Effect of heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) apheresis on hepatitis C plasma virus load.

Association of the hepatitis C virus (HCV) with apolipoprotein B containing lipoproteins has been suggested, and this led to the concept that the low-density lipoprotein (LDL) receptor may also serve as a candidate receptor for HCV uptake into the liver. We have investigated whether heparin-induced extracorporeal LDL precipitation (HELP) LDL apheresis treatment reduces HCV plasma load in 6 patients, all infected for more than 4 years with HCV and resistant against established anti-HCV therapy. HELP apheresis treatment caused an HCV-RNA decrease of 77.3% in mean. This decline was not correlated with LDL-cholesterol reduction. HCV-RNA was retained on the HELP filter as shown for 1 patient. The effect of RNA lowering was only transient due to the high turnover of HCV. However, HELP apheresis may open a window of opportunity for an immune-modulating and antiviral therapy in the interval between two apheresis procedures in patients with high virus load.     

Heparin-induced lipoprotein precipitation apheresis in dyslipidemic patients: A multiparametric assessment

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors. More knowledge needs to be gathered on the effects of LA, and particularly on its ability to modify blood components other than lipids. We performed a multiparametric assessment of the inflammatory, metabolic and proteomic profile changes after Heparin-induced lipoprotein precipitation (H.E.L.P.) apheresis on serum samples from nine dyslipidemic patients evaluating cholesterol and lipoproteins, plasma viscosity and density, metabolites, cytokines, PCSK9 levels and other proteins selectively removed after the treatment. Our results show that H.E.L.P. apheresis is effective in lowering lipoprotein and PCSK9 levels. Although not significantly, complement and inflammation-related proteins are also affected, indicating a possible transient epiphenomenon induced by the extracorporeal procedure.     

Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy. © 1996 Wiley-Liss, Inc.     

Heparin-mediated extracorporeal low-density lipoprotein precipitation: rationale for a specific adjuvant therapy in cardiovascular disease

Various radical measures for the treatment of severe hypercholesterolemia such as partial ileal bypass, portocaval shunt, liver transplantation and plasma exchange have been tested in patients in whom drug and diet failed or were insufficient. Although effective, most of these treatments have severe side effects and are not routinely used. For hypercholesterolemic patients LDL-apheresis has proved to be the most promising and safe way as an adjuvant therapy. Several LDL-apheresis procedures with a varying degree of selectivity and efficiency have subsequently been developed. One of them is the H.E.L.P. system which was introduced in 1984 and has now been widely used. Besides the marked reduction of LDL particles by all techniques it has become apparent that only the H.E.L.P. system results in an equally significant change in hemostaseology, hemorheology and vasomotion because of its simultaneously removal of LDL, Lp(a), fibrinogen and CRP. This contribution reviews the application of the H.E.L.P. system as a valuable therapeutic tool for the treatment of various atherothrombotic and microcirculatory disorders such as prevention of early graft occlusion after coronary artery bypass grafting, treatment of peripheral vascular disease, stroke and preeclampsia.     

Application of a new LDL apheresis system using two dextran sulfate cellulose columns in combination with an automatic column-regenerating unit and a blood cell separator

Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.     

Lipid apheresis, indications, and principles

Low-density lipoprotein apheresis (LDL apheresis) is a term that describes a group of apheresis techniques and devices that selectively remove apolipoprotein B containing lipoproteins. A number of different devices are available worldwide, which all effectively remove low-density lipoprotein cholesterol while sparing other important plasma components. LDL apheresis is used to treat familial hypercholesterolemia (FH), an inherited condition of accelerated atherosclerosis and severe coronary artery disease resulting in premature death. It has also been used to treat other disorders, although the evidence for its use is limited. This review describes the underlying pathophysiology of FH, the mechanism of action of the various LDL apheresis devices available, and how LDL apheresis is used to treat this uncommon metabolic condition.     

Genetic and biochemical analyses in dyslipidemic patients undergoing LDL apheresis

Objective : Familial hypercholesterolemia (FH) can be due to mutations in LDLR, PCSK9, and APOB. In phenotypically defined patients, a subset remains unresponsive to lipid‐lowering therapies and requires low density‐lipoprotein (LDL) apheresis treatment. In this pilot study, we examined the genotype/phenotype relationship in patients with dyslipidemia undergoing routine LDL apheresis. Design : LDLR, APOB, and PCKS9 were analyzed for disease‐causing mutations in seven patients undergoing routine LDL apheresis. Plasma and serum specimens were collected pre‐ and post‐apheresis and analyzed for lipid concentrations, Lp(a) cholesterol, and lipoprotein particle concentrations (via NMR). Results : We found that four patients harbored LDLR mutations and of these, three presented with xanthomas. While similar reductions in LDL‐cholesterol (LDL‐C), apolipoprotein B, and LDL particles (LDL‐P) were observed following apheresis in all patients, lipid profile analysis revealed the LDLR mutation‐positive cohort had a more pro‐atherogenic profile (higher LDL‐C, apolipoprotein B, LDL‐P, and small LDL‐P) pre‐apheresis. Conclusion : Our data show that not all clinically diagnosed FH patients who require routine apheresis have genetically defined disease. In our small cohort, those with LDLR mutations had a more proatherogenic phenotype than those without identifiable mutations. This pilot cohort suggests that patients receiving the maximum lipid lowering therapy could be further stratified, based on genetic make‐up, to optimize treatment. J. Clin. Apheresis 29:256–265, 2014. © 2014 Wiley Periodicals, Inc.     

Plasma constituents other than low-density lipoprotein adsorbed by dextran-sulfate column.

The dextran-sulfate cellulose (DSC) column used for low-density lipoprotein (LDL) apheresis adsorbs plasma constituents other than LDL that have the following characteristics: proteins containing apolipoprotein B, proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high molecular weight kininogen and prekallikrein), factors with lipophilic characteristics (coagulation factor VII, VIII, and vitamin E), and proteins with adhesive or other characters (von Willebrand factor, fibronectin, and serum amyloid P components). Adsorption of these proteins seems to serve in the prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of such inexorable diseases as amyloidosis. On the other hand, the column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain hypotension during LDL apheresis observed in patients taking angiotensin converting enzyme (ACE) inhibitors.     

Efficacy of different low-density lipoprotein apheresis methods.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran-sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL-C) (64-67%) and lipoprotein a [Lp(a)] (61-64%) were decreased more effectively by HELP, immunoadsorption, and dextran-sulfate apheresis than by the less specific cascade filtration system [LDL-C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran-sulfate) to 49% (cascade filtration) and high-density lipoproteins (HDL) by 9% (dextran-sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL-C reduction 25.0%/L plasma), followed by dextran-sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre-apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.     

First steps toward the establishment of a German low-density lipoprotein-apheresis registry: recommendations for the indication and for quality management.

New recommendations for the indication of treatment with selective extracorporeal plasma therapy low-density lipoprotein apheresis (LDL-apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL-apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug-induced and documented therapy in combination with a cholesterol-lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high-risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL-apheresis previously mentioned, standardized treatment guidelines for LDL-apheresis need to be established in Germany that should be supervised by an appropriate registry.     

Composition and immunoreactivity of serum low density lipoproteins (LDL) before and after LDL-apheresis on dextran sulfate-cellulose columns

The changes in low density lipoprotein (LDL) composition and immunoreactivity occurring after LDL-apheresis on dextran sulfate-cellulose columns (DSC) were investigated in 4 hypercholesterolemic patients. After apheretic treatment, serum levels of total cholesterol, triglycerides and apolipoprotein B (apo B) were decreased by 63, 80 and 65%, respectively, whereas the high density lipoprotein (HDL)-cholesterol remained unchanged. At the end of apheresis, LDL contained less triglycerides, more phospholipids and apo E and the ratio of LDL core lipid components, cholesteryl esters and triglycerides, to LDL surface lipid components, unesterified cholesterol and phospholipids was significantly lower. The post-apheretic LDL were characterized by the presence of subfractions slightly larger than those observed in the pre-apheretic LDL. The modifications of the composition and size of LDL after apheresis were accompanied by a relative increase in the immunoreactivity of 4G3 epitope, an apo B epitope located near the LDL-receptor binding site, with no change in the affinity of 1D1, an apo B epitope located in the amino-terminal region of the molecule. The changes in LDL composition, size and immunoreactivity following apheresis, suggest that postapheresis LDL could contain newly synthesized LDL, different from mature LDL. Thus, LDL-apheresis treatment could provide the opportunity to study the structural change of LDL during intravascular metabolism.     

The role of low density lipoprotein apheresis in the treatment of familial hypercholesterolemia.

The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30-50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.     

Effects of two whole blood systems (DALI and Liposorber D) for LDL apheresis on lipids and cardiovascular risk markers in severe hypercholesterolemia

LDL apheresis is an extracorporal modality to lower the concentration of atherogenic lipoproteins, e.g., LDL cholesterol. We compared two recently introduced whole-blood LDL apheresis systems inpatients with hypercholesterolemia in a randomized cross-over trial with respect to their effects on lipoproteins as well as on other cardiovascular risk markers. Six patients (4 women, 2 men, median age 62.5 years, median BMI 25.9 kg/m(2)) on regular LDL apheresis were randomly assigned to receive six weekly treatments with either DALI (Fresenius) or Liposorber D (Kaneka). After 6 weeks, the patients were switched to the other device (again six weekly treatments). Blood was drawn before and immediately after LDL apheresis at three time points (last regular apheresis before the study; after six treatments with DALI and after six treatments with Liposorber D). LDL cholesterol concentration before the sixth apheresis (DALI 129 mg/dL, Liposorber D 132 mg/dL) as well as LDL cholesterol reduction during the sixth apheresis (DALI 68.3% and Liposorber D 68.4%) were similar with the two systems. CRP and fibrinogen concentrations were lower but interleukin-6, myeloperoxidase, and resistin concentrations were higher after the last Liposorber treatment compared with DALI (P < 0.05, respectively). No differences were observed concerning adiponectin, ghrelin, and PYY levels. In conclusion, both devices were highly effective in eliminating atherogenic lipoproteins. CRP and fibrinogen were better eliminated with Liposorber D. However, following Liposorber D, interleukin-6 levels were higher than after DALI possibly indicating an increased inflammatory activation.     

Low-density lipoprotein apheresis and changes in plasma components.

Several different techniques of low-density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran-sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high-molecular-weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors.     

Apolipoprotein E in hepatocellular liver disease

Apolipoprotein E concentrations in plasma were investigated in 17 patients with hepatocellular (non-cholestatic) liver disease. Ninety-five per cent of plasma apolipoprotein E was recovered in density fractions less than 1.063 kg/l and it was therefore associated with very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Very low-density lipoproteins and LDL apolipoprotein E correlated positively (r = 0.63, p less than 0.01) with plasma bile salt concentrations when a decrease in liver protein synthesis was taken into account. This may be due to a down-regulation of the hepatic apolipoprotein B, E receptors concomitant with increasing plasma bile salt concentrations.     

Review: the oxidant/antioxidant balance during regular low density lipoprotein apheresis.

Low density lipoprotein (LDL) apheresis is a safe procedure to treat severe hypercholesterolemia in patients with chronic heart disease (CHD). However, both hypercholesterolemia and extracorporeal treatment have been associated with oxidative stress. Even though LDL lowering has been proven to reduce CHD, the oxidative modification of LDL has been suggested to render these lipoproteins more atherogenic. It is therefore important to know whether LDL apheresis is safe with respect to oxidative stress including LDL oxidation. The contact of living cells such as leukocytes with artificial surfaces during extracorporeal treatment induces the liberation of various chemokines and cytokines as well as oxygen-derived radicals also known as respiratory burst. These effects justify the consideration of leukocyte activation resulting from extracorporeal treatment as an inflammatory reaction. In extracorporeal circuits such as those used for hemodialysis, the release of oxygen radicals has been shown and depends on the fiber material used in the dialyzer membranes. Reactive oxygen radicals can interact with different cell components such as carbohydrates, DNA, proteins, and lipids. Antioxidants in the form of low molecular weight molecules such as glutathione or radical scavenging enzymes such as superoxide dismutase offer protection against the damaging effects of prooxidants. The disturbed balance between prooxidants and antioxidants is considered as oxidative stress. Therefore, either an increase in oxygen radical formation or a decrease of antioxidants will lead to oxidative stress. During LDL apheresis, a decrease of low molecular weight antioxidants has been reported. In contrast, we have observed an increase in plasma glutathione concentrations but no severe reduction in the activity of antioxidant enzymes in plasma, red cells, or granulocytes, which may explain the lack of plasma lipid peroxidation shown during this kind of extracorporeal treatment. In addition, LDL isolated at the end of apheresis procedures are more resistant to oxidation. These findings suggest that LDL apheresis is safe with respect to radical mediated injury.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment.     

Evolocumab and lipoprotein apheresis combination therapy may have synergic effects to reduce low‐density lipoprotein cholesterol levels in heterozygous familial hypercholesterolemia: A case report

A 49 years old woman (weight 68 kg, BMI 27.3 kg/m²) with heterozygous familial hypercholesterolemia (HeFH) and multiple statin intolerance with muscle aches and creatine kinase elevation, presented at the Outpatient Lipid Clinic of Verona University Hospital in May 2015. Hypercholesterolemia was firstly diagnosed during adolescence, followed in adulthood by a diagnosis of Cogan's syndrome, a rheumatologic disorder characterized by corneal and inner ear inflammation. No xanthomas, corneal arcus, or vascular bruits were detectable at physical examination. Screening for macrovascular complications did not reveal relevant damages. Ongoing medical therapy included salicylic acid, methylprednisolone, methotrexate, and protonic‐pump inhibitor. In the absence of specific lipid‐lowering therapy, plasma lipid levels at first visit were: total‐cholesterol = 522 mg/dL, LDL‐cholesterol = 434 mg/dL, HDL‐cholesterol = 84 mg/dL, triglycerides = 120 mg/dL, Lp(a) = 13 mg/dL. On December 2015, evolocumab 140 mg sc every 2 weeks was initiated. After a 24‐week treatment, the LDL‐cholesterol levels decreased by an average of 21.2% to 342 ± 22 mg/dL (mean ± SD). On May 2016, LDL‐apheresis (H.E.L.P.system) was started as add‐on therapy. Compared to the average levels obtained during the evolocumab monotherapy period, the LDL‐cholesterol was reduced by 49.4%, thus reaching an inter‐apheresis level (mean ± SD) of 173 ± 37 mg/dL. This report suggests that a combination therapy with evolocumab and lipoprotein‐apheresis may have synergic effects on circulating lipid levels. Its relevance as a highly effective treatment option for hyperlipidemia in HeFH patients warrants further investigation in larger datasets.     

An alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis

An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.