Detoxification by plasma exchange (synonyms: plasmapheresis, plasmaseparation, therapeutic plasma exchange (TPA), plasma exchange, PE) is a therapeutic procedure used in nephrology and neurology, among others, for the effective removal of unwanted antibodies such as cryoglobulins, endothelial immunoglobulins, and myelin antibodies. Furthermore, this procedure represents an important therapeutic component in the long-term treatment of existing massive fat metabolism disorders. The use of plasmapheresis specifically for lipid metabolism disorders is called lipidapheresis. The term pheresis describes in Greek the “taking away of a part from the whole”. The basic principle of plasmapheresis is that the separated plasma portion of the blood is directly discarded and replaced by an adequate solution. However, the problem here is that non-pathological substances such as coagulation factors are also eliminated by the non-selective substitution of the entire plasma fraction. Nevertheless, the benefits of plasma exchange are rated higher than its negative characteristics, making the procedure an important therapeutic treatment option.
Indications of plasma exchange
Confirmed treatment indications
- Thrombotic thrombocytopenic purpura – in TTP, also known as Maschcowitz syndrome, characterized by fever, hemolytic anemia, and renal insufficiency, performing plasma exchange can support therapy with von Willebrand protease substitution.
- Hemolytic uremic syndrome – this syndrome is associated with hemolytic anemia, thrombocytopenia, and renal failure. It may be associated with impaired complement activation, for example, due to factor H disruption. In the early stage, microthrombi are prominent histologically. In the advanced stage of thrombotic microangiopathy (disease of small blood vessels), arteriolar and glomerular sclerosis (hardening of organs or tissues due to an increase in connective tissue), stenosing fibroelastosis in interlobular arteries, and tubular atrophy and interstitial fibrosis are found.
Presumed treatment indications
- Anti-glomerular basement membrane antibody glomerulopathy – this renal indication is a disease pattern based on the presence of anti-GMB-AK. Patients, often young males, initially present with vague pulmonary symptoms (cough, dyspnea), and in severe cases, massive pulmonary hemorrhage occurs. Shortly thereafter, glomerulonephritis sets in. However, the course of pulmonary symptomatology can also be mild, occasionally glomerulonephritis occurs first.
- Renal failure in cryoglobulinemia – Cryoglobulins (antibodies (immunoglobulins) that become insoluble in cold and return to solution in warmth) play a critical role in the pathophysiology of diverse diseases. As an example, multiple myeloma (is a cancer of the bone marrow; a so-called monoclonal gammopathy with pathological production of immunoglobulins) can be mentioned. Within 10 years, almost half of the patients suffering from cryoglobulinemia develop terminal renal failure (kidney failure). Several randomized and nonrandomized controlled trials have shown that delayed onset of renal failure in cryoglobulinemia can be caused by plasma exchange.
- Systemic lupus erythematosus (SLE) – generalized lupus erythematosus is a generalized autoimmune disease that can affect all organs in its chronic course, leading to massive damage, especially to the skin, joints, and kidneys. It is characterized by the appearance of autoantibodies directed against cell nuclear components (antinuclear antibodies, ANA), double-stranded DNA (anti-ds-DNA antibodies) or histones (anti-histone antibodies). The use of plasma exchange can reduce the occurrence of symptoms, if necessary.
Questionable treatment indications
- Pemphigus vulgaris – is a skin disease belonging to the group of blistering autoimmune dermatoses. Pemphigus vulgaris should be distinguished from bullous pemphigoid and is characterized by blistering due to acantholysis of the lower layers of the epidermis.The cause is IgG autoantibodies against desmoglein 3 (a protein component of the desmosome), which can be detected in the intercellular spaces of the affected areas of the skin, as well as in the serum of the diseased.
- Multiple sclerosis (chronic inflammatory demyelinating disease of the central nervous system, CNS) – plasma exchange can be performed during an acute episode, but the outcome of this treatment is considered particularly questionable. Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system, the cause of which has not yet been determined.
The mechanism of action of plasma exchange is based on the principle that the disease present in the patient is associated with pathologically altered plasma components in the blood or is present due to a pathological increase in plasma components. The exchange of approximately 2,500-3,200 ml of plasma volume results in a decrease of purely intravascular substances, which cannot be substituted with the exchange solution, by approximately 60% of the initial value. If plasma exchange is performed five times within a two-week period, a significant reduction of the IgG content by up to 80 % is usually achieved with simultaneous immunosuppression therapy. However, therapeutic success is not measurable by antibody reduction alone, because autoantibody titer is not associated with autoimmune disease severity with sufficient precision.
The procedure
Performance of plasma exchange
- Separation of blood components can be achieved in several ways. Either this is performed using universally applicable cell separators whose separation mechanism is based on differential centrifugation, or the separation is performed using special membrane plasma separators.
- Regardless of which system is used to separate the blood components, virtually cell-free plasma can be separated by both methods. However, there is a relevant difference in the amount of plasma to be separated and in the speed of the collection flow.
- Apheresis through the cell separator requires a lower blood flow rate than differential centrifugation to function. In addition, it should be emphasized that the amount of processable plasma volume is not limited procedurally when using the cell separator in contrast to differential centrifugation.
- Analogous to other continuously operating hemapheresis systems, an extracorporeal blood circuit is established using two venous accesses. For the function of the system, it is essential that the blood is supplied to the centrifugation chamber without interruption via the collection leg with the addition of an anticoagulant substance. After the blood is fed into the chamber, the separation of the desired fraction takes place, so that subsequently the corpuscular components of the patient’s blood can be returned to the patient’s bloodstream in combination with the substitution solution.
- In addition to the continuous method described so far, discontinuous systems are also used for plasma exchange. The use of these discontinuously functioning systems, in which either the collection or retransfusion phase is active, require only vascular access. Both collection and retransfusion occur through the same vascular access.
- Furthermore, it should be noted that all devices used have computer-controlled roller pumps and valves. This computer control makes it possible that direct functional monitoring of the apheresis system can be ensured.
- Anticoagulation is of particular importance when performing the plasma exchange procedure. With the help of anticoagulation, on the one hand, it can be ensured that the risk of clotting in the tubing system can be relevantly reduced or prevented in order to achieve an optimal flow of blood through the system. On the other hand, anticoagulation can prevent activation of the complement cascade. Substances used for anticoagulation include citrate solutions, heparin, or a combination of both. The use of citrate is considered to be particularly favorable, since with the help of this method of anticoagulation the calcium-dependent steps of complement activation can be almost completely prevented.For better control of the anticoagulant effect, primarily short-acting substances should be used to prevent side effects such as an undesirable prolonged bleeding tendency of the affected patient.
