Efficacy of Rituximab Combined with Plasma Exchange in the Treatment of Thrombotic Thrombocytopenic Purpura(TTP)

Objective:To analyze the curative effect of rituximab combined with plasma exchange in the treatment of thrombotic thrombocytopenic purpura.Methods:70 patients with thrombotic thrombocytopenic purpura that were treated in our hospital from January 2022 to January 2023 were selected for this study.They were divided into two groups according the treatment method they were about to receive.The patients in the control group received plasma exchange.The observation group was given rituximab in addition to plasma exchange.Then,the therapeutic effects of the two groups were observed,and the incidence of adverse reactions was compared.Results:The rate of effectiveness of the treatment received in observation group and the control group was 97.14%and 82.86%,respectively.The treatment received in observation group had a better therapeutic effect(P<0.05).The incidence of adverse reactions in the observation group(22.86%)was lower than that of the control group(5.71%),with P<0.05.Conclusion:Rituximab combined with plasma exchange is relatively more effective than plasma exchange alone,with less adverse reaction,making it a viable treatment option.

Therapeutic plasma exchange in liver failure

The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure(ACLF)is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors.Therapeutic plasma exchange(TPE)has been proven to be an efficacious therapy in autoimmune conditions and altered immunity,with more recent data supporting its use in the management of liver failure.Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation(LT),who are ineligible for LT or who have no access to LT.TPE has been shown to reduce the levels of inflammatory cytokines,modulate adaptive immunity with the potential to lessen the susceptibility to infections,and reduce the levels of albumin-bound and water-bound toxins in liver failure.In patients with acute liver failure,high volume TPE has been shown to reduce the vasopressor requirement and improve survival,particularly in patients not eligible for LT.Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF.TPE may be most favorably employed as a bridge to LT in patients with ACLF.In this review,we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-onchronic liver failure:a nationwide prospective multicenter study in China

BACKGROUND： Plasma exchange （PE）-centered artificial liver support system reduced the high mortality rate of hepa titis B virus （HBV）-related acute-on-chronic liver failure （ACLF）. But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.

Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review

BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant.Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODS Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were assessed.Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist device.RESULTS Three hundred twenty four records were reviewed,of which 62 studies were found to be duplicates.Of the 262 records screened,211 studies were excluded.Fifty-one articles were assessed for eligibility,for which 7 were excluded.Twenty-nine studies were included for ALF only,and 9 studies for ACLF only.Six studies included both ALF and ACLF patients.A total of 44 publications were included.Of the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case reports.All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange.In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was seen.Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT.Using the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high.Plasma exchange in ACLF improves survival at 30-and 90-d in nontransplanted patients.Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE)in combination with continuous renal replacement therapy(CRRT) (PE+CRRT) for AFLP still needs evaluation.METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT.RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results and they were cured and discharged home after the treatment One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively.CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

The MELD scoring system for predicting prognosis in patients with severe hepatitis after plasma exchange treatment

BACKGROUND: Hepatic failure caused by severe hepatitis is a clinical syndrome where the major liver functions, particularly detoxification, synthetic functions, and metabolic regulation are impaired to different degrees, and may result in major life-threatening complications such as hepatic encephalopathy, ascites, jaundice, cholestasis, bleeding and hepatorenal syndrome. Plasma exchange (PE) has been found useful in treating patients with fulminant hepatic failure by removing hepatic toxins and replacement of clotting factors, so PE treatment has temporary supportive effects on liver failure caused by severe viral hepatitis. in this study, our aim was to predict the prognosis of patients with severe hepatitis after PE treatment using the end-stage liver disease (MELD) scoring system. METHODS: Two hundred and twenty patients were randomly divided into PE and control groups, and the MELD score was calculated for each patient according to the original formula. The efficacy of PE was assessed by mortality or improvement in biochemical parameters and MELD score. RESULTS: The levels of total bilirubin and international normalised ratio (INR) in patients whose MELD scores were between 30 and 39 were lower than those before PE treatment, as those in patients whose MELD scores were 40 or higher. The mortality of patients in the PE group with MELD scores from 30 to 39 was 50.0%, while it was 83.3% in the control group (P<0.01). The mortality of patients with MELD scores higher than 40 was 90.0% in the PE group and 98.0% in the control group (P>0.05). CONCLUSIONS: PE treatment can decrease the serum total bilirubin level and INR and MELD score of patients with severe hepatitis and improve liver function. Compared with the control group, PE can significantly decrease the mortality of patients with MELD scores from 30 to 39, but has no effect in patients with MELD scores of 40 or higher.

Therapeutic plasma exchange for hyperlipidemic pancreatitis:Current evidence and unmet needs

With changes in lifestyle and diet worldwide,the prevalence of hyperlipidemic acute pancreatitis(HLAP)has greatly increased,and it has become the most common cause of acute pancreatitis not due to gallstones or alcohol.There are many available therapies for HLAP,including oral lipid-lowering agents,intravenous insulin,heparin,and therapeutic plasmapheresis(TPE).It is believed that the risk and severity of HLAP increase with rising levels of serum triglycerides(TG),thus a rapid decrease in serum TG level is the key to the successful management of HLAP.TPE has emerged as an effective modality in rapidly reducing serum TG levels.However,due to its cost and accessibility,TPE remains poorly evaluated until now.Some studies revealed its efficacy in helping to treat and prevent the recurrence,while some studies suggested that TG levels were not correlated with disease severity,mortality,or length of hospital stay.Thus TPE might have no beneficial effect for the outcome.This article gives an overview of the published evidence of TPE in the treatment of HLAP and outlines current evidence regarding individual outcome predictors,adverse effects of the procedure,and TPE in special occasions such as for pregnant patients and patients with diabetic ketoacidosis.Future direction of TPE research for HLAP is also discussed in this review.

The critical role of therapeutic plasma exchange in ABO-incompatible liver transplantation

Background:The shortage of donor liver restricts liver transplantation(LT).Nowadays,donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor liver.Although it is now possible to perform ABO-incompatible(ABO-I)LT,antibody-mediated rejection(AMR)has been recognized as the primary cause of desperate outcomes after ABO-I LT.Anti-A/B antibody is the trigger of immune response to ABO-I LT graft injury.Therapeutic plasma ex-change(TPE)can quickly reduce the titer of plasma antibodies and effectively inhibit humoral immunity.Data sources:We searched PubMed and CNKI databases using search terms“therapeutic plasma ex-change”,“ABO-incompatible liver transplantation”,“ABO-I LT”,“liver transplantation”,“LT”,“antibody-mediated rejection”,and“AMR”.Additional publications were identified by a manual search of references from key articles.The relevant publications published before September 30,2020 were included in this review.Results:Different centers have made different attempts on whether to use TPE,when to use TPE and how often to use TPE.However,the control standard of lectin revision level is always controversial,the target titer varies significantly from center to center,and the standard target titer has not yet been estab-lished.TPE has several schemes to reduce antibody titers,but there is a lack of clinical trials that provide standardized procedures.Conclusions:TPE is essential for ABO-I LT.Hence,further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

Successful use of plasma exchange in fulminant lupus myocarditis coexisting with pneumonia: A case report

BACKGROUND Fulminant lupus myocarditis is a rare but fatal manifestation of systemic lupus erythematosus.Aggressive immunosuppressive treatments are important in its successful management.However,they can significantly damage the immunity and are associated with a considerable risk of infection development and spread.We present a rare and complicated case of a 20-year-old female diagnosed with fulminant lupus myocarditis accompanied by pneumonia.The patient was successfully treated with plasma exchange(PE)for fulminant lupus myocarditis.CASE SUMMARY A 20-year-old Chinese woman presented to the Hematology Department complaining of fatigue and knee pain.Blood test showed anemia and thrombocytopenia.On the second day of hospitalization,she was transferred to the ICU due to dyspnea and hypotension.Autoimmune profiles showed hypocomplementemia and positive antinuclear antibodies.Computer tomography showed an enlarged heart and pneumonia.Ultrasound revealed an enlarged heart with a low left ventricular ejection fraction.Fulminant lupus myocarditis with cardiogenic shock was initially considered.Due to the accompanying pneumonia,aggressive immunosuppression was contraindicated.Her cardiac function remained critical after the initial therapy of intravenous immunoglobulin and corticosteroids at a conventional dose,but she responded well to later PE therapy plus corticosteroids administration.The patient fully recovered with normal cardiac function.CONCLUSION This case indicates that PE is a valuable treatment choice without adverse effects of immunosuppression in patients with fulminant lupus myocarditis and coexisting infection.

Retrospective Analysis of Plasma Exchange Combined with Glucocorticosteroids for the Treatment of Systemic Lupus Erythematosus-related Acute Pancreatitis in Central China

Systemic lupus erythematosus-related acute pancreatitis（SLEAP） has a poor prognosis with a high mortality. We described the clinical features of SLEAP, and discussed the feasibility of plasma exchange（PE） combined with glucocorticosteroids（GC） in short-term prognosis and possible mechanism in reducing serum inflammatory cytokine IL-6 and removing serum lipids. A retrospective study was performed by an independent rheumatologist. Medical records of SLEAP from March 2010 to December 2014 were retrieved from Tongji Hospital information system, and patients were divided into two groups according to whether PE therapy was adopted. Sixteen patients treated with PE in combination with GC were classified as group A, and the other 10 patients who were treated with merely GC were classified as group B. Patients＇ clinical remission rate and average daily GC dosage after two-week therapy were compared between the two groups. Patients＇ serum inflammatory cytokines and lipid concentration were compared between baseline and after two-week treatment in both groups. Pearson correlation test was performed to determine association between serum cytokines and Ranson score. SLEDAI score in group A patients at baseline（14.8±3.1） showed no statistical difference from that in group B（14.1±3.3）. At baseline serum IL-6 levels had no significant difference between group A [13.14（11.12, 16.57） mg/L] and group B [14.63（11.37, 16.37） mg/L]; after two-week therapy IL-6 decreased significantly in group A [9.16（7.93, 10.75）mg/L] while it did not show decreasing trend in group B [13.62（9.29,17.63） mg/L]. Serum lipid concentration after two-week therapy in group A [（TC=5.02±0.53, TG=1.46±0.44） mmol/L] decreased significantly compared to baseline [（TC=6.11±0.50, TG=2.14±1.03） mmol/L], while similar tendency was not observed in group B. The remission rate after two-week therapy was higher in group A（70.0%） than in group B（25.0%）. Acute pancreatitis（AP） was one of the clinical manifestations of active SLE. PE combined with GC could reduce serum IL-6 level, and remove serum lipid to improve short-term prognosis. Therefore, it might be a safe and effective way in treating SLEAP and was worth continuing to explore its feasibility.

Streptococcal pneumonia-associated hemolytic uremic syndrome treated by T-antibody-negative plasma exchange in children: Two case reports

BACKGROUND The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS)is increasing.Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS,and T-antibody-negative plasma exchange(PE)may be effective in the treatment of severe cases of SP-HUS.CASE SUMMARY We retrospectively reviewed two pediatric patients with SP-HUS.Both clinical features and laboratory examination results of the children were described.Tantibody-negative PE was performed in both cases.Both children made a full recovery after repeated PE and remained well at a 2 year follow-up.CONCLUSION Streptococcal pneumonia continues to be an uncommon but important cause of HUS.The successful treatment of the presented cases suggests that T-antibodynegative PE may benefit patients with SP-HUS.

Successful treatment of plasma exchange-refractory thrombotic thrombocytopenic purpura with rituximab:A case report

BACKGROUND Thrombotic thrombocytopenic purpura(TTP),a subtype of thrombotic microangiopathy,has a very high fatality rate if there is no timely diagnosis or treatment.Here,we report a case of TTP refractory to high displacement plasma exchange,which was later successfully treated with rituximab.CASE SUMMARY Here we report a case of refractory TTP in a 63-year-old woman with a low platelet count and decreased ADAMTS13 activity.Her platelet count was 9×109/L,hemoglobin level was 81 g/L,and ADAMTS13 was<5%.She was diagnosed with thrombotic thrombocytopenic purpura.After 8 d of daily plasma exchange(PEX),her platelet levels were still low.However,after 6 d of treatment with rituximab,her platelet count increased and ADAMTS13 activity returned to normal.CONCLUSION PEX can cure most patients,but the relapse rate can be up to 50%-60%.This case suggested that rituximab can improve the curative efficiency of PEX and prevent disease relapse in TTP.

The Clinical Effects Study of Hepatic Failure by Intraperitoneal Injection of Antibiotics,Intravenous Injection of Terlipressin,and Combined Therapy of Coloclysis and Plasma Exchange

Objective To observe the therapeutic effects of intraperitoneal injection of antibiotics,intravenous injection of terlipressin,and combined treatment of coloclysis and plasma exchange on hepatic failure(HF),the subjects included 494 inpatient cases of hepatic failure who were treated in Department of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China from 1997 to2008.Methods The patients that met the inclusion criteria were divided into intraperitoneal antibiotic injection group,intravenous terlipressin injection group,coloclysis group,plasma exchange group,combination group of coloclysis and plasma exchange in terms of treatment given and a control group was set up for each of the treatment group.In the intraperitoneal injection group,the prognosis and changes in clinical manifestations were observed in HF patients complicated with spontaneous peritonitis(SBP).In terlipressin injection group,HF patients complicated with hepatorenal syndrome(HRS) were observed for prognosis and changes in serum creatinine.In the combination group,the improvement in serum total bilirubin and prothrombin activity were observed.Results Two weeks after intraperitoneal injection of antibiotics,the ease ratios of abdominal pain,pressure pain and rebound tenderness were 87.64%,82.02%and 82.02%in the intraperitoneal injection group,respectively and the volume of ascites obviously decreased in 69 patients(77.53%).The survival rate in intraperitoneal injection group was significantly higher than in control group(P = 0.004).Four to eight days after the intravenous injection of terlipressin,the survival rate and the rate of serum creatinine decline of the treatment group were significantly higher than those in the control group(P = 0.003,P = 0.000).After 4 weeks of treatment,the ratio of clinical symptoms improvement(acratia,anorexia,abdominal distension,constipation) in coloclysis group were60.27%,57.53%,91.78%and 94.52%,in plasma exchange group were 71.83%,69.44%,75%and 72.22%,and in combination group were 82.14%,79.46%,92.85%and 95.54%.The serum total bilirubin was decreased and the prothrombin activity increased and the differences were statistically significant as compared with control group(P= 0.000).Conclusions The intraperitoneal injection of antibiotics,intravenous injection of terlipressin and combined treatment of coloclysis and plasma exchange were all effective for the treatment of HF and its complications.

Treatment of Sepsis by Hemofiltration Combined with Plasma Exchange in One Case

Female patients,44 years old,due to'regular peritoneal dialysis5 years,stomach ache 1 week'admission.Previous had 2 times for'Peritoneal dialysis related peritonitis'in hospital,after anti-infection treatment patients symptoms improved and discharged.1 week ago in patients admitted to hospital because of abdominal pain again.Physical:abdominal tenderness,bowel sounds hyperthyroidism.Laboratory inspection index:CRP:172.22 mg/l,WBC:23.26×10~9/L,NEU%:89.23%,D dimer:3 800 ng/ml,PCT:14.86 ng/ml。

Combination therapy using low dose radiation,plasma exchange,and a robust antiviral may induce synergic beneficial interactions for mitigating severe COVID‐19

Recent studies confirm that current antiviral drugs are not fully effective on coronaviruses.Our research team introduced the idea of radiotherapy at low doses for coronavirus disease 2019(COVID-19)in March 2020.This issue later received much attention from many scientists around the world.Low dose radiation therapy exerts modulatory effects in acute inflammation,potentiate the anti-viral immune responses,and can be localized to the organ affected by inflammatory reactions,such as lungs.The findings of the first clinical trial show that low dose radiation therapy is safe,and reveal early promise of efficacy.Moreover,plasma exchange therapy may be a rescue therapy in severe COVID-19 patients,as it can quickly eliminate the cytokines and chemokines from the circulation.Remdesivir was introduced as an anti-virus agent that prevents viral RNA synthesis and coronavirus replication and reduces the viral load.If antiviral therapy is poor,the virus has ample opportunity to mutate and increase its fitness through adaptive mutations.Given this consideration,instead a single treatment,we preferentially recommend a combination therapy using low dose radiation therapy plasma exchange and a robust antiviral agent(not yet available).This review provides a viewpoint concerning the potential synergistic effects of low dose radiation therapy,plasma exchange therapy and robust antiviral agent in severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)-infected patients as a more effective strategy for possible treatment of severe COVID-19 patients.

Double Plasma Molecular Adsorption System with Sequential Low-dose Plasma Exchange in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure:A Prospective Study

Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.