Lipoprotein Apheresis Methods Research Articles

Comparison of The Two Lipoprotein Apheresis Methods in The Treatment of Familial Hypercholesterolemia

Objective: Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder that causes a significant increase in low-density lipoprotein (LDL) cholesterol levels and leads to early coronary heart disease and cardiac mortality. Although this disease has a heterozygous (HeFH) and homozygous (HoFH) form, the incidence of HeFH is reported to be 1: 500, while HoFH is reported to be 1: 1 000 000. This disease is often caused by LDL receptor (most common), apolipoprotein B (Apo B), Proprotein Convertase Subtilisin/Kexin 9 (PCSK9), and LDL receptor adaptor protein (LDLRAP) gene mutations. Patients with FH do not respond well to lipid-lowering therapies such as a statin, and so lipoprotein apheresis is the treatment of choice. Material and Methods: We compared the results of lipoprotein apheresis in a 20-year-old female patient diagnosed with HoFH with two different methods [double-filtration plasmapheresis (DFPP) and dextran sulfate column (DSC) methods]. 40 lipoprotein apheresis procedures including 20 sessions of DFPP and 20 sessions of DSC were evaluated. Results: When the two methods were compared the changes in high-density lipoprotein, white blood cells, platelets, potassium, calcium, prothrombin time (INR) and activated partial thromboplastin time values were statistically significant. Conclusions: In conclusion, our study suggests that it would be more appropriate to choose the apheresis method according to the clinical and laboratory findings of the patient since it shows that two different methods have different effects on serum electrolyte values, hemostasis criteria and leukocyte and platelet counts.

Commentary: Effects of different lipoprotein apheresis methods on serum protein levels

Commentary: Effects of different lipoprotein apheresis methods on serum protein levels

Asparaginase-associated concurrence of hyperlipidemia, hyperglobulinemia, and thrombocytosis was successfully treated by centrifuge/membrane hybrid double-filtration plasmapheresis

Asparaginase-associated concurrence of hyperlipidemia, hyperglobulinemia, and thrombocytosis is a rare complication requiring aggressive lipoprotein apheresis, but no one of currently available lipoprotein apheresis methods can simultaneously resolve the 3 abnormalities. Herein, we reported a construction of double-filtration plasmapheresis (DFPP) using a combination of centrifugal/membranous plasma separation techniques to successfully treat a patient with hyperlipidemia, hyperglobulinemia, and thrombocytosis. A male presented with severe hyperlipidemia, hyperglobulinemia, and thrombocytosis during asparaginase treatment for NK/T-cell lymphoblastic lymphoma and was scheduled to receive lipoprotein apheresis. To simultaneously remove lipoproteins, immunoglobulin, and deplete platelets from blood, a centrifuge/membrane hybrid DFPP was constructed as following steps: plasma and part of platelets were separated first from whole blood by centrifugal technique and then divided by a fraction plasma separator into 2 parts: platelets and plasma components with large size, which were discarded; and those containing albumin, which were returned to blood with a supplement of extrinsic albumin solution. DFPP lasted 240 minutes uneventfully, processing 5450-mL plasma. The concentrations of plasma components before DFPP were as follows: triglycerides 38.22 mmol/L, total cholesterols 22.98 mmol/L, immunoglobulin A (IgA) 15.7 g/L, IgG 12.7 g/L, and IgM 14.3 g/L; whereas after treatment were 5.69 mmol/L, 2.38 mmol/L, 2.5 g/L, 7.7 g/L, and 0.4 g/L, respectively. The respective reduction ratio was 85.1%, 89.6%, 83.9%, 39.4%, and 96.9%. Platelet count decreased by 40.4% (from 612 × 109/L to 365 × 109/L). Centrifuge/membrane hybrid DFPP can simultaneously remove lipoproteins, immunoglobulin, and deplete platelets, with a success in treatment of asparaginase treatment-induced hyperlipidemia, hyperglobulinemia, and thrombocytosis, and may be useful for patients requiring DFPP but with particular situations.

Effects of different lipoprotein apheresis methods on serum protein levels

BackgroundA total plasma exchange was the first extracorporeal method to treat patients with severe hypercholesterolemia. But in the long run it has several disadvantages. The newer lipoprotein apheresis (LA) methods claim to be more selective with respect to the removal of atherogenic lipoproteins and thus are supposed to avoid an additional protein loss. MethodsWe wanted to compare the effect of these methods on serum protein concentrations (total serum protein, albumin, proteins measured with electrophoresis, immunoglobulins, fibrinogen, transferrin, and ferritin) which were checked before and after a single LA session in 75 patients. All patients underwent active LA treatment using 6 different LA methods (HELP, TheraSorb® LDL, DALI, Lipidfiltration, Liposorber D, MONET). Post-apheresis concentrations were corrected for changes in hematocrit. ResultsThe slightest impact on total serum protein was observed with the whole-blood methods. Liposorber D showed the least reduction of albumin levels. All LA methods had a small effect on alpha1-globulins and beta-globulins, but alpha2-and gamma-globulins were reduced to a different extent. A major effect was seen on the immunoglobulins when filtration methods were applied. In the patients treated with MONET, both pre- and post-apheresis Immunoglobulin M concentrations were below the normal range. HELP and the filtration methods significantly reduced the fibrinogen concentrations. The filtration methods also decreased ferritin levels but the post-apheresis ferritin levels were still in the normal range. ConclusionAll LA methods had an influence on protein concentrations. At present, these findings will not yield an individualized treatment approach for any selective LA method due to the lack of prospective comparative studies. At minimum, special attention should be paid to protein concentrations in patients suffering from protein deficit.

Treatment of primary hypertriglyceridemia states – General approach and the role of extracorporeal methods

Hypertriglyceridemia (HTG) is a common metabolic disorder in which the concentration of very low density lipoproteins (VLDL) and of chylomicrons (CMs) is elevated in the plasma. HTG may be caused by primary and/or secondary causes and affected subjects may express HTG when children or in adulthood. In children and adults a genetic cause may underlie HTG which can be expressed as CMs a severe clinical picture known as Familial Hyperchylomicronemia due to lipoprotein lipase (LPL) or apolipoprotein (apo) CII deficiencies. Genetically determined HTG includes Familial Dysbetalipoproteinemia due to deficiency of apolipoprotein EIII of VLDL and Familial HTG. However, recent data suggest that classical Fredrickson phenotypes describing clinically HTG, which were once considered to be distinct based on biochemical features, have a shared genetic set up. The HTG has been classified according to a recent international paper: mild HTG: 2–10 mmol/L (176–882 mg/dL); severe HTG: > 10 mmol/L (>882 mg/dL) associated to CMs remnants, or Intermediate Density lipoprotein (IDL) like particles, and/or CMs. The treatment includes limitation of dietary content of saturated fat and alcohol, fibrates and omega3 fatty acids. When TG are severely elevated and associated to CMs the risk of acute pancreatitis suggests the use of more drastic therapeutic option such as therapeutic plasma exchange. This paper summarizes the experience with conventional plasmapheresis (Plasma-Exchange, PEX) and different Lipoprotein Apheresis methods with respect to acutely lowering TG levels in patients with normal TG, with mild and severe HTG. Upcoming promising therapies are gene therapy, novel apolipoprotein CIII inhibitors and lomitapide.

Lipoprotein apheresis: an update

Since the 1980s, several lipoprotein apheresis methods that eliminate atherogenic lipoproteins (LDL and lipoprotein(a) [Lp(a)]) have been developed. These methods are based on the following principles: precipitation, adsorption and filtration. In Dresden (Germany), we started to perform extracorporeal treatment in 1990; in the 1980s we were working as a lipidologic center and saw patients dying due to severe atherosclerotic diseases. At present, 80 patients are being treated with six different methods at the Apheresis center at the University Hospital Dresden. The effectiveness of these methods with respect to lowering of LDL cholesterol and Lp(a) is somewhat different. The number of patients with high Lp(a) levels and with severe atherosclerotic complications has increased steadily since 2008. Several studies have shown a high effectiveness for apheresis treatment in these patients. In the future, new drugs (e.g., lomitapide, mipomersen or PCSK9 inhibitors) will probably modify the position of apheresis in the therapeutic regimen.

Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations

ObjectivesThere is evidence of iron deficiency (ID) in patients treated with lipoprotein apheresis. Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous (i.v.) iron formulations. MethodsInclusion criteria were defined as a) serum ferritin < 300 μg/l and transferrin saturation < 20%, b) ferritin < 100 μg/l. Both iron deficient alone and ID anemic (IDA) patients were included. Other causes for anemia were ruled out by thorough history-taking and examination/blood tests. Patients were treated with six different lipoprotein apheresis methods: DALI, Liposorber D, TheraSorb LDL, HELP, MONET and Lipidfiltration. 50 patients were randomized to either ferric carboxymaltose (FCM, 500–1000 mg as single shot infusion over 20 min) or ferric gluconate (FG, 62.5 mg once weekly). Results50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency. Both i.v. iron formulations studied were equally safe (no serious adverse events (SAEs), 6 patients/group showed adverse events (AEs)) and both effective (clinically and with respect to laboratory data) in lipoprotein apheresis patients, however FCM led to a more rapid and steeper rise of iron parameters. ConclusionsID and IDA are common findings in lipoprotein apheresis patients. The pathogenesis remains yet poorly understood and is probably multifactorial. Differential diagnosis of ID/IDA is as essential as differential therapy. Handled with care, older i.v. iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients. However, novel formulations like FCM can be administered rapidly at higher doses due to high complex stability, allowing faster filling of iron stores.Newer laboratory parameters (Reticulocyte-He, low/medium/high fluorescence reticulocytes (LFR/MFR/HFR)) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy.

Why an Apheresis Center Should Offer More Than One Lipoprotein Apheresis Method

We describe our experience with the performance of six lipoprotein apheresis methods (HELP, TheraSorb LDL, DALI, lipidfiltration, Liposorber D, MONET) which have been used in 68 patients. Thirty-four of them have been treated with more than one method. The calculations presented in this paper are based on laboratory data measured at the last three available apheresis sessions before the switch to another method and at the end of the observation period, respectively. With respect to the reduction of low-density lipoprotein (LDL) cholesterol, DALI and Liposorber D appeared to be the most effective lipoprotein apheresis methods, for reduction of lipoprotein(a), Liposorber D. Data on the influence of these lipoprotein apheresis methods on parameters of the coagulation system (prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen) are also reported. The histories of three patients who have been switched to several lipoprotein apheresis methods are given as examples. The major reason for switching was the low efficiency of a given lipoprotein apheresis method with respect to lowering of LDL cholesterol; the reason for this phenomenon was not clear in each case. In three patients who took an oral anticoagulant and were treated with HELP, the influence on the coagulation system is reported; they were submitted to another apheresis method. In two patients we observed an allergy to heparin-they were then treated with a heparin-free apheresis method. In conclusion, we point out that there are several reasons why an apheresis center should offer more than one lipoprotein apheresis method.