Therapeutic Apheresis for Management of Lp(a) Hyperlipoproteinemia

Pokrovsky, S.; Afanasieva, O.; Ezhov, M.

doi:10.1007/s11883-020-00886-0

Cited by 15 publications

(8 citation statements)

References 97 publications

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“…DALI (“Direct Adsorption of Lipoproteins”, Fresenius Medical Care, Bad Homburg, Germany) consists of polyacrylamide beads (particle size 150–200 µm, surface area 50 m 2 /g, mean pore diameter 180 nm) functionalized with poly(acrylic acid). It binds to lipoproteins containing apolipoprotein B100 (apoB100) moieties, including low-density lipoprotein (LDL) and lipoprotein(a), via electrostatic interactions and is clinically applied to treat patients suffering from homozygous familial hypercholesterolemia [ 3 , 34 , 35 , 36 ]. CG161c (Amberchrom CG161c, Dow Chemical, Philadelphia, PA, USA) consists of polystyrene-divinylbenzene beads (average particle size 120 µm, surface area 900 m 2 /g, mean pore diameter 15 nm).…”

Section: Methodsmentioning

confidence: 99%

“…Adsorbent-based extracorporeal therapies are clinically established to deplete pathogenic factors, such as lipoproteins, toxic metabolites, protein-bound substances, as well as autoantibodies from the circulation of patients suffering from severe hypercholesterolemia, liver dysfunction, or autoimmune diseases [ 1 , 2 , 3 ]. Beyond that, extracorporeal approaches are emerging for the depletion of inflammatory mediators in patients suffering from systemic inflammation and hypercytokinemia (cytokine storm) [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Polyzwitterionic Coating of Porous Adsorbents for Therapeutic Apheresis

Semak

Eichhorn

Weiss

et al. 2022

JFB

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Adsorbents for whole blood apheresis need to be highly blood compatible to minimize the activation of blood cells on the biomaterial surface. Here, we developed blood-compatible matrices by surface modification with polyzwitterionic polysulfobetainic and polycarboxybetainic coatings. Photoreactive zwitterionic terpolymers were synthesized by free-radical polymerization of zwitterionic, photoreactive, and fluorescent monomers. Upon UV irradiation, the terpolymers were photodeposited and mutually crosslinked on the surface of hydrophobic polystyrene-co-divinylbenzene and hydrophilic polyacrylamide-co-polyacrylate (DALI) beads. Fluorescent microscopy revealed coatings with an average thickness of 5 µm, which were limited to the bead surface. Blood compatibility was assessed based on polymer-induced hemolysis, coagulation parameters, and in vitro tests. The maintenance of the adsorption capacity after coating was studied in human whole blood with cytokines for polystyrene beads (remained capacity 25–67%) and with low-density lipoprotein (remained capacity 80%) for polyacrylate beads. Coating enhanced the blood compatibility of hydrophobic, but not of hydrophilic adsorbents. The most prominent effect was observed on coagulation parameters (e.g., PT, aPTT, TT, and protein C) and neutrophil count. Polycarboxybetaine with a charge spacer of five carbons was the most promising polyzwitterion for the coating of adsorbents for whole blood apheresis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyzwitterionic Coating of Porous Adsorbents for Therapeutic Apheresis

Semak

Eichhorn

Weiss

et al. 2022

JFB

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“…In addition to lowering Lp(a), lipoprotein apheresis lowers LDL concentrations by 60% to 85%. 103,104 Limited clinical trial data suggest that Lp(a) lowering with lipoprotein apheresis may reduce the risk of ASCVD events, 105 but definitive studies are needed.…”

Section: Lp(a)-lowering Therapies: Existing and Investigationalmentioning

confidence: 99%

Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association

Reyes‐Soffer¹,

Ginsberg²,

Berglund³

et al. 2022

ATVB

382

207

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High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

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“…Lifestyle measures and conventional LLA do not have much effect on Lp(a) levels. Therefore, for many years, LA is used as the most effective Lp(a) lowering therapy with 50-75% reduction [13,52,53]. The special immune-adsorption polyclonal antibody columns are available since 1993 for the selective elimination of Lp(a) [53 •• ].…”

Section: Apheresis Therapy For High Lipoprotein Amentioning

confidence: 99%

“…In recent years with the development of new anti-Lp(a) agents, the popularity of Lp(a) and its treatments including LA increased [54 • ]. Though the evidence is generated from small sized studies, Lp(a) apheresis reduces the inflammatory and prothrombotic proteins, and ameliorates the risk of CV events after 2-5 years of therapy [53,55,56]. But, clinical benefits of LA therapy for isolated high Lp(a) is still unclear and we need more evidence to define the treatment targets of Lp(a).…”

Section: Apheresis Therapy For High Lipoprotein Amentioning

confidence: 99%

LDL Apheresis and Lp (a) Apheresis: A Clinician’s Perspective

Kayıkçıoğlu

2021

Curr Atheroscler Rep

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Purpose of Review Lipoprotein apheresis is the most effective means of lipid-lowering therapy. However, it’s a semi-invasive, time consuming, and chronic therapy with variable adherence. There are still no specific guideline recommendations for the management of patients on lipid apheresis. The purpose of this review is to discuss the clinical indications and major drawbacks of lipid apheresis in the light of recent evidence. Recent Findings Lipoprotein apheresis should be initiated at early ages and performed frequently to receive the expected cardiovascular benefits. However, in clinical practice, most patients experience ineffective apheresis and fail to reach lipid targets. This real-world failure is due to several factors including late diagnosis, delayed referral, and improper frequency of procedures. All these denote that awareness is still low among physicians. Another important factor is the semi-invasive, time consuming nature of the apheresis, leading to high refusal and low adherence rates. Moreover, apheresis decreases quality of life and increases the risk of depression. Mental status is also deteriorated in patients with familial hypercholesterolemia on lipid apheresis. New effective lipid lowering agents are underway with promising cardiovascular results. Summary To overcome the drawbacks, a structured approach, including standardized protocols for lipoprotein apheresis with regular cardiovascular follow-up is warranted. New effective lipid lowering agents with documented cardiovascular benefit, should be integrated into the treatment algorithms of patients on lipoprotein apheresis.

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Therapeutic Apheresis for Management of Lp(a) Hyperlipoproteinemia

Cited by 15 publications

References 97 publications

Polyzwitterionic Coating of Porous Adsorbents for Therapeutic Apheresis

Polyzwitterionic Coating of Porous Adsorbents for Therapeutic Apheresis

Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association

LDL Apheresis and Lp (a) Apheresis: A Clinician’s Perspective

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