresis sets are not available for return for evaluation.This report is being filed due to patient death, though at this time there is not an allegation that the device caused or contributed to the patient death.
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Manufacturer Narrative
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Lot number and expiry are not available at this time.Article citataion: zhang, x.,tu, y.,shen, j.,feng, y.,ma, h.,bai, l.,li, x.,lin, z.,dai, l.,gong, f.,lu, t.,zhou, j.,chen, h.,lv, q.,zhu, z.,ruan, c.(2022) effectiveness and safety of leukapheresis in hyperleukocytic leukemias: a retrospective multicenter study.Leukemia and lymphoma.63:11, 2636-2644, doi: 10.1080/10428194.2022.2086246.Investigation is in process.A follow up report will be provided.
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Event Description
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The journal, 'effectiveness and safety of leukapheresis in hyperleukocytic leukemias: a retrospective multicenter study' describes a retrospective study on leukapheresis among 420 patients with acute myeloid leukemia (aml), acute lymphoblastic leukemia (all) and chronic myeloid leukemia (cml).Per the article there were adverse events (aes) seen during the study period.Anemia was most frequent in aml patients, which was significantly higher than that in all and cml patients.Thrombocytopenia was less frequent in cml patients than in aml patients and all patients.Thrombocytopenia might deteriorate with increasing cycles of apheresis, but statistical significance was observed only in the aml cohort.Regarding the nonhematological aes, 49.76% of aes were related to serum biochemical changes after leukapheresis, of which the most common aes included hypoalbuminemia, increased creatinine and hypocalcemia.All and aml patients had a higher risk of coagulation dysfunction, presenting as decreased fibrinogen levels.There was also a risk of aptt prolongation, but there was no difference among the three cohorts.The incidences of bleeding events were 23.58% in the aml cohort (5 cases of severe organ bleeding, 21 cases of skin ecchymosis, 17 cases of gingival, oral and nasal bleeding, 4 cases of gastrointestinal bleeding, 6 cases of bloody expectoration and 1 case of hematuria), 20.00% in the all cohort (3 cases of organ bleeding, 9 cases of skin ecchymosis, 13 cases of gingival, oral and nasal bleeding), and 15.15% in cml (1 case of organ bleeding, 5 cases of epistaxis and 4 cases of skin ecchymosis).A total of 25.33% had infections in the aml cohort, 13.60% in all, and 10.61% in cml.Most of these aes were caused by the leukemia rather than the leukapheresis procedure.Within 30 days postprocedure, 7 patients (5.6%) died in the all cohort, compared to 15 patients (6.6%) in the aml cohort (p¼0.723).Deaths in the first week were 10 cases (4.4%) in aml and 1 case in all (0.8%) (p¼0.065).The main causes of death were infection (14/22 cases, 63.6%), bleeding (5/22, 22.7%), leukostasis (1/22, 4.54%), tls (1/22, 4.54%) and respiratory failure (1/22, 4.54%).Specific details regarding patient information, were not included in the article for these events, therefore this report is being provided as a summary of the events.The apheresis sets are not available for return for evaluation.This report is being filed due to patient death, though at this time there is not an allegation that the device caused or contributed to the patient death.
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Manufacturer Narrative
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This report is being filed to provide additional information in h.6 and h.10.Investigation: since this was a journal publication presenting data of a retrospective study on leukapheresis among 420 patients with aml, all and cml at four participating centers from (b)(6) 2009 through (b)(6) 2020, 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.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.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.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 non bleeding 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.18 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 the scientific journal by nayak, ¿tpe induces marked changes in electrolytes but these changes are transient and do not warrant any intervention¿.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, 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.There is no evidence to indicate that the optia device caused or contributed to the reported increased creatinine and infections.Therefore, there is no failure mode or associated risk that can be evaluated for spectra optia.According to therapeutic apheresis: a physician's handbook, miscellaneous reactions such as delayed complications of apheresis include hemorrhage, thrombosis, infection related to access lines or blood components, anemia, and protein depletion.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.An investigation was conducted for a journal publication presenting data of a retrospective study on leukapheresis among 420 patients with acute myeloid leukemia (aml), acute lymphoblastic leukemia (all) and chronic myeloid leukemia (cml) at four participating centers from (b)(6) 2009 through (b)(6) 2020.Aes were evaluated from the beginning of leukapheresis to 24 h after the procedure.Hematological toxicities were the major concerns, and the patients in the three cohorts had varying degrees of hemoglobin and platelet loss during the procedure.Anemia was most frequent in aml patients, which was significantly higher than that in all and cml patients.Thrombocytopenia was less frequent in cml patients (22.7%) than in aml patients (49.3%) and all patients (42.4%).Thrombocytopenia might deteriorate with increasing cycles of apheresis, but statistical significance was observed only in the aml cohort.Regarding the nonhematological aes, 49.76% (209/420) of aes were related to serum biochemical changes after leukapheresis, of which the most common aes included hypoalbuminemia (aml: 51.00%; all: 27.20%, cml: 28.79%), increased creatinine (aml: 33.33%; all: 8.00%, cml: 12.90%) and hypocalcemia (aml: 27.93%; all: 22.00%, cml: 35.48%).All and aml patients had a higher risk of coagulation dysfunction, presenting as decreased fibrinogen levels.There was also a risk of aptt prolongation, but there was no difference among the three cohorts.The incidences of bleeding events were 23.58% in the aml cohort (5 cases of severe organ bleeding, 21 cases of skin ecchymosis, 17 cases of gingival, oral and nasal bleeding, 4 cases of gastrointestinal bleeding, 6 cases of bloody expectoration and 1 case of hematuria), 20.00% in the all cohort (3 cases of organ bleeding, 9 cases of skin ecchymosis, 13 cases of gingival, oral and nasal bleeding), and 15.15% in cml (1 case of organ bleeding, 5 cases of epistaxis and 4 cases of skin ecchymosis).A total of 25.33% had infections in the aml cohort, 13.60% in all, and 10.61% in cml.Most of these aes were caused by the leukemia rather than the leukapheresis procedure.Deaths in the first week were 10 cases (4.4%) in aml and 1 case in all (0.8%) (p=0.065).The main causes of death were infection (14/22 cases, 63.6%), bleeding (5/22, 22.7%), leukostasis (1/22, 4.54%), tumor lysis syndrome (tls) (1/22, 4.54%) and respiratory failure (1/22, 4.54%).In conclusion, leukapheresis can safely reduce the leukemic burden, especially for patients with acute leukemias.There were no allegation of device malfunction.Root cause: 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) * inaccurate entry of the patient's hematocrit * inlet flow rate was too high to adequately separate red cells from buffy coat 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 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: * 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 hyponatremia.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 underlying disease * large volume depletion conducted over a relatively short period 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.A root cause assessment was performed for the reported citrate reactions.These reactions occur due to decreased ionized calcium in circulation as a result of exogenous citrate administered during the apheresis procedure and are influenced by patient physiology, the patient's disease state, the rate of ac infusion, the citrate contents in the replacement fluid, 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.A root cause assessment was performed for the reported increased creatinine and infections.The authors stated that ¿most of these aes were caused by the leukemia rather than the leukapheresis procedure.¿ a root cause assessment was performed for the hypoalbuminemia.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 underlying disease * large volume depletion conducted over a relatively short period treatment.Article citataion: zhang, x.,tu, y.,shen, j.,feng, y.,ma, h.,bai, l.,li, x.,lin, z.,dai, l.,gong, f.,lu, t.,zhou, j.,chen, h.,lv, q.,zhu, z.,ruan, c.(2022) effectiveness and safety of leukapheresis in hyperleukocytic leukemias: a retrospective multicenter study.Leukemia and lymphoma.63:11, 2636-2644, doi: 10.1080/10428194.2022.2086246.
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