Membrane plasmapheresis

Equation 8.7 [6] was obtained to correlate the experimental data on membrane plasmapheresis, which is the MF of blood to separate the blood cells from the plasma. The filtrate flux is affected by the blood velocity along the membrane. Since, in plasmapheresis, all of the protein molecules and other solutes will pass into the filtrate, the concentration polarization of protein molecules is inconceivable. In fact, the hydraulic pressure difference in plasmapheresis is smaller than that in the UF of plasma. Thus, the concentration polarization of red blood cells was assumed in deriving Equation 8.7. The shape of the red blood cell is approximately discoid, with a concave area at the central portion, the cells being approximately 1-2.5 pm thick and 7-8.5 pm in diameter. Thus, a value of r (= 0.000257 cm), the radius of the sphere with a volume equal to that of a red blood cell, was used in Equation 8.7. 

In contrast to hemodialysis that uses ultrafiltration membranes, plasma separation (also called plasmapheresis) requires microfiltration membranes with a pore size from 0.2 to 0.6 pm, in order to transmit all proteins and lipids, including LDL cholesterol (2000kDa) and retain completely platelets (2 pm diameter), red blood cells (8 pm diameter) and white blood cells. Thus, membrane plasmapheresis can yield high-quality platelet-free plasma and red cells can be either continuously returned to the donor or saved in another bag for blood transfusion. But it is important, in the case of plasma collection from donors, to minimize the membrane area, in order to reduce the cost of disposable hollow-fiber filters and to avoid the risk of hemolysis (free hemoglobin release) due to RBC damage by contact at the membrane if the pressure difference across the membrane is too high. 

Membrane plasmapheresis is also the first step for treatment of pathological plasma in the case of autoimmune diseases, as the patient retains his own red blood cells while his plasma is replaced by an albumin solution or fresh frozen plasma obtained from donors (plasma exchange therapy). Other more selective plasma purification techniques consist in eliminating pathologic immunoglobulins or LDL cholesterol familial hypercholesterolemia, either by a secondary filtration, chemical adsorption or immunoadsorption. A description of various applications of plasmapheresis can be found in the book edited by Smit Sibinga and Rater [15]. 

Although proven effective in years of clinical practice, membrane plasmapheresis faces competition from improved centrifuges capable of continuous cell separation. Both approaches are likely to continue playing important roles in the area of extracorporeal therapy. 

Jaffrin MY, Ding LH, and Gupta BB, Rationale of filtration enhancement in membrane plasmapheresis by pulsatile blood flow. Life Support Systems, J. Eur. Society Artif. Organs. 1987 5 267-271. 

Heal JM, Bailey G, Helphingstine C, Thiem PA, Leddy JP, Buchholz DH, Nusbacher J. Non-centrifugal plasma collection using cross-flow membrane plasmapheresis. Vox Sang 1983 44(3) 156-66. 

Solomon, B. A. Colton, C. K. Friedman, L. 1. Castino, F. Wiltbank, T. B. Martin, D. M. "Microporous Membrane Filtration for Continuous-Flow Plasmapheresis" In Ultrafiltration Membranes and Applications Vol. 3 of Polymer Science and Technology Cooper, A. R., Ed. Henum Press New York, N.Y., 1980, pp 489-505. Zydney, A. L. "Cross-flow membrane plasmapheresis an analysis of flux and hemolysis PhD Thesis, Massachusetts Institute of Technology, 1985. 

Zydney, A. L., and Colton, C. K. (1982). Continuous flow membrane plasmapheresis Theoretical models for flux and hemolysis predictions. Trans. ASAIO 28, 408. 

The following processes can be described as selective therapeutic plasmapheresis. In a first step, blood is withdrawn from the patient and separated by crossflow filtration in a hollow-fiber membrane cartridge water and some plasma solutes are transferred through a semipermeable membrane under a convection process. The transmembrane pressure applied from blood to filtrate compartment ensures flow and mass transfers. Then, the filtrate perfuses the adsorption columns where toxins are retained and is finally mixed with blood cells and other plasma components before returning to the patient (Figure 18.11). 

In the ASAHI KASEI Medical (Tokyo, Japan) system, the plasmapheresis step is performed by a microporous membrane (Plasmaflo) made of a copolymer of ethylene and vinyl alcohol (PEVA), with a maximum pore size of0.3 pm. The extracted plasma flows through an activated charcoal column Hemosorba and an anion-exchange column (copolymer of styrenedivinyl benzene) Plasorba that binds bilirubin and bile acids [28]. Each column contains 350 mL of adsorbent. 

Plasmapheresis typically employs a membrane module of similar configuration as a high-flux hemodialyzer. Alternatively, a rotating membrane separation element is used in which the tendency of the blood cells to deposit on the membrane surface is counteracted with hydrodynamic lift forces created by the rotation. The membrane element and the associated plasmapheresis circuitry are shown in Fig. 49. Worldwide, about 6 million plasmapheresis procedures are performed annually using this system, making this one of the largest biomedical membrane applications after hemodialysis. 

FIGURE 49 (a) Plasmapheresis system and (b) rotating membrane separation device. (Source Baxter Healthcare Corporation.)... 

In recent years, the fractionation and purification of blood and blood products has emerged as a significant enterprise. Separation of blood and plasma into various cellular and protein fractions has become more of a necessity, given the specific requirements of newer therapies. The first step, the separation of plasma from whole blood (a procedure known as plasmapheresis), is now carried out with a filtration process using synthetic microporous membranes. Chemical engineers pioneered the development of this process and have provided the understanding of what determines its performance in terms of fundamental transport principles. 

Polyolefins. Low density polyethylene and polypropylene have been developed as sheet and hollow fiber mlcroporous membranes, respectively, for use In plasmapheresis. Polyethylene Is made porous by stretching the annealed film ( ), while polypropylene la made porous by coextruding hollow fibers with a leachable plasticizer. Neither membrane has been prepared with small pore dimensions suitable for protein rejection. These polyolefin membranes are characterized by good chemical stability, but require special surfactant treatments to make them wettable. Their low deformation temperature precludes the use of steam sterilization. Because they are extruded without the usual antl-oxldants and stabilizers, their stability la lower than Injection molding formulations of the same polymer. 

The products of the thermal phase-separation membranes form a wide range of styles and configurations. Three pore sizes are currently In commercial production In polypropylene flat stock, rated at 0.45, 0.2, and 0.1 micrometers, having maximum pore sizes of about 1.0, 0.55, and 0.3 micrometers, respectively. The last two are particularly attractive for depyrogenatlon work which has been described by J. R. Robinson, et al W. A similar membrane-manufacturing process Is also used for making hollow fibers and tubes which are especially useful in cross-flow applications (10) and plasmapheresis ( ). 

Plasmapheresis. The separation of plasma from whole blood by continuous membrane filtration represents an improvement over conventional centrifugation techniques in terms of efficiency, safety and cost. In the past, plasmapheresis was carried out with blood donors by collecting their whole blood in plastic bags which were then centrifuged to separate the red cells from the plasma. The supernatant plasma was then decanted and the red cells returned to the donorenabling plasma to be drawn from the same person as frequently as three times per week. Most of this plasma is then processed to yield purified components such as albumin or anti-hemophilic factor (Factor VIII). 

In the late sixties, Blatt and co-workers at Amicon developed a thin-channel cross-flow device for plasmapheresis.30 In this device, red cells and plasma could be readily separated with a 0.6 ju MF membrane at an acceptable flux. As shown in Figure 2.60, the flux increases with the cross flow velocity. However, there is a limiting velocity above which the degree of hemolysis is unacceptable. We discovered that pore sizes above 0.8 ju occasionally leaked nonhemolyzed red cells while pore sizes below 0.2 ju retained some of the higher molecular weight plasma proteins (notably albumin and IgG). Therefore, pore sizes between 0.4 and 0.6 ju were selected with 0.6 ju preferred because of higher plasma fluxes. 

Figure 2.60 Plasmapheresis membrane flux and hemolysis as a function of cross-flow velocity.

Poly(vinyl chloride) (PVC) Plasmapheresis membranes Blood bags... 

Low-density polyethylene and polypropylene in the form of flat-sheet and hollow-fiber membranes are used in plasmapheresis and as oxygenators in the heart-lung machine. Other materials commonly used in plasmapheresis are cellulose acetate, polycarbonate, and polysulfone [129]. 

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