MAUDE Adverse Event Report: TERUMO BCT SPECTRA OPTIA; SPECTRA OPTIA EXCHANGE SET

Model Number 10220

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Anemia (1706); Hypersensitivity/Allergic reaction (1907)

Event Date 04/14/2022

Event Type  Injury  

Event Description

The journal article, 'optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease', describes a study regarding haematopoietic stem and progenitor cell (hspc) apheresis collection from patients with sickle cell disease (scd) by targeting deep buffy coat collection using medium or low collection preference (cp), and by increasing anticoagulant¿citrate¿dextrose¿solution a dosage.Forty-three adverse events (aes) were reported, including one grade 4 ae (delayed haemolytic transfusion reaction related to rbc exchange; 2.3%) and 11 grade 3 aes (eight pain-related and three anaemia; 25.6%).Specifically, anaemia (hb¿<80¿g/l on the next day of the collection) was seen in one participant in the medium-cp group, one participant on two occasions in the low-cp group.Three incidents of apheresis-related hypocalcaemia (grade 1¿2, 7.0%) and six hypomagnesaemia (grade 1¿2, 14.0%) were reported.All aes resolved with supportive care.The article does not provide details related to specific patient information, therefore this report is being filed as a summary of events.The disposable collection sets are not available for return.

Manufacturer Narrative

Investigation is in process, a follow-up report will be provided.Article citation: sharma a, leonard a, west k, et al.2022.Optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease.Br j haematol, 2022;00:1-5.

Manufacturer Narrative

This report is being filed to provide additional information in h.6 and h.10.Investigation: the purpose of the journal article study is noted in the article abstract: the authors adjusted haematopoietic stem and progenitor cell (hspc) apheresis collection from patients with sickle cell disease (scd) by targeting deep buffy coat collection using medium or low collection preference (cp), and by increasing anticoagulant¿citrate¿dextrose¿solution a dosage.In 43 hspc collections from plerixafor mobilized adult patients with scd, we increased the collection efficiency to 35.79% using medium cp and 82.23% using low cp.Deep buffy coat collection increased red blood cell contamination of the hspc product, the product haematocrit was 4.7% with medium cp and 6.4% with low cp.These adjustments were well-tolerated and allowed efficient hspc collection from scd patients.Adult scd patients enrolled on two clinical trials ((b)(6)) at (b)(6) hospital and national institutes of health were included.This study was approved by both institutional review boards.Participants who underwent rbc exchange with goals of haemoglobin s (hbs)100g/l (methods s1), received 240 g/ kg of plerixafor for hspc mobilization, followed by hspc collection 2¿4 h later with processing up to four total blood volumes.We used the spectra optia continuous mononuclear cell collection protocol (terumo bct) for hspc collection.Acda dose was increased by lowering the inlet/ac ratio from 12 (standard) to 8¿12.Citrate toxicity was prevented/reduced by concurrent infusion of calcium gluconate (3 g in 250ml of 0.9% saline).Additional oral calcium carbonate was given if the patient experienced paraesthesia.Summary of terumo bct product in relation to the journal article: forty-three adverse events (aes) were reported, including one grade 4 ae (delayed haemolytic transfusion reaction related to rbc exchange; 2.3%) and 11 grade 3 aes (eight pain-related and three anaemia; 25.6%).Specifically, anaemia (hb <80 g/l on the next day of the collection) was seen in one participant in the medium-cp group, one participant on two occasions in the low-cp group.Three incidents of apheresis-related hypocalcaemia (grade 1¿2, 7.0%) and six hypomagnesaemia (grade 1¿2, 14.0%) were reported.All aes resolved with supportive care.In summary, the optimized hspc collection depth and acd-a dosage allowed safe and highly efficient autologous hspc collection in scd patients.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.The threshold for developing clinical features of hypocalcemia is related to the absolute ionized calcium level and also the rate of decrease.Plasma ph, the presence of sedatives, and concomitant decreases in magnesium, potassium, or sodium or a combination of the three may also affect the threshold.According to the aabb circular of information for the use of human blood components (revised 2017), delayed hemolytic transfusion reactions occur in previously red-cell-alloimmunized patients in whom antigens on transfused red cells provoke anamnestic production of antibody.The anamnestic response reaches a significant circulating level while the transfused cells are still present in the circulation; the usual time frame is 2 to 14 days after transfusion.Signs may include unexplained fever, development of a positive dat result, and unexplained decrease in hemoglobin/hematocrit.Hemoglobinemia and hemoglobinuria are uncommon, but elevation of lactate dehydrogenase (ldh) or bilirubin may be noted.Most delayed hemolytic reactions have a benign course and require no treatment.Hemolytic transfusion reactions in patients with sickle cell anemia may be particularly severe, with destruction of autologous as well as transfused red cells, resulting in a lower hemoglobin level after transfusion.This is suggestive of hyperhemolysis syndrome.In such patients, serologic investigations may not reveal the specificity of the causative antibody.Immediate treatment may include steroid use, ivig, avoiding transfusions, if possible.Consultation with a transfusion medicine specialist is required in these cases.Prospective matching for rh and kell antigens may decrease risk.The customer did not provide the lot number pertaining to this event, therefore a device history record (dhr) search could not be conducted for this specific incident.All lots must meet acceptance criteria before release.Investigation is in process, a follow-up report will be provided.Article citation: sharma a, leonard a, west k, et al.2022.Optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease.Br j haematol, 2022;00:1-5.

Event Description

The journal article, 'optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease', describes a study regarding haematopoietic stem and progenitor cell (hspc) apheresis collection from patients with sickle cell disease (scd) by targeting deep buffy coat collection using medium or low collection preference (cp), and by increasing anticoagulant¿citrate¿dextrose¿solution a dosage.Forty-three adverse events (aes) were reported, including one grade 4 ae (delayed haemolytic transfusion reaction related to rbc exchange; 2.3%) and 11 grade 3 aes (eight pain-related and three anaemia; 25.6%).Specifically, anaemia (hb¿<80¿g/l on the next day of the collection) was seen in one participant in the medium-cp group, one participant on two occasions in the low-cp group.Three incidents of apheresis-related hypocalcaemia (grade 1¿2, 7.0%) and six hypomagnesaemia (grade 1¿2, 14.0%) were reported.All aes resolved with supportive care.The article does not provide details related to specific patient information, therefore this report is being filed as a summary of events.The disposable collection sets are not available for return.

Event Description

The journal article, 'optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease', describes a study regarding haematopoietic stem and progenitor cell (hspc) apheresis collection from patients with sickle cell disease (scd) by targeting deep buffy coat collection using medium or low collection preference (cp), and by increasing anticoagulant¿citrate¿dextrose¿solution a dosage.Forty-three adverse events (aes) were reported, including one grade 4 ae (delayed haemolytic transfusion reaction related to rbc exchange; 2.3%) and 11 grade 3 aes (eight pain-related and three anaemia; 25.6%).Specifically, anaemia (hb<80 g/l on the next day of the collection) was seen in one participant in the medium-cp group, one participant on two occasions in the low-cp group.Three incidents of apheresis-related hypocalcaemia (grade 1¿2, 7.0%) and six hypomagnesaemia (grade 1¿2, 14.0%) were reported.All aes resolved with supportive care.The article does not provide details related to specific patient information, therefore this report is being filed as a summary of events.The disposable collection sets are not available for return.

Manufacturer Narrative

This report is being filed to provide additional information in h.6 and h.10.Investigation: the purpose of the journal article study is noted in the article abstract: the authors adjusted haematopoietic stem and progenitor cell (hspc) apheresis collection from patients with sickle cell disease (scd) by targeting deep buffy coat collection using medium or low collection preference (cp), and by increasing anticoagulant¿citrate¿dextrose¿solution a dosage.In 43 hspc collections from plerixafor mobilized adult patients with scd, we increased the collection efficiency to 35.79% using medium cp and 82.23% using low cp.Deep buffy coat collection increased red blood cell contamination of the hspc product, the product haematocrit was 4.7% with medium cp and 6.4% with low cp.These adjustments were well-tolerated and allowed efficient hspc collection from scd patients.Adult scd patients enrolled on two clinical trials (b)(4) at (b)(6) health were included.This study was approved by both institutional review boards.Participants who underwent rbc exchange with goals of haemoglobin s (hbs)100g/l (methods s1), received 240 g/ kg of plerixafor for hspc mobilization, followed by hspc collection 2¿4 h later with processing up to four total blood volumes.We used the spectra optia continuous mononuclear cell collection protocol (terumo bct) for hspc collection.Acda dose was increased by lowering the inlet/ac ratio from 12 (standard) to 8¿12.Citrate toxicity was prevented/reduced by concurrent infusion of calcium gluconate (3 g in 250ml of 0.9% saline).Additional oral calcium carbonate was given if the patient experienced paraesthesia.Summary of terumo bct product in relation to the journal article: forty-three adverse events (aes) were reported, including one grade 4 ae (delayed haemolytic transfusion reaction related to rbc exchange; 2.3%) and 11 grade 3 aes (eight pain-related and three anaemia; 25.6%).Specifically, anaemia (hb <80 g/l on the next day of the collection) was seen in one participant in the medium-cp group, one participant on two occasions in the low-cp group.Three incidents of apheresis-related hypocalcaemia (grade 1¿2, 7.0%) and six hypomagnesaemia (grade 1¿2, 14.0%) were reported.All aes resolved with supportive care.In summary, the optimized hspc collection depth and acd-a dosage allowed safe and highly efficient autologous hspc collection in scd patients.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.The threshold for developing clinical features of hypocalcemia is related to the absolute ionized calcium level and also the rate of decrease.Plasma ph, the presence of sedatives, and concomitant decreases in magnesium, potassium, or sodium or a combination of the three may also affect the threshold.According to the aabb circular of information for the use of human blood components (revised 2017), delayed hemolytic transfusion reactions occur in previously red-cell-alloimmunized patients in whom antigens on transfused red cells provoke anamnestic production of antibody.The anamnestic response reaches a significant circulating level while the transfused cells are still present in the circulation; the usual time frame is 2 to 14 days after transfusion.Signs may include unexplained fever, development of a positive dat result, and unexplained decrease in hemoglobin/hematocrit.Hemoglobinemia and hemoglobinuria are uncommon, but elevation of lactate dehydrogenase (ldh) or bilirubin may be noted.Most delayed hemolytic reactions have a benign course and require no treatment.Hemolytic transfusion reactions in patients with sickle cell anemia may be particularly severe, with destruction of autologous as well as transfused red cells, resulting in a lower hemoglobin level after transfusion.This is suggestive of hyperhemolysis syndrome.In such patients, serologic investigations may not reveal the specificity of the causative antibody.Immediate treatment may include steroid use, ivig, avoiding transfusions, if possible.Consultation with a transfusion medicine specialist is required in these cases.Prospective matching for rh and kell antigens may decrease risk.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.The customer did not provide the lot number pertaining to this event, therefore a device history record (dhr) search could not be conducted for this specific incident.All lots must meet acceptance criteria before release.Root cause: based on the available information within the journal article, a definitive root cause for the documented adverse events associated with spectra optia could not be determined.A root cause assessment was performed for the reported hypocalcemia and hypomagnesaemia.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.Symptoms of hypocalcemia may be treated with oral or intravenous calcium supplements or by adjusting the ac infusion rate.Symptoms of hypomagnesaemia may be treated with oral or intravenous magnesium supplements.A root cause assessment was performed for the reported delayed hemolytic transfusion reaction.The authors attributed the ¿delayed haemolytic transfusion reaction related to rbc exchange¿.A root cause assessment was performed for the reported anemia.Possible causes include but are not limited to: patient physiology/disease state incorrect setting of collection preference resulting in too many rbcs in the collected products side effects of mobilization regimen a root cause for the reported pain could not be determined but may be related to: discomfort at the patient access and/or return site patient¿s underlying disease state or sensitivity to the apheresis procedure.Side effects of mobilization regimen article citation: sharma a, leonard a, west k, et al.2022.Optimizing haematopoietic stem and progenitor cell apheresis collection from plerixafor-mobilized patients with sickle cell disease.Br j haematol, 2022;00:1-5.

• Brand Name: SPECTRA OPTIA
• Type of Device: SPECTRA OPTIA EXCHANGE SET
• Manufacturer (Section D): TERUMO BCT; lakewood CO 80215
• Manufacturer (Section G): TERUMO BCT; 10810 w. collins ave; lakewood CO 80215
• Manufacturer Contact: scot hilden ; 10810 w. collins ave; lakewood, CO 80215
• MDR Report Key: 15043140
• MDR Text Key: 296078392
• Report Number: 1722028-2022-00234
• Device Sequence Number: 1
• Product Code: GKT
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: BK150251
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Literature
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup,Followup
• Report Date: 07/18/2022

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 07/18/2022
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Model Number: 10220
• Device Catalogue Number: 10220
• Device Lot Number: NOT PROVIDED
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 01/23/2024
• Was Device Evaluated by Manufacturer?: No
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Other