Infectious Disease Testing for Blood Transfusions

November 1, 1995

To adress questions relative to the safety of the blood supply ,the National Heart,Lung and Blood Institute, together

To adress questions relative to the safety of the blood supply,the National Heart,Lung and Blood Institute, together with theOffice of Medical Applications of Research of the National Institutesof Health (NIH), convened a Consensus Development Conference onInfectious Disease Testing for Blood Transfusions. The conference, held early in 1995, was cosponsored by the Transfusion MedicineBranch of the NIH Clinical Center and the National Institute ofAllergy and Infectious Diseases.The panel's findings aresummarized below.

The United States has had an organized blood collection systemfor more than 50 years. During this time, various blood testshave been mandated, recommended by regulatory authorities, oradopted voluntarily to make blood transfusions as safe as possible.In the last 10 years alone, blood collection agencies have implementedfive new tests for donated blood.

The continuing contribution that some of these tests make to transfusionsafety has been uncertain. This is particularly true of the hepatitisB core antibody (anti-HBc) test, the serum alanine aminotransferase(ALT) test, and the serological test for syphilis (STS). It hasbeen many years since any transmission of syphilis by blood transfusionhas occurred. In addition, now that a more specific assay forhepatitis C virus (HCV) is available, the continuing need forthe nonspecific tests for post-transfusion non-A, non-B (PT-NANB)hepatitis, with their low positive predictive values and frequentfalse positives, should be reconsidered. False positive valuesnot only contribute to unnecessary deferral of donors and attendantloss of useful blood but also result in emotional, psychological,and financial costs to the donor.

To maintain the safety of blood transfusions, it is also importantto establish mechanisms to cope with the entry into the communityof new infectious diseases that may be blood-borne and, therefore,a hazard of transfusion. Chagas disease is one example.

Background for the Role of ALT and Anti-HBc Testing

The ALT and anti-HBc tests were introduced in 1986-1987 to identifydonors at risk of transmitting PT-NANB hepatitis. Several yearslater, HCV was identified, a test for antibodies to HCV was developed,and HCV was shown to be responsible for at least 90% of the casesof PT-NANB hepatitis. The more sensitive second-generation testfor anti-HCV, combined with improved donor selection, has effectivelyeliminated 85% to 90% of post-transfusion hepatitis due to HCV,and a newer test will likely further improve this level of protection.

The ALT Test

The ALT test might still be useful in reducing the risk of post-transfusionHCV, and non-A, non-B, non-C agents. However, this utility mustbe weighed against the costs and unnecessary donor deferrals itproduces.

Setting criteria for discarding units of donated blood becauseof ALT elevations has been difficult. Modest elevations are commonin apparently healthy blood donors. They may reflect factors notrelated to transfusion-transmitted diseases. Furthermore, valuesof ALT in normal males are higher than those in normal femalesso that a single cutoff value for ALT results in deferral of ahigher proportion of men than women. Finally, different methodsare avail able to measure ALT, and the interpretation of the testis affected by the assay and laboratory used.

Prior to the introduction of anti-HCV testing, surrogate markers,including ALT, may have contributed to a reduction in the overallpost-transfusion hepatitis rate by 30% to 40%. However, data showthat added to anti-HCV testing, retention of the ALT test provideslittle or no additional value. Furthermore, there are no datato indicate that ALT screening is useful in detecting HCV infectionin the "window period" prior to anti-HCV seroconversionor in detecting post-transfusion hepatitis not identified by theanti-HCV test.

Although the direct cost of the test is low, the indirect costsare high: the loss of approximately 200,000 usable units of bloodand the temporary or permanent deferral of about 150,000 donorsannually; the cost to the health care system of evaluating donorswith elevated ALT; and the unwarranted anxiety and stress andrisk of insurance denial for healthy deferred donors.

The panel, therefore, recommends that ALT testing of volunteerblood donors be discontinued. Persons previously deferred foronly an isolated elevation in ALT may now be re-evaluated fordonor eligibility.

The Anti-HBc Test

Although there is no reason to retain the anti-HBc test to preventpost-transfusion HCV, it is recommended that use of the test becontinued. Anti-HBc testing is likely to help reduce the riskof hepatitis B virus (HBV) transmission. Also, because of theoverlapping epidemiology of HBV and HIV, anti-HBc testing servesas a surrogate marker for HIV, primarily for recently infecteddonors who are in the window period of HIV infection prior tothe detectability of HIV antibodies.

Nonetheless, the present anti-HBc test produces many false positiveresults. Its positive predictive value for past or present infectionwith the hepatitis B virus must be improved.

The Syphilis Test

Because the contribution of the serologic test for syphilis inpreventing transfusion-transmitted syphilis is not understood,the panel concludes that use of this test should continue.

Syphilis is one of the oldest recognized infectious risks of bloodtransfusion, and serologic tests for syphilis have been routinelycarried out for more than 50 years. In recent years, transfusion-transmittedsyphilis has become exceptionally rare. Such factors as improveddonor selection processes, the uniform application of testingto all donors, and the use of refrigerated blood for transfusionmay possibly contribute to the absence of reported cases, butfew data specifically address these issues. In addition, it isnot certain that current surveillance would detect a rare caseof transfusion-transmitted syphilis. Antibiotics received by manyhospitalized, transfused patients may partially treat transfusion-transmittedsyphilis, obscuring the diagnosis but not necessarily preventinglong-term complications of the infection.

Current blood storage conditions may not provide an adequate marginof safety against transfusion-transmitted syphilis if donor screeningwere eliminated. Although Treponema pallidum, the organismresponsible for syphilis, may lose its viability after severaldays of refrigerated storage, a few organisms may survive up to96 hours under such storage conditions, and some units of bloodare refrigerated for shorter periods prior to transfusion. Inaddition, platelet concentrates are stored at room temperature.More information is needed to better assess this issue.

The data also do not support the rationale that the serologicaltest for syphilis has value as a surrogate marker for other transfusion-transmitteddiseases, especially HIV.

Management of Potential Threats to Transfusion Safety

Public health surveillance and collaboration between public healthand medical specialists are critical in responding to emerginginfectious disease threats to the blood supply. An organized multidisciplinaryapproach to these threats must be formulated. In particular, theblood transfusion community should arrange for periodic communicationwith the Centers for Disease Control and Prevention to proactivelyreview emerging infectious disease threats to the United States.

In assessing a potential threat to transfusion safety, numerousissues need to be addressed, including its potential transmissibilitythrough blood products; the length of the asymptomatic but infectiousperiod; its severity, incidence, and prevalence in the donor population;and its potential for secondary spread. Once a potential threatto transfusion safety has been identified, the appropriate responseswill balance the magnitude of the problem against the need tomaintain an adequate blood supply and the availability of proceduresto remove the threat from the donor pool. Intervention strategiesmay include redesigning donor recruitment and selection practices;implementing reliable assays or, in their absence, institutingsurrogate testing; and evaluating outcomes to demonstrate thatthe interventions favorably influence component safety. Implementationof a response will also require training personnel, obtainingnew equipment and supplies, preparing procedures and policies,and supervising blood banks closely to ensure that the changesentailed do not produce errors.

Future Research

More research is needed on a wide range of issues, including betterunderstanding of viral and bacterial agents that threaten theblood supply; improved tests for infectious agents and methodsfor eliminating or inactivating them in blood components; implicationsof transfusion-transmitted diseases in neonates; improved understandingof donor motivation and impact of deferral; and development ofartificial blood components.