• Vol. 34 No. 10, 615–624
  • 15 November 2005

Plasma Filtration



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Therapeutic plasma exchange (TPE) or plasmapheresis involves the separation of plasma from whole blood. In so doing, plasma-borne humoral disease mediators are removed from the body. This can attenuate the course and severity of the underlying disease. Diseases that can be treated with TPE are classified into the following categories: (1) endocrinological, (2) neurological, (3) renal/rheumatological, and (4) haematological. TPE is adjuvant in most of these settings. Disease-specific pharmacological treatment remains the cornerstone of treatment in many of these conditions. Plasma separation can be achieved with either (1) centrifugation (CF) or (2) membrane plasma filtration (PF). The latter is the focus of this review. It can be performed using either a continuous renal replacement therapy (CRRT) or haemodialysis (HD) machine. Standard plasma filtration has also been modified to incorporate sorbent technology which obviates the need for plasma volume replacement fluids. Larger clinical issues such as timing of initiation and intensity of therapy are examined.

Many immune-mediated and autoimmune diseases are caused by dysregulation of the cell-mediated and/or humoral-mediated arms of the immune system.1-3 Some conditions are caused mainly by cellular immune mechanisms involving the macrophage/lymphocyte system. 4,5 The immunopathogenesis of other diseases involve both the cellular and humoral pathways.6,7 Humoral disease mediators consist of a diverse range of substances of varying molecular weights (MW). These could be pathogenic antibodies, antibody complexes, immune complexes, autoantibodies and antigen appearing de novo during acute disease. Cytokines are one such group of mediators, consisting of many distinct subtypes such as interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10).8 A study by Reeves et al9 comparing continuous plasma filtration with protocol-driven, standard critical care without plasma filtration in patients with severe sepsis showed that both groups of patients at baseline had comparably elevated cytokines such as interleukin-6 (IL-6) and granulocyte colony-stimulating factor. Evidence supporting the role of plasma-borne humoral disease mediators is found in other studies. Sera from patients with Guillain-Barré syndrome (GBS) was shown to disrupt the function of the blood-nerve barrier (BNB). A factor identified as anti-GM1 antibody was implicated since incubation with pure GM1 antigen appeared to attenuate the BNB damage induced by this pathogenic antibody.10 Besides causing disease, certain humoral mediators also have diagnostic value in clinical management. It is well established that the anti-dsDNA antibody is diagnostic of systemic lupus erythematosus (SLE). A recent study by Villalta et al11 demonstrated the importance of differentiating high-avidity anti-dsDNA autoantibodies, which is more specific for SLE, from the low-avidity forms, since the latter can also be found in other inflammatory diseases. Another aspect of SLE relates to the increased apoptosis of peripheral T-lymphocytes in active disease. Moreover, this is associated with increased expression of both membrane-bound and soluble (s) Fas. It was found that sFas had a pro-apoptotic effect, which partly explains the increased apoptosis seen in active lupus.12 Further evidence of the importance of humoral and cellular immune mechanism interactions was found in a study of patients with thrombotic thrombocytopaenic purpura (TTP). 13 TTP is a clinical syndrome consisting of microangiopathic haemolytic anaemia, consumptive thrombocytopaenia, predilection for neurological involvement and formation of platelet thrombi in small vessels. Plasma from 4 such TTP patients was studied for their effects on human blood phagocyte activation as measured by reactive oxygen species production and CD11b expression. Plasma from these patients with active TTP contained activated phagocytes. Cryoglobulins are another group of blood-borne humoral disease mediators. These are circulating immunoglobulin (Ig) complexes that can deposit on small vessel walls and elicit inflammatory tissue injury. They are currently classified into 3 types: Type I cryoglobulins are monoclonal and found in association with lymphoproliferative diseases, type II cryoglobulins are mixed monoclonal and polyclonal IgG or IgM antibodies and type III are mixed polyclonal IgG antibodies. Of these, type II cryoglobulins are the most common and are usually found in association with viral hepatitis C infection. These mediators can be cleared from the blood compartment with therapeutic plasma exchange (TPE). 14 Specific humoral-cellular immune system interaction causing disease can also be seen, albeit indirectly, in a case report of 2 SLE patients who responded to long-term rituximab (anti-CD20 monoclonal antibody) therapy.15 Accelerated acute humoral rejection (AHR) can occur in renal transplant recipients and is diagnosed by the twin findings of characteristic histopathological changes on renal biopsy and detection of anti-HLA antibodies in the serum. In one series, these patients were treated with TPE and intensification of their immunosuppressive regimen. Such an approach appeared to reverse AHR in their renal allografts and maintain graft function.16

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