Membrane-based therapeutic plasma exchange: Hemodynamics and operational characteristics leading to procedure failure.

BACKGROUND AND OBJECTIVES: Therapeutic plasma exchange (TPE) is a blood purification treatment capable of removing large molecular weight substances from plasma. It is commonly used for the removal of circulating pathogenic immunoglobulins presumed to be the cause of many autoimmune diseases. TPE can be performed with a membrane-based system (mTPE) or a centrifugal-based system (cTPE). When plasma separation is performed with a membrane, filter clotting can lead to longer treatment time, higher cost and can negatively impact patient satisfaction. In this study, we examine the operational characteristics that might influence filter life. DESIGN, SETTING, PARTICIPANTS, & MEASURES: We report on 24 patients, with a total of 135 mTPE treatments in a single tertiary care academic center using the NxStage machine. The study focuses on treatment specific parameters that may lead to procedure failure. The main parameters of interest were transmembrane pressure (TMP) and the filtration fraction as displayed on the machine (FFd) compared to the calculated filtration fraction (FFc). Primary outcome was to measure whether TMP, FFc, and FFd influenced filter survival. Secondary outcomes included factors that might have indirectly resulted in filter failure, including hematocrit (Hct), platelet count, heparin use, and intra-treatment calcium administration. RESULTS: In this study, we demonstrated that machine displayed filtration fractions (FFd) were lower than FFc and this difference was significantly larger in TPE sessions that experienced a clotting event (7.58 vs 6.22, P = .031). TPE sessions that clotted had a higher mean TMP (57.48 mmHg vs 44.43 mmHg, P = .001) and clotting events tended to have a lower mean blood flow rate (175.83 mL/min vs 189.55 mL/min, P = .002). In TPE sessions that received prefilter calcium administration, a higher mean dose of calcium gluconate was found in the sessions that experienced clotting (3.27 g vs 2.70 g, P = .013). Patients who experienced at least one clotting event were noted to be heavier than those patients without any clotting events (91.52 kg vs 72.15 kg, P = .040). Prefilter heparin administration was not associated with a lower incidence of filter clotting. We did not find a statistically significant difference in clotting events based upon type of intravenous access, pretreatment hematocrit, or pretreatment platelet counts. CONCLUSION: Among patients undergoing mTPE, machine FFd on the NxStage system are consistently lower than FFc. Treatments where there was a greater difference between displayed and FFc had a greater likelihood of filter clotting. Treatments with higher TMP were associated with failed treatments. Prefilter calcium administration during treatment was associated with increased filter clotting. Lower blood flow rates and higher patient weight were also associated with increased filter clotting. Prefilter heparin administration did not reduce the incidence of filter clotting.

Nationwide practices in the use of central venous catheters for therapeutic plasma exchange in the inpatient setting.

INTRODUCTION: Therapeutic plasma exchange (TPE) is often impacted by difficulties in obtaining an adequate and safe vascular access. This study evaluated the rates, predictive factors, and clinical outcomes associated with central venous catheter (CVC) use during the inpatient TPE procedures. METHODS: The Nationwide Readmissions Database, 2016 to 2017 was used to identify hospitalizations with TPE with and without CVC insertion. RESULTS: During the study period, there were 35 429 hospitalizations with TPE (pediatric 6.1%, mean ± standard deviation (SD) age 50.9 ± 20.0 years, female 52.7%). CVC insertion was documented in 24 414 (73.4%) adult and 1596 (73.5%) pediatric hospitalizations. In pediatric patients, age >15 years, higher disease severity, and private insurance were associated with higher odds of CVC insertion. In adults, female sex, obesity, concurrent hemodialysis, and higher disease severity were associated with CVC insertion. Adults with private insurance and both adult and pediatric hospitalizations at the teaching hospitals had lower odds of CVC placement. All patients with CVC insertion had longer length of hospital stay, and adults with CVC insertion also had higher hospital charges, higher in-hospital mortality, and lower likelihood of being discharged to home. CONCLUSION: CVC insertion is performed for the majority of inpatient TPE procedures and CVC use appears to correlate with worse clinical outcomes.

Efficiency of Double Plasma Molecular Absorption System on the Acute Severe Cholestatic Hepatitis.

BACKGROUND: Cholestasis may lead to hepatic cirrhosis and a longer hospital stay. A part of the patients with cholestasis requires liver transplantation. However, most of the treatment efficiency of cholestatic hepatitis (CH) is not satisfactory. For the patients with severe CH after artificial liver support, there was a lack of systemic evaluation on the treatment efficiency of double plasma molecular absorption system (DPMAS) for acute severe CH. OBJECTIVE: We aim to investigate the treatment efficiency of DPMAS on acute severe CH. METHODS: This retrospective study involved 309 cases diagnosed with acute severe CH admitted to the First Affiliated Hospital, Zhejiang University. We compared the prognosis of patients received standard medical therapy (SMT) and SMT + DPMAS. Besides, the effects of DPMAS on total bilirubin (TBIL) and prothrombin time (PT) were investigated. RESULTS: DPMAS could significantly reduce the requirements for liver transplantation in the CH patients. After DPMAS therapy, significant decline was noticed in the TBIL, direct bilirubin (DBIL), total bile acid, and cholesterol. The baseline ratio of neutrophil showed significant elevation in the patients received 4 or more DPMAS compared with those received less DPMAS. CONCLUSIONS: DPMAS could significantly eliminate the necessity of liver transplantation. The artificial liver support system should be conducted to bring down the bilirubin level and the ratio of cases with severe conditions. In general, DPMAS should be preferred as an artificial liver support therapy for the patients with acute severe CH.

Safety and Efficacy of Tandem Hemodialysis and Selective Plasma Exchange in Pretransplant Desensitization of ABO-Incompatible Kidney Transplantation.

INTRODUCTION: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. METHODS: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. RESULTS: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. DISCUSSION/CONCLUSION: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

Effect of artificial liver blood purification treatment on the survival of critical ill COVID-19 patients.

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID-19). A total of 101 severe and critical patients with coronavirus SARS-CoV-2 infection were enrolled in this open, case-control, multicenter, prospective study. According to the patients' and their families' willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28-day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre-treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin-6 (IL-6) level. The serum IL-6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL-6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28-day follow-up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID-19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short-term mortality.

Double filtration plasmapheresis: Review of current clinical applications.

Double filtration plasmapheresis (DFPP) is a semi-selective blood purification modality derived from the plasma exchange (PE) modality. In the DFPP treatment, two types of filters with different pore sizes are used: a plasma separator and a plasma component separator. Blood is separated into plasma and blood cells using a plasma separator. The separated plasma is fractionated into large and small molecular weight components by a plasma component separator. Large molecular weight components, including pathogenic substances, are discarded. Small molecular weight components, including valuable substances such as albumin, are returned to the patient. The advantage of DFPP is that the volume of replacement fluid can be significantly reduced compared to PE. By selecting the optimal pore size model for the plasma component separator, DFPP can be applied to various disorders. The clinical applications of DFPP are reviewed based on recent articles on metabolic disorders, organ transplants, rheumatic disorders, neurological disorders, and dermatologic disorders.

Therapeutic plasma exchange with standard hemodialysis machine as an alternative to dedicated apheresis device: A 5-year experience.

Patients suffering from various diseases have been shown to benefit from therapeutic plasma exchange (TPE). However, in developing countries, there are many obstacles hindering the establishment and initiation of TPE programs. These include inadequate funding and lack of government healthcare coverage. Our center in Thailand practices a unique membrane plasma separator technique using a hemodialysis machine incorporated with a plasma separator. Over a 5 year period, there were 130 such sessions conducted in 24 patients. The indications for TPE treatment included neurological, hematological, and nephrological diseases. Overall, response to TPE was good. Some TPE-related adverse events did occur, but none were life-threatening. Unfortunately, infection remained a problem and was sometimes a cause of death. Future challenges include minimization of infection rates and making TPE treatment readily accessible to patients.

Membrane-Based Therapeutic Plasma Exchange in Intensive Care.

The principles and use of plasmapheresis are often little understood by intensivists. We propose to review the principles, the main indications, and the methods of using this technique.

Isovolemic filter-based therapeutic plasma-exchange with fresh frozen plasma is associated with minimal thromboelastometric changes in noncoagulopathic patients.

The aim of this study was to assess the effects of isovolemic therapeutic plasma-exchange using fresh frozen plasma on coagulations parameters assessed by standard coagulation tests and rotational thromboelastometry in noncoagulopathic patients. Twenty patients who underwent isovolemic filter-based therapeutic plasma-exchange of approximately 1.5 plasma volume per session were included in the current study. Standard coagulation tests and rotational thromboelastometry (ExTEM, InTEM, FibTEM and ApTEM) were performed 30 min before and after the procedure. Isovolemic therapeutic plasma-exchange was associated with decreased fibrinogen levels (P = 0.01). Thromboelastometric assay demonstrated an increased clotting time in both ExTEM (P = 0.03) and InTEM (P = 0.01) and a decreased thrombodynamic potential index in ExTEM (P = 0.03). No significant difference in FibTEM maximum clot firmness was recorded (P = 0.41). Therapeutic plasma-exchange in noncoagulopathic patients is associated with minimal changes in thromboelastometric parameters, mainly by an increase in clotting time in both intrinsic and extrinsic pathways.

Therapeutic Plasma Exchange Using Membrane Plasma Separation.

Therapeutic plasma exchange is a blood purification technique designed for the removal of large molecular weight toxins such as pathogenic antibodies and lipoproteins. Plasma exchange can be performed either by membrane separation or centrifugation. Centrifugal plasma exchange is more common in the United States, while membrane separation is more popular in Germany and Japan. The membrane separation technique is similar to the ultrafiltration procedures performed with a standard dialysis machine but in which the membrane's pores are large enough to allow removal of all circulating molecules while retaining the cellular components. The current availability of plasma separation membranes compatible with CRRT systems has dramatically increased the potential for almost all nephrologists to perform these treatments. This review describes the membrane separation techniques available in the United States, the practical aspects of ordering and operating a membrane separation plasma exchange procedure, and its possible complications.

Plasma exchange in neurological disease.

Plasma exchange is a highly efficient technique to remove circulating autoantibodies and other humoral factors rapidly from the vascular compartment. It was the first effective acute treatment for peripheral disorders such as Guillain-Barré syndrome and myasthenia gravis before intravenous immunoglobulin became available. The recent recognition of rapidly progressive severe antibody-mediated central nervous system disorders, such as neuromyelitis optica spectrum disorders and anti-N-methyl-D-aspartate-receptor encephalitis, has renewed interest in using plasma exchange for their acute treatment also. In this review we explain the principles and technical aspects of plasma exchange, review its current indications, and discuss the implications for its provision in the UK.

Performance characteristics of the PowerFlow apheresis port: Early experience.

We prospectively evaluated the Bard PowerFlow Implantable Apheresis IV Port in four patients undergoing outpatient therapeutic plasma exchange over 18 to 97 days. Three had bilateral internal jugular access ports, and one had a single left internal jugular access port for the inlet line with return via antecubital vein. Two patients receiving 5% albumin as replacement fluid achieved peak inlet flow of 99 ± 5 mL/min and 101 ± 6 mL/min, and peak plasma flow of 53 ± 6 and 47 ± 6 mL/min, respectively. Two patients receiving plasma as replacement fluid achieved peak inlet flow of 46 ± 7 and 85 ± 4 mL/min and peak plasma flow of 27 ± 3 and 35 ± 4 mL/min, respectively. Apheresis nurses accessed the ports on the first attempt in all procedures. Pressure alarms occurred in 6 of 47 procedures and were easily resolved by lowering the inlet rate by 10% in 5 of them. The PowerFlow shows promise as an implantable venous access device for apheresis.

Plasma exchange activity in the European Union.

In spite of a relatively high number of diseases where therapeutic plasma exchange (TPE) is recommended as a first (category I) or second line of therapy (category II), according to the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the American Society for Apheresis, evidence exists that the number of procedures that are performed varies widely depending on the countries and even between centers in a given country. The aim of this work was to analyze the number of TPE that are performed in different European countries and calculate the rate of TPE per 1,000,000 inhabitants. We contacted the three manufacturers of disposables for performing TPE by centrifugation in Europe (Fresenius Kabi, Haemonetics, and Teurmo BCT) and asked them for the number of disposables sold in each of the countries of the European Union (EU) in 2014 as a surrogate indicator of the TPE performed in the country. A total of 101,767 disposable units to perform TPE using centrifugation devices were sold in the EU in 2014. A huge variation exists in the number of disposable units of PTE sold in the different EU countries. A factor of 51 separates the rate of TPE per 1 million inhabitants performed by centrifugation in the country with the highest number (Belgium, 459) from the country with the lowest (Romania, 9). That variation probably is due to differences in healthcare expenditure but also differences in practice.

Therapeutic plasma exchange: Review of current indications.

Therapeutic plasma exchange (TPE) is the extracorporeal technique performed in an apheresis device were patient's plasma is separated from whole blood and removed, while the cellular blood components are returned to the patient together with a replacement fluid. By the extracorporeal removal of pathological substances and the replacement of deficient plasma components, it constitutes an important tool for the management of several disorders and it is a well-known and established treatment for numerous diseases. Additionally, overall available data confirm the safety and efficacy of TPE. Nevertheless, the quality of the evidence supporting the utility and efficacy of the procedure is diverse. This review attempts to compile the current indications of TPE in different disorders according to an extensive and updated literature review, with special focus on its present role and its validity in the twenty-first century medicine.

A Solution Kinetics Simulation Method for Conventional and Selective Plasma Exchange Using a Complete Mixed Reactor Model.

At present, conventional plasma exchange (CPE) sets removal rate, replacement fluid volume and replacement fluid albumin (Alb) concentration according to the first-order kinetics of mass balance for removal of pathogenic substances. With the spread of selective plasma exchange (SePE), it has become necessary to set the removal rate and replacement fluid Alb concentration based on the initial concentration for each performance of the plasma separator. Considering the patient as a single reactor we devised a complete mixed reactor model simulating the concentration change in the reactor. Our formula is obtained by adding membrane performance and replacement fluid concentration to formulas currently available and can be used for both CPE and SePE. For the in vitro experiment, fresh frozen plasma stored in a bag was used to simulate a patient's circulating plasma. Plasma was separated by plasma separator Evacure EC-4A10 (EC-4A) (Kawasumi Laboratories Inc., Tokyo, Japan) while a replacement Alb solution was simultaneously entered into the circuit at the same rate as separation. IgG, Alb, total protein (TP), and fibrinogen (Fib) concentrations were measured every 10 min and examined for correlation with the value predicted by the mass balance formula. The concentration of each solute was measured 21 times during the 195 min of the experiment. The rate of change of each solute was IgG 76%, Alb 58%, TP 58%, and Fib 32%. Experimental values and predicted values showed significant correlation (IgG: r2 = 0.9962; Fib: r2 = 0.9535; Alb: r2 = 0.9808; TP: r2 = 0.9721, all P < 0.05). Since the solute concentration change in SePE can be predicted, this mass balance formula is useful for setting treatment conditions for both CPE and SePE.

Plasma exchange for heparin-induced thrombocytopenia in patients on extracorporeal circuits: A challenging case and a survey of the field.

Current management of heparin-induced thrombocytopenia (HIT) involves prompt discontinuation of all heparin products and concomitant initiation of a direct thrombin or anti-Xa inhibitor for anticoagulation. In the setting of HIT complicated by an urgent need for cardiopulmonary bypass (CPB), the safety and the efficacy of short-term heparin-based anticoagulation after therapeutic plasma exchange (TPE) have been previously demonstrated. Patients with HIT requiring TPE are frequently on extracorporeal circuits (either CPB, extracorporeal membrane oxygenation [ECMO] or external ventricular assist devices [VADs]). Performing TPE in parallel with these circuits involves additional consideration for circuit size, anticoagulant/citrate management, as well as flow rates, and risk of air embolus. We report a case of a patient with HIT on external biventricular assist device (BiVAD) requiring urgent CPB who experienced thrombotic and hemolytic complications related to anticoagulation management around apheresis line placement for TPE. We also present results from a national survey of academic apheresis services regarding specific practices in managing patients with HIT on extracorporeal circuits who require TPE. In addition, we demonstrate the utility of TPE in patients with HIT on extracorporeal circuits and the risks of this procedure and the need to develop practice guidelines.