Therapeutic Plasma Exchange Group Research Articles

Comparative efficacy of therapeutic plasma exchange and insulin in hypertriglyceridemia-induced acute pancreatitis.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents a therapeutic challenge with no currently definitive treatment, including therapeutic plasma exchange (TPE) and insulin. TPE aims to quickly reduce serum triglyceride (TG); however, its efficacy lacks convincing evidence. Intravenous insulin is a promising and convenient alternative, while comparative data is limited. This retrospective, single-center study compared TPE and insulin treatment in HTG-AP patients. The primary outcome measured was the percentage of TG reduction within 48hours of admission. The study included 33 TPE-treated and 56 insulin-treated patients. The TPE groups were more severe than those with medical therapy at baseline characteristics. A trend towards higher TG reduction within 24hours was observed in the TPE group (62.5% [IQR 51.7-83.3] vs. 55.7% [IQR 34.2-74.7], p = 0.038). However, no significant difference in TG reduction at 48hours was found between insulin and TPE groups (83.6% and 81.9%, respectively, p = 0.715). The TPE group exhibited extended hospital stays (10.0 [IQR 7.0-13.5] days vs. 6.0 [4.0-8.7] days, p = 0.001) without any difference in in-hospital mortality or time needed to lower TG below < 11.3mmol/L. In patients with HTG-AP, TPE decreased plasma triglyceride levels faster in the first 24hours than insulin therapy. However, there was no significant advantage after 48hours. Therefore, insulin may be a promising alternative and convenient treatment in carefully selected patients with HTG-AP.

Comparative analysis of therapeutic plasma exchange vs. standard management in hypertriglyceridemia-induced acute pancreatitis: triglyceride reduction and clinical outcomes.

The use of therapeutic plasma exchange (TPE) for treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) remains controversial in the literature. This study compared the clinical outcomes of TPE versus conventional therapy in patients with HTGP. Fifty-five patients with HTGP were included. Patients were retrospectively compared in pairs: those who received TPE treatment and those who did not, those whose triglyceride level fell below 500mg/dL within 48h, and those who did not, those with and without persistent organ failure. The primary outcome was the percentage of triglyceride reduction within 48h. Secondary outcomes were the length of hospital stay, mortality, cost-effectiveness, and persistent organ failure. Percentage decrease in triglyceride levels, medical hospitalization costs, and length of hospital stay were higher in the TPE group compared to the non-TPE group (p < 0.05, for each). However, there was no difference regarding persistent organ failure and mortality (p > 0.05, for each). The length of hospital stay, average cost, persistent organ failure, and mortality were similar in both groups whose triglyceride level fell below 500mg/dL within 48h and those who did not (p > 0.05, for each). Among patients with persistent organ failure, average cost was higher in the TPE group compared to the non-TPE group (p < 0.05). An independent relation was found between the average cost and persistent organ failure, TPE, length of hospital stay, albumin, and urea values in all patients (p < 0.05, for each). The approach of using TPE for treatment of HTGP was not found to be superior to the conventional treatment. Randomized controlled studies with larger number of patients are needed to gain better understanding of this issue.

Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

#1491 Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange

Abstract Background and Aims Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. The anti-VWF nanobody Caplacizumab is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. This study evaluates the treatment of acute iTTP with caplacizumab and immunosuppression, but without TPE, in comparison to the conventional management with TPE, caplacizumab and immunosuppression. Method All patients in this study were identified from the Austrian Thrombotic Microangiopathy Registry (ATMAR) and the German REACT-2020 TTP registry (ClinicalTrials.gov identifier: NCT04985318). A total of 42 acute iTTP episodes in 41 patients were managed with a treatment regimen aimed at avoiding first-line TPE if the platelet count increased after the first dose of 10 mg caplacizumab, and the patient's condition and organ function remained stable (TPE-free cohort). This treatment modification was implemented based on shared decision making. An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 iTTP patients, receiving frontline caplacizumab treatment with TPE and immunosuppression (TPE cohort). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractoriness, and iTTP-related deaths. Results The primary outcome parameter, time to platelet count normalization, was not significantly different between TPE-free and TPE-based management (Kaplan-Meier estimator and log-rank test, Table 1 and Fig. 1). The median time to platelet count normalization was 3 days in the TPE-free cohort and 4 days in the TPE cohort. There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths. For evaluation of the short-term treatment response, both cohorts were assessed for the time to platelet count doubling. The median time to platelet count doubling was 1 day in both cohorts. Four patients in the TPE-free cohort did not immediately respond to the first caplacizumab injection and subsequently underwent TPE, after a maximum monitoring period of 40 hours. In these patients, TPE was initiated at a median of 1.5 days after the first caplacizumab dose, and TPE was performed for a median of 4.5 days. This delayed platelet response could be attributed to concomitant diseases and factors, e.g. active HIV and hepatitis B virus coinfection, active CMV infection, concomitant antiplatelet antibodies in association with an ovarian teratoma, and multiple platelet transfusions before the correct diagnosis. During overall follow-up, complications were observed in 11 patients (26.2%) in the TPE-free group and 16 patients (27.1%) in the TPE group, excluding complications of iTTP that were evaluated as outcome parameters. Serious complications occurred in 4 patients (6.8%) from the TPE cohort while on TPE, including severe systemic anaphylactic reactions with severe hypotension, generalized seizure and supraventricular tachycardia. Bleeding complications were reported without a significant difference between groups. Conclusion For the first time since the introduction of TPE in the early 1990s, the results of our study systematically challenge the absolute need for TPE and suggest a paradigm shift in acute iTTP management. In detail, our treatment approach was successfully implemented in 38 of 42 acute iTTP episodes (90.5%). We observed no significant difference in the time to platelet count normalization between patients with iTTP treated with and without TPE. The analysis of key secondary outcomes did not reveal significant differences in the proportion of patients who achieved a clinical response or experienced exacerbations, refractoriness, or TTP-related deaths. In conclusion, Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP.

Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

Therapeutic plasma exchange in the treatment of COVID-19 induced cytokine storm: the first Moroccan experience

IntroductionCOVID-19 induced cytokine storm is a well-documented phenomena that contributes significantly in the disease’s evolution and prognosis. Therefore, therapies such as therapeutic plasma exchange, constitute a mainstay of therapeutic management especially for critically-ill patients.MethodsWe conducted a monocentric retrospective cohort study in the Resuscitation Department of the Mohammed VI University Hospital of Oujda-Morocco, to evaluate the efficiency of therapeutic plasma exchange on critically-ill COVID-19 patients over a 6 months period.We divided our patients into two groups: patients who received TPE (Therapeutic Plasma Exchange) sessions (TPE group) and patients who only benefited from the standard protocol treatment (non TPE group).ResultsOur study included a total of 165 patients, 34.5% of which benefited from TPE sessions.We observed an improvement of oxygenation parameters (SpO2 and PaO2/FiO2 ratio) and a progressive respiratory weaning, as well as a significant decrease of biomarkers indicative of inflammation (lymphocyte count, CRP (C Reactive Protein), IL-6, Ferritin) and coagulopathy (d-dimers, fibrinogen) in the TPE group after 5 consecutive TPE sessions.In comparison with the non-TPE group, The TPE-group patients had a shorter ICU (Intensive Care Unit) length of stay, required less frequently mechanical ventilation, and we more likely to be extubated. Furthermore, the TPE group had a lower mortality rate.DiscussionMultiple studies have reported the safety and efficiency of therapeutic plasma exchange in the COVID-19 induced cytokine storm. Given the urgent character of the pandemic at the time, each center followed its own protocol in implementing plasma exchange.ConclusionSimilar to the results reported in the literature, our study reports positive results after using TPE specifically in terms of respiratory weaning and an improvement of the cytokine storm biomarkers, and more importantly a lower mortality rate.

Efficiency and safety of total plasma exchange in critically ill cirrhotic patients with acute on chronic liver failure: a pilot study.

Treatment of patients with acute on chronic liver failure (ACLF) admitted to the ICU is very limited. The aim of this pilot study was to evaluate the efficiency on liver function and safety of therapeutic plasma exchange (TPE) in critically ill cirrhotic patients admitted with ACLF in a liver ICU. This is a prospective cohort of patients with ACLF grade > 2 treated by TPE admitted to the ICU that was matched to a control group. TPE was performed using a plasma filter (TPE2000, BAXTER®) on a CRRT machine (Prismaflex®, Baxter®). Ratio and type of fluid replacement were 50% with 5% albumin solution followed by 50% with fresh frozen plasma. Seven patients with a mean age of 50.6 ± 7.8 years (all males) and 14 controls matched to age, sex, etiology and cause of decompensation were recruited. At ICU admission, mean MELD score was 39.1 ± 2.7, mean SOFA score was 11.6 ± 5.2 and mean CLIF SOFA score was 12.9 ± 2.6. The grade of ACLF was 3 for 3 patients (42.9%) and 2 for 4 patients (57.1%). The TPE group had significantly higher levels of bilirubin (392.3 ± 117.1 vs. 219 ± 185, p = 0.04), and INR values (5.7 ± 3.4 vs. 3.5 ± 0.9, p < 0.005) compared to the control group. Patient survival was respectively 28.6% and 14.3% at 30 and 90 days in the TPE group and 35.7% and 7.14% in the control group respectively (HR: 1 (95% CI 0.19- 5.2; p = 1). One patient in the TPE group had a liver transplantation 13 days after admission to ICU and is still alive and none in the control group. Two (28.6%) patients died from complications related to the double lumen catheter used for TPE. This pilot study of TPE in patients with ACLF grade 2 and 3 showed a marked but transient improvement in liver function tests. TPE worth to be evaluated in large trials in ACLF patients, with a liver transplant project, and less organ failure.

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Therapeutic Plasma Exchange in Early-Onset Preeclampsia: A 7-Year Monocentric Experience.

Different therapeutic apheresis techniques have been clinically tested to delay preterm delivery in the case of eoPE (early-onset preeclampsia). Our study evaluated the feasibility of TPE (therapeutic plasma exchange) compared to standard-of-care treatment. Twenty patients treated with 95 TPE sessions were included in the final analysis and retrospectively matched with 21 patients with comparable placental dysfunction. Gestational age at admission was 23.75 ± 2.26 versus 27.57 ± 2.68 weeks of gestation (WoG) in the control group (p = < 0.001), mean sFlt-1/PlGF ratio was 1946.26 ± 2301.63 versus 2146.70 ± 3273.63 (p = 0.821) and mean sEng was 87.63 ± 108.2 ng/mL versus 114.48 ± 88.78 ng/mL (p = 0.445). Pregnancy was prolonged for 8.25 ± 5.97 days when TPE was started, compared to 3.14 ± 4.57 days (p = 0.004). The median sFlt-1/PlGF Ratio was 1430 before and 1153 after TPE (-18.02%). Median sEng fell from 55.96 ng/mL to 47.62 mg/mL (-27.73%). The fetal survival rate was higher in TPE-treated cases. NICU (Neonatal Intensive Center Unit) stay was in the median of 63 days in the TPE group versus 48 days in the standard-of-care group (p = 0.248). To date, this monocentric retrospective study, reports the largest experience with extracorporeal treatments in eoPE worldwide. TPE could improve pregnancy duration and reduce sFlt-1 and sEng in maternal serum without impairing neonatal outcomes.

Plasma exchange-A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction.

Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied. We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end-organ damage and disease severity scores were recorded at the time of admission, post-RBCx, post-TPE, and at discharge. Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups. The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.

Effect of Plasma Exchange Treatment in Patients with Hypertriglyceridemia-Induced Acute Pancreatitis.

Background and Objectives: To describe the clinical and biological characteristics of patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) and to evaluate the effectiveness of therapeutic plasma exchange (TPE) in the management of HTG-AP. Materials and Methods: A cross-sectional study was conducted on 81 HTG-AP patients (30 treated with TPE and 51 treated conventionally). The main outcome was a decrease in serum triglyceride levels (<11.3 mmol/L) within 48 h of hospitalization. Results: The mean age of participants was 45.3 ± 8.7 years, and 82.7% were male. Abdominal pain was the most frequent clinical sign (100%), followed by dyspepsia (87.7%), nausea or vomiting (72.8%), and a bloated stomach (61.7%). The HTG-AP patients treated with TPE had significantly lower calcemia and creatinemia levels but higher triglyceride levels than those who received conservative treatment. They also had more severe diseases than those treated conservatively. All patients in the TPE group were admitted to the ICU, whereas the ICU admission rate in the non-TPE group was 5.9%. The TPE patients were more likely to experience a rapid decrease in triglyceride levels within 48 h of treatment than those treated conventionally (73.3% vs. 49.0%, p = 0.03, respectively). The decrease in triglyceride levels did not depend on the age, gender, or comorbidities of the HTG-AP patients or the severity of disease. However, TPE and early treatment in the first 12 h of disease onset were effective in rapidly reducing serum triglyceride levels (adjusted OR = 3.00, p = 0.04 and aOR = 7.98, p = 0.02, respectively). Conclusions: This report demonstrates the effectiveness of early TPE in reducing triglyceride levels among HTG-AP patients. More randomized clinical trials studies with a large sample size and post-discharge follow-up are needed to confirm the effectiveness of TPE methods in managing HTG-AP.

Efficacy of therapeutic plasma exchange in severe COVID-19 disease: A meta-analysis.

Therapeutic plasma exchange (TPE) has been used in severe COVID-19 disease to eliminate the cytokine storm. This meta-analysis aims to assess the effectiveness of TPE in reducing mortality in severe COVID-19 disease compared to standard treatment. A comprehensive literature search was performed in PubMed, the Cochrane database and the International Clinical Trial Registry Platform (ICTRP). The random-effect model was used to calculate the risk ratio and standardized mean difference (SMD) as pooled effect size for the difference in mortality and length of the intensive care unit (ICU) stay. The risk of bias and publication bias were assessed in R version 4.1.0. The certainty of the evidence was calculated using the GradePro tool. The database identified 382 participants from six studies, including one randomized control trial. Egger's test did not detect any publication bias (p=0.178). The random model analysis for mortality evaluated a risk ratio of 0.38 (95% CI: 0.28-0.52) with a significant reduction in the TPE group. The certainty of the evidence was moderate, with a risk ratio of 0.34 (95% CI: 0.24-0.49). Length of ICU stays between TPE versus standard care showed an SMD of 0.08 (95% CI: -0.38, 0.55) and was not significant. The length of ICU stay in the TPE group was not different from standard care. However, this meta-analysis revealed a significant benefit of TPE in reducing mortality in severe COVID-19 disease compared to standard treatment.

Efficacy of therapeutic plasma exchange and convalescent plasma therapy in moderate-to-severe COVID-19 patients

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global health catastrophe since its first reported cases in late December 2019. Critically ill COVID-19 patients have been related to cytokine storms leading to acute respiratory distress syndrome and high mortality rates. Therapeutic plasma exchange (TPE) and convalescent plasma (CP) therapy improve clinically by removing inflammatory cytokines excess and using passive antibody-containing blood, respectively. This study aimed to evaluate TPE and CP treatment for moderate-to-severe COVID-19 infection. Method: The patients were randomly divided into TPE group (n = 10), CP group (n = 11), and control group (n = 10). This 1-week quasi-experimental study with a pretest–post-test control group design was conducted in the Intensive Care Unit (ICU) of Dr. Moewardi General Hospital and Universitas Sebelas Maret (UNS) Hospital. The study comparison between groups included blood gas analysis profile (pH, base excess, PaCO2, PaO2, hematocrit, HCO3, total CO2, SaO2), FiO2, P/F ratio, COVID-19 severity, and D-dimer. The paired t-test was used to analyze every group's pretest–post-test mean difference. One-way ANOVA was performed to analyze the mean difference across the three groups. SPSS version 22.0 for Windows was used to perform statistical analyses. Result: TPE and CP groups showed significant clinical-laboratory improvement than control (p &gt; 0.05). Furthermore, high clinical-laboratory improvement tendency was observed in CP therapy than TPE. Conclusion: The use of TPE and CP in moderate-to-severe COVID-19 patients has been related to improving clinical-laboratory outcomes.

Our Clinical Experience in the Treatment of Myasthenia Gravis Acute Exacerbations with a Novel Nanomembrane-Based Therapeutic Plasma Exchange Technology.

According to the American Academy of Neurology 2011 guidelines, there is insufficient evidence to support or refute the use of therapeutic plasma exchange (TPE) for myasthenia gravis (MG). The goal of this study was to determine whether a novel nanomembrane-based TPE could be useful in the treatment of MG. Thirty-six adult patients, MGFA 4/4B and 5, with acute MG episodes were enrolled into a single-center retrospective before-and-after study to compare a conventional treatment group (n = 24) with a nanomembrane-based TPE group (n = 12). TPE or intravenous immunoglobulins (IVIG) infusions were used in impending/manifested myasthenic crises, especially in patients at high-risk for prolonged invasive ventilation (IMV) and in those tolerating non-invasive ventilation (NIV). The clinical improvement was assessed using the Myasthenia Muscle Score (0–100), with ≥20 increase for responders. The primary outcome measures included the rates of implemented TPE, IVIG, and corticosteroids immunotherapies, NIV/IMV, early tracheotomy, MMS scores, extubation time, neuro-ICU/hospital LOS, complications, and mortality rates. The univariate analysis found that IMV was lower in the nanomembrane-based group (42%) compared to the conventional treatment group (83%) (p = 0.02). The multivariate analysis using binary logistic regression revealed TPE and NIV as independent predictors for short-term (≤7 days) respiratory support (p = 0.014 for TPE; p = 0.002 for NIV). The novel TPE technology moved our clinical practice towards proactive rather than protective treatment in reducing prolonged IMV during MG acute exacerbations.

Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial

BackgroundRecently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.MethodsIn the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.ResultsA continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).ConclusionsAdjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994).

Therapeutic plasma exchange for the management of hypertriglyceridemia-induced acute pancreatitis

<b>BACKGROUND:</b> Hypertriglyceridemia (HTG) is the third-most important cause of acute pancreatitis (AP) and its early diagnosis is essential to prevent AP-associated morbidity and mortality. Therapeutic plasma exchange (TPE) is a promising treatment option for improving patient outcomes and prognosis in HTG-induced AP (HTG-AP). <b>OBJECTIVE:</b> This study assessed the severity of disease in patients with HTG-AP and evaluated the therapeutic effects, safety, and procedural challenges of TPE in its management. <b>METHODS:</b> Patients with HTG-AP, diagnosed according to the Atlanta classification, and exhibiting serum triglyceride (TG) concentrations ≥11.3 mmol/L were included in the study. Consenting patients received TPE using the PRISMAFLEX^® system (TPE group), and the remaining were treated in accordance with the guidelines of Vietnam's Ministry of Health, 2015 (non-TPE group). The duration of hospital or intensive care unit (ICU) stay in patients and mortality rates were compared between the TPE and non-TPE groups. The reduction in serum TG levels was also evaluated in the TPE group. <b>RESULTS:</b> This prospective study included 165 patients with HTG-AP (<i>n</i> = 83, TPE group; <i>n</i> = 82, non-TPE group). The mean age of the patients was 41.0 ± 9.3 years. The duration of hospital and ICU stay was significantly lower in the TPE group compared to that of the non-TPE group (<i>P</i> < 0.05). A significant reduction in TG levels over baseline was noted in patients who received TPE (77%; <i>P</i> < 0.05), which was observed after the first TPE session (70.81%; <i>P</i> < 0.05). <b>CONCLUSION:</b> TPE using the PRISMAFLEX^® system is safe and well-tolerated in patients with HTG-AP and is associated with minimal technical constraints.

Management of thrombocytopenia-associated multiple organ failure: plasma infusion vs plasma exchange

Thrombocytopenia-associated multiple organ failure (TAMOF) causes a high ratio of mortality in pediatric patients. Only anticoagulants and profibrinolytic molecules can be replaced with plasma infusion (PI), while therapeutic plasma exchange (TPE) eliminates antifibrinolytic and thrombogenic molecules and charges inadequate anticoagulants and profibrinolytic molecules. This study aims to compare the efficacy of plasma exchange to plasma infusion in pediatric TAMOF patients. Twenty-seven patients with TAMOF were included and the efficacy of PI and TPE was compared. The demographic data, admission laboratory values, Pediatric Logistic Organ Dysfunction (PELOD) scores before the beginning of treatment and PELOD at the end of treatment, and outcomes of groups were compared. Sixteen children were in the plasma infusion group, eleven children were in the plasma exchange group. The total mortality rate of all patients was 37%. The PELOD scores were significantly reduced on the 5th day of treatment in both groups and also PELOD scores were significantly higher on the 5th day of study in the non-survivor group (p: < 0.001). The fifth day of PELOD scores and ferritin had a significant effect on mortality (OR: 1.85, 95% CI: 1.02-2.69; p: 0.04, OR: 1.43, 95% CI: 0.97-2.03; p: 0.05). The overall mortality ratio was not different between TPE and PI groups (p: 0.12). Although there was no difference in mortality rates in children who received plasma exchange compared to children who received plasma infusion, mechanical ventilation and length of pediatric intensive care unit (PICU) day were shorter in the TPE group. The small patient population may be the major cause for the lack of significant statistical difference.

Therapeutic Plasma Exchange for Management of Early Allograft Dysfunction After Living Donor Liver Transplant: An Unmatched Cohort Study.

Therapeutic plasma exchange has been reported to be useful in the management of acute liver failure and acute-on-chronic liver failure. This retrospective study evaluated therapeutic plasma exchange as an adjunct to standard supportive care for early allograft dysfunction after living donor liver transplant. All consecutive adult living donor liver transplants performed from January 2015 to February 2019 were included. Patients treated without or with therapeutic plasma exchange for early allograft dysfunction (Olthoff criteria) were compared. There were 465 adult transplant recipients, and 67 (14.4%) had early allograft dysfunction, of which 43 (64%) had therapeutic plasma exchange and 24 (36%) did not. Fourteen patients were excluded, as they had both preoperative and immediate postoperative therapeutic plasma exchange (5 patients with acute liver failure and 9 with acute-on-chronic liver failure). The therapeutic plasma exchange group (n = 29) had more preoperative acute kidney injury (55.2% vs 25.0%; P = .009), lower graft-recipient weight ratio (0.96 vs 1.09; P = .043), and slightly higher final portal pressure (11 vs 10 mg/dL; P = .027). Therapeutic plasma exchange was started at a median of postoperative day 9, with median serum bilirubin of 13.6 mg/dL and a median of 3 sessions per patient. There was no 90-day mortality in the group without therapeutic plasma exchange; however, in the therapeutic plasma exchange group, 13 patients (45%) died (P < .001). Patients who received therapeutic plasma exchange had more septic complications (62.1% vs 12.5%; P < .001) and needed more postoperative renal replacement therapy (51.7% vs 8.3%; P < .001). This is the first study to compare patients treated with or without therapeutic plasma exchange for early allograft dysfunction in the living donor liver transplant setting. Within the limitations of this retrospective study, we were unable to confirm whether therapeutic plasma exchange could increase early mortality.

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO2/FiO2 ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34–63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO2/FiO2 ratio (HR, 0.98, 95% CI 0.96–1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82–0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43–8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

Clinical efficacy of plasma exchange in patients with autoimmune encephalitis.

ObjectiveTo determine the clinical and antibody response after therapeutic plasma exchange (TPE) in patients with severe refractory antibody‐associated autoimmune encephalitis (AE).MethodsThis single‐center prospective cohort included all patients consecutively admitted to our hospital because of severe refractory AE over the period from July 2014 to June 2019. All patients received immunotherapy (steroids, intravenous immunoglobulin (IVIG), and/or TPE). The primary outcome was evaluated at 1‐ and 2‐month postenrollment, and the long‐term outcome was followed up at 6 and 12 months. AE antibody titers in the cerebrospinal fluid and plasma were evaluated before and after TPE/IVIG.ResultsThis study enrolled 57 patients with severe refractory AE, including anti‐NMDA receptor encephalitis (n = 51), anti‐GABAb receptor encephalitis (n = 3), anti‐LGI 1 encephalitis (n = 2), and anti‐AMPA receptor encephalitis (n = 1). Of all 57 patients, 33 patients received TPE for a total of 193 procedures, and 24 patients with contraindications or refusal of TPE were in the non‐TPE group. Compared with the non‐TPE group, the TPE group exhibited greater clinical improvement: 21 (37%) versus 8 (14%) after 1 month (P = 0.03) and 31 (54%) versus 16 (28%) after 2 months (P = 0.01), respectively. Complications and adverse events associated with TPE occurred in 91 procedures (47%) without serious adverse events associated with the use of TPE.InterpretationTPE might be an effective rescue therapy associated with rapid functional improvement in patients with severe steroid/IVIG refractory antibody‐associated AE from this nonrandomized control trial.