Development of Immunosorbents for apoB‐Containing Lipoproteins Apheresis

Low density lipoprotein (LDL) apheresis is at present one method of treatment in homozygous cases of familial hypercholesterolemia (FH). It is also effective in the prevention of the development of coronary atherosclerosis in patients with heterozygous FH and other types of mild hypercholesterolemia, leading to the regression of the stenosing lesions. In this paper, an overview is presented on the development of the devices for LDL apheresis and its short- and long-term effects on FH mainly based upon experience with the Liposorber system. LDL apheresis has served to protect the lives of patients from life threatening diseases like myocardial infarction although observations for more than 10 years in some laboratories have shown that the progression of atherosclerosis has taken place in many patients, and more importantly, the involvement of the aortic valve with calcification has developed, especially in patients who had homozygous FH, making this the most obstinate complication of FH. Therefore, more aggressive treatment or the combination of LDL apheresis with other therapies is required in the future. LDL apheresis has also been approved for the treatment of glomerulosclerosis and arteriosclerosis obliterans.

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“…Antibody column: anti-LDL antibody, polyclonal or (T. Bosch) monoclonal (28)(29)(30) brane pressure was another problem of this method.…”

Section: Continuous Hemoperfusion (Direct Adsorption Of Lipids)mentioning

confidence: 99%

“…Regarding the specificity of adsorption, the antibody column is superior (28)(29)(30). However, the leakage of the antibody, which is a foreign protein, from the column may cause an anaphylactic reaction, and thus special care in manipulation is required.…”

Section: Adsorption Specificity and The Safety Of Dextran Sulfate Celmentioning

confidence: 99%

Apheresis Technology for Prevention and Regression of Atherosclerosis: An Overview

Yamamoto

Kawaguchi

Harada‐Shiba

et al. 1997

Therapeutic Apheresis

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“…Therefore, Lp(a) coremoval is regarded to be beneficial (11). In the present study, excess Lp(a) was found in a subgroup of 5 patients, and its reduction averaged 43%.…”

mentioning

confidence: 62%

LDL Hemoperfusion‐A New Procedure for LDL Apheresis: First Clinical Application of an LDL Adsorber Compatible with Human Whole Blood

et al. 1997

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To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase I1 clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 * 8% and triglycerides by 23 * 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 * 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future. Key Words: Low-density lipoprotein apheresisHemoperfusion-DALI-Low-density lipoprotein cholesterol-Lipoprotein(a).During the last 30 years, lipid apheresis has been established as a means of extracorporeal cholesterol removal in patients suffering from refractory hypercholesterolemia (1). The acute effects of lipid apheresis comprise risk factor removal, resulting in a decrease of low-density lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), and fibrinogen plasma levels as well as improvement of hemorheological parameters (2). Long-term reduction of risk factors can result in the regression of coronary stenoses and ultimately in reduced coronary morbidity and mortality (3).

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“…This system has been shown in in-vitro and in-vivo experiments to be highly specific for Lp(a) removal [9]. It should be noted that the currently available LDL apheresis systems are effective for removal of Lp(a) as well as LDL.…”

Section: Lipoprotein(a) Apheresismentioning

confidence: 96%

Incorporation of low-density lipoprotein apheresis into the treatment program of patients with severe hypercholesterolemia

Gordon

2000

Curr Atheroscler Rep

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Treatment to low-density lipoprotein (LDL) cholesterol targets has become a focus in the management of patients with coronary heart disease (CHD). Many patients with familial hypercholesterolemia (FH) are unable to reach targets because of drug intolerance or extremely high baseline LDL cholesterol levels. Consequently, LDL apheresis has become a useful modality for the treatment of patients with severe hypercholesterolemia. Commonly used LDL apheresis systems utilize immunoadsorption columns, dextran sulfate cellulose columns, or heparin precipitation. A new and simpler treatment modality is emerging which uses whole blood compatible columns. All systems require systemic anticoagulation, extracorporeal processing of blood, and venous vascular access. Acute LDL lowering is 70% to 80% and time-averaged LDL lowering is 40% to 50%. Lipoprotein(a) is also substantially lowered. Clinical efficacy has been shown in several studies. Mechanisms for clinical improvement in addition to regression of atherosclerotic plaque have been suggested by recent research.

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Development of Immunosorbents for apoB‐Containing Lipoproteins Apheresis

Cited by 11 publications

References 16 publications

Apheresis Technology for Prevention and Regression of Atherosclerosis: An Overview

Apheresis Technology for Prevention and Regression of Atherosclerosis: An Overview

LDL Hemoperfusion‐A New Procedure for LDL Apheresis: First Clinical Application of an LDL Adsorber Compatible with Human Whole Blood

Incorporation of low-density lipoprotein apheresis into the treatment program of patients with severe hypercholesterolemia

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