Specific Aptamer Functionalization of Dense Ceramic by Click Chemistry Towards Circulating Tumor Cells Apheresis.

BACKGROUND/AIM: Circulating tumor cells (CTC) are tumor cells which can be disseminated at distance of the primary tumor and form metastatic niche. Moreover, their quantity is an important parameter which can induce cluster metastasis. A solution, can be the creation of a system that allow the capture and elimination from the blood of patients by using the medical device developed which is an inert bioceramic functionalized by aptamer target to CTC. MATERIALS AND METHODS: Herein we develop chemical reactions to bind a modified MUC1 specific DNA aptamer on an alumina (Al2O3) dense ceramic surface. In fact, MUC1 biomarker is very present on the surface of tumor cells. RESULTS: The specific developed chemical reactions led to the covalent binding of the aptamer while preserving its biological characteristics. CONCLUSION: This functionalization of dense alumina would allow the potential capture of circulating tumor cells.

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia.

There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.

Supplemental findings of the 2019 National Blood Collection and Utilization Survey.

INTRODUCTION: Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). METHODS: National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. RESULTS: Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. CONCLUSION: Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.

Effectiveness of supplemental oral calcium drink in preventing citrate-related adverse effects in peripheral blood progenitor cell collection.

Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.

A loxoscelism case received therapeutic apheresis and hyperbaric oxygen therapy.

Loxosceles reclusa (L.reclusa) is known to bite humans, and its venom includes several enzymes that cause clinical symptoms. Loxoscelism, a condition due to being bitten by Loxosceles spiders, commonly known as recluses, can involve a range of clinical conditions, from local cutaneous lesions to severe systemic involvement. The diagnosis of loxoscelism is usually made by anamnesis and clinical findings. Magnetic resonance imaging is recommended for patients at high risk of necrotizing fasciitis. Treatment modalities are still controversial and there is no standardized treatment approach. Reported here, our case of loxoscelism involved a 24-year-old man presenting with a Loxosceles spider bite, dermonecrotic lesion, vomiting, diarrhea, acute renal injury, and rhabdomyolysis, who was successfully treated with hyperbaric oxygen therapy, therapeutic apheresis, hemodialysis, wound debridement, and cutaneous autografting. Early diagnosis and multidisciplinary approach can be life-saving in spider bites that can cause systemic involvement. Loxoscelism should be considered in patients with skin necrosis, acute renal injury, and rhabdomyolysis.

[Iatrogenic non uremic calciphylaxis: A case report]. / Calciphylaxie non urémique iatrogène : une nouvelle observation.

Calciphylaxis is a rare and severe condition, characterized by calcification and thrombosis of small vessels, mainly affecting the skin. It is most often described in patients with end-stage renal disease on dialysis. Rarer cases of non-uremic calciphylaxis are reported. The prognosis is grim and the treatment is not well codified. Sodium thiosulfate has been used for more than a decade in the treatment of uremic calciphylaxis and has been shown to be effective. Its use in non-uremic cases has been reported in a few rare observations. Rheopheresis is a technique very recently used as an adjuvant treatment in uremic calciphylaxis. We describe a case of non-uremic calciphylaxis in a patient with normal renal function and with calcium supplementation. Sodium thiosulfate was introduced, then discontinued due to the patient's poor tolerance for this treatment. Rheopheresis was then used and allowed the acceleration of healing process and a significant reduction in pain. These two treatments are promising, larger studies are needed to establish their effectiveness in non-uremic calciphylaxis.

Hipertrigliceridemia severa refractaria a tratamiento médico y pancreatitis aguda recurrente: uso de plasmaféresis crónica ambulatoria en el Hospital San Pablo de Coquimbo. Reporte de un caso

Severe Hypertriglyceridemia (HTG) is associated with complications such as acute pancreatitis (AP) with high morbidity and mortality rates. We report a 42 years-old man with refractory HTG diagnosed at 19 years of age, and multiple episodes of AP, admitted with the suspicion of a new AP episode. Serum triglycerides were over 2000 mg/dl. His body mass index was 18 kg/m2, there was no evidence of xanthomas or xanthelasmas, but lipemia retinalis was found. Management included heparin and insulin, added to his usual treatment with fibrates, statins, omega-3 fatty acids, and orlistat. Due to lack of response, apheresis was started. After five sessions, triglycerides decreased to 588 mg/dl (82% reduction) and levels remained below 1000 mg/dl with daily apheresis. The patient continued with weekly sessions as outpatient with a sustained good response.

[Factors Influencing Mononuclear Cell Collection in Tumor Cell Biotherapy].

OBJECTIVE: To investigate the factors affecting counting and collection efficiency of the final product- mononuclear cells (MNCs) in the collection of mononuclear cells for tumor cell biotherapy. METHODS: The collected data of 142 tumor patients and healthy donors were analyzed, including age, sex, height, weight, BMI, the total blood volume, diagnostic category, vascular access, operator, final product volume, ACD anticoagulant usage, flow rate and circulation times, pre-apheresis Hb, RBC, Plt, WBC, lymphocyte count, monocyte count, neutrophil count, circulating blood volume without anticoagulant, final product MNC and collection efficiency of MNC. CE(collection efficiency)%= final product MNC×100/(pre-apheresis MNC×circulating blood volume without anticoagulant). The factors affecting final products MNC and CE of MNC were detected by T test and multiple linear regression analysis. RESULTS: The CE of tumor patients was higher than that of healthy donors （24.41±1.91,vs 20.01±0.99)，(P=0.043）, and CE of MNC was different among different operators (P=0.01, H=18.59). There was a positive correlation of the final MNC with the volume of final product, ACD anticoagulant usage and pre-apheresis lymphocyte count (P= 0.00, P= 0.01, P= 0.00， r=0.811); CE of MNC negatively correlated with flow rate and pre-apheresis RBC, but positively correlated with operator's working age and ACD anticoagulant usage (P=0.01, P=0.04, P=0.03, P= 0.00, r=0.495). CONCLUSION: more higher pre-apheresis lymphocyte , more amount of the final product and ACD anticoagulant usage, and more high the final MNC. During the collecting process, more ACD anticoagulant usage and more high operator's seniority, lead to the higher MNC'S CE; while more high pre-apheresis RBC and more fast flow rate, cause the lower the CE of MNC.

Flaxseed (Linum Usitatissimum L.) Supplementation in Patients Undergoing Lipoprotein Apheresis for Severe Hyperlipidemia-A Pilot Study.

Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly-in addition to their normal lipoprotein apheresis regimen-a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0-18.8) and 7.3% (4.4-26.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.

[Refractory severe hypertriglyceridemia treated with apheresis. Report of one case]. / Hipertrigliceridemia severa refractaria a tratamiento médico y pancreatitis aguda recurrente: uso de plasmaféresis crónica ambulatoria en el Hospital San Pablo de Coquimbo. Reporte de un caso.

Severe Hypertriglyceridemia (HTG) is associated with complications such as acute pancreatitis (AP) with high morbidity and mortality rates. We report a 42 years-old man with refractory HTG diagnosed at 19 years of age, and multiple episodes of AP, admitted with the suspicion of a new AP episode. Serum triglycerides were over 2000 mg/dl. His body mass index was 18 kg/m2, there was no evidence of xanthomas or xanthelasmas, but lipemia retinalis was found. Management included heparin and insulin, added to his usual treatment with fibrates, statins, omega-3 fatty acids, and orlistat. Due to lack of response, apheresis was started. After five sessions, triglycerides decreased to 588 mg/dl (82% reduction) and levels remained below 1000 mg/dl with daily apheresis. The patient continued with weekly sessions as outpatient with a sustained good response.

Activation of Lipid Mediator Formation Due to Lipoprotein Apheresis.

Lipoprotein apheresis reliably reduces low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). Besides lowering lipoproteins and triglycerides, apheresis also decreases levels of essential omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFAs) in blood plasma. In contrast, heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) lipid apheresis might increase the formation of potentially pro-inflammatory and pro-thrombotic lipid mediators derived from n-6 and n-3 PUFAs. The study presented here analyzed lipid mediator profiles in the plasma of patients with hyperlipidemia treated by one of three different apheresis methods, either HELP, direct absorption (DA), or membrane filtration (MDF), in a direct pre- and post-apheresis comparison. Using gas chromatography and liquid chromatography tandem mass spectrometry (LC-MS/MS) we were able to analyze fatty acid composition and the formation of lipid mediators called oxylipins. Our data illustrate-particularly in HELP-treated patients-significant decreases of essential omega-6 and omega-3 polyunsaturated fatty acids in blood plasma but significant increases of PUFA-derived lipoxygenase-, as well as cyclooxygenase- and cytochrome P450-derived lipid mediators. Given that n-3 PUFAs in particular are presumed to be cardioprotective and n-3 PUFA-derived lipid mediators might limit inflammatory reactions, these data indicate that n-3 PUFA supplementation in the context of lipid apheresis treatment might have additional benefits through apheresis-triggered protective n-3 PUFA-derived lipid mediators.

Application of Component Apheresis in Pre-deposited Autotransfusion.

OBJECTIVE: This study aims to evaluate the effects of preoperative autologous blood donation (PABD) using apheresis in patients who underwent elective surgical procedures, and investigate its clinical usefulness. METHODS: Data from 109 patients who underwent general and orthopedics elective surgery were analyzed in this study. Patients were divided into three groups: control group, patients who did not donate autologous blood; whole blood (WB) PABD group, patients who underwent preoperative autologous WB donation; autologous apheresis group, patients who donated autologous blood using erythrocytapheresis. Hb, Hct, and PLT levels in all patients were measured and compared before the operation and on postoperative days one and three. Furthermore, postoperative recovery indexes in the three groups were compared including allogeneic blood transfusions and postoperative hospitalization days. RESULTS: Hb, Hct, and PLT levels in the three groups after the operation were lower than levels before the operation. However, Hb levels were higher than 110 g/L and the Hct levels were not less than 33%. Differences in Hb and Hct drop values on postoperative days one and three among the three groups were statistically significant (P>0.05). Furthermore, PLT level in the control group was lower than in the WB PABD group and autologous apheresis group (P<0.05). PABD using erythrocytapheresis reduced blood transfusion (P<0.05). CONCLUSION: Erythrocytapheresis PABD led to an equal or even better postoperative recovery effect than WB PABD, and erythrocytapheresis PABD is feasible for blood transfusion therapy in patients undergoing elective surgical procedures.

Effect of different lipid apheresis methods on plasma polyunsaturated fatty acids.

Lipoprotein apheresis has been shown to improve the cardiovascular outcome in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). An elevated intake of omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with a reduced cardiovascular risk. However, until now only little is known about the effect of apheresis treatment on the levels of omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA) in patients. Using gas chromatography (GC) the present study analyzed the content of n-6 and n-3 PUFA as well as saturated fatty acids and monounsaturated fatty acids in the plasma of 20 patients with hyperlipidemia undergoing regular lipoprotein apheresis procedures in direct pre- and post-therapy measurements. Lipoprotein apheresis uniformly reduced the concentrations of arachidonic acid (AA), EPA and DHA fatty acids analyzed in the plasma. However, the three different apheresis methods analyzed (heparin precipitation, membrane filtration and direct absorption) had different effects on the fatty acid profile in the plasma. We found that heparin precipitation and direct absorption apheresis procedures led to a significant decrease of plasma n-3 and n-6 PUFA by 40-50%. In contrast, patients undergoing membrane filtration apheresis, levels pre- and post-apheresis did not change significantly, with AA and EPA being only reduced by approximately 10% while levels of DHA were maintained pre- and post-apheresis. In contrast, total triglyceride levels were lowered most potently by membrane filtration apheresis. In summary, heparin precipitation and direct absorption apheresis approaches significantly lowered polyunsaturated fatty acids in plasma, while membrane filtration did not. This might have implications for cardiovascular and inflammatory risk/benefit profiles associated with n-6 and n-3 PUFA levels in the body.

[Apheresis Techniques]. / Tecniche di Aferesi.

Apheresis therapies play an important role in the treatment of many pathologies, both as first-line and rescue therapies after drug failure or drug toxicity and, furthermore, when it is important to reach a therapeutic goal in a short time. Apheresis devices have evolved at an astounding rate over the last decades. Therapeutic apheresis are usually part of a treatment plan, so, a patient-centered approach to select the most appropriate treatment for each patient, balancing personal preferences, medication interferences and technological availability can significantly influence the choice of the protocol to be used. But, if the wide diversity of apheresis treatments may offer a tailored-patient approach, it can also create concerns on the right decision about the most appropriate protocol. Therapeutic apheresis - whose purpose is to cure diseases due to abnormality of blood cells or to toxicity of plasma substances - and, productive apheresis - whose purpose is to produce autologous or allogeneic therapeutic hemocomponents - are widely known as plasma-treatments and cytapheresis. The elementary techniques in apheresis are well represented by three physical separation methods of blood components: 1. differential centrifugation; 2. membrane filtration; 3. adsorption of proteins or cells, from whole blood or from plasma already separated. Starting from these three processes, several apheretic techniques have been developed to ensure, in expert hands, excellent therapeutic efficacy together with a low profile of adverse events.

In Vitro Evaluation of the Fresenius Kabi CATSmart Autotransfusion System.

Use of autotransfusion systems to collect, wash, and concentrate shed blood during surgical procedures is a widely used method for reducing postoperative anemia and the need for blood transfusions. The aim of this study was to evaluate the CATSmart Continuous Autotransfusion System wash program performance with small (200 or 700 mL) and large volumes (1,000 mL) of shed blood and to determine non-inferiority of the CATSmart to the C.A.T.S plus system. Human whole blood was collected in citrate phosphate dextrose, diluted, and divided into two aliquots to be processed as a pair using the C.A.T.S plus and CATSmart systems with their corresponding wash programs: low-volume, high quality/smart, or emergency wash. Final packed red cell product was analyzed for red blood cell (RBC), white blood cell, and platelet counts; hemoglobin; hemolysis; RBC recovery rates; and elimination of albumin, total protein, and potassium. The mean hematocrit (HCT) after processing with CATSmart and C.A.T.S plus systems were 59.63% and 57.71%, respectively. The calculated overall RBC recovery rates on the CATSmart and C.A.T.S plus systems were 85.41% and 84.99%, respectively. Elimination of albumin (97.5%, 98.0%), total proteins (97.1%, 97.5%), and potassium (92.1%, 91.9%) were also calculated for the CATSmart and C.A.T.S plus systems. The CATSmart and C.A.T.S plus systems both provided a high-quality product in terms of HCT, protein elimination, and hemolysis rates across the range of tested shed blood volumes and all wash programs. The study was able to confirm the CATSmart is non-inferior to the C.A.T.S plus system.

Spectra Optia® for Automated Red Blood Cell Exchange in Patients with Sickle Cell Disease: A NICE Medical Technology Guidance.

The Spectra Optia® automated apheresis system, indicated for red blood cell exchange in people with sickle cell disease, underwent evaluation by the National Institute for Health and Care Excellence, which uses its Medical Technologies Advisory Committee to make recommendations. The company (Terumo Medical Corporation) produced a submission making a case for adoption of its technology, which was critiqued by the Newcastle and York external assessment centre. Thirty retrospective observational studies were identified in their clinical submission. The external assessment centre considered these were of low methodological and reporting quality. Most were single-armed studies, with only six studies providing comparative data. The available data showed that, compared with manual red blood cell exchange, Spectra Optia reduces the frequency of exchange procedures as well as their duration, but increases the requirement for donor blood. However, other clinical and patient benefits were equivocal because of an absence of robust clinical evidence. The company provided a de novo model to support the economic proposition of the technology, and reported that in most scenarios Spectra Optia was cost saving, primarily through reduced requirement of chelation therapy to manage iron overload. The external assessment centre considered that although the cost-saving potential of Spectra Optia was plausible, the model and its clinical inputs were not sufficiently robust to demonstrate this. However, taking the evidence together with expert and patient advice, the Medical Technologies Advisory Committee considered Spectra Optia was likely to save costs, provide important patient benefits, and reduce inequality, and gave the technology a positive recommendation in Medical Technology Guidance 28.

Therapeutic plasma exchange performed in tandem with hemodialysis without supplemental calcium in the apheresis circuit.

Therapeutic plasma exchange (TPE) and hemopoietic progenitor cell (HPC) collection are apheresis procedures that can safely be performed in tandem with hemodialysis. Despite the return of citrate-anticoagulated blood to the patient during HPC collection, it is not necessary to administer supplemental calcium during these procedures because the ionized calcium concentration is restored as the returning blood passes through the dialyzer. It is not known whether this applies to TPE, in which a mixture of blood and pharmaceutical albumin, an avid binder of plasma ionized calcium, is returned to the patient through the dialyzer. We report on three dialysis-dependent patients who required TPE and underwent tandem treatments without supplemental calcium in the apheresis circuit. Overall, ionized calcium fell 4-12% (P = 0.0.024) and patients reported no symptoms of hypocalcemic toxicity. Tandem hemodialysis/TPE can be performed without supplemental calcium in the apheresis circuit. J. Clin. Apheresis 32:154-157, 2017. © 2016 Wiley Periodicals, Inc.

LDL apheresis activates the complement system and the cytokine network, whereas PCSK9 inhibition with evolocumab induces no inflammatory response.

BACKGROUND: Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk coronary patients. It may, however, induce complement activation and downstream inflammation due to bio-incompatibility. OBJECTIVE: We explored changes in soluble inflammatory markers when changing from LDL apheresis to the novel PCSK9 inhibitor evolocumab. METHODS: Three patients with familial hypercholesterolemia participated. Blood samples (EDTA plasma) for complement activation and markers of inflammation were obtained before (baseline) and after LDL apheresis week at 0 and before biweekly administration of evolocumab at weeks 1, 3, 5, and 7. Complement activation was measured by ELISA and cytokines by multiplex technology. RESULTS: Complement activation products C3a and Bb were both significantly higher after LDL apheresis compared to baseline (P = .01), returned to baseline levels before administration of evolocumab and remained low through week 7. C4d was unchanged during LDL apheresis, whereas TCC was slightly higher after apheresis compared to baseline and week 7 without statistical difference. MCP-1 was higher after LDL apheresis compared to baseline (P = .04), returned to baseline levels before administration of evolocumab and remained low through week 7. There were minor changes for other cytokines including TNF, IFN-γ, MIP-1α, MIP-1ß, with some higher and some lower after apheresis; however, none of these changes were statistically significant. Fibrinogen and CRP were lower after LDL apheresis and had returned to levels comparable to baseline at week 7, statistically significant however only for fibrinogen. CONCLUSIONS: LDL apheresis activated the alternative complement system significantly as reflected by an increase in C3a and Bb. PCSK9 inhibition did not affect complement or cytokines during 7 weeks follow-up.

Comprehensive technical and patient-care optimization in the management of pediatric apheresis for peripheral blood stem cell harvesting.

BACKGROUND: Pediatric apheresis for peripheral blood stem cell transplantation should be carried out with due concern for low corporeal blood volume and vulnerability to hypocalcemia-related complications, hypovolemic shock, and hypervolemic cardiac overload. STUDY DESIGN AND METHODS: We retrospectively investigated a total of 267 apheresis procedures from 1990 to 2013 on 93 children between 0 and 10 years old, including 89 patients and 4 healthy donors, with body weights of 6.3 to 44.0 kg. RESULTS: The median CD34+ cell yield per apheresis procedure was 2.3 × 106 CD34+ cells/kg (0.2-77.9 × 106 CD34+ cells/kg). Adverse events occurred in 11.6% of procedures (n = 31), including mild perivascular pain (n = 12), emesis (n = 9), hypotension (n = 3), urticaria (n = 2), numbness (n = 2), chest pain (n = 1), facial flush (n = 1), and abdominal pain (n = 1). Among hypotensive events, shock in a 9.6 kg one-year-old boy required emergency treatment in 1996. Thereafter, we adopted continuous injection of calcium gluconate, ionized calcium monitoring, central venous catheter access and circuit priming with albumin in addition to concentrated red cells. Since then we have had fewer complications: 16.4% per apheresis during 1990-1997 versus 5.8% during 1998-2013. No healthy pediatric donors suffered from any late-onset complications related to apheresis or G-CSF administration. CONCLUSION: By employing appropriate measures, peripheral blood stem cell apheresis for small children can have an improved safety profile, even for children weighing <10 kg.