Apheresis Methods Research Articles

Blood reserves and availability of blood preparations in University Clinical Center Tuzla, Bosni and Herzegovina

INTRODUCTIONTransfusiontreatmentinmodernclinicalpracticeincludessubstitutiontherapy certaincomponentsoftheblood,whichadequatelyandeffectivelycontributetoquickrecoveryandhealing diseases[1].Almosteverybranchofmedicineistransfusion-dependent,startingwithsurgeryandinternalmedicine branchtodiagnosticones,wherethesafetyofthepatientisensuredbysubstitutionwithcertainblood preparations[2]. Bloodandbloodproductsdifferfromotherdrugsandpharmaceuticalpreparationswhile the only source is humanbloodfromvoluntarydonors[3].Inpractice theyusetwowaysofgettingblood,byvoluntarydonation,whenwholebloodistaken,whichisthemostcommon usedasastartingpointfortheproductionofotherdrugsfromblood,andbytheapheresisprocedureon cellseparator,whenonlyonebloodcomponentistaken,suchasplatelets,plasma, erythrocytes[1,4] Anadequatebloodtransfusionsupplyiscrucialforthefunctioningofthehealthsystem[5].Althoughtheyare bloodanditscomponentsrecentlyaddedtotheWHOessentialdruglist,insufficientbloodsuppliesinmost oflow-andmiddle-incomecountriesstillleadtomortalityandmorbidity,whichcan preventbyensuringsufficientbloodreserves[6,7]. Ensuringsufficientamountsofbloodimpliesstrategicconsiderationoflocal,epidemiological factors,demographicstructure,equipmentandabilitytoproducemedicinesfromwholeblood[8,9]. Currently,voluntaryblooddonationinmanylow-andmiddle-incomecountriesisnot adequately[10].Themainreasonsfortheunavailabilityofbloodisthehighprevalenceofviralhepatitisand inadequateproductionofbloodcomponents[11].Overallrelationsinsociety,socio-economicand demographicsareanimportantfactorforassessingthepossibilitiesofensuringstablereservesofsafeblood,which theyrepresentthenationalresourceofacountry[12].Theestimationofthedailyconsumptionofbloodproductsis unpredictablenature,duetopossibleincidentsituations,naturaldisasters,andlimited lifetimeofdifferentpreparations.Thelimitedlifespanofbloodincreasesthenumberofunuseddoses, resultinginadecreaseinstablereservesandhighcosts[6]. AccordingtoWHOguidelines,recommendationsforensuringstablebloodreservesinclude10to20 donationsper1000inhabitants[13].Theseassessmentsareimportantbecausetheycanservetoguidefurtherones investmentsinstrategiestoensuresufficientamountsofblood,thenanalysisofcurrenttransfusionpractice, introductionofrationalizationmeasuresduringtransfusiontreatmentandimplementationofthesystemfor bloodmanagement[14,15].IntheareaofTuzlaCanton,theannualblooddonationisapprox. 13000doses.Formorethanthreedecades,thePolyclinicforTransfusionhasbeenproducingvariousmedicinesfrom blood,whoselifespanandstoragemethodaredifferent,namely:wholeblood,erythrocyteconcentrate,concentrateerythrocyteswithareducednumberofleukocytes,irradiatederythrocyteconcentrate,freshfrozenplasma, plateletconcentrate,plateletconcentratewithreducednumberofleukocytes,irradiatedconcentrate platelets,plateletapheresisconcentrateandcryoprecipitate. MATERIALANDMETHODSThis retrospective study was carried out at the Polyclinic for Transfusion, University Clinical Center Tuzla data from the Renovatio information system in the period from July 1, 2022 to December 31, 2022. Data were analyzed on voluntary blood donors (age and gender), who donated blood during that period. Then data on the number of blood doses collected, as well as the number and type of medicines produced from blood (whole blood, erythrocyte concentrate, erythrocyte concentrate with reduced number of leukocytes, irradiated concentrate platelets, fresh frozen plasma, cryoprecipitate, platelet concentrate, platelet concentrate with a reduced number of leukocytes, irradiated platelet concentrate, irradiated platelet concentrate with reduced number of leukocytes, as well as platelet concentrate produced by the apheresis method using of the Amicus cell separator. Also, data was collected for patients who received blood preparations: age, gender, diagnosis, type of blood preparation indicated, name of the clinic where the patients were hospitalized, and the type and quantity of blood products issued. RESULTSThelargestnumberofdonatedbloodunitswasusedinthepreparationoffreshfrozenplasma,5742units,then5498unitsofplateletconcentrate,797unitsofcryoprecipitate,and308unitsofconcentrate plateletswithareducednumberofleukocytes,200unitsofirradiatedplateletconcentrateand119units irradiatedplateletconcentratewithareducednumberofleukocytes (Figure 1).

#805 Successful application of DALI for extracorporeal hemocorrection in a patient with LDL cholesterol serum levels (case study)

Abstract Background and Aims Plasma lipoidosis type 4 (PLD4) is a rare hereditary disease characterized by disorders of fat metabolism in the body. PLD4 occurs rare in the general population. The exact frequency of occurrence is unknown, as it depends on hereditary factors in a particular population. The relevance of the disease lies in its rarity and potential association with various complications. Patients with PLD4 have decreased levels of low-density cholesterol (LDL) and increased levels of triglycerides in the blood, which can lead to the development of atherosclerosis and other cardiovascular diseases. Plasma lipoidosis type 4 requires further researches for better understanding of its epidemiology, mechanisms of development and possible treatment strategies. In this case, we describe the case of a patient with type 4 plasmatic lipoidosis who was treated with the DALI (Direct Adsorption of Lipoproteins) technique. Anticoagulation is initiated with heparin and maintained by ACT. This technique is accompanied by decreasing the level of LDL and Lp (a) without decreasing the level of HDL and fibrinogen. The pore sizes of the polyacrylamide bed are small enough to avoid the removal of red blood cells and platelets. Activation of leukocytes and complement is minimal and clinically insignificant. Depending on the initial level of lipidemia during this procedure, it is possible to select the appropriate adsorber (DALI-500, -750, -1000). Methods of extracorporeal correction of lipid metabolism disorders should be widely introduced into healthcare practice. It should be noted that during DALI apheresis, the fibrinogen level does not decrease so sharply and is not accompanied by changes in erythrocyte aggregation. (Richter W. O., 2003). Aim of study The purpose of our study was to evaluate the effectiveness of using DALI (Direct Adsorption of Lipoproteins) in a patient with type 4 plasmatic lipoidosis. Method Patient N., 67 years old, diagnosed with IHD. Angina pectoris FC 2. Plasma lipoidosis type 4, hyperbetalipoproteinemia by autosomal dominant type of inheritance. Cysts of both kidneys. In 1997, diagnosed with: plasma lipoidosis type 4, hyperbetalipoproteinemia by an autosomal dominant type of inheritance. The plasmapheresis sessions were recommended against the increased lipid metabolism indexes. The patient regularly receives antilipidemic therapy and plasmapheresis sessions up to 2 times a year. The patient is admitted with complaints of fatigue and general weakness. According to the patient's ambulatory card, discharge summaries: CREA - 147 µmol/l, UREA – 6.3 mmol/l. GFR – 34 ml/min/1.73 m2. Total bilirubin - 9 µmol/l, direct bilirubin - 3 µmol/l. Considering the severity of the condition and the activity of the main diagnosis, a procedure with the DALI technique was started. During the hospitalization period, 3 procedures were performed, the whole of them were tolerated satisfactorily. The general condition is of moderate severity. Consciousness is clear. Hemodynamics is stable. Urination is free and painless. Diuresis is adequate. Results Hemodynamics: when connected - blood pressure – 120/82 mm Hg, heart rate – 61 beats/min. When disconnected, the patient's condition is the same, hemodynamics - blood pressure – 119/59 mm Hg, heart rate – 65 beats / min. Conclusion The usage of the apheresis method with the DALI system can effectively reduce the level of low-density lipoprotein (LDL) and Lp (a), while maintaining the content of high-density lipoprotein (HDL) and fibrinogen at a constant level. This reduction in LDL concentrations has the potential to reduce patients' risk of developing cardiovascular disease and the mortality from it.

Extracorporeal Methods of Hemocorrection in Patients with Abdominal Sepsis

BACKGROUND. Theoretical data convincingly support the use of extracorporeal hemocorrection (ECHC) methods in the treatment of sepsis. However, a large number of researchers have still not been able to convincingly prove the advantage of ECHC methods; there is no unanimity of opinion. We tried to analyze our own experience in using ECHC methods in the treatment of abdominal sepsis over the past 3 years. AIM OF STUDY. To analyze the use of ECHC methods in the early stages of treatment of abdominal sepsis, to determine whether their use had an advantage for survival. STUDY DESIGN. Prospective cohort. DESCRIPTION OF THE METHOD. In 50 cases (group 1), ECHC was performed early after surgery. The median time from admission to the intensive care unit after surgery to the start of ECHC was 25.3 (17.7; 36.5) hours. When determining the ECHC modality, we were guided by the individual approach and clinical experience of the ECHC specialist. Apheresis methods alone were performed in 8 % of patients (4/50), a combination of apheresis methods and renal replacement therapy was performed in 40 % (20/50), renal replacement therapy (RRT) methods were performed in 98 % (46/50), plasmapheresis/plasma exchange/selective plasma filtration were performed in 30 % (15/50), selective hemosorption of cytokines was performed in 4 % (2/50), selective hemosorption lipopolysaccharides was performed in 24 % (12/50). We analyzed outcomes, assessments of the severity of functional disorders and sepsis-associated organ dysfunction according to the APACHE scales II and SOFA and their dynamics, probabilities of outcomes depending on the scores on the indices (logistic regression); life times, cumulative survival rate (Kaplan-Meier method). SAMPLE CHARACTERISTICS. There were 113 patients after emergency laparotomy due to widespread peritonitis, abdominal sepsis, aged from 23 to 90 years. 67 men, 46 women. In 50 cases of observation (group 1), ECHC was performed in the early stages ; in 63 cases, methods of active hemocorrection were not used (group 2). In group 1 there were 35 patients with septic shock and 15 patients with stable hemodynamics (subgroup 1/shock and subgroup 1/sepsis). In group 2 there were 20 patients with shock and 43 with stable hemodynamics (subgroup 2/shock and subgroup 2/sepsis). RESEARCH RESULTS ECHC. Methods allowed survival of patients with more severe APACHE scores II and SOFA: in survivors in subgroup 1/shock Me 29 (24; 31) versus 23 (14; 26) in the subgroup 2/shock and 8 (4; 10) versus 4 (2; 6) points, p=0.048 and p = 0.010; with stable hemodynamics in survivors in subgroup 1/sepsis Me 20 (17; 22) versus 15 (11; 19) in subgroup 2/sepsis, p=0.016. ECHC changed the survival threshold in favor of more severe patients from 29 to 33 points; reduced the likelihood of an unfavorable outcome 1.2-fold for each point on the APACHE scale II and 1,276 times over the entire range of estimates; prolonged survival time in hemodynamically unstable patients at a significance level of p = 0.083, shifting the first quartile of survival from 1 to 12 days, the median from 12 to 20, the third quartile from 27 to 45 days. When performing ECHC, the cumulative survival rate was higher throughout the entire hospital observation period: 0.886 (95 % CI 0.780–0.939) in 2 days versus 0.700 (95 % CI 0.499–0.802); 0.800 (95 % CI 0.667–0.868) in 10 days versus 0.545 (95 % CI 0.325–0.658); 0.653 (95 % CI 0.494–0.734) in 14 days versus 0.416 (95 % CI 1.185–0.533). Overall mortality from all causes was 35.4 % (40/113), 67.3 (37/55) with shock, 5.2 % (3/58) with stable hemodynamics. The maximum risk of an unfavorable outcome occurred in the early stages: 30 % (12/40) of all deaths occurred in the first 4 days after surgery, 20 % (8/40) in the first 24 hours. In shock patients, 10-day mortality was lower when performing ECHC: 20.0 % (7/35) versus 45.0 % (9/20), p = 0.050, 1st stage. Fisher’s test, P = 0.38 insufficient. Hospital mortality in the shock subgroups was equal, all the advantages of ECHC achieved in the early stages were lost; although in most late outcomes the peritonitis was relieved; which was confirmed during the section. CONCLUSIONS. The power of the study was sufficient to identify statistically significant advantages of extracorporeal hemocorrection in the treatment of abdominal sepsis based on APACHE index estimates II and SOFA. For the Kaplan–Meier method, differences were obtained for shock patients at a significance level of 0.083; the number of observations must be doubled to detect statistically significant differences. The final results of hospital mortality require additional in-depth analysis, since in the later stages many deaths were not associated with abdominal sepsis and occurred with already resolved peritonitis. It is necessary to understand to what extent they were associated with experienced sepsis, and to what extent with comorbid pathology; whether there was an association with methods of extracorporeal hemocorrection.

Apheresis methods in COVID-19 era: What about Long COVID?

Apheresis methods in COVID-19 era: What about Long COVID?

The efficiency of a continuous versus an intermittent apheresis method for collection of hematopoietic progenitor stem cells: A systematic review.

Peripheral blood hematopoietic progenitor stem cells (HPSCs) are the most common source of stem cells for autologous and allogenic transplantation. Currently, systematic reviews comparing the collection efficiency of a continuous to an intermittent method are lacking despite the existence of primary studies. Therefore, the objective of this review was to synthesize the best available evidence to compare the efficiency of the continuous vs the intermittent method for the collection of hematopoietic progenitor stem cells required for HPC transplantation. A search using MEDLINE, CINAHL, EMBASE, Google scholar, and MedNar for both published and unpublished studies was conducted in December 2021. The systematic review was conducted in accordance with JBI methodology. A critical appraisal of the studies was undertaken by two independent reviewers using the JBI quasi-experimental critical appraisal checklist. A total of six studies were included in the review. The findings of this review demonstrated that there was no statistically significant difference in the collection efficiency, length of procedure time, and total blood volume processed between the continuous and intermittent programs. The evidence suggests that the continuous method is as safe and effective as the intermittent method to collect HPSCs. Until further evidence becomes available clinicians should be guided by the policies of their individual hospitals.

Abstract 4426: Removal of soluble TNF receptors as a novel form of immunotherapy for patients with advanced solid tumors

Abstract Immunicom, Inc. has developed a novel subtractive immunotherapeutic apheresis method (Immunopheresis®) to selectively remove soluble tumor necrosis factor receptors, sTNF-R1 and sTNF-R2 (sTNF-Rs) generated by tumors. sTNF-Rs block the tumoricidal activities, hence their removal restores the anticancer immunotherapeutic activity of native TNF-α. Past use of systemic administration of TNF-α to treat solid tumors resulted in unacceptable toxicities. Immunicom’s LW-02 Column contains a bead matrix covalently bonded to a single-chain, TNF-α capture ligand (scTNF) with high affinity and selectivity to remove sTNF-Rs from plasma. Three clinical trials (NCT04004910, NCT04142931, NCT04690686) have been conducted in patients with various advanced-stage breast cancers (BC), melanoma (M), renal cell carcinoma (RCC) and non-small cell lung cancers (NSCLC). Patients were assigned to receive LW-02 Column Immunopheresis® monotherapy or combined with various chemo- or immunotherapies. Immunopheresis® was administered 3x/week for each trial’s 12 or 16-week Primary Treatment period with each procedure processing 2 plasma volumes (2PV). Patients with (at least) clinical stability and/or tumor responses could receive additional treatment. Compared to healthy persons, patients in all 3 trials were noted as having significantly elevated baseline blood concentrations of sTNF-R1 and sTNF-R2. For instance, sTNF-R1 plasma levels were 3.5 ng/mL, 3.5 ng/mL, 2.2 ng/mL and 2.1 ng/mL for BC, M, RCC and NSCLC, respectively, which were 5-8-fold higher than normal values. Likewise, sTNF-R2 plasma concentrations (which can be 4-fold, or more, greater than sTNF-R1) were 4-9-fold higher for BC (16.5 ng/mL), M (19.1), RCC (22.7) or NSCLC (11.1 ng/mL) than normal values. Through the data cutoff, >1,600 LW-02 Column Immunopheresis® procedures were performed. On average, 95% of sTNF-R1 and 80% of sTNF-R2 are removed from plasma at the 30-minute procedure timepoint. At the 2PV timepoint, overall mean reductions of sTNF-R1 and sTNF-R2 in whole blood were 51 and 52%. Further, minimal leaching (mean of 113 ng per procedure), of the scTNF capture ligand was detected, a quantity that is insufficient to cause any meaningful clinical effects. In vitro testing determined that the LW-02 Column has no discernable evidence of unintended or “off-target” removal of other cytokines or blood constituents or any non-specific binding. Moreover, the trial results demonstrate Immunopheresis® is safe with minimal side effects determined to be related to treatment with the column. Results from 3 trials indicate that cancer patients with advanced solid tumors present with significantly upregulated levels of immune inhibitory sTNF-Rs. LW-02 Column Immunopheresis® can safely and selectively remove sTNF-Rs thus allowing endogenous TNF-α to instigate its multiple anticancer pathways. Citation Format: Piotr J. Wysocki, Piotr Tomczak, Tomasz Jankowski, Tomasz Nowikiewicz, Gal Markel, Ronnie Shapira, Gokhan Demir, Mustafa Bozkurt, Sameera Bilgrami, Annette Marleau, Adam Ostrowski, Lawrence Florin, Victoria Manax, Robert Segal. Removal of soluble TNF receptors as a novel form of immunotherapy for patients with advanced solid tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4426.

Double filtration plasmapheresis for children with different types of critical kidney diseases: a single-center retrospective cohort study.

Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

Quality assessment of platelet concentrates prepared by platelet-rich plasma, buffy-coat, and apheresis methods in a tertiary care hospital in South India: A cross-sectional study.

In blood banking and transfusion medicine, it is of paramount importance to improve transfusion safety and provide a higher quality of product to maximize the therapeutic outcomes and minimize the risk of developing transfusion-associated complications for patients receiving a blood transfusion. This was a cross-sectional study conducted at the department of transfusion medicine in a tertiary care hospital of South India from February 2019 to December 2020. The primary objective of the study was to assess the quality of platelet concentrates (PC) prepared by platelet-rich plasma (PRP), buffy-coat (BC), and apheresis method. A total of 760 PCs were subjected to quality assessment, among which 124 were PRP-PC, 176 were BC-PC, and 460 were single donor platelet (SDP). The total percentage of platelets meeting all the six quality control parameters in PRP, BC and SDP was 78.23%, 81.81%, and 89.96%, respectively. Apheresis PCs showed a significantly higher platelet concentration per µL on comparison with whole-blood-derived platelets. BC-PCs were found to be better than PRP-PC with regard to lower white blood cell (WBC) contamination (P < 0.05) and red blood cell (RBC) contamination (P < 0.01). No statistically significant difference was found with regard to platelet yield, volume, swirling, and pH. Ex vivo quality of PCs prepared by BC-PC, PRP-PC, and apheresis-PC fulfilled the desired quality control parameters. BC-PC was better than PRP-PC in terms of lesser WBC and RBC contamination and comparable in terms of volume, platelet yield, swirling, and pH. Apheresis PCs showed a higher platelet concentration per microliter on comparison with whole-blood-derived platelets; hence in a blood center where facilities for collection of apheresis product are available, SDPs should be the choice of platelet transfusion.

Therapeutic Apheresis, Immunosuppression, and Human Monoclonal Antibodies in Hematologic Diseases

To cure a patient by removing his illness by extracting blood is a very old one. Now this old process, bloodletting, placed on a rational basis with therapeutic apheresis using hollow fiber membranes, is being our clinical practice. Based on many years of experience with extracorporeal circulation in end-stage renal disease, the authors herein give an overview of TA in hematologic diseases, with immunologic or non-immunologic origin. Immunology and molecular biology of the different hematologic diseases are discussed in relation to the rationale for apheresis therapies, and its place alone or in combination with other modern therapies, such as immunosuppression, HMAs, tyrosine kinase inhibitors, recombinant factor VVII, VIII, and others. The prognosis of the most of the hematologic diseases has improved in recent years, due in part to very aggressive therapy methods. Therapeutic apheresis is indicated most only in severe hematologic diseases. The guidelines of the Apheresis Application Committee of the American Society for Apheresis for the hematologic diseases, which could be treated with apheresis methods are cited. Therapeutic apheresis has been shown to effectively remove autoantibodies, toxins, and other pathologic substances from blood and lead to rapid clinical improvement, and it can safely be performed even in all severe ill patients, most in combination with immunosuppression, and/or human monoclonal antibodies.

LW-5 DENDRITIC CELL IMMUNOTHERAPY FOR MALIGNANT GLIOMA: RESEARCH HISTORY FOR 25 YEARS AND THE FUTURE PROSPECTS

Abstract We started a research of dendritic cell (DC) immunotherapy for malignant glioma in late 1997, and were continuing the clinical study for more than 20 years with making several improvements of methods. The presenter has been participating in this research from its inception, and has continued to conduct research as the life's work. We will present research history and the future prospects. Autologous cultured tumor cells were established from tumor tissue obtained from a surgery of patient with malignant glioma in our hospital. Mature DCs were induced from autologous peripheral blood mononuclear cells (PBMC), and were fused with the established tumor cells. Cell manufacturing performed at a cell processing facility (CPF) maintained and managed by our university. Before 2004, the tumor-fused DCs (TFDC) were co-administrated with rIL-12. Since 2014, TFDCs were stimulated with Poly(I:C) and IL-10-siRNA in order to increase IL-12 secretion levels of them. Since 2014, PBMCs were collected by the apheresis method. Since 2006, the TFDC immunotherapy was combined with temozolomide (TMZ) chemotherapy. 111 cases were enrolled in the clinical study. The TFDC-immunotherapy was combined with the TMZ chemotherapy in 88 cases enrolled after 2006. No serious problem was confirmed in the cell manufacturing. The therapeutic effect in this study will be compared with a historical control that were the cases of malignant glioma treated with a standard therapy at the other affiliated hospitals at the same period. The results will be reported in the presentation. The safety and efficacy of this treatment were confirmed in the previous study. We would like to establish a provision system of the TFDCs by use of our CPF by preparing product uniformity, transport safety, preservation methods, etc., and aim to expand the hospitals that can perform this immunotherapy.

COVID-19 and Therapeutic Apheresis.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented challenge for the global community. The pathogenesis of COVID-19, its complications and long term sequelae (so called Long/Post-COVID) include, in addition to the direct virus-induced tissues injury, multiple secondary processes, such as autoimmune response, impairment of microcirculation, and hyperinflammation. Similar pathological processes, but in the settings of neurological, cardiovascular, rheumatological, nephrological, and dermatological diseases can be successfully treated by powerful methods of Therapeutic Apheresis (TA). We describe here the rationale and the initial attempts of TA treatment in severe cases of acute COVID-19. We next review the evidence for the role of autoimmunity, microcirculatory changes and inflammation in pathogenesis of Long/Post COVID and the rationale for targeting those pathogenic processes by different methods of TA. Finally, we discuss the impact of COVID-19 pandemic on patients, who undergo regular TA treatments due to their underlying chronic conditions, with the specific focus on the patients with inherited lipid diseases being treated at the Dresden University Apheresis Center.

Application of Extracorporeal Apheresis in Treatment of COVID-19: a Rapid Review.

Spread of a novel coronavirus infection in 2019 caused by SARS-CoV-2 virus has become a real threat to public health all around the world. The new pandemic required the mobilization of all resources for effective treatment of COVID-19 patients. Extracorporeal apheresis methods were suggested as an addition to the therapy of severe COVID-19 patients, especially when there is a threat of cytokine storm. Cytokine storm has a complex and not fully understood mechanism, and it can result in the multiple organ failure syndrome, associated with high mortality. The main cytokines that play the key role in the cytokine storm are IL-6, IL-10, and TNF-alpha. Removal of the target pro-inflammatory cytokines from the bloodstream can be beneficial in reducing the risk of complications as well as the mortality rate. We describe and compare different methods of extracorporeal apheresis: hemoadsorption, selective plasma filtration, and plasma exchange therapy in the context of their potential use in COVID-19 treatment.

PERBANDINGAN HASIL PEMERIKSAAN KONTAMINASI BAKTERI PADA PRODUK TROMBOCYTE CONCENTRATE METODE KONVENSIONAL DAN APHERESIS

Platelet Concentrate (PC) is one of the blood products that is often used for transfusion. The storage temperature for TC products is in the range of 20-24OC which is the optimal temperature for bacterial growth. TC products contaminated with bacteria can cause a dangerous septic reaction. With the development of blood transfusion, apheresis methods emerged for the manufacture and aseptic collection of TC products. The apheresis method is considered safer than the conventional method which has a high chance of bacterial contamination. This study aims to compare the results of the examination of bacterial contamination in conventional TC products and apheresis methods. This study is a comparative descriptive study with a retrospective approach in the form of examining data on bacterial contamination of TC PMI Semarang City during 2019. The results of the examination of the TC apheresis method product showed that there were no TC products that were contaminated with bacteria (0.0%; 0 of 48), while in conventional method, there is 1 TC product that has bacterial contamination (0.3%; 1 out of 360). Fisher exact test on each TC product obtained p value = 1.00 (&gt; 0.05) so that the difference that appears is not significant. Examination of bacterial contamination in conventional TC products and apheresis gave the same good results.

Comparison of Acidity Degree (pH) on Thrombocyte Concentrate Products: Apheresis Method and Pooling Method

One indicator of the decreasing quality of thrombocyte concentrate (TC) during storage is the pH value. Thrombocyte making can use pooling and apheresis methods. The pooling method is carried out by combining 4-6 bags of single thrombocytes with sterile connecting device, while apheresis method is done automatically using apheresis machine. Quality Control Inspection of TC product is conducted to ensure the quality of the product in accordance with applicable specifications. This study aims to find out the difference in acidity degree value (pH) in thrombocyte concentrate apheresis and pooling methods. This type of research is descriptive comparative with the design of cross sectional section study. The population of research was all the results of pH value examination on thrombocyte apheresis and pooling in UDD PMI Semarang city in 2020, with the number of 48 bags each. The sampling technique used is total sampling. Analysis of research data was conducted univariate and bivariate with the help of SPSS version 25. The average pH value in thrombocyte apheresis 7,145 and in thrombocyte pooling 7,417. Bivariate analysis of thrombocyte apheresis and pooling using Independent Sample T-Test has a significance value of 0.000. From the results of the analysis of research data, there is a significant difference between the pH value in thrombocytes apheresis and pooling method. Because there are differences between the two pH values in thrombocyte products, there needs to be an improvement in the evaluation and monitoring of each product.

C-reactive protein: pathogenetic characteristics and possible therapeutic target

It is known that the key mediator of acute phase response and marker of inflammation is C-reactive protein (CRP), the study of the role of which in the development of not only cardiovascular, but also infectious diseases has acquired particular relevance at the present time. CRP can be involved in all stages of the atherosclerotic process, including activation of the complement system and vascular endothelial cells, thrombosis, lipid accumulation, and apoptosis.The review describes modern concepts of the structure, biological and pathophysiological properties of CRP, its value as a cardiovascular risk predictor, as well as existing methods for reducing its blood level.According to recent studies, cardiovascular patients who achieved lower CRP levels with drug therapy had better clinical prognosis, making CRP an attractive therapeutic target. Currently, a search is underway for approaches to correct CRP levels associated with both the development of novel drugs and therapeutic apheresis methods to remove CRP from blood plasma.

Biochemical and cellular markers differentiate recovered, in-line filtered plasma, and plasma obtained by apheresis methods.

Background and ObjectivesAssessment of plasma quality often focuses on the common safety tests for minimizing the risk of transmitting blood‐borne pathogens. Little attention is paid to the possible quality attributes that ensure a consistent biochemical composition of plasma for fractionation. We therefore investigated the suitability of selected biochemical and haematological attributes that could be used as markers of plasma quality obtained by different separation and pre‐treatment procedures.Material and MethodsWe characterized six plasma types, including source plasma, plasma recovered by classic means and in‐line filtered plasma, by determining the analytical attributes protein content, coagulation factors and markers of coagulation, contact and complement activation. Residual cell content and cell‐specific variables were also measured.ResultsWe found relevant differences between the plasma types in complement activation, as indicated by C3a measurements, while thrombin antithrombin complex values and, to a minor extent, activated factor XII concentrations indicated only moderate differences in activation levels of coagulation and contact systems. The most striking differences, however, were detected in residual cell content and concentrations of the platelet‐associated proteins, platelet factor 4 and β‐thromboglobulin. We showed that leucocyte reduction filters disrupt cells. This includes platelets, thereby releasing the platelet‐associated proteins platelet factor 4 and β‐thromboglobulin, and leucocytes as demonstrated by the release of elastase from polymorphonuclear leucocytes. Furthermore, the filtration processing of whole blood can lead to activation of the complement system.ConclusionOur results show that biochemical and cellular surrogate markers are valuable discriminators of plasma types.

Therapeutic plasma exchange in critically ill children: experience of the pediatric intensive care unit of two centers in Chile

IntroductionTherapeutic plasma exchange (TPE) is an extracorporeal blood purification technique used in a wide spectrum of diseases. We aim to review the indications, complications, and outcomes of critically ill children who received TPE and to compare a membrane versus centrifugal method in this cohort. MethodsA retrospective observational study in two pediatric intensive care units in Chile during eight years (2011–2019) Results: A total of 36 patients underwent 167 TPE sessions (20 centrifugation and 16 membrane-based). The more frequent indications for TPE were autoimmune neurological diseases in 14 cases, renal diseases (9), and rheumatological disorders (5). 58 % of children received other immunomodulatory therapy. According to ASFA, 45 % of cases were I-II category, 50 % to III, and 5% not classified. Response to treatment was complete in 64 % (23/36) and partial in 33 % (12/36). Complications occurred in 17.4 % of sessions, and the most frequent was transient hypotension during the procedure. Overall survival at discharge from the PICU was 92 %. Patients who received TPE as a single therapy (n = 26) survived 96 %. The clinical outcomes between the two apheresis methods were similar. Survivors had a significantly lower PELOD score on admission (14.5 vs. 6.5, p = 0.004). ConclusionsTPE is mainly indicated as a rescue treatment in neurological autoimmune diseases refractory to conventional immunomodulatory treatment.Complications in critically ill children are mild and low. The outcome in children requiring TPE as a single therapy is good, and no differences were observed with centrifugation or membrane method.

Comparison of The Two Lipoprotein Apheresis Methods in The Treatment of Familial Hypercholesterolemia

Objective: Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder that causes a significant increase in low-density lipoprotein (LDL) cholesterol levels and leads to early coronary heart disease and cardiac mortality. Although this disease has a heterozygous (HeFH) and homozygous (HoFH) form, the incidence of HeFH is reported to be 1: 500, while HoFH is reported to be 1: 1 000 000. This disease is often caused by LDL receptor (most common), apolipoprotein B (Apo B), Proprotein Convertase Subtilisin/Kexin 9 (PCSK9), and LDL receptor adaptor protein (LDLRAP) gene mutations. Patients with FH do not respond well to lipid-lowering therapies such as a statin, and so lipoprotein apheresis is the treatment of choice. Material and Methods: We compared the results of lipoprotein apheresis in a 20-year-old female patient diagnosed with HoFH with two different methods [double-filtration plasmapheresis (DFPP) and dextran sulfate column (DSC) methods]. 40 lipoprotein apheresis procedures including 20 sessions of DFPP and 20 sessions of DSC were evaluated. Results: When the two methods were compared the changes in high-density lipoprotein, white blood cells, platelets, potassium, calcium, prothrombin time (INR) and activated partial thromboplastin time values were statistically significant. Conclusions: In conclusion, our study suggests that it would be more appropriate to choose the apheresis method according to the clinical and laboratory findings of the patient since it shows that two different methods have different effects on serum electrolyte values, hemostasis criteria and leukocyte and platelet counts.

Therapeutic Apheresis and Immunosuppression in Renal Diseases

Therapeutic plasma exchange (TPE) with hollow fiber modules is used in different severe diseases since more than 40 years. The authors try to give an overview of therapeutic apheresis (TA) in renal diseases. The updated information on immunology and molecular biology of different renal diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different renal diseases can be treated by various apheresis methods such as TPE with substitution solution, or with online plasma or blood purification using adsorption columns, which contain biological or non-biological agents. The following diseases are discussed: rapidly progressive glomerulonephritis (RPGN) including anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM RPGN), RPGN with or without glomerular deposition (ANCA-ab), pauci-immune RPGN, immune complex nephritis (ICN), and various glomerulonephritis with nephrotic syndrome (NS), acute kidney injury (AKI), myoglobulinemic renal failure, hemolytic-uremic syndrome (HUS), and kidney transplant rejection. For the renal diseases, which can be treated with TA, the guidelines of the Apheresis Applications Committee (AAC) of the American Society for Apheresis (ASFA) are shown.

Qualitative Evaluation of Platelet Concentrates Prepared with Different Methods

Introduction: One of the most important responsibility of Blood Bank is to ensure uninterrupted supply of quality blood products, namely Platelet Concentrate (PC), which are in high demand particularly during pandemic. In India, PCs are of three types prepared by different methods like Platelet Rich Plasma-Platelet Concentrate (PRP-PC), Buffy Coat Platelet Concentrates (BC- PC), and Single Donor Platelets (SDP) units. Hence, establishing optimum quality standards across all the three types of PC remains a challenge in order to maximum benefit to recipients. Aim: To assess and compare the quality parameters of platelet concentrate prepared by PRP-PC, BC-PC and apheresis methods (SDP). Materials and Methods: This laboratory based observational study was conducted at rural, tertiary care, postgraduate, teaching hospital located at South India from December 2018 to November 2019. A total of 156 PCs were studied with 52 units belonging to PRP method, 52 units BC-PC method and the remaining were 52 units of SDP prepared by apheresis method. Quality parameters include volume, pH, swirling, White Blood Cell (WBC) count/bag, platelet count/bag and platelet indices. Platelet indices include Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), and Platelet Large Cell Ratio (PLCR). Arterial Blood Gas (ABG) analysis was also done to assess (pH, partial pressure of Carbon Dioxide (pCO2), plasma bicarbonate (pHCO3-)). The p-value less than 0.05 were considered statistically significant. Statistical Package for the Social Sciences (SPSS) software version 23.0 used for statistical analysis. Results: All the 156 PC units were analysed as per the Director General of Health Services (DGHS) India, criteria. Among the 156 platelet concentrates scored as per DGHS criteria, a score of 5 was obtained for 34.61% [18/52], 30.76 [16/52] and 11.5% [6/52] SDP, BC-PC and PRP-PC units, respectively. All the PC units were sterile and Red Blood Cell (RBC) contamination was within acceptable limits. Conclusion: In this study, quality parameters of SDP was better than BC-PC and PRP-PC but with improvement and more standardisation of procedures and storage, BC-PC units can give a yield similar to that of SDP units.