1. What is the definition of plasmapheresis, and when is it indicated?
The term “apheresis” is Greek for “taking away” and refers to a procedure where the therapeutic removal of macromolecules from the plasma is done for therapeutic reasons. It is indicated for conditions where substances that are not removable with conventional dialysis must be removed from the blood.
2. Describe the techniques for plasma separation during the plasmapheresis procedure.
The two major modalities to separate the plasma from the blood during a plasmapheresis procedure are by centrifugation and membrane filtration. The centrifugation method uses centrifugal force to separate whole blood into plasma and cellular fractions according to their density. The membrane filtration technique is based on a synthetic membrane filter composed of different pore sizes. This filter is similar to a hemodialysis filter and is composed of many hollow fiber tubes with relatively large pore sizes (0.2 to 0.6 μm in diameter) and arranged in parallel.
3. What are the different modalities of the plasmapheresis procedure?
Plasma exchange involves the withdrawal of blood from the circulation and its separation into cellular and plasma fractions by centrifugal separation or perfusion of a synthetic filter. In both methods, the cellular components are returned to the patient and the plasma is removed.
Double filtration plasmapheresis uses two filters with different pore sizes to separate toxic substances from plasma; the second filtration step is to separate useful substances that are returned to the circulation from higher-molecular-weight pathogenic substances that are removed.
Plasma adsorption procedure involves plasma exchange followed by delivery to an adsorption column to which pathogenic substances bind and are then removed from circulation.
4. Define the possible mechanisms of action for plasmapheresis leading to clinical improvement.
There are two general mechanisms that may lead to improvement: (1) removal of pathologic substances or (2) replacement of a missing or abnormal plasma component (such as A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif (ADAMTS-13) in thrombotic thrombocytopenic purpura [TTP]). The pathologic factors that can be removed by plasmapheresis are:
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Auto-antibodies
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Immune complexes
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Cryoglobulins
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Complement products
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Lipoproteins
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Protein-bound toxins
The success of plasmapheresis depends on the rate of production of the abnormal protein or antibody and the efficiency of removal with plasmapheresis. Plasmapheresis is most often utilized with other immunosuppressive strategies to decrease production and reduce inflammation. Other additional benefits may include reversal of impaired splenic function to remove immune complexes and improvement of macrophage and monocyte function.
5. What type of venous access can be used for plasmapheresis?
The clinical scenario, especially the possibility for long-term venous access, and the type of plasmapheresis being used are important factors to consider when deciding on peripheral or central venous access. A peripheral vein allows a maximum flow of up to about 50 to 90 mL/min, so a single venous access is adequate for intermittent centrifugation. Continuous centrifugation techniques require two venous access sites or a central venous catheter. If long-term (>1 to 2 weeks) plasmapheresis is planned, a central venous catheter is required.
6. Which anticoagulants can be used during the plasmapheresis procedure?
The most common anticoagulants used are sodium citrate, unfractionated heparin, and hirudin; nafamostat mesylate, a synthetic serine protease inhibitor, has been commonly used in Japan as an anticoagulant in hemodialysis and plasmapheresis procedures.
There are some reports of plasmapheresis without anticoagulation as a safe and effective procedure in patients at high risk of bleeding.
8. What replacement fluid should be used during the plasmapheresis procedure?
The choice of replacement fluids includes 5% albumin, fresh-frozen plasma (FFP), and crystalloid (e.g., 0.9% saline, Ringer’s lactate) solutions. Albumin is generally combined 1:1 with 0.9% saline, and does not contain calcium, potassium, coagulation factors, or immunoglobulins. FFP contains complement and coagulation factors and is the replacement fluid of choice in patients with TTP, because the infusion of normal plasma may contribute to the replacement of the deficient plasma factor, ADAMTS-13. Plasma may also be preferable in patients at risk of bleeding, or those requiring intensive therapy, because frequent replacements with albumin solution will eventually result in postplasmapheresis coagulopathy and a net loss of immunoglobulins.
9. What are the main complications of plasmapheresis, and how often do they occur?
Plasmapheresis is a relatively (but not entirely) safe procedure. Some registries reported a 4.2% incidence of adverse events, and just 1% of all apheresis procedures had to be interrupted due to an adverse event.
The most common adverse effects reported are paresthesias (0.52%), hypotension (0.5%), urticaria (0.34%), shivering, nausea, and electrolyte disturbances such as hypocalcemia, hypo- or hypernatremia, metabolic alkalosis, hypokalemia, and rarely hypophosphatemia.
Death is rare, occurring in less than 0.1% of all the procedures.
10. Why does citrate cause paresthesias?
Paresthesias are often related to hypocalcemia caused by the citrate infusion as anticoagulant for the extracorporeal system or in the FFP administered as a replacement fluid. Citrate binds to free calcium to form soluble calcium citrate, thereby lowering the free but not the total serum calcium concentration.
11. What are the main clinical indications of plasmapheresis for kidney diseases?
Table 54.1 summarizes the most important clinical indications for kidney diseases by category.
| DISEASE | CATEGORY |
|---|---|
| Anti-GBM disease | I |
| TTP | I |
| Rapidly progressive glomerulonephritis | II |
| Cryoglobulinemia | II |
| Desensitization for kidney transplantation | II |
| Hemolytic uremic syndrome | III |
| Recurrent FSGS | III |
| Systemic lupus erythematosus | III |
| Kidney transplant rejection | IV |
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