Plasmafiltration-Adsorption-Dialysis System

Molecules are present in the plasma dissolved in plasmatic water or bound to specific and unspecific proteic carriers. Albumin is the most important proteic carrier in the plasma. Consequently, according to their characteristics of solubility, plasma molecules are present as solutes in the plasmatic water, if water soluble, or bound to carriers, if hydrophobic.

Extracorporeal blood purification techniques such as hemodialysis (HD), hemofiltration (HF), and their combination, hemodiafiltration (HDF) and high-flux dialysis (HFD), are able to remove small molecules (urea and creatinine) and medium-sized molecules, such as the β ₂ -microglobulin, depending on the membrane cutoff value (HD/HDF/HFD) and the volume of reinfusion (HF/HDF). To improve the efficiency and the specificity of molecule removal, convective and/or diffusive techniques may be combined with adsorption. Adsorption allows removal of a wide range of hydrophobic and higher-molecular-weight substances, such as bilirubin, salt acids, cytokines, and myoglobin. The possibility of using specific physical interactions in some resin adsorbers (ion exchange, chemical affinity, van der Waals forces) allows the removal of specific molecule targets, such as cytokines in the patient with sepsis, and bile acids and bilirubin in the patient with acute or chronic liver failure. The adsorption process acts on protein-bound substances (bilirubin, toxins, drugs) and high-molecular-weight toxins present as solutes in the plasma (cytokines and proteins). Convection and diffusion cannot achieve good clinical clearances for high-molecular-weight and hydrophobic molecules owing to their theoretical and practical limitations related to the limited volume of infusion in convection and limited membrane permeability/cutoff in diffusion.

According to all these elements we can identify a central role of plasma as transporter of toxic molecules and its potential role as medium of purification in the extracorporeal blood purification techniques. Through its intrinsic capacity to bind and transport molecules, plasma is the best fluid to perform a purification process. In physiologic and pathologic conditions, molecules are present and transported by the plasma or in plasmatic water or bound to selective/unselective proteic carriers. In this view, it seems useful to combine diffusion, convection, and adsorption in the same technique to improve and obtain the best removal of substances with a broad spectrum of molecular weight.

According to this concept, coupled plasmafiltration-adsorption, an innovative technique, combines plasma adsorption with hemofiltration. In general, the adsorption process is specific to removal cytokines while the convective process is able to reestablish fluid balance, acid-base status, and electrolytes balance. Clinical applications of coupled plasmafiltration-adsorption are sepsis, septic shock, and systemic inflammatory response syndrome (SIRS). Further evolution of a combined system is Molecular Adsorbent Recycling System (MARS; Gambro AG, Lund, Sweden). This technique bases its mechanism on the transporter role of albumin. The closed loop of albumin is used as a medium to transport albumin-bound toxins from whole blood to the sites of purification (cartridges and a dialyzer with a low-permeability-cutoff membrane, where hemofiltration or hemodialysis of albumin is performed). Albumin from donors in the closed loop is regenerated and reused continuously. The clinical application of the MARS is liver failure and hepatorenal syndrome.

In these two techniques, plasma is viewed as a substrate of purification and the albumin, one of its components, is used as a medium of purification (MARS). The combination of more purification principles allows coupled plasmafiltration-adsorption and MARS to improve the clearance and the total removal of the substances implicated in the pathophysiology of the treated disease. This new concept of plasma as medium and substrate of purification at the same time opens a new view of purification for an innovative technique.

The plasmafiltration-adsorption-dialysis (PFAD) system combines a process of high-volume hemofiltration directly on plasma with a process of plasma adsorption on specific adsorber. The regenerated patient's plasma can be reinfused to the patient through the venous line or used as a dialysate in a process of “plasma dialysis” through a membrane with a very high cutoff (HCO).