Therapeutic plasma exchange (plasmapheresis)

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:

• Auto-antibodies

• Immune complexes

• Cryoglobulins

• Complement products

• Lipoproteins

• 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.

7. How much plasma should I remove, and how is the volume calculated?

Each plasmapheresis session should remove 1 to 1.5 times the plasma volume, and this can be calculated from the following formula: