Banking Blood

Advances in positive identification, typing, matching, processing, and storage are constant.

The blood bank is one of many settings in health care where emphasis on high-quality output and efficient operation is accompanied by pressure to contain costs and handle high volumes. There are few settings, though, where the stakes are so high. If lives are to be saved by transfusion, blood donations must be processed in an unending stream; if lives are not to be lost to blood-borne diseases or transfusion reactions, those donations must be perfectly identified, tested, typed, matched, and stored.

Disease Prevention

The possibility of disease transmission through the transfusion of infected blood products drives a large sector within blood-bank activities. This is also an area in which change is relatively constant, in response to technological advances and to newly identified pathogens.

Diseases of concern transmitted through transfusion can be viral, bacterial, or parasitic. Viruses for which all donated blood is screened include HIV-1 and HIV-2, hepatitis types B and C, West Nile virus, and human T-lymphotropic virus (HTLV) types I and II.

Thanks to universal testing, beginning with antibody testing in 1985 and adding nucleic acid amplification in 1999, HIV transmission through blood products is now exceedingly rare. Only one in about 2 million units of blood or blood components is even able to transmit the HIV virus. Research in this area is still active, however, with further improvements expected.

Hepatitis B screening of donated blood became mandatory in 1972 and has been credited with reducing not only transfusion transmission, but the overall incidence of the disease. Blood is tested for the hepatitis B surface antigen and core antibody.

Since 1990, blood has been screened for Hepatitis C using antibody testing. Nucleic acid testing began in 1999. Thanks to screening, the risk of acquiring hepatitis C through transfusion is now less than one in a million, by some estimates. Rates of new infection are decreasing, but nearly one in 50 people may have been infected already. This not only leads to rejection of a considerable fraction of donated blood, but is the precursor of chronic liver disease in about four fifths of cases.

West Nile virus testing has been instituted for all donated blood. After transfusion-related transmission was first reported in 2002, the FDA initially permitted use of a nucleic acid test, but its use was based on a series of regional, seasonal, and donor factors that were considered to increase the likelihood of infection. Testing was also a two-stage process, with pooled samples from six donations first tested together. Individual testing then followed if the pooled sample was positive. Some now advocate a return to this system, since West Nile virus is so rarely detected in blood; the cost per case prevented by today’s individual testing of each donation has been estimated at $1.7 million.¹

Even though the risk of transmission of HTLV-I and HTLV-II is not considered great, it is highly preventable. For this reason, all donated blood is screened for both viruses. HTLV-I is normally found in Caribbean islands and Japan, where it causes diseases of the nervous system or blood in about 5% of cases. HTLV-II is endemic to the western hemisphere; it causes fairly minor decreases in immunity in a small percentage of cases.

Transmission of cytomegalovirus and hepatitis (type A) is also possible via transfusion. For cytomegalovirus, blood is more likely to be tested when it is intended for a patient who is immunocompromised or for an infant of low birth weight; the infection can be serious in these patients, although the virus is already carried by most adults.

Hepatitis A, unlike types B and C, is usually food-borne or water-borne and is acute rather than chronic. While it can be transmitted in blood, this happens only rarely; testing has been introduced, however.

Bacterial screening of blood donations is not required (except for syphilis testing, which is mandatory). Transmission of bacterial disease has been noted roughly two times for every million blood products. Bacterial culture on a massive scale has simply not been seen as practical, especially since many bacterial infections are readily treated using antibiotics. This may change, however, as more strains of drug-resistant superbugs are seen.

A promising product now being developed is BacSTAT from GenPrime, Spokane, Wash. This 20-minute test detects bacterial contamination in platelets collected via apheresis or separated from whole blood. Computerized or visual analysis of results is followed by automated database logging. FDA approval has not yet been granted for BacSTAT.

The parasitic infections most often seen as a concern in blood transfusion are babesiosis, Chagas disease, Lyme disease, and malaria. Better, more practical tests for these disorders are being developed, but no testing is mandatory. For these parasites, donor-deferral questions are used to prevent donation by people who have had the disease or have been exposed though residence, work, or travel.

At least one prion disease can also be transmitted through transfusion. Screening for variant Creutzfeldt-Jakob disease is not being conducted in the United States at present, however; potential donors are deferred using questions about possible exposure to affected beef supplies or diagnosed family members. Research in this area is continuing, so a practical test may become available.

Bio-Rad Laboratories, Hercules, Calif, offers reagents and instrumentation for donation testing, including an automated strip processor. This small-footprint unit uses robotic pipetting for strip assay protocols and can be programmed to handle any Western blot or strip immunoassay procedures. The user only needs to load specimens and select a program; the processor completes the testing without further attention.

The Abbott Prism is a fully automated system that can screen 160 samples or run 800 tests per hour. The test menu includes assays for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), and HBsAg confirmatory.

BBI Diagnostics, a SeraCare Co, W Bridgewater, Mass, makes Accurun 1® multimarker positive and negative controls for donor screening. Designed in formats for use with specific test kits, these controls are stable for 60 days after opening and can prevent repeated runs. The ready-to-use controls contain hepatitis B surface antigen and HIV, hepatitis, HTLV, and cytomegalovirus antibodies.

Infection must be prevented in donor-center staff as well as transfusion recipients. Myco Medical, Cary, NC, makes the Vaku-8 Plus blood-collection set. Because the shielded needle is activated with just one hand, the possibility of needle-stick injury (with the attendant risk of serious infection) is reduced. The needle remains covered at all times, in compliance with standards recently issued by OSHA. According to the CDC, about 75% of the roughly 2,000 needle-stick injuries that occur in the United States each day could be eliminated through the use of safety devices.

Typing and Matching

Because giving a patient an incompatible blood product can lead to results ranging from useless to deadly, careful analysis of every donation’s Rh factor and ABO type has been necessary since the earliest days of transfusion medicine. The need for ABO compatibility has just two exceptions (although transfusions are still matched whenever possible): type O negative blood can be given to any recipient, and the type AB patient can be given any type of blood.

Screening for antibodies to red blood cells is used to prevent bad reactions to transfusion. A newer introduction is molecular testing to detect blood-group polymorphism. Since the variations in red cells detected so far number more than 300, blood typing and matching are areas of ongoing investigation; the finer the donor-recipient compatibility assessment becomes, the less likely transfusion reactions will be.

Ortho-Clinical Diagnostics, Ortho, NJ, offers an innovative system that minimizes handling of specimens and improves efficiency. The ID-Micro Typing System uses gels that incorporate reagents for antibody testing, ABO/Rh typing, compatibility, and antigen typing. Tests use prefilled cards instead of tubes, and the cell-washing process is eliminated. The operator only pipettes, incubates, spins, and reads to complete testing. Cell washing, resuspension, and tube shaking are no longer needed.

The PK7200 microplate agglutination system is available from Olympus America Inc, Diagnostic Systems Group, Center Valley, Pa. This patented technology provides fully automated ABO and Rh testing in addition to antibody detection for syphilis, cytomegalovirus, and other disorders. The system can process 240 samples (or 2,880 tests) per hour and provides positive sample identification using bar codes.

The ABO typing process may be profoundly changed if the promising enzymatic-conversion technology reaches broad application. ZymeQuest Inc, Beverly, Mass, has completed some clinical trials and is now launching others for enzymatic-conversion systems consisting of an automated device, single-use processing kits, enzymes, solutions, and reagents. These will allow regional blood centers to convert red blood cells of types A, B, and AB to the new enzyme-converted O (ECO) type. ECO red cells are being called universal blood, since they could be given to any patient.

Processing and Storage

At all times, blood products require precise, controlled handling. Blood that has become too warm cannot be used, and its loss after so much time and money has been expended in acquiring and testing it is frustrating, both financially and clinically. For this reason, storage and processing technologies were refined long ago, but continue to be the subject of further research and development.

Donated blood is typically separated into red blood cells, platelets, and plasma. Cryoprecipitates and granulocytes may also be separated from the donation at some facilities, with more specialized blood products (such as albumin, immunoglobulins, and concentrated clotting factors) produced commercially.

Each of these blood components has its own storage requirements and shelf life. Red blood cells are refrigerated for 42 days or frozen for as long as a decade. Platelets may be kept for only a week and are shelved at room temperature. Plasma and its cryoprecipitates are kept frozen for up to a year. Granulocytes are used within a day.

QuickThaw plasma-thawing systems from Helmer, Noblesville, Ind, shorten thawing time by using a combination of agitation and a controlled-temperature water bath. They are available in four-bag or eight-bag models with independent controls. Plasma stored at -30°C need not be thawed in advance, so less plasma is wasted when it must be discarded because the blood bank’s prediction of how much would be needed that day is incorrect. Instead, bags of various types and sizes can be thawed as required. The system can also thaw red blood cells and cryoprecipitate and can warm saline.

The Leukotrap A1, recently introduced by Sarstedt Inc, Newton, NC, solves a storage problem: It extends the refrigerated shelf life of whole blood to 42 days by reducing the quantity of white cells and platelets. Normally, this would also make detection of bacterial contamination more difficult, but the Leukotrap A1’s closed blood-collection system draws 15 mL of blood into a separate predonation pouch (for later testing) before it filters the remainder of the donation.

The Drucker Co, Philipsburg, Pa, manufactures the model 755 VES centrifuge. This variable-speed centrifuge permits plasma to be separated in versions that are platelet rich, platelet poor, or platelet free. Its brushless motor is maintenance free and quiet, with centrifugation time and acceleration/deceleration controlled by the user. Speed can be precisely controlled, in 50-rpm increments, from 500 to 4,000 rpm.

Data Innovations, Inc, S Burlington, Vt, received FDA clearance in early 2007 for Instrument Manager. This middleware for blood banks and transfusion centers manages sample processing (preanalytical, analytical, and postanalytical phases), scheduled equipment maintenance, and specimen archives. It works with various vendors’ instruments and blood bank information systems.

Eppendorf North America, Westbury, NY, produces the 5804 and 5810 refrigerated centrifuges. These benchtop units can manage nearly any refrigerated or nonrefrigerated process because they handle test tubes holding 1.5 to 400 mL, tube strips, flasks, filter plates, and various proprietary vessels.

For more information, search for “Blood Bank” in our online archives.

HemoTemp II from Biosynergy Inc, Elk Grove Village, Ill, is a blood-bag temperature monitor that also indicates previous mishandling, in compliance with FDA standards. The indicator has a reversible portion that shows that the current temperature of the blood (not the bag’s surface) is in the acceptable range, but it also has an irreversible portion that shows whether the blood’s temperature reached or exceeded 10°C during its handling.

Fortunately, the importance of a safe and sufficient blood supply means that technological innovation has been constant. The need for blood is understood, so the operating pressures that blood banks face are often accompanied by a willingness to invest in their infrastructure.

Kris Kyes is CLP Technical Editor.

Reference

1. Korves CT, Goldie SJ, Murray MB. Cost-effectiveness of alternative blood-screening strategies for West Nile virus in the United States. PLoS Med. 2006;3:e21.