Membrane plasmapheresis was introduced in 1978 as a new method for performing therapeutic plasma exchange. Its principal advantages over traditional techniques include speed, ease of performance, and ready adaptability to clinical centers already performing routine extracorporeal therapy. The appearance of a membrane plasmapheresis circuit (vascular access, anticoagulation, connectology) is similar to that of hemodialysis and especially hemofiltration; the operating protocols (treatment time, filtration rates, pressures, pharmacokinetics) are quite different. Particular attention must be paid to avoiding operating conditions that lead to hemolysis.In clinical use membrane plasma separation is as effective as centrifugal plasma exchange in removing plasma proteins. The sieving coefficients for proteins with a molecular weight (MW) ranging from 67,000 (albumin) to 2,400,000 (P-lipoprotein) daltons are unity. An exchange of one patient plasma volume has been shown to cause a 55% reduction of the serum levels of intravascular proteins. There are no significant differences between membrane and centrifugal plasmapheresis in substitution fluid requirements (human albumin or fresh frozen plasma), indications for treatment and complications.The next major advance in plasmapheresis technology will almost certainly be development of a "closed loop" circuit in which filtered plasma is treated to remove the offending moiety and returned to the patient. This would eliminate both the cost and the possible side effects of replacement fluid. Membrane-based systems are already available for removing cryoglobulins or proteins with MW of at least 900,000 daltons.

A 39 year old male patient was treated with daily 5 X 10(6) IU interferon alpha 2b s.c. for 22 months because of advanced carcinoid tumor. Objective response was achieved with greater than 50% reduction of 5-HIAA-excretion. Multiple metastases (liver, lung, bones, thyroid gland) were not progressing in size. An unintentional omission of treatment resulted in a rapid biochemical and morphological tumor progression. Reversibility was achieved with reinstitution of effective interferon therapy. Thus, interferon therapy of advanced carcinoid tumor is able to induce a long-term objective response. It seems to be superior to conventional chemotherapy.

In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ranging in molecular weight from 66,500 daltons (albumin) to 2.4 million (beta-lipoprotein) daltons for three commercially available membrane plasma separation devices: the Plasmaflo 0.1, Plasmaflo 02, and Plasmaflux. A model relating serum level of a protein to pretherapy level, plasma volume, plasma filtration rate, membrane SC, and duration of treatment has been used to investigate the influence of SC on exchange efficiency. Comparison of predicted and clinically obtained reductions in serum solute levels demonstrated the validity of the model. The results of the analysis suggest that all three plasma separators are capable of delivering equally acceptable therapy. The model further demonstrates the decreasing effectiveness, and increased cost in terms of replacement fluid per unit of solute removed, with prolonged treatment times.

Since plasma exchange was introduced in the management of thrombotic thrombocytopenic purpura (TTP) in 1977, patient survival rate has increased from 10 to 80%. However, approximately 50 subsequent case reports in the literature provide no consensus as to the optimal therapy. We review here 4 episodes of TTP in 3 patients. In all cases, treatment was started with intensive FFP plasma exchange combined with administration of antiplatelet agents and corticosteroids. Remission was achieved in 3 out of 4 episodes although all required individualization of the medication regimen. In the remaining patient, cytotoxic therapy (vincristine) and ultimately splenectomy were required to achieve stable remission. The variable clinical response to these therapeutic protocols indicates that TTP may not represent a single homogeneous disease entity but rather may involve various underlying pathologies. We conclude that the most effective present therapy for the management of TTP is daily plasma exchange with fresh frozen plasma infusions combined with antiplatelet agents and steroids. Vincristine and splenectomy should only be employed if this protocol proves ineffective.

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis causes end-stage renal failure in up to a third of cases even with treatment. The disease recurs occasionally after kidney transplantation, but new onset of ANCA-associated vasculitis after transplantation is highly unusual. The use of rituximab or plasmapheresis for de novo disease after transplantation has not previously been reported.Case presentationRoutine post-transplant follow-up for a 66-year old asymptomatic woman revealed a rise in creatinine from 1.8 to 2.6 mg/dl and increased proteinuria. She had received a cadaveric kidney transplant 20 months previously for end-stage autosomal dominant polycystic kidney disease. Renal allograft biopsy unexpectedly demonstrated pauci-immune glomerulonephritis with extracapillary proliferation and interstitial inflammation. Concurrent serum tested strongly positive for ANCA specific to proteinase 3 (PR3), but stored pre- and post-transplantation serum samples tested negative. These findings established a diagnosis of de novo ANCA-associated vasculitis in the renal allograft.We started treatment with high-dose corticosteroid and rituximab. Despite this, serum creatinine continued to rise and glomerulonephritis remained active in a repeat biopsy. Escalation of the treatment with seven sessions of plasmapheresis led to a temporary improvement in creatinine. No further features of vasculitis emerged and PR3-ANCA titres declined. However, multiple infections complicated the recovery period and were associated with progressive loss of renal transplant function. Four months after the index presentation, transplant function became insufficient and dialysis was restarted.ConclusionsDe novo ANCA-associated vasculitis after renal transplantation is exceptionally rare. It poses a significant risk to graft survival even in the context of intensified immunosuppression. Management relies on clinical evidence from populations with native renal function, yet post-transplant patients may be at increased risk of treatment-related adverse events. Precautions against these risks are crucial in the delivery of care.