Plasma donors screening

Human tetanus immunoglobulin is a solution of human immunoglobulin G (IgG) containing a high level of anti-tetanus toxin antibodies. It is prepared from the plasma of screened, human donors immunised against tetanus toxin and is administered by intramuscular injection. The product also contains isotonic sodium chloride, glycine, as a stabiliser, sodium acetate and a small amount of sodium hydroxide used to maintain pH. The product is generally well-tolerated. 

Manufacturing processes have evolved dramatically over the last few years. In the late 1980s, 76 /o of hemophiliacs were HCV positive, ° and between 1979 and 1985, approximately 50 /o of hemophiliacs had acquired HIV from plasma-derived FVIII. Since then, however, most U.S.-licensed plasma derivatives have not transmitted HBV, HCV, or HIV as a result of improvements in donor screening and test methods, and the inclusion of effective upstream virus-reduction and terminal virus-inactivation steps in manufacturing processes. Residual risks of virus transmission from plasma-derived products are now largely associated with non-enveloped viruses. " Thus, the need for additional terminal or upstream virus inactivation/removal steps still exists, but the current challenge is to develop cost effective methods against physico-chemically resistant non-enveloped viruses, such as human parvovirus B19. 

Several different plasma-derived factor VEI products are avaUable (see Table 100 ). These products are derived from the plasma of thousands of donors, and therefore potentially can transmit infection. Donor screening, testing plasma pools for evidence of infection, viral reduction through purification steps, and viral inactivation procedures (e.g., dry heat, pasteurization, and solvent detergent treatment) have all resulted in a safer product. No cases of HIV transmission from factor concentrates have been reported since 1986. However, there have been isolated reports of hepatitis C infection with the use of plasma-derived products. Additionally, there have been outbreaks of hepatitis A viral infections associated with plasma-derived products, likely because solvent detergent treatment does not inactivate this nonenveloped virus. Parvovirus has also been reported to be present in both plasma-derived and recombinant factor VIII products. " Finally, there remains concern about the possibility for infection with as yet unidentified viruses that currently used methods would not inactivate. 

In the past, bleeding episodes have been managed primarily by administration of Factor VIII, sometimes referred to as antihemophilia cofactor. Unfortunately, the concentration of Factor VIII in plasma is quite low (0.3 uM compared with 8,800 uM for fibrinogen), requiring that it be prepared from multiple human donors. Before donor screening and virus inactivation procedures during preparation... 

A competitive ELISA assay for Lp(a) was recently described (Y4) in which the microtiter plate was coated with Lp(a) purified from a pool of donors. The method is simple and easy to perform, with satisfactory analytical parameters. A good stability and a reproducible coating of plates with the large Lp(a) lipoprotein is, however, critical in this type of assay. Wang et al. (W6) described an indirect sandwich assay for the measurement of Lp(a) in plasma and in dried blood spots, which can be applied to screening elevated Lp(a) levels in newborns (V3, V4). 

Human normal immunoglobulin (HNIG) is prepared from screened, human plasma. The antibody fraction is extensively purified and contains immunoglobulins in glycine. Some products may contain sorbitol (refer to product information). HNIG is also used to treat possible infections as it contains antibodies to infectious pathogens against which the donors have been immunised. 

Hepatitis B vims (HBV) Since the detection of HBsAg by Blnmberg and the introdnction of HBsAg screening for donors of blood and plasma in aU developed countries, hepatitis B virns transmission throngh the use of blood and blood prodncts has been effectively prevented. Estimates of the risk of infection, based on the sensitivities of cnrrent tests for HBsAg and for anti-HBcAg, are in the order of 1 in 200000 per nnit (159). 

Transmission of blood-borne viruses is always a concern when blood and blood-derived products are used. The infection of a large number of hemophiliac patients with hepatitis viruses and HIV during the 1980s prompted the development of virucidal methods to inactivate infectious agents. All currently available plasma-derived factor concentrates come from screened donors and undergo viral... 

The implementation of screening for HBV in blood banks since 1970s has greatly reduced the transfusion related infection. Screening of plasma, organ, tissue, and semen donors, virus inactivation of plasma-derived products and maintenance of strict control by the authorities over the precautions that need to be followed in healthcare, dental and cosmetic application centres are mandatory as shown by Schmunis et al. (2001). 

---