Single Plasma Exchange Research Articles

#2956 Hemodynamic evaluation of different replacement fluids during therapeutic plasmapheresis with Crit-line™

Abstract Background and Aims Therapeutic plasmapheresis (TP) is an extracorporeal technique used to remove pathogenic macromolecules from the plasma. Human serum Albumin (HSA) or fresh frozen plasma can be used as replacement fluid, alone or in combination, and with or without the addition of a crystalloid such as saline. There is wide practice variation in the type of replacement fluid and according the procedure of TP such as single plasma exchange (SPE) or double plasmafiltration (DFPP). Replacing plasma with crystalloid carries a risk of hypotension if the proportion of replacement with crystalloid exceeds 30%. CRIT-LINE™ monitor estimate RBV changes during HD based on measurements of hematocrit and could be used in hemodialysis to prevent hypotensive episodes. Method We conducted a retrospective case series study in a tertiary center to evaluate RBV changes during TP (SPE & DFPP) in three patients with PIDC treated with chronic TP using SPE or DFPP according to guidelines. For each patient and procedure (SPE or DFPP) we compare different substitution fluid infusion protocol between 2021 and 2023. We evaluated each patient's sessions with CRITLINE™ continuous RBV monitoring during either SPE or DFPP with comparison of different replacement fluid protocols. For DFPP with plasmafractionator EC30 (Asahi Kasei Medical Co., Japan) or medopen30 (Infomed, Switzerland), we compare protocols as follows (1) continuous infusion of 500 ml of HSA 4% throughout the session and (2) 500 ml HSA 4% at the last 20 min of the session. For SPE, we compare protocols as follows (1) 100% volume of HSA 4% supplementation (2) a combination of 70% HSA 4% and 30% of saline started at the last part of the session (3) a combination of 70% HSA 4% and 30% of saline started at the first part of the of the session. Results BVM decreased by 15% ± 5% in DFPP session with 500 ml HSA 4% at the last 20 min of the session and by 12% ± 3 in DFPP session with continuous infusion of 500 ml of HSA 4% throughout the session . In SPE, BVM decreased by 18% ± 2 in session with a combination of 70% HSA 4% and 30% of saline and by 10% in session with 100% albumin substitution. Hypotensive episodes occurred in session with a combination of 70% albumin 4% and 30% of saline at the end of session. Conclusion CRITLINE IV continuous RBV monitoring is an interesting tool that can be used to evaluate the optimal substitution fluid in TP and for prevention of hypotension. Randomized control trial are needed to confirm the results.

#2972 Comparison cTPE & DFPP in PIDC patients for procedure time, clinical, biological tolerance and microcosting estimation: lymphapheresis study

Abstract Background and Aims Therapeutic plasmapheresis (TP) is an established therapy in different pathology according to international guidelines. There is different method of TP such as single plasma exchange (SPE) and Double plasmafiltration (DFPP) defined as non selective or semi selective method. Centrifugal (cSPE) and Filtration-membrane based (mSPE) are two different methods of SPE. These methods were already compared but few data exist about comparison of cSPE and DFPP. Objective of this ancillary study is to compare procedure time, biological variation and microcosting of patients treated with cSPE vs DFPP in a prospective single case study (Moranne O BMC neurology 2022). Method Lymphapheresis study included 5 patients with idiopathic CIPD treated with chronic TP with regular interval time and clinically stable. Vascular access was central venous catheter (CVC) for 2 patients and peripheral venous access (PVA) for 3 others. cSPE or DFPP was randomized at inclusion then patient was alternatively treated for 6 consecutive session by SPEc (Comtec, FMC KABI) or DFPP (HF 440 Infomed) sessions for a total of 30 session. The target plasma TPV) volume to be processed was 1.5 of total plasma volume and was not modified during the study. Anticoagulation was non fractionated heparin for DFPP with CVC and regional citrate for others. For each session replacement fluid was 100% human serum albumin (HSA) 4% for cSPE and 500 mls HSA for DFPP. We compare cSPE and DFPP considering each patient for (i) time session (including time preparation, time device and time before living) (ii) clinical tolerance (iii) biological tolerance (variation before and after session of Hb, Platelet, Fibrinogen) and (iv) microcosting. Quantitative values were described with median interquartile and compared with mixed model regression analysis. Results Patients have median age of 62 [56-68] years with 100% male and a BMI of 27 [23-31]. Patients were treated alternatively with 15 session of cSPE and 15 session of DFPP without difference of TPV between session (4500 mls) but significant higher blood volume process because of lower plasma fraction filtration with DFPP. Time session was not different between TP method but depend on vascular access. No difference was observed for clinical tolerance and Hemoglobin variation between methods. However a significant higher decreased of platelet and fibrinogen was observed during session with cSPE vs DFPP. The quantity of SHA infused during session was significantly higher with cSPE vs DFPP (180 g vs 20 g). Finally according to hospital's perspectives the cost is not very different between cSPE and DFPP but depends on specific material resources and pharmaceutical products of methods. Conclusion We show some differences between methods.

Protocol of comparison of the effects of single plasma exchange and double filtration plasmapheresis on peripheral lymphocyte phenotypes in patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: a monocentric prospective study with single-case experimental design

BackgroundChronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare disorder affecting young adults, causes gradual weakness of the limbs, areflexia and impaired sensory function. New CIDP phenotypes without pathogenic antibodies but with modified cell profiles have been described. Treatments include corticotherapy, intravenous immunoglobulins, and plasmapheresis but the latter’s action mechanisms remain unclear. Plasmapheresis supposedly removes toxic agents like antibodies from plasma but it is uncertain whether it has an immune-modulating effect. Also, the refining mechanisms of the two main plasmapheresis techniques—single plasma exchange and double filtration plasmapheresis (DFPP) – are different and unclear. This study aims to compare the evolution of peripheral lymphocyte profiles in patients with CIDP according to their treatment (single centrifugation plasmapheresis or DFPP) to better grasp the action mechanisms of both techniques.MethodIn this proof-of-concept, monocentric, prospective, Single-Case Experimental Design study, 5 patients are evaluated by alternating their treatment type (single plasma exchange or DFPP) for 6 courses of treatment after randomization to their first treatment type. Each course of treatment lasts 2–4 weeks. For single plasma exchange, 60 ml/kg plasma will be removed from the patient and replaced with albumin solutes, with a centrifugation method to avoid the immunological reaction caused by the membrane used with the filtration method. For DFPP, 60 ml/kg plasma will be removed from the patient with a plasma separator membrane, then processed via a fractionator membrane to remove molecules of a greater size than albumin before returning it to the patient. This technique requires no substitution solutes, only 20 g of albumin to replace what would normally be lost during a session. The primary outcome is the difference between the two plasmapheresis techniques in the variation of the TH1/TH17 ratio over the period D0H0-D0H3 and D0H0-D7. Secondary outcomes include the variation in lymphocyte subpopulations at each session and between therapeutic plasmapheresis techniques, the clinical evolution, tolerance and cost of treatments.DiscussionUnderstanding the action mechanisms of single plasma exchange and DFPP will help us to offer the right treatment to each patient with CIPD according to efficacy, tolerance and cost.Trial registrationClinicalTrials.gov under the no. NCT04742374 and date of registration 10 December 2020.

Severe Hypertriglyceridemia Associated with Pegylated Asparaginase Successfully Treated with Plasma Exchange

Asparaginase (ASP), a chemotherapy treatment used for acute lymphoblastic leukemia (ALL), is known to provoke severe hypertriglyceridemia (HTG). We report the case of a woman with a history of obesity and diabetes mellitus who developed severe HTG (up to 7305 mg/dL) after receiving a pegylated form of ASP for ALL. The patient was treated with one plasma exchange without incident via peripheral veins using 5% albumin as a replacement solution. Her triglycerides were reduced to 485 mg/dL. A single plasma exchange was an efficient, fast, and safe way to decrease triglycerides concentration in plasma.

Plasma exchange in patients with myocarditis: comparison study

Abstract Background Cardiac auto-antibodies (AABs) are detected frequently in patients with inflammatory dilated cardiomyopathy (iDCM) of arrhythmias due to myocarditis. Elimination of AABs with apheresis improves left ventricular function as well as the immunosuppressive drugs (ISDs) do. There is no data on the combined use of ISDs and apheresis. Aims To investigate the clinical efficiency of plasma exchange (PE) in patients with myocarditis in comparison with patients without PE. Methods There were 38 patients with iDCM under stable oral medication with maximal tolerated dose of β-blockers/angiotensin-converting enzyme inhibitor/aldosterone antagonists at least 3 month before study inclusion; and 48 patients with arrhythmias due to myocarditis resistant to antiarrhythmic drugs (AADs). Patients underwent evaluation including heart CT scan, MRI, endomyocardial biopsy, myocardial perfusion scan, and coronary angiography to diagnose myocarditis. All the patients had a high level of AABs against cardiac antigens. PE group were consisted of 19 patients with iDCM (left ventricular ejection fraction (LVEF) 35±7%) and 22 patients with arrhythmias (premature atrial (PACs) or ventricular (PVCs) contractions more than 3000/day or atrial fibrillation (AF)). All the patients in PE group underwent a single volume PE filled with 0.9% sodium chloride. Another 19 iDCM patients and 26 arrhythmic patients were controls without PE. Echocardiographic parameters, a 6-minute walk test (6MWT) distance, Holter monitoring and AABs level were assessed at baseline, 6 and 12 month follow-up. Some patients were treated by ISDs before PE. PE group patients got methylprednisolone (MP) significantly rare than controls after PE. The mean doses of MP were significantly lower than in controls too. Results AABs level significantly decreased just after PE and during the follow-up only in PE group. iDCM patients also had significant improvement in LVEF 35±7% vs. 45±11% at a year follow up, and 6MWT distance in comparison with LVEF 33±7% vs. 37±11% at a year follow up in controls. There were 58% PE group patients with absolute LVEF improvement >10% classified as responders in comparison with 32% responders in controls. There were 86% PE group patients with arrhythmias in and 58% patients in control group who were classified as responders as they achieved a decrease of PAVs and PVCs or AF frequency >75% relative to baseline. AADs were eliminated in 46% PE group patients and in 23% control group patients with arrhythmias. We also tried to predict good response for PE in both iDCM and arrhythmic patients. iDCM responders were characterized by LVEF≤37% at baseline. Arrhythmic group responders were characterized by higher level of AABs to cardiac conduction cells antigens at baseline. Conclusions PE improves both cardiac function and daily activities in patients with iDCM and arrhythmias due to myocarditis. PE is safe and high effective, and helps avoid using high doses of ISDs Funding Acknowledgement Type of funding source: None

Single plasma exchange in six pediatric patients with severe septic shock

Despite advances in the management of severe sepsis, the mortality rate of septic shock in children and adults remains high. Meningococcal disease is the leading cause of sepsis affecting previously healthy children and young adults. In a septic infection, the production and release of mediators of inflammation may lead to severe organ damage. The use of plasma exchange is intended to reduce the level of inflammatory mediators as an adjunctive therapy accompanying the standard medical care. We retrospectively studied six patients (median age 6.5 years, range 0.8–16 years) suffering from primary septic shock (4/6 with a proven meningococcal disease) who were treated with a single plasma exchange. The inclusion criteria for plasma exchange were clinical impression of a septic shock showing typical skin lesions and a refractory hypotension after volume therapy. The plasma exchange was conducted once between 3 and 8 hours after admission for a period of 1–3.3 hours. The Pediatric Risk of Mortality (PRISM-I) score ranged from 10 to 36. The mortality rate was 33%, but all of the four patients suffering from meningococcal sepsis survived. Neither circulatory conditions nor oxygenation showed relevant improvement during plasma exchange or in the two hours afterwards. All patients with proven meningococcal sepsis survived, but based on the limited number of patients in this study further conclusions can not be drawn. From the clinical and pathophysiological studies available so far, there is insufficient evidence to justify the use of plasma exchange as standard treatment in primary septic shock in children.

Primary and Secondary Thrombotic Microangiopathy Referred to a Single Plasma Exchange Center for Suspected Thrombotic Thrombocytopenic Purpura: 2000-2011

Background: Patients who present with unexplained thrombocytopenia, that is, hemolytic anemia with end-organ dysfunction with a normal coagulation profile are suspected to have thrombotic thrombocytopenic purpura (TTP) and are usually referred to a plasma exchange (PE) center for immediate treatment to prevent mortality. Here, we describe the distribution and outcomes of patients with suspected TTP referred to a single center for PE therapy. Methods: In this retrospective cohort study, we reviewed the data of all consecutive patients who were treated with PE for suspected TTP at our center between January 2000 and December 2011 (Canada). Patients were followed for a median of 73 months. Results: Of 137 patients, 70 (51%) were determined to have primary (idiopathic) TTP and 67 (49%) secondary TTP or hemolytic uremic syndrome (HUS). Patients with primary TTP were twice as likely to be refractory than those with secondary TTP or HUS: 27 vs. 12%; p = 0.03. Patients with primary TTP were more likely to experience remission (61/70 (87%) vs. 45/67 (67%); p = 0.01); however, the relapse rate was higher in patients with primary versus secondary TTP-HUS: 11 vs. 1.5%, respectively (p = 0.03). The overall mortality rate was 23% (13 vs. 33% in those with primary vs. secondary TTP-HUS; p = 0.007). After excluding deaths from scleroderma renal crisis (100% mortality), malignancy (75% mortality) and stem cell transplant (50% mortality), the survival rate for secondary TTP was 85%. Conclusions: In contrast to patients with secondary TTP or HUS, those with primary TTP have a higher refractory and relapse rate, but are also more likely to achieve remission and survive.

Clinical Study of Simple Plasma Exchange in the Treatment of Severe Autoimmune Hepatitis

<p><strong>Objectives: </strong>Plasma Exchange (PE) in the treatment of severe autoimmune hepatitis and the clinical outcome of the clinical data were retrospectively analyzed. The clinical efficacy and safety of single plasma exchange (PE) in the treatment of autoimmune hepatitis were also evaluated. <strong>Method: </strong>The PE group of 22 patients was given conventional treatment of combined treatment of patients with simple PE while 21 cases of the control group were treated with comprehensive treatment. The efficacy of PE group and control group were compared within 2 weeks. <strong>Results</strong><strong>: </strong>The clinical symptoms of 22 patients in PE group were significantly improved (<em>p </em>< 0.05); in total bilirubin (TBIL), (AST), (INR), (ALT) where the PE group (17/22) 77.27%, and control group (10/21) 47.62%. The difference was statistically significant (<em>p </em>< 0.05). <strong>Conclusion: </strong>Pure plasma exchange (PE) is an effective method for the treatment of severe autoimmune hepatitis (AIH).</p>

Posttransplant outcome of atypical haemolytic uraemic syndrome in a patient with thrombomodulin mutation: a case without recurrence.

Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia and renal impairment. Mutations in genes encoding inhibitors of the alternative pathway of the complement system are involved in ∼50% of the cases. Thrombomodulin (THBD) gene mutations occur in ∼3–5% of the cases. The risk of aHUS recurrence after kidney transplantation depends on the complement abnormality involved. In all three cases of THBD mutation reported to date, aHUS recurred after kidney transplantation (KT) with early graft loss. No data exist about therapeutic approaches before kidney transplantation to reduce the risk of recurrence in patients carrying this mutation. Favourable data on the use of eculizumab have been reported, in terms of plasmatherapy withdrawal and renal function recovery in aHUS recurrence after KT. To our knowledge, this case report presents the first case of successful kidney transplantation in a patient with aHUS due to THBD mutation who was treated with a single plasma-exchange immediately before surgery without recurrence of the disease 12 months after transplantation.

Caplacizumab, Anti-Vwf Nanobody Potentially Changing the Treatment Paradigm in Thrombotic Thrombocytopenic Purpura: Results of the TITAN Trial

▪ INTRODUCTIONThe TITAN trial achieved its primary endpoint in the ITT analysis of 75 subjects treated either with caplacizumab or placebo added to daily plasma exchange (PE). METHODSCaplacizumab is a Nanobody which binds the A1 domain of vWF and thereby blocks the interaction of multimeric vWF with the GPIb-IX-V platelet receptor, preventing platelet aggregation typical of TTP. TITAN was a randomized, placebo controlled, single-blind, parallel design study. The primary endpoint was time to confirmed platelet response defined as platelet count normalization confirmed 48 hours later. Analysis was prospectively stratified according to whether or not subjects received a single PE prior to randomization. Treatment consisted of one IV bolus injection of caplacizumab 10mg (CAP) or placebo (PLC) prior to first on-study PE, followed by daily SC administration after PE. Once PE was stopped, CAP or PLC SC administration continued, daily for 30 days. RESULTSThe ITT population consisted of 36 and 39 subjects randomized 1:1 to CAP or PLC, respectively. Treatment arms were well balanced for age, race, body mass index. Presentation of TTP as an initial TTP episode or recurrent TTP was similar for both groups with 2/3 first episode and 1/3 recurrent. Platelet count and LDH were similar as summarized in table 1.Table 1at baselineCAP N=36PLC N=39Platelets (10³/mm³) mean ± SD21.1 ± 18.228.0 ± 20.0LDH (U/L) mean ± SD1277 ± 8531270 ± 939% subjects with ADAMTS-13 activity < 5% (FRET)58.3 %56.4 %Time to reach platelet response was almost 2 days shorter for CAP versus PLC, with a 39% reduction in time to response in the stratum with no prior PE, and 43% reduction in time to response in the stratum with a single prior PE. The overall hazard ratio was 2.197 for obtaining the confirmed platelet response with CAP over PLC, with a significance of p=0.013. The distribution of time to response was narrower for CAP in comparison to the distribution of subjects receiving PLC which was skewed towards longer confirmed platelet response time in table 2.Table 2CAPPLCMedian days to confirmed platelet response - subjects with no prior PE (95% CI)3.00 (2.74, 3.88)N = 344.92 (3.21, 6.59)N = 3525th & 75th percentile2.72 & 4.313.01 & 11.37Median days to confirmed platelet response - subjects with one single prior PE (95% CI)2.44 (1.92, 2.97)N = 24.31 (2.91, 5.68)N = 425th & 75th percentile1.92 & 2.973.37 & 5.23N = 36N = 39Overall Hazard Rate Ratio for CAP vs. PLC (95% CI)2.197 (1.278, 3.778)Stratified Log-rank Test p-value0.013Exacerbation of TTP occurred in 3 (8%) subjects receiving CAP versus 11 (28%) in the PLC arm. Complete remission defined as confirmed platelet response and absence of exacerbation up to 30 days after end of daily PE was achieved in 29 (81%) subjects of the CAP arm versus 18 (46%) subjects receiving PLC. The greater proportion of complete remission, coupled with the faster and narrower distribution of time to confirmed platelet response supports a greater predictability of patient response to PE in the CAP arm, and is reflected in number of days of PE. The number of consecutive days of PE was (mean ± st dev) 6.6 ± 3.4 days for CAP versus 8.1 ± 6.5 days for PLC with a total plasma volume administered including tapering of 22.5 ± 15.9 liters for CAP versus 28.4 ± 21.3 liters for PLC. The proportion of subjects with exacerbation and/or relapse up to the 1 month follow-up was even for both groups: 13 (36.1%) and 13 (33.3%) for both arms. Higher number of early relapses in the CAP arm substantiates a protective effect and warrants longer CAP treatment in some patients.Treatment emergent adverse events (TEAE) and deaths are summarized in table 3.Table 3Safety populationCAP N=35PLC N=37Subjects with any TEAE N (%)34 (97%)37 (100%)Subjects with bleeding related TEAEs N (%)19 (54%)14 (38%)Subjects with any TE Serious AEs N (%)20 (57%)19 (51%)Deaths N (%)02 (5%) CONCLUSIONSCaplacizumab, as a novel treatment, improved standard of care of patients affected with acquired TTP by a more rapid achievement of platelet normalization and lower number of exacerbations with manageable side effects and bleeding episodes. The TEAEs were consistent with the serious and potentially life-threatening condition of TTP. Further reducing PE and optimizing duration of caplacizumab should be investigated in future clinical trials. DisclosuresPeyvandi:Ablynx: Investigator fees Other. Duby:Ablynx: Employment.

Clinical application of blood purification (artificial liver) in treatment of acute liver failure in children

To investigate the clinical application, indication, timing and prognosis of blood purification (artificial liver, BP) in treatment of acute liver failure in children. Artificial liver was used to treat 30 cases of pediatric acute liver failure (PALF), who were hospitalized in pediatric intensive care unit of Bayi Children's Hospital Affiliated to Beijing Military Command General Hospital, during March 2010 to July 2013. Simple plasma exchange (PE) mode was used for PALF without complications, while PE combined with continuous veno-venous hemodiafiltration (CVVHDF) mode was used for PALF with cerebral edema and/or hepatorenal syndrome and/or serious abnormality of electrolyte and acid-base balance. Sixteen cases survived and restored hepatic function, with a survival rate of 53.3%. Single PE therapy could significantly decrease total bilirubin (TBIL) from (293.96 ± 214.52) µmol/L to (155.64 ± 140.97) µmol/L (P = 0.033), increase prothrombin time activity (PTA) from (34.50 ± 18.34) % to (60.50 ± 33.97) % (P = 0.013), while it did not significantly influence ammonia from (156.43 ± 67.23) µmol/L to (124.03 ± 62.58) µmol/L (P = 0.156) and alanine transarninase (ALT) from (752.53 ± 1 291.84) U/L to (132.00 ± 98.57) U/L (P = 0.066). PE + CVVHDF therapy could significantly ameliorate TBIL from (326.90 ± 233.85) µmol/L to (157.53 ± 125.31) µmol/L (P = 0.033), ALT from (1 476.64 ± 1 728.18) U/L to (169.38 ± 207.18) U/L (P = 0.019), ammonia from (215.83 ± 83.92) µmol/L to (141.25 ± 63.09) µmol/L (P = 0.022) and PTA from (36.68 ± 23.13)% to (71.75 ± 50.50) % (P = 0.044). Prothrombin time (PT) from (29.71 ± 17.75)s to (16.27 ± 6.38)s (P = 0.008) , ALT from (1 574.11 ± 1 775.96) U/L to (145.81 ± 113.89 ) U/L (P = 0.003) , TBIL from (233.16 ± 219.70) µmol/L to (75.19 ± 86.07) µmol/L (P = 0.012) , ammonia from (182.75 ± 90.07) µmol/L to (101.81 ± 37.14) µmol/L (P = 0.002) and PTA from (38.38 ± 20.39)% to (83.13 ± 41.68)% (P = 0.001) in survived cases significantly ameliorated after BP therapy. TBIL from (394.04 ± 192.80) µmol/L to (249.34 ± 113.97) µmol/L (P = 0.023) in died cases declined significantly after BP therapy, while alteration of PT, ALT, ammonia , and PTA had no statistical significance (P > 0.10) after BP therapy. PE + CVVHDF therapy could significantly ameliorate not only TBIL and PTA but also ammonia and ALT compared with single PE therapy. The decline of only an index like TBIL or ALT after BP therapy could not improve the prognosis. The inconsistency between serum bilirubin and ALT levels was an important factor that suggested poor prognosis of ALF, and it might increase survival rate to use BP therapy before that inconsistency emerged.

Plasmapheresis as treatment for hyperlipidemic pancreatitis

BackgroundSevere hypertriglyceridemia with an accumulation of chylomicrons and triglyceride figures >1000mg/dL can cause acute pancreatitis, a potentially fatal complication. The option of rapid reduction in triglyceride concentrations is attractive and possible with plasmapheresis. MethodsWe present the results of an analysis of 11 patients admitted to the intensive care unit with severe hypertriglyceridemic pancreatitis and treated with plasmapheresis. The procedure was repeated until serum triglycerides were below 1000mg/dL. We recorded anthropometric, clinical data as well as final outcome. ResultsIn eight patients a single plasma exchange was sufficient to reduce triglyceride figures <1000mg/dL. Only three patients died, all with the worst severity indexes and who experienced the longest delay before the procedure. ConclusionsOur results, together with a review of the literature, confirm the need for a randomized clinical trial to compare conventional treatment vs. plasmapheresis in patients with severe hypertriglyceridemic pancreatitis.

Hypercytokinemia-induced metabolic encephalopathy in a multiple myeloma patient on hemodialysis undergoing autologous stem cell transplantation: Clinical response after plasma exchange

We report here a 50-years old female with multiple myeloma-associated chronic renal failure who underwent high-dose chemotherapy supported by autologous hematopoietic stem cell transplantation. She developed progressive encephalopathy on day 5 progressing to coma despite hemodialysis and no obvious organ failure. She finally recovered after a single 1-liter plasma exchange. The final diagnosis was metabolic encephalopathy due to hypercytokinemia, particularly high serum TNF levels. We discuss here the pathogenesis and raise an alert for monitoring cytokine levels in patients with renal failure undergoing high-dose chemotherapy.

A Case Report of Amitriptyline Poisoning Successfully Treated With the Application of Plasma Exchange

Amitriptyline is a very frequently prescribed antidepressant agent and is very often involved in attempted suicides. Amitriptyline intoxication necessitates primary therapeutic approaches that include gastric irrigation and recurrent administration of activated charcoal. In the case of pronounced anticholinergic findings, physostigmine is of proven benefit and hypertonic sodium bicarbonate can be used to shorten the QRS duration and AV interval. In cases of a comatosed state, hemoperfusion and plasma exchange can be used. In this case report we present a case of severe amitriptyline poisoning that we successfully managed with plasma exchange. We confirmed a 59.5% reduction in the amitriptyline plasma level in our patient after a single plasma exchange session. She was discharged by the third day of admission without any complications. According to current literature, our patient is the fifth patient treated with plasma exchange to be the subject of a publication.

Successful Deceased-Donor Kidney Transplantation in Crossmatch-Positive Patients With Peritransplant Plasma Exchange and Rituximab

Sensitized patients awaiting renal transplantation have a markedly reduced probability of receiving a crossmatch (XM)-negative renal allograft, and, even if transplanted with a negative complement-dependent cytotoxicity (CDC)-XM, they are at an increased risk of antibody-mediated humoral rejection with early graft loss. We report here for the first time on the effectiveness of a single pretransplant plasma exchange session in rendering a positive complement-dependent cytotoxicity-XM negative and, in combination with anti-CD20 therapy, allowing successful renal transplantation in two sensitized deceased-donor kidney allograft recipients. In a third patient with high donor-specific reactivity, the therapy was unsuccessful. Plasma exchange treatments were continued during the posttransplant period until stable allograft function was achieved. Both patients showed good graft outcome at 27 and 21 months after transplantation with serum creatinine values of 1.60 and 1.25 mg/dL, respectively.

Effect of Plasma Exchange on Acute Graft Versus Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft versus host disease (aGVHD) is one of the major complications after allogenic hematopoietic stem cell transplantation (allo-HSCT) with high morbidity and mortality. Myeloablative treatment and the application of immuno-suppressive drugs (such as CsA, FK506 and MMF) are the main methods of prevention and cure. As it can separate pathogen, toxin, antigen and antibody from the plasma, plasma exchange (PE) is widely used to prevent and treat autoimmune disease, the rejection of stereo-organ transplantation, acute intoxication, severe hepatitis and acute hepatic failure. But up to now, PE is still rarely used to treat aGVHD. Here we present our review of cases where PE was accepted as a treatment modality for refractory aGVHD at our center. From October 2001 to March 2004, eight patients underwent PE due to aGVHD after Allo-HSCT with little response to immuno-suppressive drugs. Four of them had initial diagnosis of chronic myeloid leukemia (CML), and the other four were diagnosed with acute myeloid leukemia M2a,M4,M5,M6 respectively. The age of patients was from 14 to 38 years old (median 31). The “BuCY2” scheme (MMF+MTX+CsA) was used to prevent GVHD. After transplantation, all of them developed II-IV degree aGVHD. Each of them underwent 1 or 2 times of PE, with a volume ranging from 2500ml to 4000ml for a single PE. The overall response rate is favorable (fever, tetter, bellyache, diarrhea and liver function were ameliorated with various degree), with 3 cases (37.5%) having overt response, which was especially seen in patients with intestinal tract symptoms. Also, the level of TNF-α in the serum of the patients after plasma exchange was lower than that of the patients before plasma exchange(P=0.018). These results suggested that intestinal tract plays an important role in magnifying illness and “cytokine storm”, and TNF-α is the pivotal cytokine in the Intestinal tract GVHD. And the non-immunity aspects of GVHD can be described as an inflammatory process. PE may block this kind of inflammation by decreasing the cytokines, especially the level of TNF-α in serum after PE. Thus, the combination of PE and immuno-suppressive drugs is a rather good therapeutic method to control the symptoms of refractory aGVHD after allo-HSCT.

The Role of Plasma Exchange in HELLP Syndrome

Plasma exchange therapy has been successfully used in selected patients with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome who have organ failure or refractory to treatment. There is no prospective study regarding plasma exchange and its effect in HELLP syndrome. The aim of this study was to investigate the effects of early postpartum use of plasma exchange in patients with HELLP syndrome on outcomes. The mortality rate and the recovery times were compared in patients with HELLP syndrome treated with plasma exchange and historic control group of patients treated conservatively. During a 3-year period (between April 2000 and December 2003), 29 consecutive patients with HELLP syndrome were treated with single or multiple plasma exchange by using fresh-frozen plasma at post-partum period. The control group consist of 26 patients with HELLP syndrome treated between 1993 and 1999. Maternal mortality rate was 23.1% in the control group; there was no death in plasma exchange group; and the mortality rate was significantly higher in the control group (p=0.006). The length of stay at the intensive care unit was shorter in the plasma exchange group (p<0.0001). Rapid improvement of the platelet, aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels were observed in the plasma exchange group. This study showed that postpartum early plasma exchange therapy improves treatment outcomes in patients with severe HELLP syndrome.

The Series‐parallel Circuit in the Treatment of Fulminant Hepatitis

We developed a series-parallel treatment method for combined plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy in fulminant hepatitis. We then compared total serum bilirubin, citrate, and cytokine levels obtained by the new methods to those obtained with treatment by the single and reverse-parallel PE methods. Ten adult patients with fulminant hepatitis consented to participate. Plasma exchange was conducted 25 times by the single method (PE only), 16 times by the reverse-parallel method, and 37 times by the series-parallel method. The percentage of total bilirubin removed was highest with the single method followed in order by that with the series-parallel and reverse-parallel methods; the differences were significant. The percentage increase in citrate level was highest with the single method, followed in order by that with the series-parallel and the reverse-parallel methods; these differences were also significant. There was no significant difference in serum interleukin (IL)-6 levels after PE, by the single or the reverse-parallel methods. However, the IL-6 level decreased significantly following PE by the series-parallel method. The serum IL-18 level decreased significantly following PE by each of the three methods. Thus, removal of excess bilirubin, citrate, and cytokines by the series-parallel method, a simple maneuver with excellent removal rates, was considered effective.

Clinical and experimental study on therapeutic effect of umbilical cord blood transplantation on severe viral hepatitis

To investigate the therapeutic effect of umbilical cord blood transplantation (UCBT) on patients with severe viral hepatitis and on liver lesions in rats. One hundred and fifty three patients with severe viral hepatitis were included in the study between April 1990 and July 2002. The patients were treated with adult plasma transfusion (control), UCBT, plasma exchange (PE) and UCBT combined with PE (UCBT+PE) respectively. The therapeutic effectiveness was evaluated by serial determinations of liver function, lipids and immune function in all patients before and after the treatment. The model of experimental hepatic failure was constructed in SD rats by injecting carbon tetrachloride. Then, the rats were given normal saline, adult plasma or neonate cord blood intraperitoneally. After detection of liver function, the rats were killed and morphological changes of the liver were microscopically observed. UCBT group and UCBT+PE group had much better improvement in liver and immune functions than control group and PE group. The patients in UCBT+PE group had the best clinical efficacy. UCBT was safe and had no side effects. The animal experiment showed significant improvements in liver function and survival rate in neonate cord blood group as compared with adult plasma group. The histopathology of rat's liver indicated that neonate cord blood application could decrease the liver injury and increase hepatocellular regeneration. UCBT demonstrated a good therapeutic effect on severe viral hepatitis and no obvious side effects. Umbilical cord blood can attenuate the liver lesions and reproduce hepatocyte. The treatment of UCBT combined with PE was much better than that of single plasma exchange, thus UCBT can enhance the therapeutic effect of plasma exchange on severe viral hepatitis.

Effects of operating conditions on selectivity of a plasma fractionator in double filtration plasmapheresis.

In a typical double filtration plasmapheresis treatment, plasma fractionation between albumin and some immunoglobulins associated with toxins is limited because none of the currently available plasma fractionators has a strict cutoff property for these proteins. Selectivity of immunoglobulins over albumin depends not only on the cutoff properties of the membrane but on the operating conditions such as the flow rate of the supplied plasma (Q(P)) and retained plasma to be discarded (Q(D)) in the plasma fractionator. We carried out an in vitro study using human plasma harvested by single plasma exchange treatments to assess the selectivity of a plasma fractionator, Evaflux 2A-F (Kawasumi Laboratories, Inc., Tokyo, Japan), under various operating conditions. The results of rate-constant filtration experiments showed that the concentrations in the feed tank and the sieving coefficient (SC) values of every protein were decreased slightly within 2 h after the start of the experiment because of membrane trapping, adsorption, and/or plugging. The time-averaged SC value of albumin increased with flow rate ratio (Q(P)/Q(D)) due to increasing filtration fraction (FF), but relative removal efficiency (mD/mP*) for albumin decreased with Q(P)/ Q(D) due to decreasing Q(D). For immunoglobulins, on the other hand, the SC values were almost unchanged, and the mD/mP* values increased with Q(P)/Q(D) due to an increase in FF. Both increasing Q(P) and decreasing Q(D) are effective means of improving selectivity between these proteins in the plasma fractionator. Membrane fouling is, however, obvious beyond a Q(P)/Q(D) value that is thought to be a critical point. Operation should be conducted below the critical Q(P)/Q(D) value, which depends on the patient's plasma components and the cutoff property of the membrane.