Comparison of different LDL apheresis methods

This article presents the generally accepted indications for LDL apheresis treatment. The available LDL apheresis methods differ with respect to acute relative reductions of LDL cholesterol; mean values after the LDL apheresis treatments are not different. Serum triglycerides, HDL-cholesterol, and lipoprotein(a) are also acutely reduced. Available LDL apheresis methods differ with respect to their impact on the coagulation system, on C-reactive protein and on leukocyte count. Cardiovascular events are clearly reduced by the LDL apheresis methods. There is an urgent need to prospectively compare the different LDL apheresis methods taking into account hard end points. The lower target values for LDL cholesterol suggested by international guidelines for high-risk patients will certainly require a more widespread use of LDL apheresis.     

LDL apheresis in Japan

LDL apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH). Currently, plasma exchange, double membrane filtration, and selective LDL adsorption are available in Japan, and selective LDL adsorption is most common method. LDL apheresis can prevent atherosclerosis progression even in homozygous (HoFH). However, in our observational study, HoFH who started LDL apheresis from adulthood had poor prognosis compared with patients who started from childhood. Therefore, as far as possible, HoFH patients need to start LDL apheresis from childhood. Although indication of LDL apheresis in heterozygous FH (HeFH) has been decreasing with the advent of strong statin, our observational study showed that HeFH patients who were discontinued LDL apheresis therapy had poor prognosis compared with patients who were continued apheresis therapy. These results suggest that high risk HeFH need to be treated by LDL apheresis even if their LDLC is controlled by lipid-lowering agents. However, by launching new class of lipid lowering agents, that is, PCSK-9 antibody and MTP inhibitor, indication of LDL-apheresis in FH may be changed near the future. LDL-apheresis can provide symptom relief of peripheral artery disease (PAD). Therefore, PAD patients who have insufficient effect by other therapeutic approach including revascularization are also treated by LDL apheresis. Thus, LDL apheresis is still one of good therapeutic options for severe atherosclerotic diseases in Japan.     

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.     

Release of microparticles in LDL apheresis.

Particle contamination of blood always takes place in extracorporeal systems and few studies have been conducted to evaluate potential risks. Particle concentration was measured in the efferent blood line on original equipment for two established LDL elimination procedures (DALI) (Fresenius) and Liposorber (Kaneka). Acquired data were compared with standards for infusion solutions from European (EP) and American (USP) Pharmacopoeia. All values were well below the given limits. Even in extreme situations (>20 pump stops) particle concentration did not exceed the standards. Considering an average treated blood volume of 7.31 for the DALI-System and 17.01 for Liposorber (long term clinical studies) the absolute amount of particles infused per treatment was 167,000 (DALI) and 465,000 (Liposorber) particles > or = 2 microm.     

Internet-based quality assurance registry for LDL apheresis QUASA--the apheresis registry.

Quality assurance measures have been demanded in the execution of extracorporeal LDL apheresis therapy (LDL apheresis) by the NUB-guidelines of the national committee of physicians and health insurance. The measures apply to specialist, organizational and mechanical requirements for the execution and billing of this method of treatment. Furthermore, as a result of the legal requirements of the SGB V, complementary BUB-guidelines were introduced in 1999. These should prove the therapeutic benefit of an LDL apheresis treatment. Beyond assuring quality of performance, documentation of the treatment is explicitly demanded. For the past two years, the non-profit QUASA gGmbH has developed a quality assurance registry for LDL apheresis based on those requirements. Since March 2003, the apheresis physicians can voluntarily take part in this registry through the internet. Beside the patient's medical history, data relevant to the treatment are also recorded. Because of the analysis of the national clinical data it will be possible for the first time, for the medical profession to fulfill the guidelines and ensure the quality of LDL apheresis.     

Disparate LDL phenotypic classification among 4 different methods assessing LDL particle characteristics

BACKGROUND: Our study seeks to clarify the extent of differences in analytical results, from a clinical perspective, among 4 leading technologies currently used in clinical reference laboratories for the analysis of LDL subfractions: gradient gel electrophoresis (GGE), ultracentrifugation-vertical auto profile (VAP), nuclear magnetic resonance (NMR), and tube gel electrophoresis (TGE). METHODS: We collected 4 simultaneous blood samples from 40 persons (30 males and 10 females) to determine LDL subclasses in 4 different clinical reference laboratories using different methods for analysis. LDL subfractions were assessed according to LDL particle size and the results categorized according to LDL phenotype. We compared results obtained from the different technologies. RESULTS: We observed substantial heterogeneity of results and interpretations among the 4 methods. Complete agreement among methods with respect to LDL subclass phenotyping occurred in only 8% (n = 3) of the persons studied. NMR and GGE agreed most frequently at 70% (n = 28), whereas VAP matched least often. CONCLUSIONS: As measurement of LDL subclasses becomes increasingly important, standardization of methods is needed. Variation among currently available methods renders them unreliable and limits their clinical usefulness.     

LDL apheresis as it relates to nursing practice

Nurses are an essential partner in the treatment of complex diseases and they have extensive influence on patient outcomes. Connecting a patient to a machine takes courage, skill, and a whole lot of trust. Anyone who has earned the title of “nurse” has shown courage. Skill comes with hours and hours of practice. Trust is earned and ongoing. Combine these three attributes and you get the “care” that goes into nursing care. Low-density lipoprotein (LDL) apheresis is a well-established therapy for hypercholesterolemia. This article will focused on the Liposorber^® MA-03 system in a brief conversation of LDL apheresis as it relates to nursing practice.     

Long-term effects of LDL apheresis in patients with severe hypercholesterolemia

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism involving mutations in the LDL receptor (LDL-R). Patients with mutation in one (heterozygous) or both (homozygous) genes have markedly elevated LDL cholesterol and are at increased risk for coronary heart disease (CHD). Aggressive lipid lowering is required for homozygous and many heterozygous FH patients. This often involves LDL-apheresis, where LDL and other apo-B containing lipoproteins are selectively removed from the plasma. We have retrospectively studied 34 patients treated with biweekly LDL-apheresis at the Hospital of the University of Pennsylvania. In our patient population, adverse events were uncommon and rarely resulted in shortened treatment time. There was a dramatic decrease in the relative risk of cardiovascular events and cardiovascular interventions in patients treated with LDL-apheresis for an average of 2.5 years. Some but not all patients had long-term reduction in their LDL levels as a result of LDL-apheresis, suggesting that time-averaged reduction in LDL and/or LDL:HDL ratios were responsible for clinical improvement. These data support the use of LDL-apheresis in patients with FH, as well as medication-intolerant patients that have elevated LDL cholesterol despite maximal pharmacological treatment.     

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.     

Two patients with acute Guillain-Barré syndrome treated with different apheresis methods.

We treated 2 patients with severe acute Guillain-Barré syndrome (GBS) with different apheresis methods. Sera from these patients in the acute phase contained a high titer of immunoglobulin (Ig)G anti-GM1 ganglioside antibody. One was a 57-year-old female treated with immunoadsorption (IA). IgG anti-GM1 antibody titer was reduced from 1:102,400 to 1:6,400 measured by ELISA after 1 month. However, her residual deficit was severe. The other patient was a 43-year-old male treated with plasma exchange (PE). IgG anti-GM1 antibody was reduced from 1:3,200 to 1:400 after 1 session of PE. After 1 month, he could walk independently. The better prognosis of the latter was possibly because of the patient's younger age and the plasma exchange that might have reduced such pathogenic factors as antiganglioside antibodies at the early stage of GBS.