| Catalog Number |
10220 |
| Medical Device Problem Codes |
Adverse Event Without Identified Device or Use Problem (2993); Insufficient Device Problem Information (3190)
|
| Health Effect - Clinical Codes |
Hemorrhage/Blood Loss/Bleeding (1888); Hematuria (2558)
|
| Date of Event |
04/21/2024
|
|
Type of Reportable Event
|
Serious Injury
|
|
Event or Problem Description
|
|
Per journal article, "a lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single-center analysis" by wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a., plasma exchange (plex) therapy is indicated for several disorders.The 5% albumin is often used as a sole replacement fluid during most plex.However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%.Although most coagulation factors recover to hemostatic levels within 24 h post-plex, fibrinogen requires 4872 h to recover.Fibrinogen is the key coagulation protein for hemostasis.Therefore, fibrinogen is often monitored during the acute course of plex, and plasma is supplemented to prevent bleeding if fibrinogen is 100 mg/dl.We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80 100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal.The study group was compared to patients with plasma fibrinogen 100 mg/dl.Results: among the 275 patients who received 1406 plexes, 62 patients (23%) who underwent 323 plexes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants.In contrast, out of 275 patients, 143 (52%) with fibrinogen levels 100 mg/dl received 751 plex treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin.Findings suggest that a pre-procedure fibrinogen threshold of 80 100 mg/dl without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.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.
|
| |
|
Additional Manufacturer Narrative
|
|
Investigation: lot number, manufacture and expiry date are not available at this time.Investigation is in process, a follow-up report will be provided.Wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a.(2024).A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single center analysis.Transfusion, 64(6), 1076, 1082.Https://doi.Org/10.1111/trf.17865.
|
| |
|
Event or Problem Description
|
|
Per journal article, "a lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single-center analysis" by wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a., plasma exchange (plex) therapy is indicated for several disorders.The 5% albumin is often used as a sole replacement fluid during most plex.However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%.Although most coagulation factors recover to hemostatic levels within 24 h post-plex, fibrinogen requires 48¿¿¿72 h to recover.Fibrinogen is the key coagulation protein for hemostasis.Therefore, fibrinogen is often monitored during the acute course of plex, and plasma is supplemented to prevent bleeding if fibrinogen is ¿¿¿100 mg/dl.We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal.The study group was compared to patients with plasma fibrinogen ¿¿¿100 mg/dl.Results: among the 275 patients who received 1406 plexes, 62 patients (23%) who underwent 323 plexes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants.In contrast, out of 275 patients, 143 (52%) with fibrinogen levels ¿¿¿100 mg/dl received 751 plex treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin.Findings suggest that a pre-procedure fibrinogen threshold of 80¿¿¿100 mg/dl without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.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.
|
| |
|
Additional Manufacturer Narrative
|
|
This report is being filed to provide additional information in h.6 and h.11.Investigation: since this was a journal publication evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal, 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.We prospectively included all consecutive adult patients treated with an acute course of plex with a replacement fluid of 5% albumin at ut southwestern medical center in dallas, tx, between may 2020 and november 2022.All patients were observed during the plex session and up to 72 h later for clinical evidence of bleeding via review of the electronic medical records.Pre-procedure fibrinogen levels were obtained with the morning blood draws 3¿¿¿4 h before the procedure.Clauss fibrinogen assay was used to measure fibrinogen level.If pre-procedure fibrinogen level was ¿¿¿80 mg/dl, plasma was added to the replacement fluid for that day's procedure.Cvc was placed for patients without adequate peripheral veins.Patient demographic data collected included age, gender, and admission diagnosis.The procedural data collected for each patient included plex indication, replacement fluid, treatment duration, equipment used, anticoagulant type, access, and incidence and type of bleeding.We also performed baseline prothrombin time (pt) and activated partial thromboplastin time (aptt) before the first plex.Patients on unfractionated heparin (ufh) were monitored using anti-xa activity without antithrombin (at), which was drawn as part of the routine morning labs for patients on steady dose, or 6 h after any dose change, per our institutional policy.Post-plex anti-xa activity without at was collected for those patients in our study who were on uf h therapy.The infusion was held for 1 h before the plex procedure and resumed 1 h after the procedure based on that value per our institution protocol.The primary team checked anti- xa 1 h after plex completion and adjusted the heparin dose per our institutional protocol.The primary endpoint in this study was the incidence of bleeding during the course of plex and 72 h after the completion of the course or at discharge, if the patient was discharged ¿¿¿72 h post-plex.Secondary endpoints included complications of bleeding during the cvc removal.Standard descriptive statistics were used to describe the characteristics of patients.Results: overall, 275 patients underwent 1406 plex treatments using the spectra optia apheresis system (terumo bct, lakewood, co) and a 12:1 ratio of acid citrate dextrose formula a (acd-a) for anticoagulation.Sixty-two (23%) patients (34 females and 28 males; mean age 51 [sd 17] years, range 18¿¿¿81 years old) had a fibrinogen value between 80 and 100 mg/dl before 323 plex treatments.Fifty-three (85%) patients received plex for neurological indications, seven for antibody-mediated rejection of heart (n = 2), kidney (n = 2), or lung transplants (n = 3), and two for pre-hematopoietic stem cell transplant desensitization.The average number of plex procedures was five over a period of 8 days.All but one patient received a 1.0 volume plex.This patient was diagnosed with myasthenia gravis exacerbation and received a 1.2 volume exchange for the first three procedures while in the medical intensive care unit and transitioned to 1.0 volume for the remaining two procedures once transferred to the floor.Six (10%) patients received a combination of 5% albumin and normal saline (ns) as replacement fluid, either at a ratio of 70% albumin to 30% ns (n = 4) or 80% albumin to 20% ns (n = 2).Baseline fibrinogen levels were collected for 61 (98%) patients, and all had fibrinogen ¿¿¿100 mg/dl (the lowest fibrinogen value was 121 mg/dl).All patients had normal baseline pt and aptt.In 57 patients, plex reduced fibrinogen by an average of ¿¿¿54% with each procedure, since there was some recovery between end of procedure and next fibrinogen.These reductions persisted throughout the observation period at 80¿¿¿100 mg/dl.For most patients, the fibrinogen level recovered up to 66% of baseline levels by 72 h post plex, based on pre-procedure fibrinogen collected prior to plex #3.Most of these patients (85%) had plexes on two consecutive days between the first and second days and then every other day.Some patients (20%) had skipped a day between the first and the second procedure.Of 62 patients, 47 (76%) had fibrinogen levels between 90 and 100 mg/dl, while 13 (21%) had a fibrinogen level of 80¿¿¿89 mg/dl at enrollment.In addition, two (3%) patients had fibrinogen of 85¿¿¿90 mg/dl prior to cvc removal without fibrinogen replacement and had no bleeding complications.Forty four of 62 (27%) patients had fibrinogen levels ¿¿¿80 mg/dl during their course of plex, and plasma was added to the replacement fluid for the subsequent procedure.Thirteen patients that did not receive fibrinogen replacement for a pre-procedure fibrinogen of 80¿¿¿100 mg/dl required fibrinogen supplementation on the subsequent procedure for fibrinogen ¿¿¿80 mg/dl.Of the 17 patients who required supplementation, only one (2%) patient needed fibrinogen supplementation more than once during the course of plex, with the fourth and the seventh treatments.In two (3%) patients, the primary team checked fibrinogen level 6 h post plex number five prior to cvc removal, per our institutional protocol, and gave plasma for fibrinogen levels of 84 and 85 mg/dl before cvc removal owing to bleeding concerns.Out of 275 patients, 143 (52%) patients who underwent 751 plexes with a fibrinogen ¿¿¿100 mg/dl and had no concern for bleeding or a history of bleeding disorder or renal disease constituted our comparator group.Patients ranged in age from 23 to 88 years (mean 55 [sd 16] years).Eighty-seven (61%) were men and 56 (39%) were women.Most patients (107, 75%) received plex for a neurological indication with a smaller subset of other diagnoses (light chain nephropathy n = 14, heart transplant rejection n = 6, lung transplant rejection n = 8, hsct with a high anti a titer n = 4, and hsct desensitization n = 4).The comparator group had higher mean age than the study group (p =.04), however the age difference was minor (51 years in the study group vs 55 in the comparator group).There was no statistically significant difference between the two groups in regards to indication for plex.These findings are summarized in table 1.The baseline fibrinogen was 164¿¿¿669 mg/dl and remained ¿¿¿100 mg/dl.Of these 143 patients, 116 (81%) patients received five sessions of plex over a period of 8 days, and 27 (19%) received more than 5 plex sessions.Ten (7%) patients received a 1.2 volume exchange with albumin, and 21 (15%) patients received a combination of 5% albumin to 30% ns (n = 16) or 80% albumin to 20% ns (n = 5).Twenty-five of 27 (93%) patients received seven treatments, one patient had 10 treatments (fibrinogen range: 146¿¿¿411 mg/dl), and another had 11 treatments (fibrinogen 113¿¿¿321 mg/dl).Average preprocedure fibrinogen values for patients in both groups that did not receive fibrinogen supplementation are summarized in table 2.Anticoagulation therapy twenty-three out of 62 (37%) patients in the study group received low-molecular-weight heparin (lmwh) for deep vein thrombosis (dvt) prophylaxis and 2 (3%) patients received ufh infusion, one each for pulmonary embolus (pe) and dvt.In the two patients on ufh, post-plex anti-xa decreased from 0.58 and 0.56 iu/ml to 0.28 and 0.26 iu/ml, respectively.Nine (15%) patients were on direct oral anticoagulants (doacs) throughout plex (apixaban, n = 4; rivaroxaban, n = 5), five (8%) patients were on subcutaneous (sq) heparin for dvt prophylaxis, and five (8%) were on vitamin k antagonists (warfarin).Only two patients had minor bleeding.One patient who received apixaban had bleeding at his femoral cvc insertion site.His hemoglobin level was 12 g/dl and remained stable.Another patient was on warfarin throughout plex and developed postprocedural peripheral intravenous catheter (piv) site bleeding that stopped, and hemostasis was achieved after pressure was applied.His baseline inr was 2.0, and subsequent inr was not checked.His hemoglobin level dropped by 0.1 g/dl (9.9¿¿¿ 9.8 g/dl).Of the 143 patients with fibrinogen ¿¿¿100 mg/dl throughout the course of plex, 49 (34%) patients received lmwh for dvt prophylaxis, and all had normal renal functions; 24 (17%) patients were on sq heparin for dvt prophylaxis.Five (3%) patients received ufh infusion for pe and dvt.Of those five patients who were on ufh, four patients had a post-plex decrease in anti-xa from 0.75¿¿¿0.64 iu/ml to 0.23¿¿¿0.32 iu/ml, and one patient had increased anti-xa from 0.48 to 1.33 after completing his third procedure.In the patient with increased anti-xa activity post-plex, heparin was held for 2 h and re-started at a decreased rate.Repeat anti-xa drawn within 1 h of restarting the infusion was 1.38, however, at 8 h after restarting ufh the anti-xa was below therapeutic range at 0.35.Seventeen (12%) patients were on doacs throughout plex (apixaban, n = 6; rivaroxaban, n = 9) and two patients were on warfarin.Only two (2%) patients experienced mild bleeding following plex.One patient had minor hematuria prior to his second plex, and the second patient reported mild bleeding from the cvc insertion site after his third plex.The bleeding stopped after direct pressure was applied, and this patient did not receive fibrinogen replacement.Both patients had fibrinogen levels between 123 and 150 mg/dl and were on lmwh (enoxaparin) 40 mg sq daily, and had normal renal functions (gfr ¿¿¿ 60 ml/min/1.73 m2, creatinine 0.83¿¿¿0.91 mg/dl, albumin ¿¿¿4 g/dl).Type of anticoagulation used in both groups is summarized in table 1.There was no statistically significant difference between anticoagulant use in the two groups.Vascular access used for the study and comparator groups is depicted in table 1.There was no statistically significant difference between groups regarding type of access used.Of the 17 (27%) patients in the study group who had plex with piv, only one patient had mild bleeding from the iv puncture site before plex #5 and received plasma for fibrinogen level ¿¿¿70 mg/dl.Of the 40 (65%) patients with cvc, 16 (40%) patients had a fibrinogen level ¿¿¿100 mg/dl before line removal, and only one patient had minimal bleeding from the femoral line 24 h after his last plex session.Of note, this patient was on apixaban twice a day.The primary team did not remove the femoral line owing to an access issue.This patient had a fibrinogen level of 97 mg/dl post-plex.His bleeding stopped after pressure was applied, and the primary team gave him 1 unit of cryoprecipitate.Of the 143 patients in the comparator group, only two patients had minor bleeding despite fibrinogen being ¿¿¿100 mg/dl; bleeding in these patients was not associated with vascular access.Discussion: in our study, 97% of patients who received an acute course of plex with fibrinogen levels between 80 and 100 mg/dl without fibrinogen supplementation did not have any reported bleeding.Only 2 (3%) patients in our study group had minor bleeding at the access site, and both were on concomitant direct oral anticoagulation therapy.In the comparator group, two patients had minor bleeding despite fibrinogen being ¿¿¿100 mg/dl and did not receive plasma or cryoprecipitate.Bleeds in both groups occurred in patients who were on anticoagulation therapy.Our prospective findings are similar to a retrospective study by z¿¿llner et al., which analyzed bleeding incidence in 67 patients (1032 treatments) undergoing plex and immunoadsorption (ias) procedures.15 severe hypofibrinogenemia (¿¿¿100 mg/dl) occurred after 20% of plex and 17% of plex/ias treatments, with a bleeding incidence of 2.3% in plex and 3.1% in (plex/ias) respectively.In our study, only 2 (3%) patients had minor bleeding at the iv insertion site, one with piv and another with a femoral cvc.The bleeding in the patient with the femoral line was noted after a physical therapy session 24 h after his last plex procedure with a fibrinogen level of 97 mg/dl, while he was also on apixaban twice daily.Therefore, it seems that the combination of physical activity and anticoagulation likely contributed to his bleeding in the setting of hypofibrinogenemia.The second patient on warfarin developed postprocedural piv site bleeding after his third plex session, and the bleeding stopped after direct pressure was applied for ~10 min.Pre-procedure fibrinogen was 82 mg/dl and the procedure was completed without fibrinogen replacement.At the time of bleeding, his fibrinogen was ¿¿¿70 mg/dl, and thus he was transfused cryoprecipitate.Unfortunately, his pt/inr and ptt levels were not checked other than prior to his first session of plex.Zantek et al.Reported similar bleeding rates in a prospective case series of eight patients on warfarin who underwent 123 plex sessions with 5% albumin replacement.16 following plex, inr increased approximately two-fold from an average of 2.09 to 4.12, and fibrinogen decreased by 60%¿¿¿65%.16 post-procedure fibrinogen was ¿¿¿100 mg/dl in 61 (50%) plex treatments and five procedures (4%) with fibrinogen ¿¿¿61 mg/dl.Pre-fibrinogen values for these procedures were between 147 and 167 mg/dl.16 only one patient developed postprocedural tunneled catheter bleeding after the sixth procedure that was resolved after a dressing change.16 the patient's inr post-procedure was 3.17 with a fibrinogen of 117 mg/dl, which increased from the pre-procedure inr of 1.66 and decrease in fibrinogen from 287 mg/dl.16 twenty-three (38%) patients in our study were on lmwh during their acute course of plex without bleeding, similar to the reported incidence in the previous study.5 in the two patients receiving ufh, anti-xa activity decreased following plex likely owing to both direct removal of heparin, as well as removal of at.This decrease in at likely offset the removal of procoagulant factors and helped to balance the coagulopathy from plex so that overall bleeding risk was not increased in patients receiving heparin drip.5 thus, the bleeding risk seems more likely associated with oral anticoagulation than parental heparin therapy.Fibrinogen decreased 54%¿¿¿80% post-procedure in our patients using 5% albumin as a replacement fluid, which was similar to that reported in the literature of 60%¿¿¿70%.7,15 in our study, plex reduced fibrinogen on average by ~54% and in some patients by up to 80% and this reduction in fibrinogen persisted throughout the observation period at 80¿¿¿100 mg/dl.For most of our patients, the fibrinogen level recovered by 66% of pre-apheresis levels by 72 h post plex.Conclusion: this prospective observational study suggests that severe hypofibrinogenemia (80¿¿¿100 mg/dl) in patients undergoing plex with 5% albumin replacement without fibrinogen supplementation is not associated with an increased bleeding risk versus the comparator group with fibrinogen ¿¿¿100 mg/dl.The primary risk factor associated with bleeding appears to be concomitant oral anticoagulation.Thus, by lowering the threshold for fibrinogen supplementation to ¿¿¿80 mg/dl, patients undergoing plex will likely benefit by avoiding unnecessary exposure to plasma or cryoprecipitate.Disposables lot history: since this was a journal publication evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.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.Investigation is in process, a follow-up report will be provided.Wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a.(2024).A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single¿¿¿center analysis.Transfusion, 64(6), 1076¿¿¿1082.Https://doi.Org/10.1111/trf.17865.
|
| |
|
Additional Manufacturer Narrative
|
|
This report is being filed to provide additional information in h.6 and h.11.Investigation: since this was a journal publication evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal, 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.We prospectively included all consecutive adult patients treated with an acute course of plex with a replacement fluid of 5% albumin at ut southwestern medical center in dallas, tx, between may 2020 and november 2022.All patients were observed during the plex session and up to 72 h later for clinical evidence of bleeding via review of the electronic medical records.Pre-procedure fibrinogen levels were obtained with the morning blood draws 3¿¿¿4 h before the procedure.Clauss fibrinogen assay was used to measure fibrinogen level.If pre-procedure fibrinogen level was ¿¿¿80 mg/dl, plasma was added to the replacement fluid for that day's procedure.Cvc was placed for patients without adequate peripheral veins.Patient demographic data collected included age, gender, and admission diagnosis.The procedural data collected for each patient included plex indication, replacement fluid, treatment duration, equipment used, anticoagulant type, access, and incidence and type of bleeding.We also performed baseline prothrombin time (pt) and activated partial thromboplastin time (aptt) before the first plex.Patients on unfractionated heparin (ufh) were monitored using anti-xa activity without antithrombin (at), which was drawn as part of the routine morning labs for patients on steady dose, or 6 h after any dose change, per our institutional policy.Post-plex anti-xa activity without at was collected for those patients in our study who were on uf h therapy.The infusion was held for 1 h before the plex procedure and resumed 1 h after the procedure based on that value per our institution protocol.The primary team checked anti- xa 1 h after plex completion and adjusted the heparin dose per our institutional protocol.The primary endpoint in this study was the incidence of bleeding during the course of plex and 72 h after the completion of the course or at discharge, if the patient was discharged ¿¿¿72 h post-plex.Secondary endpoints included complications of bleeding during the cvc removal.Standard descriptive statistics were used to describe the characteristics of patients.Results: overall, 275 patients underwent 1406 plex treatments using the spectra optia apheresis system (terumo bct, lakewood, co) and a 12:1 ratio of acid citrate dextrose formula a (acd-a) for anticoagulation.Sixty-two (23%) patients (34 females and 28 males; mean age 51 [sd 17] years, range 18¿¿¿81 years old) had a fibrinogen value between 80 and 100 mg/dl before 323 plex treatments.Fifty-three (85%) patients received plex for neurological indications, seven for antibody-mediated rejection of heart (n = 2), kidney (n = 2), or lung transplants (n = 3), and two for pre-hematopoietic stem cell transplant desensitization.The average number of plex procedures was five over a period of 8 days.All but one patient received a 1.0 volume plex.This patient was diagnosed with myasthenia gravis exacerbation and received a 1.2 volume exchange for the first three procedures while in the medical intensive care unit and transitioned to 1.0 volume for the remaining two procedures once transferred to the floor.Six (10%) patients received a combination of 5% albumin and normal saline (ns) as replacement fluid, either at a ratio of 70% albumin to 30% ns (n = 4) or 80% albumin to 20% ns (n = 2).Baseline fibrinogen levels were collected for 61 (98%) patients, and all had fibrinogen ¿¿¿100 mg/dl (the lowest fibrinogen value was 121 mg/dl).All patients had normal baseline pt and aptt.In 57 patients, plex reduced fibrinogen by an average of ¿¿¿54% with each procedure, since there was some recovery between end of procedure and next fibrinogen.These reductions persisted throughout the observation period at 80¿¿¿100 mg/dl.For most patients, the fibrinogen level recovered up to 66% of baseline levels by 72 h post plex, based on pre-procedure fibrinogen collected prior to plex #3.Most of these patients (85%) had plexes on two consecutive days between the first and second days and then every other day.Some patients (20%) had skipped a day between the first and the second procedure.Of 62 patients, 47 (76%) had fibrinogen levels between 90 and 100 mg/dl, while 13 (21%) had a fibrinogen level of 80¿¿¿89 mg/dl at enrollment.In addition, two (3%) patients had fibrinogen of 85¿¿¿90 mg/dl prior to cvc removal without fibrinogen replacement and had no bleeding complications.Forty four of 62 (27%) patients had fibrinogen levels ¿¿¿80 mg/dl during their course of plex, and plasma was added to the replacement fluid for the subsequent procedure.Thirteen patients that did not receive fibrinogen replacement for a pre-procedure fibrinogen of 80¿¿¿100 mg/dl required fibrinogen supplementation on the subsequent procedure for fibrinogen ¿¿¿80 mg/dl.Of the 17 patients who required supplementation, only one (2%) patient needed fibrinogen supplementation more than once during the course of plex, with the fourth and the seventh treatments.In two (3%) patients, the primary team checked fibrinogen level 6 h post plex number five prior to cvc removal, per our institutional protocol, and gave plasma for fibrinogen levels of 84 and 85 mg/dl before cvc removal owing to bleeding concerns.Out of 275 patients, 143 (52%) patients who underwent 751 plexes with a fibrinogen ¿¿¿100 mg/dl and had no concern for bleeding or a history of bleeding disorder or renal disease constituted our comparator group.Patients ranged in age from 23 to 88 years (mean 55 [sd 16] years).Eighty-seven (61%) were men and 56 (39%) were women.Most patients (107, 75%) received plex for a neurological indication with a smaller subset of other diagnoses (light chain nephropathy n = 14, heart transplant rejection n = 6, lung transplant rejection n = 8, hsct with a high anti a titer n = 4, and hsct desensitization n = 4).The comparator group had higher mean age than the study group (p =.04), however the age difference was minor (51 years in the study group vs 55 in the comparator group).There was no statistically significant difference between the two groups in regards to indication for plex.These findings are summarized in table 1.The baseline fibrinogen was 164¿¿¿669 mg/dl and remained ¿¿¿100 mg/dl.Of these 143 patients, 116 (81%) patients received five sessions of plex over a period of 8 days, and 27 (19%) received more than 5 plex sessions.Ten (7%) patients received a 1.2 volume exchange with albumin, and 21 (15%) patients received a combination of 5% albumin to 30% ns (n = 16) or 80% albumin to 20% ns (n = 5).Twenty-five of 27 (93%) patients received seven treatments, one patient had 10 treatments (fibrinogen range: 146¿¿¿411 mg/dl), and another had 11 treatments (fibrinogen 113¿¿¿321 mg/dl).Average preprocedure fibrinogen values for patients in both groups that did not receive fibrinogen supplementation are summarized in table 2.Anticoagulation therapy twenty-three out of 62 (37%) patients in the study group received low-molecular-weight heparin (lmwh) for deep vein thrombosis (dvt) prophylaxis and 2 (3%) patients received ufh infusion, one each for pulmonary embolus (pe) and dvt.In the two patients on ufh, post-plex anti-xa decreased from 0.58 and 0.56 iu/ml to 0.28 and 0.26 iu/ml, respectively.Nine (15%) patients were on direct oral anticoagulants (doacs) throughout plex (apixaban, n = 4; rivaroxaban, n = 5), five (8%) patients were on subcutaneous (sq) heparin for dvt prophylaxis, and five (8%) were on vitamin k antagonists (warfarin).Only two patients had minor bleeding.One patient who received apixaban had bleeding at his femoral cvc insertion site.His hemoglobin level was 12 g/dl and remained stable.Another patient was on warfarin throughout plex and developed postprocedural peripheral intravenous catheter (piv) site bleeding that stopped, and hemostasis was achieved after pressure was applied.His baseline inr was 2.0, and subsequent inr was not checked.His hemoglobin level dropped by 0.1 g/dl (9.9¿¿¿ 9.8 g/dl).Of the 143 patients with fibrinogen ¿¿¿100 mg/dl throughout the course of plex, 49 (34%) patients received lmwh for dvt prophylaxis, and all had normal renal functions; 24 (17%) patients were on sq heparin for dvt prophylaxis.Five (3%) patients received ufh infusion for pe and dvt.Of those five patients who were on ufh, four patients had a post-plex decrease in anti-xa from 0.75¿¿¿0.64 iu/ml to 0.23¿¿¿0.32 iu/ml, and one patient had increased anti-xa from 0.48 to 1.33 after completing his third procedure.In the patient with increased anti-xa activity post-plex, heparin was held for 2 h and re-started at a decreased rate.Repeat anti-xa drawn within 1 h of restarting the infusion was 1.38, however, at 8 h after restarting ufh the anti-xa was below therapeutic range at 0.35.Seventeen (12%) patients were on doacs throughout plex (apixaban, n = 6; rivaroxaban, n = 9) and two patients were on warfarin.Only two (2%) patients experienced mild bleeding following plex.One patient had minor hematuria prior to his second plex, and the second patient reported mild bleeding from the cvc insertion site after his third plex.The bleeding stopped after direct pressure was applied, and this patient did not receive fibrinogen replacement.Both patients had fibrinogen levels between 123 and 150 mg/dl and were on lmwh (enoxaparin) 40 mg sq daily, and had normal renal functions (gfr ¿¿¿ 60 ml/min/1.73 m2, creatinine 0.83¿¿¿0.91 mg/dl, albumin ¿¿¿4 g/dl).Type of anticoagulation used in both groups is summarized in table 1.There was no statistically significant difference between anticoagulant use in the two groups.Vascular access used for the study and comparator groups is depicted in table 1.There was no statistically significant difference between groups regarding type of access used.Of the 17 (27%) patients in the study group who had plex with piv, only one patient had mild bleeding from the iv puncture site before plex #5 and received plasma for fibrinogen level ¿¿¿70 mg/dl.Of the 40 (65%) patients with cvc, 16 (40%) patients had a fibrinogen level ¿¿¿100 mg/dl before line removal, and only one patient had minimal bleeding from the femoral line 24 h after his last plex session.Of note, this patient was on apixaban twice a day.The primary team did not remove the femoral line owing to an access issue.This patient had a fibrinogen level of 97 mg/dl post-plex.His bleeding stopped after pressure was applied, and the primary team gave him 1 unit of cryoprecipitate.Of the 143 patients in the comparator group, only two patients had minor bleeding despite fibrinogen being ¿¿¿100 mg/dl; bleeding in these patients was not associated with vascular access.Discussion: in our study, 97% of patients who received an acute course of plex with fibrinogen levels between 80 and 100 mg/dl without fibrinogen supplementation did not have any reported bleeding.Only 2 (3%) patients in our study group had minor bleeding at the access site, and both were on concomitant direct oral anticoagulation therapy.In the comparator group, two patients had minor bleeding despite fibrinogen being ¿¿¿100 mg/dl and did not receive plasma or cryoprecipitate.Bleeds in both groups occurred in patients who were on anticoagulation therapy.Our prospective findings are similar to a retrospective study by z¿¿llner et al., which analyzed bleeding incidence in 67 patients (1032 treatments) undergoing plex and immunoadsorption (ias) procedures.15 severe hypofibrinogenemia (¿¿¿100 mg/dl) occurred after 20% of plex and 17% of plex/ias treatments, with a bleeding incidence of 2.3% in plex and 3.1% in (plex/ias) respectively.In our study, only 2 (3%) patients had minor bleeding at the iv insertion site, one with piv and another with a femoral cvc.The bleeding in the patient with the femoral line was noted after a physical therapy session 24 h after his last plex procedure with a fibrinogen level of 97 mg/dl, while he was also on apixaban twice daily.Therefore, it seems that the combination of physical activity and anticoagulation likely contributed to his bleeding in the setting of hypofibrinogenemia.The second patient on warfarin developed postprocedural piv site bleeding after his third plex session, and the bleeding stopped after direct pressure was applied for ~10 min.Pre-procedure fibrinogen was 82 mg/dl and the procedure was completed without fibrinogen replacement.At the time of bleeding, his fibrinogen was ¿¿¿70 mg/dl, and thus he was transfused cryoprecipitate.Unfortunately, his pt/inr and ptt levels were not checked other than prior to his first session of plex.Zantek et al.Reported similar bleeding rates in a prospective case series of eight patients on warfarin who underwent 123 plex sessions with 5% albumin replacement.16 following plex, inr increased approximately two-fold from an average of 2.09 to 4.12, and fibrinogen decreased by 60%¿¿¿65%.16 post-procedure fibrinogen was ¿¿¿100 mg/dl in 61 (50%) plex treatments and five procedures (4%) with fibrinogen ¿¿¿61 mg/dl.Pre-fibrinogen values for these procedures were between 147 and 167 mg/dl.16 only one patient developed postprocedural tunneled catheter bleeding after the sixth procedure that was resolved after a dressing change.16 the patient's inr post-procedure was 3.17 with a fibrinogen of 117 mg/dl, which increased from the pre-procedure inr of 1.66 and decrease in fibrinogen from 287 mg/dl.16 twenty-three (38%) patients in our study were on lmwh during their acute course of plex without bleeding, similar to the reported incidence in the previous study.5 in the two patients receiving ufh, anti-xa activity decreased following plex likely owing to both direct removal of heparin, as well as removal of at.This decrease in at likely offset the removal of procoagulant factors and helped to balance the coagulopathy from plex so that overall bleeding risk was not increased in patients receiving heparin drip.5 thus, the bleeding risk seems more likely associated with oral anticoagulation than parental heparin therapy.Fibrinogen decreased 54%¿¿¿80% post-procedure in our patients using 5% albumin as a replacement fluid, which was similar to that reported in the literature of 60%¿¿¿70%.7,15 in our study, plex reduced fibrinogen on average by ~54% and in some patients by up to 80% and this reduction in fibrinogen persisted throughout the observation period at 80¿¿¿100 mg/dl.For most of our patients, the fibrinogen level recovered by 66% of pre-apheresis levels by 72 h post plex.Conclusion: this prospective observational study suggests that severe hypofibrinogenemia (80¿¿¿100 mg/dl) in patients undergoing plex with 5% albumin replacement without fibrinogen supplementation is not associated with an increased bleeding risk versus the comparator group with fibrinogen ¿¿¿100 mg/dl.The primary risk factor associated with bleeding appears to be concomitant oral anticoagulation.Thus, by lowering the threshold for fibrinogen supplementation to ¿¿¿80 mg/dl, patients undergoing plex will likely benefit by avoiding unnecessary exposure to plasma or cryoprecipitate.Disposables lot history: since this was a journal publication evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.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.Root cause: 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.* patients received anticoagulation therapy.Citation: wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a.(2024).A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single¿¿¿center analysis.Transfusion, 64(6), 1076¿¿¿1082.Https://doi.Org/10.1111/trf.17865.
|
| |
|
Event or Problem Description
|
|
Per journal article, "a lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: a prospective single-center analysis" by wodajo, a., sarode, r., valiyaparambil, s., webb, c., de simone, n., rebecca, d., & usmani, a., plasma exchange (plex) therapy is indicated for several disorders.The 5% albumin is often used as a sole replacement fluid during most plex.However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%.Although most coagulation factors recover to hemostatic levels within 24 h post-plex, fibrinogen requires 48¿¿¿72 h to recover.Fibrinogen is the key coagulation protein for hemostasis.Therefore, fibrinogen is often monitored during the acute course of plex, and plasma is supplemented to prevent bleeding if fibrinogen is ¿¿¿100 mg/dl.We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of plex with a fibrinogen level of 80¿¿¿100 mg/dl without plasma supplementation during the procedure or before central venous catheter removal.The study group was compared to patients with plasma fibrinogen ¿¿¿100 mg/dl.Results: among the 275 patients who received 1406 plexes, 62 patients (23%) who underwent 323 plexes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants.In contrast, out of 275 patients, 143 (52%) with fibrinogen levels ¿¿¿100 mg/dl received 751 plex treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin.Findings suggest that a pre-procedure fibrinogen threshold of 80¿¿¿100 mg/dl without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.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.
|
| |
|
Search Alerts/Recalls
|
|
