Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection
Blood research. 2023
BACKGROUND With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. METHODS This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. RESULTS CRP (p<0.001), D-dimer (p<0.001), ferritin (p=0.039), and hemoglobin (p=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (p<0.001). However, plasmapheresis did not affect the length of hospital stay (p=0.076), which could have significantly increased survival rates (p<0.001). CONCLUSION Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.
Critically ill patients with cancer and severe COVID-19 (n= 86).
Plasmapheresis in addition to routine management (intervention group, n= 45).
Routine medications for COVID-19 management (control group, n= 41).
C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, haemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. CRP, D-dimer, ferritin, and haemoglobin levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the intervention group than in the control group. Plasmapheresis did not affect the length of hospital stay.
Efficacy and Safety of Plasma Exchange as an Adjunctive Therapy for Rapidly Progressive IgA Nephropathy and Henoch-Schönlein Purpura Nephritis: A Systematic Review
International journal of molecular sciences. 2023;24(4)
Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.
Safety and efficacy of double plasma molecular adsorption system with sequential low-volume plasma exchange in intermediate-stage hepatitis B virus-related acute-on-chronic liver failure
Journal of medical virology. 2023
BACKGROUND Current evidence suggests that the mortality rate of intermediate-stage hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains high. We aimed to investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-volume plasma exchange (LPE) treatment in intermediate-stage HBV-related ACLF. METHODS This prospective study recruited intermediate-stage HBV-related ACLF patients and was registered on ClinicalTrials.gov (NCT04597164). Eligible patients were randomly divided into a trial group and a control group. Patients in both groups received comprehensive medical treatment. Patients in the trial group further received DPMAS with sequential LPE. Data were recorded from baseline to week 12. RESULTS 50 patients with intermediate-stage HBV-related ACLF were included in this study. The incidence of bleeding events and allergic reactions in the trial group was 12% and 4%, respectively, with no other treatment-related adverse events. The levels of TBIL and PT-INR, and MELD scores after each session of DPMAS with sequential LPE were significantly lower than those before treatment (all p<0.05). The 12-week cumulative liver transplantation-free survival rates in the trial and control groups were 52% and 24%, respectively (p=0.041). The 12-week cumulative overall survival rates in the trial and control groups were 64% and 36%, respectively (p=0.048). The Kaplan-Meier survival analysis revealed significant differences in liver transplantation-free survival (p=0.047) and overall survival (p=0.038) between the trial and control groups. COX regression analysis indicated that BUN (p=0.038), DPMAS with sequential LPE (p=0.048) and COSSH-ACLF II score (p<0.001) were significant risk factors for mortality. CONCLUSION DPMAS with sequential LPE treatment is safe and effective for patients with intermediate-stage HBV-related ACLF. This article is protected by copyright. All rights reserved.
Impact of therapeutic and low volume plasma exchange on clinical laboratory parameters in patients treated for Alzheimer's disease from the AMBAR study
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2023
INTRODUCTION Little is known about the impact of plasma exchange (PE) on clinical laboratory parameters in Alzheimer's disease (AD) patients. METHODS AD patients in the AMBAR trial (N = 322) received weekly therapeutic PE (TPE) for 6 weeks followed by monthly low-volume PE (LVPE) for12 months. Treatment were placebo (sham PE), low-albumin, low-albumin + IVIG (i.e., albumin alternated with intravenous immunoglobulin) and high-albumin + IVIG. RESULTS Coagulation parameters transiently increased post-TPE. Blood calcium, platelets, and albumin levels decreased but remained within the reference range. Leukocyte counts increased. Fibrinogen, hemoglobin, total protein, gamma globulin, and IgG, transiently dipped below the reference range. Hypogammaglobulinemia (7.2 g/L) persisted in pre-TPE measurements. No changes were observed during the LVPE period. Cerebrospinal fluid parameters and vital signs were unchanged throughout. CONCLUSION Laboratory parameters of AD patients were affected by TPE similarly to effects of PE-treatment for other pathologies. These effects were less pronounced or non-existent for LVPE.
Plasma exchange for acute and acute on chronic liver failure: A systematic review and Meta-Analysis
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2023
Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared to standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients > 18 years of age with ALF and ACLF. Pooled risk-ratios (RR) with corresponding 95% confidence intervals (CIs) were calculated by Mantel-Haenszel method within a random-effect model. Primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared to SMT, PE was significantly associated with higher 30-day (RR 1.41, 95%CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95%CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95%CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95%CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials (RCT), results remained unchanged in ALF but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates, or as a bridge to LT in otherwise eligible patients. Further RCTs are needed to confirm the survival benefit of PE in ACLF.
The Impact of Therapeutic Plasma Exchange on Inflammatory Markers and Acute Phase Reactants in Patients with Severe SARS-CoV-2 Infection
Medicina (Kaunas, Lithuania). 2023;59(5)
Background and Objectives: Due to the poor prognosis and the very high mortality rate associated with severe SARS-CoV-2 infections, various regimens have been tried to stop the evolution of the inflammatory cascade, such as immunomodulatory therapy and plasma clearance of the acute phase reactants involved. Therefore, the objective of this review was to analyze the effects of using therapeutic plasma exchange (TPE), also known as plasmapheresis, on the inflammatory markers of critically ill COVID-19 patients admitted to the intensive care unit (ICU). Materials and Methods: A thorough scientific database search was performed, and it included a review of articles published on PubMed, Cochrane Database, Scopus, and Web of Science from the beginning of the COVID-19 pandemic in March 2020 until September 2022 that focused on the treatment of SARS-CoV-2 infections using plasma exchange for patients admitted to the ICU. The current study included original articles, reviews, editorials, and short or special communications regarding the topic of interest. Results: A total of 13 articles were selected after satisfying the inclusion criterion of three or more patients enrolled with clinically severe COVID-19 that were eligible for TPE. From the included articles, it was observed that TPE was used as a last-resort salvage therapy that can be regarded as an alternative treatment method when the standard management for these patients fails. TPE significantly decreased the inflammatory status as measured by Interleukin-6 (IL-6), C-reactive protein (CRP), lymphocyte count, and D-dimers, as well as improving the clinical status measured with PaO(2)/FiO(2) and duration of hospitalization. The pooled mortality risk reduction after TPE was 20%. Conclusions: There are sufficient studies and evidence to show that TPE reduces inflammatory mediators and improves coagulation function and the clinical/paraclinical status. Nevertheless, although it was shown that TPE decreases the severe inflammatory status without significant complications, the improvement of survival rate remains unclear.
Efficacy and Safety of Plasma Exchange Combined with Hemoperfusion in the Treatment of Organophosphorus Poisoning: A Meta-Analysis
Blood purification. 2023;:1-13
INTRODUCTION The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning. METHODS PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria. RESULTS 14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-α (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group. CONCLUSIONS The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-α, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.
Efficacy of therapeutic plasma exchange in patients with severe COVID-19: A systematic review and meta-analysis
Reviews in medical virology. 2023;:e2435
We conducted this systematic review and meta-analysis to evaluate the existing evidence and to quantitatively synthesise evidence on the impact of therapeutic plasma exchange (TPE) on severe COVID-19 patients. This systematic review and meta-analysis protocol was prospectively registered on PROSPERO (CRD42022316331). We systemically searched six electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, clinicaltrial.gov, and Cochrane Central Register of Controlled Trials) from inception until 1 June 2022. We included studies comparing patients who received TPE versus those who received the standard treatment. For risk of bias assessment, we used the Cochrane risk of bias assessment tool, the ROBINS1 tool, and the Newcastle Ottawa scale for RCTs, non-RCTs, and observational studies, respectively. Continuous data were pooled as standardized mean difference (SMD), and dichotomous data were pooled as risk ratio in the random effect model with the corresponding 95% confidence intervals (CI). Thirteen studies (one randomized controlled trials (RCT) and 12 non-RCTs) were included in the meta-analysis, with a total of 829 patients. There is a moderate-quality evidence from one RCT that TPE reduces the lactic dehydrogenase (LDH) levels (SMD -1.09, 95% CI [-1.59 to -0.60]), D-dimer (SMD -0.86, 95% CI [-1.34 to -0.37]), and ferritin (SMD -0.70, 95% CI [-1.18 to -0.23]), and increases the absolute lymphocyte count (SMD 0.54, 95% CI [0.07-1.01]), There is low-quality evidence from mixed-design studies that TPE was associated with lower mortality (relative risk 0.51, 95% CI [0.35-0.74]), lower IL-6 (SMD -0.91, 95% CI [-1.19 to -0.63]), and lower ferritin (SMD -0.51, 95% CI [-0.80 to -0.22]) compared to the standard control. Among severely affected COVID-19 patients, TPE might provide benefits such as decreasing the mortality rate, LDH, D-dimer, IL-6, and ferritin, in addition to increasing the higher absolute lymphocyte count. Further well-designed RCTs are needed.
Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review
Annals of medicine. 2023;55(1):2227422
OBJECTIVES To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). METHODS AND ANALYSIS We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data. RESULTS Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543). CONCLUSIONS There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD. Aggregate current data of this systematic review is insufficient to definitively conclude whether therapeutic PLEX is effective in improving VA in cases of NMO or NMOSD. eng
Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition
The Cochrane database of systematic reviews. 2023;7(7):Cd015775
BACKGROUND The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. OBJECTIVES Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. SEARCH METHODS Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms 'COVID', 'amyloid', 'fibrin', 'fibrinogen'. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID-19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. SELECTION CRITERIA Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. DATA COLLECTION AND ANALYSIS Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre-developed methods for laboratory studies. We planned to perform synthesis without meta-analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post-COVID-19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). MAIN RESULTS Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria. AUTHORS' CONCLUSIONS In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.
Any person diagnosed with post‐COVID‐19 condition (PCC), (5 laboratory studies).
Plasmapheresis performed with the intention of removing amyloid fibrin(ogen) particles.
Placebo or standard of care.
No randomised controlled trials or ongoing trials where patients with PCC had undergone plasmapheresis with the intention of removing amyloid fibrin(ogen) particles were found. Five laboratory studies that assessed whether amyloid fibrin(ogen) particles were present in the blood of patients with post‐COVID‐19 condition were included. Amyloid fibrin(ogen) particles were identified in participants across the included studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls.