Comparative evaluation of a heparin-citrate anticoagulation for LDL-apheresis in two primary apheresis systems.

BACKGROUND: As COBE Spectra has been replaced in many parts of the world, we describe a new protocol for low-density lipoprotein (LDL)-apheresis performed on familial hypercholesterolemia patients for the Spectra Optia platform. METHODS: For all procedures, after administering a bolus of heparin of 2,500 U, 10,000 U of heparin added to a 600 ml ACD-A bag was used as anticoagulant (AC). In a first phase (A), 16 apheresis procedures with COBE Spectra using an inlet:AC ratio of 25:1 were compared to 18 LDL-apheresis treatments with Spectra Optia at split Inlet:AC ratios of 16:1/18:1 or 20:1/25:1. Platelet activation and coagulation markers were assessed. In a follow-up phase (B), 20 procedures on Spectra Optia using an inlet:AC ratio of 20:1 were performed. RESULTS: Although coagulation markers and platelet activation analyzed were similar in both apheresis devices used, COBE Spectra procedures did not show any visual clumping in the sets. Visual analysis of clumping was highest in the Spectra Optia's 20:1/25:1 AC regimen (5/8 procedures). For the lowest Spectra Optia, AC regimen and during the follow-up phase reversible clump formation in the disposable set was similar (1/10 procedures). Clumping was successfully reversed in all cases by temporarily lowering the inlet:AC ratio to 18:1. Blood cell counts (WBC, Plt, Hct) were similar for both COBE Spectra and Spectra Optia procedures. Spectra Optia had a significantly higher plasma removal efficiency versus COBE Spectra (84% vs.75%, P < .05). No serious adverse events were observed. CONCLUSION: Apheresis procedures on the Spectra Optia system with low-dose heparin-citrate anticoagulation are feasible and safe.

The lower the better: target values after LDL-Apheresis and semi-selective LDL-elimination therapies.

Prior to 1980 the drug therapy of hereditary hypercholesterolaemia was, as compared to nowadays standards, rather limited. There was virtually no effective therapy for homozygous patients, though plasma exchange introduced in France and Britain, demonstrated the use-fullness of the introduction of apheresis techniques. Parallel to the improvement of cholesterol lowering drug therapy for heterozygous patients, apheresis was developed as therapeutic affinity chromatography since 1980 at the university of Cologne for both homozygous and therapy refractory heterozygous patients. This development was named LDL-Apheresis based on the specificity for the removal of Apoprotein B bound cholesterol, the capacity due to the development of a repetitive cycling technique and the economy determined from the reuse of affinity chromatography columns for each single patient. The capacity of the system allowed for the introduction of new standards of post-treatment values such as 100mg/dl total cholesterol or alternatively 50mg/dl LDL-cholesterol and if cholesterol lowering drugs can also applied for a limited extent the rebound can be also slowed down. After 33 years of experience with seven homozygotes and 32 heterozygotes without treatment alternative, we found that in addition to the improvement of the quality of live the extension of live expectancy are the real proof of a therapeutic success as compared to other diagnostic procedures. The average live expectancy of our seven homozygous patients is 45.6 years; our oldest heterozygous patient is 81 years. There are no comparable long term data at present available neither from studies using drugs nor from subsequently developed apheresis techniques which also removed LDL-cholesterol together with plasma constituents not participating in the development of atherosclerosis. Also two homozygous patients giving birth to four children without complication support our concept of aggressive cholesterol lowering therapy being without major side effects (3-4% minor undesired reactions).

Comparison of different Lp (a) elimination techniques: a retrospective evaluation.

Lipoprotein (a), abbreviated Lp (a), is accepted as a potential selective or additional risk factor for premature atherosclerosis. Though it may be considered to be closely related to low density lipoprotein, so far attempts to keep it under control with diet or cholesterol lowering medications have failed. Thus, extracorporeal elimination is the only effective treatment approach for patients with premature atherosclerosis. As different techniques for differential elimination such as precipitation, adsorption and filtration exist, it appeared of interest for us to retrospectively evaluate adsorption and filtration procedures in their capacity to lower Lp (a). Four patients with selectively elevated Lp (a) and eight patients with familial hypercholesterolaemia and additional elevated Lp (a) could be evaluated. All patients had Lp (a) values of 80-120 mg/dl without treatment in common. Different plasma or whole blood volumes were processed to obtain 30 mg/dl Lp (a) as post-treatment target values. In patients with a selective elevation Lp (a)-apheresis, as developed from Prokovski, was the most potent elimination procedure, decreasing the Lp (a) by at least 81% of the initial value after processing 6L of plasma followed from LDL-(immune) apheresis with 71%. Plasma differential filtration using the Kuraray LA 4 filter decreased Lp (a) by 70% processing only 3.4 L, however was less selective and limited by the loss of fibrinogen and other high molecular weight proteins. In patients with familial hypercholesterolaemia and Lp (a) elevation in a range of 80-120 mg /dl LDL-(immune) apheresis removed >80% of Lp (a) processing 6L of plasma whereas if 5L were processed a removal of 76% was comparable to liposorption. Neither whole blood perfusion (DALI, Fresenius) nor filtration applying the Kuraray LA 5 filter was able to reach the desired target values.

Quo vadis haemapheresis. Current developments in haemapheresis.

The techniques of haemapheresis originated in the development of centrifugal devices separating cells from plasma and later on plasma from cells. Subsequently membrane filtration was developed allowing for plasma-cell separation. The unspecificity of therapeutic plasma exchange led to the development of secondary plasma separation technologies being specific, semi-selective or selective such as adsorption, filtration or precipitation. In contrast on-line differential separation of cells is still under development. Whereas erythrocytapheresis, granulocytapheresis, lymphocytapheresis and stem cell apheresis are technically advanced, monocytapheresis may need further improvement. Also, indications such as erythrocytapheresis for the treatment of polycythaemia vera or photopheresis though being clinically effective and of considerable importance for an appropriate disease control are to some extent under debate as being either too costly or without sufficient understanding of the mechanism. Other forms of cell therapy are under development. Rheohaemapheresis as the most advanced technology of extracorporeal haemorheotherapy is a rapidly developing approach contributing to the treatment of microcirculatory diseases and tissue repair. Whereas the control of a considerable number of (auto-) antibody mediated diseases is beyond discussion, the indication of apheresis therapy for immune complex mediated diseases is quite often still under debate. Detoxification for artificial liver support advanced considerably during the last years, whereas conclusions on the efficacy of septicaemia treatment are debatable indeed. LDL-apheresis initiated in 1981 as immune apheresis is well established since 24 years, other semi-selective or unspecific procedures, allowing for the elimination of LDL-cholesterol among other plasma components are also being used. Correspondingly Lp(a) apheresis is available as a specific, highly efficient elimination procedure superior to techniques which also eliminate Lp(a). Quality control systems, more economical technologies as for instance by increasing automation, influencing the over-interpretation of evidence based medicine especially in patients with rare diseases without treatment alternative, more insight into the need of controlled clinical trials or alternatively improved diagnostic procedures are among others tools ways to expand the application of haemapheresis so far applied in cardiology, dermatology, haematology, immunology, nephrology, neurology, ophthalmology, otology, paediatrics, rheumatology, surgery and transfusion medicine.

Rheohaemapheresis of ophthalmological diseases and diseases of the microcirculation.

Blood rheology was considered to be of limited clinical importance, until extracorporeal technologies enabling the treatment of cellular and plasmatic hyperviscosity syndromes were introduced. However, a wide range of applications, mainly referring to rheologically determined diseases of the microcirculation exists but has so far hardly been taken into consideration. The extension of indications was due to modern technical developments leading to different approaches of secondary separation such as precipitation, ad- or absorption and filtration. Based on 18 years of experience with different separation technologies the combination of some centrifugal devices applied for cell--plasma separation with secondary filtration (Rheohemapheresis) appears to be the most efficacious and economical approach for such extracorporeal treatments. The sequence and frequency of rheohaemapheresis treatments depends on the measurement of rheological measurements in combination with clinical--chemical data which are related to the distribution kinetics and synthesis rate of both blood cells and plasma proteins. Standardised treatment protocols proved the efficacy of initial therapies and were applied for controlled trials whereas long term therapies may need more flexible treatment approaches. So far an increasing experience exists for the treatment of ophthalmologic diseases, otologic disorders, diabetic complications and cardiological diseases. Rheohemapheresis was shown to be a safe treatment approach, if a careful risk assessment prior to the initiation of the therapies is performed. The treatment cannot cure diseases but enables a substantial improvement of the quality of life in patients without treatment alternatives.

The effect of membrane differential filtration on the colloid osmotic pressure in patients with age-related macular degeneration: significance to visual function?

To investigate the effect of membrane differential filtration (MDF) on plasma colloid osmotic pressure (COP) and visual functions in age-related geographic macular degeneration (AMD). Ten consecutive patients with non-exudative AMD underwent one MDF cycle. Primary endpoint was COP. Secondary endpoints were visual acuity and the mean defect of visual field. The COP was markedly reduced after one MDF cycle by 23.9% (P = 0.001). Compared with the baseline examination, visual acuity and the mean defect of visual field improved significantly after MDF. A significant positive correlation was found between the improvement in visual field and the decrease in COP (Pearson's coefficient = 0.65; P = 0.04). Membrane differential filtration lowers plasma colloid osmotic pressure in patients with non-exudative AMD. Based on the observation that visual field and COP are correlated, one may hope for a means to improve decreased central retinal function in eyes with geographic AMD by modulation of COP plasma level.