Identification of complement activators and elucidation of the fate of complement activation products during extracorporeal plasma purification therapy.

It has been known for many years that the complement system is activated during extracorporeal plasma purification (ECCP) therapy. In a previous study, we showed that high concentrations of complement activation products (CAPs) are returned to the patient during immunoadsorption treatment. In the present study, we investigated the question of where complement activation takes place with different forms of ECPP equipments as well as the fate of the CAPs. Eleven patients (8 men and 3 women), mean age 52 +/- 18 years, were included in the study. They were treated either with plasmapheresis (PP), immunoadsorption, bilirubin adsorption, or low density lipoprotein (LDL) apheresis. It was found that during all ECPP treatments and after the plasma separation filter, the plasma concentrations of CAPs were increased, and that high concentrations of CAPs were returned to the patients, except with PP. The plasma levels of individual CAPs varied between different types of ECPP. These variations were due to several factors: (1) complement activation (CA) on the plasma separator and a secondary device, e.g., column or membrane; (2) adsorption of specific CAPs to separation columns; and (3) reduction of CAPs due to separation and waste. Since CAPs have inflammatory and immunological effects, it is possible that high serum concentration of CAPs in the treated patients may influence the clinical outcome of the treatment. In conclusion, complement activation is a fact that should not be ignored during performance of any form of an ECPP. It is the plasma separator that plays a key role in the process of complement activation. Different ECPP treatments may have different effects regarding the levels of individual CAPs.

Treatment of homozygous familial hypercholesterolemia with low density lipoprotein apheresis: a 4 year follow-up study.

Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50-60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70-75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.

Effects of LDL apheresis on blood rheology in two patients with homozygous familial hypercholesterolaemia.

Changes in haemorheological and lipid variables were investigated in 2 patients with homozygous familial hypercholesterolaemia (FH) treated with low-density lipoprotein (LDL) apheresis using dextran sulphate adsorbent. The immediate effect of LDL apheresis was a fall in plasma fibrinogen by 50%, total and LDL cholesterol by 60%, plasma viscosity by 12% and whole blood viscosity by 17%. Before the 12th treatment session, plasma fibrinogen concentration remained reduced by 22%, whole blood viscosity by 17% and the plasma viscosity by 11% compared with the initial values. Total and LDL cholesterol in plasma also remained reduced by about 50%. We conclude that LDL apheresis, using dextran sulphate adsorbent, improves blood rheology. The decrease in plasma fibrinogen concentrations, plasma viscosity and LDL cholesterol might be factors contributing to the improved haemorheological properties.

Effects of extracorporeal hemapheresis therapy on blood rheology.

The blood flow property is one of the factors determining blood perfusion and oxygen supply. The viscosity of the blood is primarily related to the hematocrit, but also to the amount of fibrinogen and other macromolecules present in the blood. Patients with ischemic heart disease have shown a rapid and safe improvement in their hemorheological state when treated with heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP). In this study we used two extracorporeal hemapheresis methods, plasmapheresis (PP) and immunoadsorption (IA), in 15 patients (eight patients treated with PP and seven patients with IA) with various diseases. Hemorheological variables and plasma fibrinogen were measured before and after the first and before the third treatment performed at 3 consecutive days. The aim of our study was to investigate the immediate effects of these two treatment modalities on the flow properties of blood. Immediately after the first PP and IA session statistically significant declines in plasma fibrinogen concentration, plasma viscosity, whole blood viscosity, and erythrocyte aggregation tendency were found. These changes persisted before the third treatment session. The erythrocyte fluidity and hematocrit remained unchanged. We conclude that extracorporeal hemapheresis therapy, with plasmapheresis or immunoadsorption, affects the blood rheology by decreasing the plasma viscosity and erythrocyte aggregation tendency. The decrease in plasma fibrinogen is probably the main factor underlying that, but other factors such as a decrease in immunoglobulins may also be of importance.

Reduction of plasma fibrinogen, immunoglobulin G, and immunoglobulin M concentrations by immunoadsorption therapy with tryptophan and phenylalanine adsorbents.

Immunoadsorption (IA) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session I plasma volume (2.8 +/- 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonparametric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.