INTRODUCTION — Traditionally, automated therapeutic plasma exchange (TPE; plasmapheresis) was performed with centrifugation devices used for donor apheresis and cell collections in blood banking. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)
Such devices permit selective cell removal (cytapheresis) but have been associated with posttreatment thrombocytopenia [1,2] and require a dedicated centrifuge device. An increasingly popular and often more efficient alternative is to perform therapeutic plasma exchange by membrane plasma separation (MPS) [3-7].
MPS utilizes a highly permeable membrane and a standard dialysis machine used in its ultrafiltration dialysis-bypass mode (similar to the technique in hemoperfusion). TPE is also possible using specialized dual-purpose NxStage and Prismaflex continuous kidney replacement therapy (CKRT) machines. The NxStage machine employs a cartridge that uses the Plasmaflo OP-05W as the filtration membrane. Prismaflex uses different sized membranes, the HF1000/HF1400 sets (for patient weight greater than 20 to 30 kg).
●(See 'Technical considerations' below.)
●(See "Short daily home hemodialysis: The low dialysate volume approach".)
●(See "Continuous kidney replacement therapy in acute kidney injury", section on 'Equipment'.)
For many years, the most commonly used membrane in the United States was the Plasmaflo AP-05H. This filter has been replaced with a slightly more porous filter, the OP-05W [8]. This filter can be used with most dialysis machines, but the Cobe 3 and Hospal machines are incompatible with the filter's tubing.
The published American experience with MPS has historically been limited even though thousands of treatments were performed in the United States each year [9-12]. In some countries, such as Germany and Japan, 90 percent of plasmapheresis treatments are performed by MPS [6,13]. A series of 998 treatments performed with the NxStage system has been reported [12].
TECHNICAL CONSIDERATIONS — When using the Plasmaflo filter with a standard dialysis machine, transmembrane pressure (TMP) should be modest (recommended TMP <75 mmHg, although the maximum TMP for the OP-05W is listed as 100 mmHg), and blood flow is often 50 to 150 mL/min in order to minimize the tendency for hemolysis and filter clotting [9,14]. Utilizing an anticoagulation-free protocol, one report suggests that those treatments with an average TMP of 54.5 mmHg were more likely to clot than those with an average TMP of 43.7 mmHg [12]. Limiting TMP can be most easily achieved by limiting blood flow and by regulating filtrate output via use of a double roller pump on the filtrate output of the filter. This double pump also regulates the infusion of replacement fluid (such as albumin or fresh frozen plasma), matching its rate of return to the volume of plasma removed, thereby eliminating the risk of hypotension or fluid overload. Unfortunately, these double-roller pumps are difficult to find.
Manufacturers generally recommend a filtration fraction of less than 20 percent. In a report cited above [12], the average filtration fraction was 25 percent with a mean blood flow of 151 mL/min, a mean plasma removal rate (exchange rate) of 31 mL/min, and a mean therapy time of 116 min for a 3635 mL exchange. A more modest experience of 46 treatments with the Prismaflex system has been reported from Korea [15]. These treatments were performed with filtration fractions of 25 to 30 percent, mean treatment time of 130 minutes, mean blood flow of 140 mL/min, and net output of 3206 mL [15].
It is important to appreciate that rapid removal and infusion of protein-containing solutions produce volume changes that are essentially limited to the intravascular compartment. Thus, even small mismatches in net plasma removal rate will have a far greater effect on systemic blood pressure than would be produced by an equivalent water shift during standard hemodialysis [16].
The protein-permeable membranes, such as the Plasmaflo, are very susceptible to concentration polarization, a phenomenon whereby protein layering on the inner surface of the membrane rapidly limits the maximum achievable filtration rate [4]. As a result, inappropriately high TMPs will not yield higher filtration rates but will increase the tendency for the filter to clog (figure 1). Dialysis nursing issues have been the subject of several reviews [14,17,18].
Biocompatibility — Testing of the OP-05W reveals a potential for increased bradykinin levels, and it would be wise to hold angiotensin-converting enzyme (ACE) inhibitors in any patient who is to be treated with this membrane [8].
Anticoagulation — Most therapeutic plasma exchange (TPE) treatments performed with standard centrifugal devices use citrate anticoagulation. Although this technique can be modified for use with a membrane plasma separation (MPS) system [12,19], most MPS treatments are performed with heparin. A bolus of low-dose heparin (eg, 2000 units) can be given at the start of the treatment, unless anticoagulation is contraindicated. The heparin dose should be increased when the hematocrit is reduced. In this setting, there is a relative increase in plasma volume removal (since more of the blood is composed of plasma), leading to enhanced removal of heparin [20].
Initial recommendations had been to start with a heparin dose of 5000 units [9] or 40 to 60 units/kg [14] followed by a maintenance dose of approximately 1000 units per hour. However, a report from Columbia using no anticoagulation documented only one case of filter clotting occurring out of 500 MPS treatments (using Bellco or Edwards-Nikkiso membranes not available in the United States) [21]. In another report of nearly 1000 treatments using the NxStage machine with an anticoagulant-free protocol, only 7 percent of treatments required anticoagulation [12]. Given the low reported incidence of clotting, some clinicians do not routinely use heparin unless clotting occurs.
Vascular access — TPE can be performed with any vascular access compatible with standard hemodialysis since the blood-flow requirements are modest. Standard TPE with centrifugal devices can often be performed with bilateral antecubital vein catheters. This approach is less likely to be successful with an MPS system, in which the blood-flow rate is frequently between 100 and 150 mL/min. However, removal of a larger catheter, such as a large bore, double-lumen catheter, is potentially hazardous after an intensive run of TPE due to a substantial "depletion" coagulopathy [16,22]. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)
SUMMARY AND RECOMMENDATIONS
●Plasmapheresis without centrifugation devices – Therapeutic plasma exchange (TPE; plasmapheresis) may be performed by membrane plasma separation (MPS), which uses a standard dialysis machine in dialysis-bypass mode. TPE is also possible using dual-purpose NxStage and Prismaflex (continuous kidney replacement therapy [CKRT]) machines. (See 'Introduction' above.)
●Technical considerations – The membrane most commonly used for this purpose in the United States is the Plasmaflo filter. The Plasmaflo filter should be operated with a very modest transmembrane pressure (TMP <75 mmHg) and blood flow (50 to 150 mL/min) in order to minimize the tendency to hemolysis and filter clotting. Limiting TMP can be achieved by limiting blood flow. (See 'Technical considerations' above.)
●Anticoagulation – Most TPE treatments performed with standard centrifugal devices use citrate anticoagulation. Although this technique can be modified for use with an MPS system, most MPS treatments are performed with heparin. A bolus of low-dose heparin (eg, 2000 units) can be given at the start of the treatment, unless anticoagulation is contraindicated. However, given the low reported incidence of clotting, some clinicians do not routinely use heparin unless clotting occurs. (See 'Anticoagulation' above.)
●Vascular access – TPE can be performed with any vascular access compatible with standard hemodialysis. Removal of a larger catheter, such as a large bore, double-lumen catheter, is potentially hazardous after an intensive run of TPE due to a substantial "depletion" coagulopathy. (See 'Vascular access' above.)
