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

Catalog Number 10220

Device Problem Insufficient Information (3190)

Patient Problems Hematoma (1884); Hypersensitivity/Allergic reaction (1907); Muscle Hypotonia (4531)

Event Date 06/27/2023

Event Type  Injury  

Manufacturer Narrative

Lot number, manufacture and expiry date are not available at this time.Investigation is in process, a follow-up report will be provided.Citation: iannaccone, a., reisch, b., kimmig, r., schmidt, b., mavarani, l., oppong, m.D., tyczynski, b., dzietko, m., jahn, m., gellhaus, a., & köninger, a.(2023).Therapeutic plasma exchange in early-onset preeclampsia: a 7-year monocentric experience.Journal of clinical medicine, 12(13), 4289.Https://doi.Org/10.3390/jcm12134289.

Event Description

Per journal article "therapeutic plasma exchange in early-onset preeclampsia: a 7-year monocentric experience" by iannaccone, a., reisch, b., kimmig, r., schmidt, b., mavarani, l., darkwah oppong, m., tyczynski, b., dzietko, m., jahn, m., gellhaus, a., köninger, a.Allergic reactions,one case of hematoma after cesarean section, probably due to the depletion of the coagulation after tpe.One patient showed vaginal bleeding associated with low fibrinogen.Another patient had a placental abruption and very low levels of fibrinogen, two patients experienced transient hypotonia during two treatments, controlled with more fluid substitution.One patient experienced an initial allergic reaction after the start of ffp substitution.Hence, this situation was handled with antihistaminic treatment without sequelae.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 the collection set is not available for return because it was discarded by the customer.

Manufacturer Narrative

This report is being filed to provide additional information in h.11.Investigation: our study cohort consists of 41 pregnant women with eope who were treated at the department of gynecology and obstetrics, university hospital essen, germany, between 2014 and 2021.21 were treated according to the standard-of-care, constituting our nontreated control group, whereas 20 cases received additional tpe and served as our study group (figure 1).Demographic and clinical characteristics of the tpe-treated and untreated groups are reported in table 1.Maternal age and the number of precedent pregnancies and deliveries did not differ between the groups.However, the mean bmi in patients treated by tpe was 33.87 + 7.67 kg/m2, significantly higher than in patients not treated by tpe (18.80 kg/m2 + 17.16, p = 0.003).In total, 95 procedures were conducted, with a mean (+ standard deviation, std) of 4.60 + 2.82 per patient, with a minimum of 1 and a maximum of 11.Tpe was started in the 24.25 + 2.59 wog, and patients stayed for 20.25 + 9.83 days in the hospital (table 1).Serial measurements of the angiogenic factors showed drops in the concentration of sflt-1 and seng after the procedure.The courses of the levels of cases 17, 21, and 23 are shown in figure 2a¿c.Sflt-1/plgf remains stable during multiple tpe treatment courses.Plgf levels revealed a fluctuating course.Interestingly, we observed higher plgf levels after tpe compared to before.Therefore, plgf rises after tpe (figure 2).The sflt-1 concentration was 19406 pg/ml before and 16,624 pg/ml after the tpes, and in the median, 4,865 pg/ml before and 11,015 pg/ml after treatments.Sflt-1 drops in the mean by -796% and in the median by -24.78% of total tpe treatments independent of single cases (table 2).The difference is statistically significant (figure 3a, p < 0.0001).The difference between the sflt-1/plgf ratio before and after the procedures remained significant (figure 3c, p = 0.009): mean 1786 before and 1364 after tpes, median 1430 before and 1153 after the tpes (table 2).During the tpe procedures, 3 l of plasma were in median replaced: during the first 10 of the 95 procedures (10.52%), exclusively fresh frozen plasma (ffp) was used.Subsequently, a 4% human albumin solution was preferred (table 3).4% human albumin was used in 34 of 95 procedures (35.79%).In 51 of 95 tpe (53.68%), we used two-thirds human albumin 4%, and one-third ffp compound.On average, 0.78 + 1.12 l of ffp were replaced, and 2.38 + 1.11 l of human albumin.The plasma flow was, on average, 41.49 + 9.24 ml/min (table 3).The course of laboratory parameters (table 5) showed slightly increased sodium and potassium levels.The levels of haptoglobin showed a median drop of -20.45%.Also, the levels of c reactive protein (-16.67%), ldh (-10.43%), total protein (-6.95%), platelets (-4.48%), and hemoglobin (-1.45%) dropped in the median.Leukocyte increase was observed by a median of 9.90% (table 5).The coagulation tests also showed significant changes: at iii and fibrinogen dropped (in the median -25.38% and -12.26%), and inr (international normalized ratio) and ptt (activated partial thromboplastin time) increased (5.56% and 10.27%, figure 5).A statistically significant difference in the levels before and after tpe for all the above parameters could be shown (figure 5).Regarding maternal complications, we had no severe adverse events but one case of hematoma after cesarean section, probably due to the depletion of the coagulation after tpe.One patient showed vaginal bleeding associated with low fibrinogen.Another patient had a placental abruption and very low levels of fibrinogen.However, this woman presented with an identical clinical problem in a further pregnancy without tpe.Two patients experienced transient hypotonia during two treatments, controlled with more fluid substitution.One patient experienced an initial allergic reaction after the start of ffp substitution.Hence, this situation was handled with antihistaminic treatment without sequelae.Two patients experienced transient hypotonia during two treatments, controlled with more fluid substitution.One patient experienced an initial allergic reaction after the start of ffp substitution.Hence, this situation was handled with antihistaminic treatment without sequelae.The gestational week at pe onset was 23.75 + 2.26 in cases treated by tpe.In contrast, in patients treated with standard-of-care, the wog at admission was 27.14 + 3.00 (p = 0.000).The gestational age in wog at delivery was also significantly lower (25.45 + 2.37) in cases treated with tpe (27.57 + 2.77¿p = 0.012¿in the control group) (table 1).The levels of angiogenic factors at presentation were not significantly different, with a mean sflt-1/plgf ratio of 1946.26 + 2301.63 in the treated group versus 2146.70 + 3273.88 in the standard-of-care cases (p = 0.826, figure 6c).Levels of sflt-1, seng, and plgf also did not differ (figure 6a,b,d).We observed a significantly lower birthweight at delivery in cases treated with tpe of 622.37 ± 323.93 g and 892.14 ± 421.98 g in non-treated cases (p = 0.028).Percentiles were also different: in mean, 16.30 ± 11.53 in treated patients and 24.37 ± 16.54 in the eope fetuses in the control group (in the median 8th in the treated cases and 20th in the control group, p = table 1).Using tpe treatments significantly increased the prolongation of pregnancy (0.004) compared to non-treated patients: on average, pregnancies complicated by eope and treated with tpe were prolonged for 8.25 ± 5.97 days, median 6 days, from the start of treatment.Instead, in the control group, delivery occurred at 3.14 ± 4.57 (median 1 day) after hospitalization (figure 7).In the case of eope, before 25wog, 11 women received tpe.In this group, 4 newborns survived, and 7 died (2 intrauterine death and 5 neonatal deaths).3 pregnant women with eope before 25 wog were treated after standard-of-care, and all newborns died (iud, s.Table 6).When tpe was started after 25wog, all 9 newborns survived.2 of the 18 newborns from eope-complicated pregnancies without the use of tpe died (iud).In total perinatal mortality was 23.80% in the control group and 35% in the tpe group, with a survival rate after 25wog of 100% in the tpe group and 88.88% in the control group (table 6).Apgar values did not differ between the two groups: the mean apgar at 1 min was 6.17 + 2.01 in both groups, with a median of 7 and apgar at 5 min was 7.56 + 1.62 versus 8 + 1.11(median 8 in both groups, p = 0.606), apgar at 10 min was 8.39 + 0.85 versus 8.53 + 0.77, in median 9 in both groups (p = 0.520).In addition, umbilical cord blood gas analysis showed overall no statistically relevant difference between the two groups: arterial ph was in mean 7.30 +0.06 versus 7.28 + 0.10, in median 7.30 versus 7.31 (p = 0.813); umbilical cord vein ph was 7.34 + 0.05 versus 7.30 + 0.11, in median 7.35 versus 7.32 (p = 0.351); base excess was 1.34 + 4.38 versus -1.44 + 3.71, in median 1.00 versus 0.00, (p = 0.100, table 6).The length of stay in the neonatal intensive care unit (nicu) was 70.22 + 51.09 days in the newborns of women treated with tpe.In contrast, the nicu stay in the non-treated group without tpe was 63.83 + 90.53 (in median 63 versus 48 days, p = 0.248).The maximal respiratory support differs between the two groups: non-invasive ventilation was used in 3 preterm newborns of the tpe group and 13 of the non-tpe group.Conversely, invasive respiratory support was necessary for 14 tpe-groups neonates and 5 non-tpe neonates.Regarding intraventricular hemorrhages, there were 5 cases in the tpe groups and 2 cases in the neonates from mothers of the control group; parenchymal bleedings were observed in 4 patients tpe-newborns, 2 of which were cerebellar, and 1 case of concomitant with a ventricular hemorrhage.In addition, one parenchymal bleeding was shown in 1 case of the non-tpe cohort.Early preeclampsia is a severe pregnancy complication affecting maternal and fetal health.This study investigates the experimental treatment of very early preeclampsia with the widespread available therapeutic plasma exchange (tpe) to reduce factors that may negatively affect preeclampsia.A low risk of morbidity and fatalities associated with plasmapheresis has been reported, but the incidence of these complications is not affected by pregnancy [18].Tpe is a frequently used and established extracorporeal clinical procedure during pregnancy for a large number of indications (e.G., ttp-thrombotic thrombocytopenic purpura, rhesus alloimmunizations, pancreatitis, ahus-atypic hemolytic uremic syndrome, acute liver failure, catastrophic antiphospholipid syndrome, sle-systemic lupus erythematosus and sle-nephritis) [19].Our data showed that tpe could significantly lower sflt-1 and seng levels and thus the sflt-1/plgf ratio.Interestingly, we observed higher plgf levels after tpe than before.We hypothesize that removing sflt-1 allows less binding of plgf to sflt-1, showing higher plgf levels after sflt-1 decreases.As a side effect, other laboratory parameters showed significant changes, i.E., c reactive protein levels, ldh, and coagulation tests, especially at iii and fibrinogen.However, these changes did not result in clinical complications, except for one patient, who presented with vaginal bleeding at low fibrinogen levels.A further patient showed placental abruption associated with very low fibrinogen levels.Afterwards, we strictly replaced fibrinogen immediately to achieve levels of 200 mg/dl.Nevertheless, the patient with placental abruption and very low fibrinogen levels presented with the same clinical symptoms in a further pregnancy without tpe.We concluded that other reasons, but not tpe, were causing this worse condition twice.The lot numbers were not provided.Hence, disposables lot history is not feasible for this journal article investigation because there are many months between collection of data, to peer review, to final publication.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.There is no evidence to indicate that the spectra optia device caused or contributed to the placental abruption.Therefore, there is no failure mode or associated risk that can be evaluated for spectra optia.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 this was a journal publication presenting data of retrospective analysis of the use of tpe in cases of 41 pregnant women with early-onset preeclampsia.A request for lot numbers is not feasible because there are many months between collection of data, to peer review, to final publication.Therefore, a dhr search could not be conducted for this specific incident.All lots must meet acceptance criteria for release.Investigation is in process, a follow-up report will be provided.Citation: iannaccone, a., reisch, b., kimmig, r., schmidt, b., mavarani, l., oppong, m.D., tyczynski, b., dzietko, m., jahn, m., gellhaus, a., & köninger, a.(2023).Therapeutic plasma exchange in early-onset preeclampsia: a 7-year monocentric experience.Journal of clinical medicine, 12(13), 4289.Https://doi.Org/10.3390/jcm12134289.

Event Description

Per journal article "therapeutic plasma exchange in early-onset preeclampsia: a 7-year monocentric experience" by iannaccone, a., reisch, b., kimmig, r., schmidt, b., mavarani, l., darkwah oppong, m., tyczynski, b., dzietko, m., jahn, m., gellhaus, a., köninger, a.Allergic reactions,one case of hematoma after cesarean section, probably due to the depletion of the coagulation after tpe.One patient showed vaginal bleeding associated with low fibrinogen.Another patient had a placental abruption and very low levels of fibrinogen, two patients experienced transient hypotonia during two treatments, controlled with more fluid substitution.One patient experienced an initial allergic reaction after the start of ffp substitution.Hence, this situation was handled with antihistaminic treatment without sequelae.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 the collection set is not available for return because it was discarded by the customer.

• 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: 18887423
• MDR Text Key: 337459027
• Report Number: 1722028-2024-00079
• Device Sequence Number: 1
• Product Code: LKN
• Combination Product (y/n): N
• Reporter Country Code: GM
• PMA/PMN Number: K183081
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Foreign,Literature
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 03/12/2024

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 03/12/2024
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Catalogue Number: 10220
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 04/17/2024
• 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