German Haemapheresis Centre

and

German Apheresis Research Centre

GENERAL

The process of separation in haemapheresis is performed permitting the blood after anticoagulation to flow from a vein of one forearm into the separation system e.g. centrifuge. If cells are more or less specifically collected or removed the procedure is named cytapheresis. If the blood fluid (plasma) is separated the term plasmapheresis or plasmaseparation is applied. All procedures are performed on-line in blood donors or patients using a continuous or discontinuous blood flow. The first separation step (separation of cells from plasma or plasma from cells) is named primary separation. For primary separation centrifuges are often superior to filtration techniques. A subsequent separation step is named secondary or differential separation, referring to both cell differential separation or plasma differential separation.

ACCESS TO THE BLOOD CIRCULATION

Standard haemapheresis procedures are performed from one vein to the other (veno - venous access) of both forearms or as single vein procedures. To apply an artificial access to the circulation especially arterio - venous fistulae (shunts) is considered as unethical from apheresis specialists unless special reasons (e.g. lack of alternatives, emergency) demands such approach. However, such conditions are extremely rare. Under standard working conditions there is no technical need for the use of a shunt, as for instance suitable blood cell separators permit flow rates of underneath 50 ml/min without technical separation problems. An artificial access may ease the treatment for the nurse or the physician but is accompagnied by (rare, but sometimes life threatening) increased risk for the patients, as it is well known dialysis where it is technically rather impossible to treat without an artificial access to the circulation. This statement is based on a 35 years experience at the University of Cologne and the German Haemapheresis Centre with at least 50 000 procedures performed for blood donation and therapy. There is additional evidence which can be drawn from corresponding statistics.

CYTAPHERESIS

The term cytapheresis means the selective separation of blood cells for their collection or removal.

DONOR CYTAPHERESIS

Donor cytapheresis is mainly performed to collect platelets (thrombocytes) generally for supportive cancer therapy substituting lacking platelets after chemotherapy or bone marrow / stem cell transplantation or alternatively white blood cells (granulocytes collected using granulocytapheresis) for the treatment of severe infection (sepsis due to infection with gram negative bacteria) occuring after aggressive chemotherapy or bone marrow/stem cell trans-plantation. Other white blood cells such as stem cells, lymphocytes or monocytes may also be collected for currently developing cytotherapy e.g. of cancer but also in other medical fields. Multi component donor cytapheresis embraces the combined donation of different cell types with plasma.

THERAPEUTIC CYTAPHERESIS

Red blood cells (erythrocytes) are removed in diseases with an increased genetic defect of the iron metabolism (haemochromatosis) or other diseases of the erythrocyte lineage. The treatment of such diseases, mainly of haemochromatosis using blood cell separators is clearly superior to conventional blood letting. Erythrocyte exchange therapy is used for the treatment of sickle cell anaemia.
White blood cells can successfully be removed for the treatment of otherwise therapy resistant patients or those who for other reasons have no treatment alternative in patients with Crohn's disease or colitis ulcerosa. The treatment is simple, easy and effective. Excessively elevated white blood cells mainly in patients with leukaemia leading to cellular hyperviscosity can easily be removed from leukaemic patients (cell depletion therapy) to normalise the cellular blood count and make these patients accessible to chemotherapy which otherwise might be too risky.
The same holds true for blood platelets if their concentration exceeds 1 - 1.5 million thrombocytes/µl.
Stem cells can be collected from the patients (or donor) blood to enable autologous stem cell transfusion or applications currently under development in cardiology and other fields.
Cell therapy can also be performed with collected monocytes and lymphocytes with or without subsequent manipulation for cancer therapy.
Photopheresis is a treatment where white blood cells are removed and treated with UV irradiation. The treatment is admitted for cutaneous T-cell lymphoma and is currently expanded to other forms of T cell mediated diseases.

PLASMAPHERESIS

In analogy to cytapheresis procedures plasmapheresis methods may serve both plasma donation and plasma therapy. As for historical reasons the term plasmapheresis is taken from plasma donation and one should speak of plasma separation or therapeutic plasmapheresis if plasma therapy is meant. It is usually an indicator of ignorance in apheresis and may lead to confusion if such terminology is mixed up.

PLASMAEXCHANGE and PLASMA (WHOLE BLOOD) DIFFERENTIAL SEPARATION

For plasma exchange therapy the blood cells of the patient are online separated from the plasma and returned to the patient whereas in parallel the plasma is exchanged against a substitution fluid. Plasma exchange is technically outdated but is still used for the treatment of some diseases or special disease conditions.
As plasma exchange is unspecific and unselective the technical development was directed towards an increased selectivity and specificity (plasma differential separation). Nowadays whole blood is also applied for some indications where a selective removal can be accepted. Nevertheless, plasma differential separation permits unspecific, semi-selective, selective and specific removal of undesired plasma components. The techniques applied are precipitation, filtration or adsorption.

LDL - APHERESIS, other LDL - ELIMINATION PROCEDURES
and IMMUNEAPHERESIS (Ig - Apheresis)

LDL - apheresis is a blood purification procedure which specifically removes Apoprotein B bound cholesterol. It is the first on-line technique using immuneapheresis, was introduced at the University of Köln in 1981 and is since then world wide applied. The name was introduced by Prof. Ahrens, Rockefeller University, during a visit at Cologne in 1982 and is reserved for this technique. It is characterised by a so far unbeaten specificity, efficacy and economy. It is a first line procedure. Nevertheless, it is frequently misused by other technologies which also may remove LDL - cholesterol. The worse the technology, the more frequent is the misuse. LDL - apheresis is technically characterised by plasma perfusion of two adsorption columns alternatively loaded and desorbed during one treatment and reused at least 50 times but frequently more than 100 times. As compared to other technologies LDL - apheresis is the least expensive LDL removal procedure.
Other techniques permitting for some extent also LDL - elimination are characterised from precipitation, semiselective filtration and selective (rather than specific) adsorption. They generally apply disposable columns or filters and their technical efficacy is limited: Either the adsorption capacity is exhausted applying an adsorber or the removal of other plasma proteins such as fibrinogen (e.g. if secondary filtration is applied) limits further application. Thus, these procedures are considered to be second line techniques. However, it has to be mentioned that the selective removal which means the simultaneous removal of other unrelated plasma components may have advantages for other lines of indications such as Rheohaemapheresis.
Using LDL - apheresis as a model immunoglobulin (Ig-) apheresis was first developed and introduced at the University of Cologne. The same type of column was subsequently developed and distributed as "Therasorb". They are applied for the removal of undesired plasma components like rheumathoid factors and antibodies or autoantibodies (immunoglobulins). Other technologies use also substrates e.g. protein A, peptides which bind immunoglobulins or immune complexes considered to be harmful in mainly rheumathoid diseases. Some types of adsorbers appear to be more effective by releasing traces of ligands than binding plasma components of such patients.

RHEOTHERAPY and RHEOHAEMAPHERESIS^®

Rheohaemapheresis is an extracorporeal rheotherapy which is characterised by the removal of a considerable amount of high molecular weight plasma components (and if necessary from a surplus of red cells) to improve organ perfusion. The technology was originally applied as double filtration in Japan but subsequently technically improved at the University of Cologne and the German Haemapheresis Centre. Double filtration is still being used but technically outdated and by far too expensive. Age related macular degeneration is the first proven indication but a considerable number of other indications was developed at Cologne since then. Rheohaemapheresis being a systemic treatment approach represents an improved or even new treatment principle of extracorporeal therapy as compared to conventional haemorheotherapy.