Red cells

Cr(VI) readily enters the red cell, where it is reduced to Cr(III). It had at one time been thought that Cr(III) was trapped in the red cell for the remaining life of the cell. However, the half-life of chromium in the red cell is substantially lower than the cell turnover time (Gray and Sterling 1950 Bishop and Surgenor 1964), and chromium has been shown to enter and leave the red cell in studies in which Cr(III) salts were administered intra-tracheally (Edel and Sabbioni 1985). The picture that emerges from these observations is that Cr(VI) rapidly enters the red cell where it is reduced to Cr(III), in which form it is slowly lost from the cell. Cr(III) also diffuses into the red cell, but much more slowly. 

In Table 2, a comparison is made of the red cell plasma chromium ratio in rats given soluble Cr(VI) by three different routes of administration. The fraction of absorbed chromium entering the systemic circulation as Cr(VI) declines in the order intravenous intestinal oral administration. If 

Administration Time post- Red cell plasma Reference 

Intratracheal instillation Intratracheal instillation Intratracheal instillation Intratracheal instillation Intravenous injection Intestinal injection Stomach tube 

Cr(VI) enters the red cell rapidly while Cr(III) does not, the red cell. plasma chromium ratio at any single time point after administration should decline in the same order. As Table 2 shows, this is in fact the case. In addition. Table 2 shows that the red cell plasma chromium ratio increases with time after administration, and suggests that the fraction of an intratracheal dose of Cr(VI) entering the systemic circulation as Cr(VI) may fall between the values for fractional absorption from intravenous and intestinal doses. 

---

Whole blood is seldom used ia modem blood transfusion. Blood is separated into its components. Transfusion therapy optimizes the use of the blood components, using each for a specific need. Red cell concentrates are used for patients needing oxygen transport, platelets are used for hemostasis, and plasma is used as a volume expander or a source of proteins needed for clotting of the blood. 

Each component of blood has a function ia the body. Red cells transport oxygen and carbon dioxide between the lungs and cells ia the tissues. White cells function as defense of the body. Platelets are important for hemostasis, ie, the maintenance of vascular iategrity. Plasma, an aqueous solution containing various proteias and fatty acids, transports cells, food, and hormones throughout the body. Some proteias ia plasma play a role ia clotting, others are messengers between cells. 

Blood can be collected ia the form of whole blood donations. In the United States, one unit, ie, 450 mL, of blood is collected from a healthy volunteer blood donor who is allowed to donate blood once every 10 weeks. A unit of blood is typically separated iato a red cell fraction, ie, red cell concentrate a platelet fraction, ie, random donor platelets (RDP) and plasma. 

Packed red cells are prepared from whole blood. These are collected ia blood coUectioa units having integrally attached transfer packs. The red cells are sedimented by centrifugation, and the plasma and huffy coat are expressed from the bag. Further processiag of the packed red cells may be needed for a number of clinical indications. To reduce the white blood cell (WBC) contamination in a red cell product, two separation techniques are used. 

The red cells also may be filtered to reduce the white cell content. This technique is needed if there is a chance of the patient developing graft versus host disease (GvHD), ie, transfused white cells attack the cells of the patient. 

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

Density Gradient Separation. Based on specific density, each cell in a test tube finds its own position (see Fig. 1), ie, red cells at the bottom, then granulocytes, monocytes, lymphocytes, platelets, and plasma on top. Table 2 Hsts average mass density of the cellular components of blood. The actual numbers vary slightly from person to person. 

Filtration Filtration (qv) is appHed in blood cell separation to remove leukocytes from ted blood cell (RBC) and platelet concentrates. Centtifugational blood cell separators do not reduce white blood cells (WBC) in red cell and platelet products sufficiently to avoid clinical complications such as GvHD and alloimmunization. A post-apheresis filtration step is needed to further reduce the WBC load. Modem filters are capable of a 3-log reduction in white cell contamination of the blood product, eg, apheresis single-donor platelet units having a typical white cell contamination of 5 x 10 white cells in 4 x 10 platelets can be reduced to a 5 x 10 white cell contamination, a sufficiently low number to avoid severe transfusion reactions. 

Barrier Phenomenon. In red cell filtration, the blood first comes into contact with a screen filter. This screen filter, generally a 7—10-) m filter, does not allow micro aggregate debris through. As the blood product passes through the deeper layer of the filter, the barrier phenomenon continues as the fiber density increases. As the path becomes more and more tortuous the cells are more likely to be trapped in the filter. 

Surface Tension. Interfacial surface tension between fluid and filter media is considered to play a role in the adhesion of blood cells to synthetic fibers. Interfacial tension is a result of the interaction between the surface tension of the fluid and the filter media. Direct experimental evidence has shown that varying this interfacial tension influences the adhesion of blood cells to biomaterials. The viscosity of the blood product is important in the shear forces of the fluid to the attached cells viscosity of a red cell concentrate is at least 500 times that of a platelet concentrate. This has a considerable effect on the shear and flow rates through the filter. The surface stickiness plays a role in the critical shear force for detachment of adhered blood cells. 

Each blood component has specific storage requirements in terms of optimal temperature, additives, expiration, and storage containers. Red blood cells (RBC) from whole blood, provided in 200 mL units, have an expiration of 42 days. Fro2en, deglycerolized RBC, in 170 mL containers, and washed red cells, in 200 mL containers, both expire 24 hours after thawing and washing, respectively leukocyte-reduced RBC, in 200 mL containers, are viable for 24 hours. 

Plasma Collection. Human plasma is collected from donors either as a plasma donation, from which the red cells and other cellular components have been removed and returned to the donor by a process known as plasmapheresis, or in the form of a whole blood donation. These are referred to as source plasma and recovered plasma, respectively (Fig. 1). In both instances the donation is collected into a solution of anticoagulant (146) to prevent the donation from clotting and to maintain the stabiUty of the various constituents. Regulations in place to safeguard the donor specify both the frequency of donation and the volume that can be taken on each occasion (147). 

An en2ymatic method for assessing riboflavin deficiency in humans has been developed (74). It is based on the fact that NADPH-dependent glutathione reductase of red cells reflects riboflavin fluctuations. 

Aperture impedance and most other automated counters measure MCV and RBC independently, in contrast to the manual methods where MCV and MCH accuracies depend on hemocytometer red cell count accuracy. 

Aperture impedance measurements of cell volume must take into account the osmolaUty and pH of the medium. A hypotonic medium causes cells to swell a hypertonic medium causes them to shrink. Some manufacturers of aperture impedance counters deHberately provide hypertonic electrolytic media for red blood cell measurements. The shmnken red cells not only become more nearly spherical and thus less affected by orientation, but also less deformable than cells in isotonic media and thus less affected by differences in hemoglobin content. 

The basic single-angle interval light-scattering method caimot accurately measure individual red blood cell or platelet volumes, but it can provide MCV and MPV. Red cells are bi-concave disks, and platelets ate rod to disk shaped Scattering intensities depend on the orientation in the flow cell. 

Artificial blood is hereia defined as consisting of red ceU substitutes. Red ceU substitutes are solutions intended for use in patients whose red cells are either not available or their use is to be avoided for other reasons. Despite enormous effort, more than 100 years of research have not produced a solution that can be used safely in humans. 

In 1983 the move to develop red cell substitutes intensified when it was recognized that the acquired immune deficiency syndrome (AIDS) could be transmitted by the blood-bome human immunodeficiency vims (HIV). Concern for the nation s blood supply followed. Since that time other retrovimses have been identified, efforts to screen blood not only for these agents but also for vimses that cause hepatitis have intensified, the indications for transfusion have been reevaluated, and the use of blood products has become much more efficient. More carehil screening of donors, testing of all donated units, and a general awareness in the donor population have all contributed to a decreased risk from transfusion-contracted AIDS. 

The idea of red cell substitutes is not new. In Ovid s Metamorphosis the witch Medea restored Jason s aged father, Aeson, by slitting his throat to let out old blood, replacing it with a magic brew she had concocted (1). Sir Christopher Wren was one of the first to apply the new knowledge about circulation to blood substitutes. In 1656 he infused ale, wine, scammony, and opium into dogs and from these efforts conceived the ideal of transfusing blood from one animal to another. Lower actually carried out the first transfusion experiments (2). 

Ringer s lactate, in which lactate is added to Ringer s solution, is probably the most popular crystalloid (salt) solution for intravenous use in humans. The lactate is gradually converted to sodium bicarbonate within the body so that an uncompensated alkalosis is prevented (13). These crystalloid solutions cannot support life without red cells saline passes rather quickly into the tissue spaces of various organs (14), especially the Hver (15). 

Blood Plasma and Serum. The terms plasma and semm are frequendy confused. Plasma refers to the Hquid that suspends the red cells within the body. Semm is that Hquid, removed from the body, from which the coagulum has been removed semm contains no coagulation factors and is severely depleted of platelets. 

Cell-Free Hemoglobin. Hemoglobin seems to be the logical choice for a red cell substitute because of its high capacity to carry oxygen (Fig. 

---