• Compartir
  • Enviar por correo
  • Insertar
  • Me gusta
  • Guardar
  • Contenido privado
Taller Banco de Sangre - Complicaciones infecciosas

Taller Banco de Sangre - Complicaciones infecciosas


  • 1,957 reproducciones




reproducciones totales
reproducciones en SlideShare
reproducciones incrustadas


Me gusta

0 insertados 0

No embeds


Detalles de carga

Uploaded via as Adobe PDF

Derechos de uso

© Todos los derechos reservados

Report content

Marcada como inapropiada Marcar como inapropiada
Marcar como inapropiada

Seleccione la razón para marcar esta presentación como inapropiada.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Tu mensaje aparecerá aquí
Publicar comentario
Edite su comentario

    Taller Banco de Sangre - Complicaciones infecciosas Taller Banco de Sangre - Complicaciones infecciosas Document Transcript

    • 26 Infectious Complications of Blood Transfusion 26 P reventing transmis-sion of infectious diseases through blood rus (EBV), and others. Infectious agents that pose a serious threat to transfusiontransfusion presents one of the greatest recipients are those that persist in thechallenges of transfusion medicine. The circulation of asymptomatic individualsemergence of acquired immunodefi- who are healthy enough to be blood do-ciency syndrome (AIDS) in the 1980’s nors.heightened public awareness of the com- Several viruses, such as HAV, circu-plications of transfusion, and for the late only transiently during the initialfirst time, many patients and clinicians acute phase of infection, when the indi-became concerned with the specifics of vidual is clinically ill and not a candidateblood collection and testing. Although for donation, and generally they are notthe risk is lower than ever before, the a serious threat to transfusion recipi-risk of transmitting viral, bacterial, and ents. However, viremia may be presentparasitic diseases through transfusion for up to 28 days before symptoms de-persists, along with the potential for velop; blood donated during this viremicnovel infectious agents. Several recent phase could be infective, but only a fewtextbooks and reviews address these is- documented transfusion-transmitted 1,2sues. cases have been reported. 3 Although HDV, formerly called the delta agent, can cause infection after transfusion or other parenteral trans-Hepatitis mission, it causes disease only whenHepatitis is inflammation of the liver there is concomitant or prior HBV infec-that can be caused by many different tion.4 HEV causes an epidemic enterictoxic and infectious agents, including form of hepatitis, but there have been nohepatitis A, B, C, D, and E viruses (HAV, reports of spread by transfusion. TheHBV, HCV, HDV, HEV), as well as cy- agent of a transfusion-associated andtomegalovirus (CMV), Epstein-Barr vi- community-acquired non-A,non-B,non- 563 Copyright © 2002 by the AABB. All rights reserved.
    • 564 AABB Technical ManualC hepatitis has been cloned and shown to Chronic Carriers of HCVbe a novel flavivirus distinct from HCV.5 Most persons infected with HCV become chronic carriers, with 70-80% havingClinical Manifestations of Hepatitis persistent infection as demonstrated by HCV RNA in serum and liver; at leastMost individuals who acquire HBV or 50% of these have biochemical or his-HCV infection have a subclinical infec- tologic evidence of chronic liver dis-tion without obvious symptoms or 9 ease. Despite this chronic inflammatory 3,4physical evidence of disease. Some de- process, most HCV-infected individualsvelop overt hepatitis with jaundice, nau- remain asymptomatic. Whereas thesea, vomiting, abdominal discomfort, fa- acute infection with HCV is clinicallytigue, dark urine, and elevation of liver benign, approximately 10% of patientsenzymes. Signs and symptoms usually with chronic HCV infection develop cir-resolve spontaneously. Hepatitis C tends rhosis and/or hepatocellular carcinomato be milder than hepatitis B, but in decades after the acute event.either hepatitis B or C, the clinicalcourse of infection may be complicatedby fulminant hepatitis, relapsing or Posttransfusion Hepatitischronic hepatitis, or long-term progres- The risk of posttransfusion HBV hassion through cirrhosis to hepatocellular fallen dramatically, from an estimated 1carcinoma. Hepatitis A tends to be quite in 10 a decade ago to an estimated 1 inmild, clinically, and virtually never pro- 50,000 transfused recipients or about 1gresses to chronic hepatitis or a chronic 9,10 per 200,000 transfused units. HCV an- 6,7carrier state. tibody testing combined with stringent selection measures for donors have con-Chronic Carriers of HBV tributed to this remarkable decline (Fig 11 26-1). After implementation of the firstAfter initial HBV or HCV infection, some generation of anti-HCV tests, the riskpatients fail to clear infectious material was estimated at one case per 3300 units 12from the bloodstream and become transfused. With presently available,chronic carriers for years or even for life. more sensitive tests, the risk is probablyHBV carriers produce, in addition to the lower, but is difficult to determine be-infectious viral particle, large amounts cause posttransfusion hepatitis is oftenof noninfectious material detected by asymptomatic.the assay for hepatitis B surface antigen(HBsAg). About 5% of those infectedwith HBV as adults become HBsAg carri- Hepatitis A Virusers; the vast majority recover and de- Because HAV infection does not cause avelop protective antibody against HBsAg chronic carrier state, transmission by(anti-HBs). The risk of becoming an blood transfusion requires the collec-HBsAg carrier is strongly age-depend- tion of blood from a viremic donor, usu-ent; 90% or more of infants infected per- ally late in the incubation phase justinatally become carriers, and many pro- before signs or symptoms occur. Severalgress to cirrhosis and cancer. There are of the rare transfusion-transmitted HAVapproximately 300 million HBsAg carri- infections occurred in infants, making 8ers worldwide with a prevalence of up to secondary transmission by fecal-oral10% in some Asian countries, 0.1-0.5% spread more frequent than would be ex-in the United States, and 0.02-0.04% in pected from adults who sustain the usu- 8US blood donors. ally mild disease. In 1991 and 1992, an Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 565Figure 26-1. The decline in posttransfusion HCV infection (reprinted with permission fromBusch MP, et al11).outbreak of hepatitis A infection oc- Figure 26-2 illustrates the sequencecurred in several European hemophilia of test results typical of individuals withcenters, associated with Factor VIII con- acute HBV infection that completely re-centrate manufactured in two plants by solves. The period between exposure toa single manufacturer, but such an out- HBV and emergence of circulatingbreak has not been reported in the 13 HBsAg is usually about 2-6 weeks. 3United States. HAV, which lacks a lipid HBsAg is the first serologic marker toenvelope, is not inactivated by sol- appear, but tests on symptomatic pa-vent/detergent treatment. tients usually show simultaneous pres- ence of antibody to hepatitis B virus core protein (anti-HBc) and either of two ad- ditional HBV markers, HBeAg or its an-Serologic Markers tibody (anti-HBe). Blood from individu-Laboratory tests can identify markers of als with circulating HBsAg can infectprevious exposure and probable current others. An asymptomatic HBsAg-posi-infectivity for HBV and HCV. Table 26-1 tive individual may either be a chroniclists the serologic tests commonly used HBV carrier or be in the early phase ofin the diagnosis of hepatitis and includes acute HBV infection. Current tests canterms and abbreviations in current use. detect as little as 100-200 pg/mL, 3 but Copyright © 2002 by the AABB. All rights reserved.
    • Table 26-1. Serologic Tests in the Diagnosis of Viral Hepatitis 566 Agent Test Reactivity Interpretation B Virus HBsAg Anti-HBc Anti-HBs HBeAg Anti-HBe Total IgM + +/– +/– – +/– – Early acute HBV or chronic carrier + + + – + – Acute HBV – + + – +/– +/– Convalescent HBV or possible early chronic carrier + + – – +/– +/– Chronic carrier* AABB Technical Manual – + – + – +/– Recovered HBV – – – + – – Vaccinated or recovered HBV – + – – – – Recovered HBV? Window? False positive? D Virus HBsAg Anti-HBc Anti-HBs Anti-delta + + – + Acute HDV or chronic HDV – + + + Recovered HDVCopyright © 2002 by the AABB. All rights reserved. A Virus Anti-HAV Total IgM + + Acute HAV + – Recovered HAV or vaccinated
    • C Virus Anti-HCV Recombinant Antigens (Screen) C-100-3 5-1-1 C22-3 C33-c + Not Available Possible acute or chronic HCV + + + + +/– Probable chronic HCV + + + – – Probable false positive + – – + + Probable chronic HCV + – – + – False positive or acute or chronic HCV + – – – + False positive or acute or chronic HCV + – – – – False positive E Virus Anti-HEV Total IgM + + Acute HEV + – Recovered HEV Abbreviations used include: HBsAg (hepatitis B surface antigen), anti-HBc (antibody to hepatitis B core antigen), anti-HBs (antibody to HBsAg), HBeAg (hepatitis B e antigen), anti-HBe (antibody to HBeAg), anti-delta (antibody to delta antigen), anti-HAV (antibody to hepatitis ACopyright © 2002 by the AABB. All rights reserved. virus), anti-HCV (antibody to hepatitis C virus) and anti-HEV (antibody to hepatitis E virus). *Those with HBeAg are more infectious and likely to transmit vertically. Chapter 26: Infectious Complications of Blood Transfusion 567
    • 568 AABB Technical ManualFigure 26-2. Serologic markers in hepatitis B virus infection that resolved without complica-tions. In the acute phase, markers often appear before onset of liver function (LFT) abnormali-ties and symptoms (SYMP). Numerous markers persist after recovery.antigen is usually present in great excess and Drug Administration (FDA) for fur-relative to the concentration of infec- ther differentiation of repeatedly reac-tious virus. tive EIA results. An individual who is Anti-HCV has been detected in 80- positive by RIBA is considered to have90% of samples from patients initially true anti-HCV antibody; in these cases,diagnosed as having non-A,non-B HCV nucleic acid is almost always de-(NANB) hepatitis, either transfusion- or tectable by polymerase chain reactioncommunity-acquired.14 Tests for anti- (PCR) and infectivity rates of 80-90%bodies to HCV are enzyme immunoas- have been reported.16,17 Regardless ofsays (EIA) using recombinant antigens RIBA results, a donation with a repeat-of HCV coated on a solid phase as the edly reactive EIA result cannot be usedcapture reagent. Figure 26-3 shows the for transfusion.proposed structure of the genome ofHCV and the specific gene products in-corporated in test kits for anti-HCV. Surrogate Markers The clinical significance of a positive Before HCV was identified and anti-HCVscreening test for anti-HCV in healthy testing feasible, several tests on donorblood donors is unclear without supple- blood were introduced to reduce NANBmental testing. Between 0.4 and 1.0% of hepatitis following transfusion. In theUS blood donors have repeatedly reac- absence of specific tests for the NANBtive EIA results.3 Some of these individu- agent, the AABB in 1987 mandated test-als have asymptomatic chronic HCV in- ing for alanine aminotransferase (ALT)fection, and their blood is potentially and anti-HBc, as surrogates for the di- 18infective; others may have false-positive rect detection of the agent. Posttrans-results. A recombinant immunoblot as- fusion hepatitis declined thereafter, butsay (RIBA) has been licensed by the Food the impact of surrogate testing on the Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 569Figure 26-3. Proposed HCV genome and recombinant proteins used in testing for anti-HCV.The second-generation test for anti-HCV detects antibody to c200 (including c33c and c100-3)and c22-3. Supplementary tests detect antibody to specific gene products including c22-3,c33c, c100-3, and 5-1-1.15safety of transfusion has been difficult to anti-HBc to have a continued role inevaluate. More stringent criteria for donor preventing HBV transmission. 21,22 AABBselection had recently been introduced in Standards no longer requires ALT test-response to reports of AIDS in transfusion ing and allows reentry of otherwise suit-recipients. Because some of the popula- able donors who had previously been ex-tions at risk for HIV infection also have cluded solely because of elevated ALT. 22high risk for NANB and HBV infection, thechanges in donor eligibility criteria mayhave affected hepatitis transmission. One study during this period observed Human Immunodeficiencya drop in the incidence of hepatitis in thegeneral population, but there were Virusmuch greater drops in posttransfusion Human immunodeficiency virus, type 1HBV and NANB infection than could be (HIV-1) is the etiologic agent of AIDS.explained simply by the change in back- This syndrome was recognized in 1981,ground rates.19 well before the discovery of the causative Current very sensitive tests for anti- virus. Wider implications of the immuneHCV have deprived surrogate tests of disorder were noted when, in 1982, AIDS 23their role in preventing NANB hepati- was reported in three hemophiliacs andtis. 2 0 A National Institutes of Health in a 17-month-old infant whose multiple(NIH) consensus conference held in transfusions at birth included a unit of1995 recommended that screening of platelets from a donor who subsequently 24volunteer blood donors for ALT be dis- developed AIDS. Within a few years,continued but considered testing for over 50% of hemophiliacs receiving clot- Copyright © 2002 by the AABB. All rights reserved.
    • 570 AABB Technical Manualting factor concentrates developed HIV- few weeks after infection, viremia is first 251 infection. detectable in the plasma. During this viremia, 20-50% of acutely infected per- sons have a mononucleosis-like illness,Properties of the Virus with fever, enlarged lymph nodes, sore 26 27Montagnier and Gallo identified HIV throat, rash, joint and muscle pain withas the viral cause of AIDS. HIV is a cy- or without headache, diarrhea, and vom-topathic retrovirus initially called lym- iting.28phadenopathy-associated virus (LAV) or As HIV-1 antibodies appear and symp-human T-cell lymphotropic virus, type toms resolve, viremia diminishes, leav-III (HTLV-III). It is a 100 nm RNA virus ing some infected peripheral blood Tthat preferentially infects CD4-positive lymphocytes. The virus can be transmit-T lymphocytes (helper cells) in lymph ted by blood or genital secretions duringnodes and other lymphoid tissue, but this phase. 28 Tissue monocytes may servealso infects other cells that express as a latent infected reservoir in nonlym- 28CD4. The core of the retrovirus con- phoid tissues.tains an enzyme, reverse transcriptase, Persistent infection of CD4+ T lym-that enables the virus to copy its single- phocytes with an asymptomatic clinicalstranded RNA into DNA; the viral DNA is status has been observed to last a medianthen integrated into host DNA. Viral rep- of 10 to 12 years.29 (See Fig 26-4.) Afterlication and release are complex proc- years of asymptomatic standoff, bothesses requiring the products of several viremia and the percentage of infected Tviral genes. lymphocytes increase. Loss of the im- HIV virus then replicates and dissemi- mune functions served by helper T cellsnates initially as cell-free virions, and a impairs immune reactivity, and thereFigure 26-4. Natural history of HIV infection and its serologic markers. Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 571 32may be inappropriate immune activation lence had stabilized in most US cities.and cytokine secretion. Eventually there Heterosexual transmission, especiallyis a sharp decline in the number of viable male-to-female, and mother-to-childCD4+ T lymphocytes and profound im- transmission have attracted increasing 28munosuppression. concern.Definition of AIDS Human Immunodeficiency Virus, Type 2As the number of CD4+ cells decreases, First discovered in 1985, human immu-the risk and severity of opportunistic ill- nodeficiency virus, type 2 (HIV-2) causesnesses increase. Enumeration of CD4+ endemic infection in many countries incells is used to guide clinical and thera- West Africa but is seldom seen else-peutic management of HIV-infected per- 33 where. The first case of HIV-2 infectionsons. The AIDS classification system de- in the United States was reported invised by the CDC evaluates the number March 1988 in a young West African whoof CD4+ T cells (≥500/µL, 200-499/µL, had recently immigrated to the Unitedor ≤ 200/µL), the presence or absence of States. The spectrum of disease attribut-systemic symptoms, and existence of any able to HIV-2 is similar to that caused byof the 26 clinical conditions considered HIV-1; however, there appears to be a 30to be AIDS-defining illnesses. Among longer incubation period and lower inci-these conditions are Kaposi’s sarcoma; 34 dence of progression to AIDS. HIV-2 iscytomegalovirus retinitis, or infection of spread both sexually and vertically, butsites other than liver, spleen, or lymph transmission is less efficient than fornodes; toxoplasmosis of the brain; pri- HIV-1. Tests in the United States on in-mary lymphoma of the brain; candidiasis jecting drug users, persons with sexuallyof the esophagus, bronchi, trachea or transmitted diseases, newborn infants,lungs; tuberculosis at any site or infec- and homosexual men confirm the verytion with atypical mycobacteria; and limited prevalence and transmission ofchronic intestinal cryptosporidiosis. the agent. 33,34Pneumocystis carinii pneumonia (PCP)is the most common serious opportunis-tic infection. Transfusion Considerations Transfusion-Transmitted HIV-1Risk Factors for HIV Infection All blood components can transmit HIV-Infected individuals are at risk of infect- 1. By the mid-1990’s over 7500 cases ofing others through sexual contact, child- AIDS had been reported in which trans-birth, breast-feeding, and parenteral ex- fusion or a tissue transplant was the onlyposure to blood. Those identified early as identifiable risk. In addition, approxi-being at highest risk were men who had mately 4200 cases occurred in hemo-sex with other men; needle-sharing drug philiacs who received clotting factorusers; hemophiliacs who received clot- concentrates. Transfusion-associatedting factor concentrates; and, to a lesser AIDS, including cases in hemophiliacs,extent, recipients of blood transfusions. constituted about 2.3% of all AIDS 35By 1989 the rate of infections spread cases. All but about 30 reflected trans-within each group was no longer in- fusions given before routine anti-HIVcreasing exponentially and appeared to testing began, in 1985. The interval be-have reached a plateau in the popula- tween transfusion and diagnosis of AIDS 31 35tions most at risk, and HIV seropreva- was a median of 58 months. Copyright © 2002 by the AABB. All rights reserved.
    • 572 AABB Technical Manual Most but not all recipients of HIV-in- Risk of Posttransfusion HIVfected blood transfusions become in-fected. In one large study, HIV infection Since 1985, the cases of HIV transmissiondeveloped in 89.5% of recipients who by transfusion have resulted from dona-received blood from anti-HIV positive tion by a recently infected individual notdonors. 36 With the exception of coagula- yet reactive on an anti-HIV screening test.tion factor concentrates, plasma deriva- With screening tests available before 1992,tives such as albumin and immune the seronegative interval (“window pe-globulins have not been reported to riod”) averaged 45 days. Presently avail-transmit HIV infection. able, more sensitive screening tests now have closed the seronegative window to 39 approximately 22-25 days. Since implementing donor testing toTransfusion-Transmitted HIV-2 prevent posttransfusion HIV infection in 1985, the risk of transfusion-transmittedThere have been two brief reports of pos- HIV has declined remarkably40 (Fig 26-5).sible HIV-2 transmission through blood In the San Francisco area, the peak risk ofcomponent use, both in Europe. Two transmitting HIV between 1978 and 1985,women were infected by whole blood ob- was almost 1% per unit. Donor screeningtained from a donor who developed AIDS policies in 1983 and 1984 lowered theat least 16 years after becoming infected transmission risk substantially and the in-with HIV-2; both women were asympto- troduction of testing for anti-HIV acceler- 37matic 14 years after transfusion. Two ated the rate of decline. Since 1985, thehemophiliac patients who received clot- sensitivity of antibody detection has con- 38ting factors were also infected. tinued to improve.Figure 26-5. Projected risk of HIV-1 infection per unit of blood transfused between January1978 and December 1984 (reprinted with permission from Busch MP, et al11). Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 573 Risk from seronegative donations will ity, calculated as True Positive/(Truevary in proportion to the incidence of HIV Positive + False Negative) × 100. Speci-infection in the donor community. Recent ficity, calculated as True Negative/(Trueoverall estimates of posttransfusion HIV Negative + False Positive) × 100, is muchrisk in the United States approximate one less significant. Current tests for anti-per 420,000 transfusions.2,41 HIV have specificity in excess of 99.5%. Specificity indicates the accuracy of findings in tested persons who do notHIV Testing of Blood Donors have the disease. If the disease has lowAABB Standards and the FDA require prevalence in the test population, thethat all units of blood and components likelihood is high that most positivebe nonreactive for anti-HIV-1 and HIV-2 screening test results will be false posi-and for HIV-1 antigen (HIV-1-Ag) before tive.they are issued for transfusion. EIA-detectable antibody develops days to a week after the onset of symp-Screening Tests for Antibodies to toms,42 about 6 days after the onset of HIV p24 antigenemia.42,43 A few daysHIV-1/2 later HIV-1 antibodies become detect-Figure 26-6 shows the sequence of able by the HIV-1 Western immunoblot.screening and confirmatory testing foranti-HIV-1/2. EIA is the test of choice of Confirmatory Testing for Antibodies tomost donor centers for donor screening. Because the consequence of missing HIV-1/2even one true positive is great, screening The most commonly used confirmatorytests are designed to have high sensitiv- test for antibodies to HIV-1/2 is theFigure 26-6. Decision tree for anti-HIV-1/HIV-2 testing of blood donors. Copyright © 2002 by the AABB. All rights reserved.
    • 574 AABB Technical ManualWestern blot (WB). With this technique, to obtain counseling and medical follow-protein components (in this instance, up. EIA anti-HIV-1/2 results not con-antigenic viral material) are separated firmed as a true positive may have tech-into bands according to molecular nical or biologic causes. Many bloodweight and transferred to a nitrocellu- donors with repeat-reactive EIA anti-lose membrane. Antibody(ies) in the test HIV-1/2 screening tests are negative onserum react with individual bands, de- WB confirmatory testing; these donorspending on the specificity(ies) present. usually have nonreactive EIA results onMost persons infected with HIV, whether a subsequent donation. Therefore, theasymptomatic or exhibiting AIDS, show FDA has approved reentry protocols tomultiple bands, representing antibodies qualify donors as suitable for subsequentto essentially all of the various gene donations (see Table 26-2). Reentry re-products. A fully reactive test serum quires retesting at least 6 months later,should react with the p17, p24, p26, and to detect delayed seroconversion; thep55 gag proteins; the p31, p56, and p66 use of EIA tests based on whole-viruspol proteins; and the gp41, gp120, and lysate; and use of either a licensed West-gp160 env glycoproteins. ern blot to ensure appropriate sensitivity A sample is defined as anti-HIV-posi- of the methods or an FDA-licensed im- 47,48tive if at least two of the following bands munofluorescence assay. The laterare present: p24, gp41, or gp120/160.44 sample must also be nonreactive in anNegative WB results have no bands pre- EIA test for anti-HIV-2, if standard test-sent. WB results classed as indetermi- ing does not include HIV-2, and a test fornate have some bands present but not HIV-1-Ag.those in the criterion for HIV positivity.Individuals infected with HIV may haveindeterminate WB patterns when in- Direct Detection of Virusitially tested, but develop additional AABB Standards and the FDA requirebands within 6 months. Healthy indi- that all units of blood and blood compo-viduals with an initial indeterminate WB n e n t s b e n o n r e a c t i ve f o r a n F D A -continue to have indeterminate results licensed test for HIV-1-Ag. HIV-1-Ag mayon repeat samples, and are negative on appear in blood early in the course ofclinical examination and additional infection, somewhat before antibody ist ests, including viral cultures and detectable. Transmission of HIV hasPCR.45,46 Healthy donors who continue been reported from transfusion of se-to show the same indeterminate pattern ronegative blood later shown to containfor more than 6 months can be reassured p24 antigen; the donors subsequently se- 29that they are unlikely to have HIV infec- roconverted. Mathematical models,tion, but they are not eligible to donate constructed with findings from geo-blood. graphic areas with very high incidence of new HIV infections, suggest that routine antigen testing would detect one anti-Confirmation and Reentry, Anti-HIV-1/2 gen-positive/antibody-negative dona- 41,49When the EIA screening test for anti- tion in every 1.6 million tested.HIV-1 is repeatedly reactive, a confirma-tory test will determine whether the do- Confirmatory Testing for HIV-1 Antigennor is a true positive and will aid incounseling the individual. Persons who When the EIA screening test for HIV-1-have true positive test results should be Ag is repeatedly reactive, a confirmatorynotified confidentially and encouraged test will aid in counseling the donor. The Copyright © 2002 by the AABB. All rights reserved.
    • Table 26-2. Reentry of Donors With Repeatedly Reactive Screening Tests Tests Anti-HIV-1 or -HIV-1/2 Anti-HIV-2 HIV-1-Ag HBsAg Initial sample Not eligible for reentry Licensed Western blot Different HIV-2 EIA RR Confirmed by Confirmed by positive or indeterminate neutralization neutralization or or IFA reactive anti-HBc RR Evaluate for reentry Licensed Western blot or Different HIV-2-EIA NR and Not confirmed by Not confirmed HBsAg IFA NR licensed Western blot or neutralization specific and anti-HBc IFA NR NR Follow-up sample (drawn 6 months later) (drawn 6 months later) (drawn 8 weeks later) (drawn 8 weeks later) Not eligible for reentry EIA RR or Western blot RR HIV-1 or different HIV-1-Ag RR, HBsAg RR or anti-HBc positive or indeterminate HIV-2 EIA RR or a neutralization RR or IFA reactive licensed Western blot or confirmed IFA reactive or indeterminate Eligible for reentry Original EIA method NR Screening test and a HIV-1-Ag and HBsAg NR and and whole virus lysate different HIV-2 EIA NR anti-HIV-1/2 NR or anti-HBc NRCopyright © 2002 by the AABB. All rights reserved. anti-HIV-1 EIA NR and and licensed Western Hiv-1-Ag RR, not licensed Western blot or blot or IFA NR confirmed IFA NR (temporary deferral for 8 weeks) NR = nonreactive RR = repeatedly reactive Chapter 26: Infectious Complications of Blood Transfusion 575
    • 576 AABB Technical Manual HIV RNA (RT-PCR) HIV Antibody in plasma and platelets HIV DNA (PCR) in PBMC Infectious Exposure HIV p24 Ag -10 0 10 20 30 40 50 60 70 Days pre/post-InfectiousnessFigure 26-7. Virologic events during primary HIV infection. After initial infection and propa-gation of HIV in lymph nodes, a blood donor becomes infectious (defined as day 0) with HIVRNA being detectable in plasma on days 14-15, HIV DNA detectable in leukocytes at day 17-20,and HIV antibodies detectable between days 20 and 25 (reproduced with permission fromBusch MP42).confirmatory test is an EIA neutraliza- ten, signed, and dated request from thetion test. Donors whose serum shows patient’s physician authorizing thisneutralization with this test are consid- shipment, 2) there is a written statementered confirmed positive for HIV-1-Ag from the transfusion service indicatingand should be permanently deferred. Do- willingness to receive this product, andnors whose serum shows no neutraliza- 3) the transfusion service takes respon-tion with this test are currently consid- sibility for ensuring that there is docu-ered not confirmed, and must be mented verification of the accurate iden-reported as HIV-1-Ag indeterminate; tity of the transfusion recipient. Thesethey should be temporarily deferred units must be labeled “BIOHAZARD” and 50from donation for a minimum of 8 “FOR AUTOLOGOUS USE ONLY.”weeks. See below for the reentry proto- In the absence of a repeatedly reactivecol for HIV-1-Ag. Units from repeatedly anti-HIV-1/2 test, a repeatedly reactivereactive donations must be quarantined, EIA HIV-1-Ag screening test should beand destroyed or not used for transfu- further tested with a neutralization testsion or for further manufacturing into for the purposes of counseling. Personsinjectable products. Units from repeat- with a confirmed HIV-1-Ag test shouldedly reactive autologous donations be notified confidentially and encour-should be withheld from transfusion. aged to obtain counseling and medicalHowever, these units may be supplied for follow-up. These persons should be in-autologous use only if: 1) there is a writ- formed that they are probably infected Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 577w ith H IV. They should be notified HIV-1 Seroprevalence in Blood Donorspromptly because they often have highviral titers and may be at high risk for When donor screening for anti-HIV wastransmitting HIV infection. Counseling first introduced in 1985, from 0.1-0.8%for persons with repeatedly reactive EIA of sera gave repeatedly reactive EIA re-and HIV antigen tests should incorpo- sults, depending on the location of therate arrangements for follow-up anti- donor center and the reagents used; onlybody testing.51 0.04% of donors were confirmed as posi- Persons testing repeatedly reactive tive by Western blot. During the secondfor HIV-1-Ag, but not confirmed by neu- and third years of testing most centerstralization probably have a low preva- reported repeat-reactive rates aroundlence of HIV infection. These people 0.1-0.2% and confirmed positive rates ofshould be requested to return for repeat 0.01-0.04%. By 1992 the proportion oftesting. If the donor is retested and confirmed positives among donors hadfound negative for the screening test for declined to 0.005-0.01% with an overall 12HIV-1-Ag, that donor could be consid- rate of 0.006%. More sensitive testsered for reentry. Donors can be reen- using PCR technology may detect addi-tered if they have been retested at least 8 tional potentially infectious donors (Figweeks after their repeatedly reactive do- 26-7). Following expected advances innation, and are found to be nonreactive automation and reliability, this technol-for the HIV-1-Ag screening test and for ogy may assume a role in future donorthe HIV antibody test. These donors screening.could be counseled that their repeatedlyreactive tests were reactive but that their Recipient and Donor Tracingsupplemental tests were not confirmed,which likely represents a false-positive (Look-Back)test. These donors can be reinstated as Identification of persons who have re-blood or plasma donors. ceived seronegative or untested blood If a donor with a repeatedly reactive from a donor later found to be infectedEIA and not confirmed HIV antigen test by HIV is referred to as “look-back.” Be-is retested after 8 weeks, and samples cause the interval between infectedtest repeatedly reactive on the EIA transfusion and onset of AIDS can bescreening test and are not confirmed by very long, recipients are usually un-neutralization, that donor could be tem- aware of their infection and may be in-porarily deferred for 8 weeks as long as fectious to others. To identify these indi-the HIV antibody test is negative.52 If a v i d u a l s , b l o o d c e n t e r s m u s t h a vereinstated donor tests repeatedly reac- procedures to notify recipients of pre-tive on any subsequent evaluation sub- vious donations from any donor latersequent to having been reinstated, that found to have a confirmed positive test 22donor should be temporarily deferred for anti-HIV or a confirmed positiveagain and is eligible for reentry 8 weeks test for HIV-1-Ag. If a patient with AIDSor later. 52 Such donors should be coun- is known to have donated previously, re-seled that their repeatedly reactive tests cipients of blood or blood products fromwere reactive on at least two donations these donations should be traced and(or samples) but that their supplemental notified. Recipient tracing and testing istests were not confirmed. This may likely usually done through the patient’s phy-represent a false-positive test, but they sician, not through direct contact withare permanently deferred from being the patient. Look-back should start withblood or plasma donors. the recipients of the most recent dona- Copyright © 2002 by the AABB. All rights reserved.
    • 578 AABB Technical Manualtions. If recipients of units (donated at HTLV, Type IIleast 6 months before the last knownnegative test) are tested and found nega- Human T-cell lymphotropic virus, typetive, earlier recipients are probably not II (HTLV-II) was described several yearsat risk, as infectivity earlier than 6 after HTLV-I. There is at least 60% simi- 54months before a negative screening test larity of genetic sequences to HTLV-I ;is extremely unlikely. antibodies to either show strong cross- The FDA recommends the quarantine reactivity in tests with viral lysates.of previously collected units of Whole HTLV-II also shows clustering, but inBlood, blood components, Source Leu- different populations. High prevalencekocytes, or Source Plasma from any per- has been noted among some Nativeson who tests repeatedly reactive by American populations and in intrave-screening test for HIV-1-Ag in the ab- nous drug users in the US, in whomsence of repeatedly reactive screening seroprevalence is 1-20%. The only dis-tests for antibodies to HIV-1 and HIV-2. ease associated with HTLV-II has been HAM; occurrence seems to be somewhat less frequent than with HTLV-I.Human T-Cell Clinical ObservationsLymphotropic Viruses For both HTLV-I and -II, infection per-Types of Viruses sists lifelong, as does the presence of antibody. Studies of prevalence andHuman T-cell lymphotropic virus, type I transmission use seroconversion as the(HTLV-I) was the first human retrovirus endpoint for diagnosis. Infection doesisolated and the first to be causally associ- not cause any recognizable acute events,ated with a malignant disease of humans, and with the exception of those develop-adult T-cell lymphoma-leukemia (ATL). ing ATL or HAM, infected individuals ex-HTLV-I is also associated with the perience no health consequences. Mostneurologic condition originally called carriers are asymptomatic and com-tropical spastic paraparesis but now often pletely unaware of the infection.called HTLV-associated myelopathy(HAM). Both these conditions occur in asmall minority (no more than 2-4%) of Transmissionpersons harboring the virus, and they de- 53velop only after many years of infection. Both viruses are very strongly cell-asso-Infection during childhood is an impor- ciated. Contact with infected viable lym-tant aspect of, possibly a requirement for, phocytes can cause infection, but plasmadeveloping ATL, whereas childhood or does not appear to be infective. Cellularadult infection can cause HAM. components from infected donors cause Prevalence of HTLV-I infection shows seroconversion in 40-60% of recipientsstriking geographic clustering, with pock- in Japan, but apparently in a much 55ets of high endemicity in parts of southern smaller proportion of US recipients. Af-Japan, of sub-Saharan Africa, of the Carib- ter refrigerated storage for 10 days orbean basin, and of Brazil. Transmission is more, red cells from an infected donorby sexual contact (predominantly male-to- are far less likely to cause seroconver-female), by parenteral exposure to blood, sion. Transfusion-transmitted HTLV-Iand by mother-to-child transmission infection has been associated with HAMthrough breast milk. of rather rapid onset. Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 579Donor Tests of high prevalence. The screening re- quirement in place since 1989 has prob-Donor screening for anti-HTLV-I began ably removed from the active donor poolin the United States in 1989; at that time most multi-unit donors with lifelong in-the rate of confirmed positive tests was fection. 530.017%, a figure that has since de-clined as seropositive persons have beeneliminated from the donor pool. The cur-rently licensed EIA screening test does Cytomegalovirusnot accurately discriminate betweenanti-HTLV-I and anti-HTLV-II. Cytomegalovirus (CMV) infection is Further testing of serum that is re- widespread; transmission can occurpeatedly reactive for anti-HTLV against through infectious body secretions, in-antigen preparations specific for the two cluding urine, oropharyngeal secre-agents (HTLV-I or HTLV-II), or by PCR tions, breast milk, blood, semen, andon material from peripheral blood cervical secretions. About 1% of new-mononuclear cells, can characterize the borns are infected, transplacentally orinfecting agent. Half or more of blood through exposure to infected cervical se-donors reactive on EIA screening prove cretions at delivery or by breast milk. Into have HTLV-II infections. A donation early childhood, CMV is often acquiredthat is repeatedly reactive on EIA may through close contact, especially daynot be used for transfusion. Although care settings; in adulthood, through sex-there is no requirement to perform addi- ual intercourse. Anti-CMV is present intional testing, most centers do so, and if 40-70% of healthy blood donors in the 56supplementary tests are positive (see Ta- United States.ble 26-3), the donor is notified and per-manently deferred. Clinical Observations In persons with an intact immune sys- tem, CMV infection may be asympto-Look-Back matic and remain latent in tissues andLook-back is required for recipients of leukocytes for many years. Infection,units drawn before the donor was found either primary or reactivation of latent 22to be seropositive. Because recipients infection, can be associated with aof units from seropositive donors do not mononucleosis-like syndrome of soreconsistently seroconvert, and because throat, enlarged lymph nodes, lympho-many seropositive donors have lifelong cytosis, fever, viremia, viruria, and hepa-infection, the time frame for look-back titis. Intrauterine infection may causeis not self-evident. Five years or five pre- jaundice, thrombocytopenia, cerebralvious donations was adopted as a reason- calcifications, and motor disabilities;able approach, but if the earliest tested the syndrome of congenital infectionrecipient proves to be seropositive, look- causes mental retardation and deafness,back should be continued backward. A and may be fatal.definite separation between infective CMV causes serious morbidity andand noninfective donations is more mortality in premature infants and inlikely to occur with donors who acquired recipients of organ and marrow trans-infection as adults, usually through in- plants. 57 Pneumonitis, hepatitis, retini-travenous drug use or through sexual tis, and multi-system organ failure arecontact with intravenous drug users or manifestations of infection, which canwith individuals from geographic areas result from blood transfusions given to Copyright © 2002 by the AABB. All rights reserved.
    • 580 Table 26-3. Recommended Actions for HTLV-I Testing First Donation to Be Tested for HTLV-I Antibodies Subsequent Donation(s) EIA Donation WB/RIPA Donor EIA Donation WB/RIPA Donor AABB Technical Manual Repeatedly Destroy* Positive Defer and Not Applicable/Donor Deferred reactive all components counsel Repeatedly Destroy* Negative No action Repeatedly Destroy* Negative Defer and reactive all components or indeterminate reactive all components or counsel indeterminate or positive Nonreactive† All components Not done No action acceptable *Destroyed unless appropriately labeled as positive for HTLV-I antibodies, and labeled for laboratory research use or further manufacture into in-vitro diagnostic reagents.Copyright © 2002 by the AABB. All rights reserved. † Assuming that separate prior donations have been repeatedly reactive for HTLV-I antibody no more than once. If separate prior donations had been repeatedly reactive for HTLV-I antibodies on two or more occasions, the donor should have been either permanently or indefinitely deferred.
    • Chapter 26: Infectious Complications of Blood Transfusion 581many premature infants and to trans- moval with high-efficiency filters (5 × 6plant recipients. Other causes, however, 10 leukocytes per component, or less)such as organ transplants from CMV- can significantly reduce if not preventpositive donors or reactivation of latent posttransfusion CMV in high-risk neo- 22,61,62virus, may be as much or more of a risk nates and transplant recipients.than transfusion. Other approaches are also important to consider, especially avoidance of un- needed transfusions. Prophylactic ther-Transfusion-Transmitted CMV apy with CMV immune globulin and pro-Although over half of blood donors are phylactic use of antiviral agents areCMV-seropositive, it has been esti- under scrutiny for high-risk immuno- 58mated that less than 2% of these are suppressed organ transplant recipi- 58able to transmit the virus. Posttransfu- ents.sion hepatitis may, rarely, be due to CMV.The postperfusion mononucleosis syn-drome that first focused attention onCMV in transfused components is now Other Viral Complicationsrarely seen. Posttransfusion CMV infec-tion is generally of no clinical conse- of Blood Transfusionquence in immunocompetent recipi- The transmissibility and clinical signifi-ents. cance of other viruses and virus-like Several categories of immunocom- agents such as Epstein-Barr virus, hu-promised patients should be protected man herpes virus 6, parvovirus, thefrom risk of CMV transmission.59 These agent of Creutzfeldt-Jakob disease, and 63include low-birth-weight premature in- others are being studied.fants born to seronegative mothers; se-ronegative recipients of bone-marrowfrom CMV-negative donors; seronegative Epstein-Barr Viruspregnant women, because the fetus is at Epstein-Barr virus (EBV) causes mostrisk of transplacental infection; and re- cases of infectious mononucleosis and iscipients of intrauterine transfusions. closely associated with the endemicOften included in this category are se- form of Burkitt’s lymphoma in the Farronegative recipients of any organ trans- East, and with nasopharyngeal carci-plant from a seronegative donor; serone- noma. Most persons have been infectedgative individuals who are candidates for by the time they reach adulthood; al-autologous or allogeneic bone marrow though usually asymptomatic, infectiontransplants; and those few patients with persists, remaining in B lymphocytes 57AIDS who are free of CMV infection. and oropharyngeal epithelium. Infec- tion is spread by contact with infected saliva. Primary infection in children isPreventive Measures either asymptomatic or is characterizedBlood from donors who test negative for by a sore throat and enlarged lymphCMV antibody has virtually no risk of nodes. Primary infection in older, immu- 57,58transmitting CMV, but the supply of nologically mature persons usuallyseronegative blood is limited. Another causes a systemic syndrome, infectiousapproach is to remove leukocytes from mononucleosis, with fever; tonsillar in-donated blood. Although the precise leu- fection, sometimes with necrotic ulcers;kocyte population that harbors the virus enlarged lymph nodes; hematologic and 60has not been defined, leukocyte re- immunologic abnormalities; and some- Copyright © 2002 by the AABB. All rights reserved.
    • 582 AABB Technical Manualtimes hepatitis or other organ involve- no evidence for a carrier state. Transmis-ment. EBV infection targets B lympho- sion of parvovirus through blood compo-cytes, which undergo polyclonal prolif- nents other than clotting concentrateseration and then provide a T-lymphocyte has not been reported. 66response, seen as “atypical lympho- Parvovirus has been found regularlycytes.” in clotting factor concentrates and has Transfusion-transmitted EBV infec- been transmitted to hemophiliacs. Be-tion is usually asymptomatic, but has cause it lacks a lipid envelope, it is notbeen a rare cause of the postperfusion reliably inactivated by solvent/detergentsyndrome that followed massive transfu- treatment, and it also resists heat in-sion of freshly drawn blood during car- activation utilizing temperatures belowdiac surgery and is a rare cause of post- 100 C. 67 The infection is usually withouttransfusion hepatitis.64 EBV plays a role serious morbidity but hypoplastic ane-in the development of nasopharyngeal mia has been reported in HIV-infectedcarcinoma and at least one form of hemophiliacs. 68,69Burkitt’s lymphoma, and has the in-vitrocapacity to immortalize B lymphocytes.Although it contributes to the develop- Colorado Tick Feverment of lymphoproliferative disorders in Colorado tick fever is an acute viral ill-immunosuppressed recipients of mar- ness acquired from tick bites in therow and organ transplants, there is no mountainous regions of the westernevidence that transfusion-transmitted United States. The virus can persist inEBV infection contributes to the devel- peripheral blood up to 90 days afteropment of malignancies in transfusion symptoms disappear, but no chronicrecipients. asymptomatic carrier state has been re- ported. The virus has been transmitted 70 by blood transfusion. In the only re-Parvovirus ported case, the blood donor developedParvovirus B19 is the cause of erythema the febrile illness 4 days after removinginfectiosum (fifth disease), a contagious an attached tick and 18 hours after do-febrile illness of early childhood. In nating blood. The virus was isolatedadults, parvovirus can infect and lyse red from a segment of the donated bloodcell precursors in the marrow; sudden after 2 weeks of storage and from periph-and severe anemia may occur in patients eral blood of the recipient who had colonwith underlying chronic hemolytic dis- carcinoma and developed a prolongedorders. Infection during pregnancy im- febrile illness.poses a risk, estimated to be less than10%, of fetal infection, which causes se-vere anemia and consequent circulatory Tick-Borne Encephalitis Virusfailure. Ti c k - b o r n e e n c e p h a l i t i s vi ru s i s a The red cell P antigen is the cellular flavivirus transmitted by the bite of ticksreceptor for parvovirus B19, and people from various parts of the world. One va-who do not have the P antigen are natu- riety (Kumlinge disease) is restricted torally resistant to infection. 65 About 30- southwestern Finland and nearby is-60% of normal blood donors have par- lands where 126 patients had serologicvovirus antibodies, which indicate evidence of infection. Of these, threeimmunity rather than chronic persist- were laboratory acquired and two were 71ent infection.66 Viremia occurs only in acquired by transfusion. The blood do-the early phases of infection and there is nors became ill with Kumlinge disease Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 583only hours after donating but they ne- (eg, dura mater, pituitary growth hor-glected to inform the blood bank. mone of human origin) and persons with a family history of CJD.22 Family history has been defined as having a blood rela-Creutzfeldt-Jakob Disease tive who has had this diagnosis. 78Creutzfeldt-Jakob disease (CJD) is a fatalinfection of the nervous system causedby a proteinaceous particle smaller thana virus. This infectious agent, now usu- Nonviral Infectiousally termed a prion, was once thought tobe a slow virus because symptoms do not Complications of Blooddevelop until many years after the initial Transfusioninfection. In the US, there is about onecase of CJD per million people, nearly all Bacterial Contaminationin older individuals. In the vast majority Bacterial contamination, one of the ear-of cases, the mode of acquisition is un- liest recognized complications of storedknown. The agent causing CJD is resis- blood, remains an important cause oftant to commonly used disinfectants and transfusion morbidity and mortality. Itsterilants. Fatal CJD has been transmit- accounted for about 16% of transfusionted through administration of growth fatalities reported to the FDA between 79hormone derived from human pituitary, 1986 and 1991. No matter how care-transplantation of cornea, allografting of fully blood is drawn, processed, anddura mater; and insertion of contami- stored, complete elimination of micro- 72nated intracerebral electrodes. bial agents is impossible. Bacteria are Early experimental studies in ani- believed to originate with the donor,mals and humans suggested the possi- either from the venipuncture site or 79bility that dementing illnesses such as from inapparent bacteremia. BacterialAlzheimer’s disease and CJD could be multiplication is more likely in compo-transmitted by blood transfusion. This nents stored at room temperature thanwas based on the demonstration of the in refrigerated components, especiallyagent in human leukocytes and the de- when room-temperature storage is in 80velopment of degenerative changes at gas-permeable containers. Organismsthe intracerebral sites where human that multiply in refrigerated blood andcells were introduced into hamsters or components are described as psychro-mice.73 Subsequent studies have failed to philic and are often gram-negative;confirm transmissibility of Alzheimer’s gram-positive organisms are more oftendisease through blood leukocytes,74 and seen at room temperature. Strict adher-population-based, case-control studies ence to phlebotomy protocols and scru-have shown no evidence that blood pulous attention to sterile techniquestransfusion is a risk factor for the devel- during component preparation and stor-opment of CJD or Alzheimer’s dis- age should minimize contaminationease.75,76 arising from sources outside the donor. Although transmission of CJD Infusion of bacterially contaminatedthrough blood transfusion has never components can cause a devastating sep-been reported, individuals at increased tic reaction, with mortality rates up torisk for CJD are excluded from donating 26%.79 In red cell components, the reac-blood77 ; this group includes persons who tions may reflect the effects of endotoxinhave received tissue or tissue derivatives produced by such gram-negative organ-known to be a source of the CJD agent isms as Pseudomonas species, Citrobac- Copyright © 2002 by the AABB. All rights reserved.
    • 584 AABB Technical Manualter freundii, Escherichia coli, a n d selection of blood donors is the first andYersinia enterocolitica. Bartonella and most important step.Brucella species have also caused septic The donor’s present appearance andtransfusion reactions. recent history should be of good health; additional questioning may be needed if there is present or recent history of an-Clinical Considerations tibiotic use, of medical or surgical inter- ventions, or of any constitutional symp-Severe reactions are characterized by toms. Questions to elicit the possibilityhigh fever, shock, hemoglobinuria, DIC, of bacteremia are especially importantand renal failure. If bacterial contamina- for autologous donors, who may recentlytion is suspected, the transfusion should have had hospitalization, antibioticbe stopped immediately and a Gram’s therapy, or invasive diagnostic or thera-stain and blood culture should be ob- peutic procedures; there have been sev-tained from the unit and recipient as eral reports of Yersinia sepsis complica-promptly as possible after the reaction is t i o ns f o l l o w i n g i n fus i on o f s toredobserved. Color change to dark purple or autologous blood.82,83 At the time of do-black, clots in the bag, or hemolysis sug- nation, the temperature and pulsegest contamination, but the appearance should be within normal limits.of the blood in the bag is often unre- There must be scrupulous attentionmarkable. Bacterial multiplication may to selection and cleansing of the donorcause the oxygen in a red cell unit to be phlebotomy site. Skin preparation re-consumed, causing hemoglobin desatu- duces but does not prevent the contami-ration and darkening of the unit when nation of components by bacteria.compared with the color of cells in the 81 Scarred or dimpled areas associated withattached sealed segments. The pres- previous dermatitis or repeated phlebot-ence of bacteria in a Gram’s stain of the omy can harbor bacteria and should becomponent is confirmatory, but absence avoided.of visible organisms does not exclude the Care in the preparation of compo-possibility, especially if blood contained nents and handling of materials used inin attached segments was used for the administration is essential. If a water-Gram’s stain. The patient’s blood, the bath is used, components should be pro-suspect component, and intravenous so- tected by overwrapping and outlet portslutions in all the administration tubing inspected for absence of trapped fluid,used should be cultured for aerobic and and the waterbath should be frequentlyanaerobic organisms at various tempera-tures. emptied and disinfected. Treatment should not await the re- The color and character of the compo-sults of these investigations, and should nent should be checked before releaseinclude immediate intravenous admini- for transfusion. Some workers suggeststration of antibiotics combined with comparing the color of blood in the con-therapy for shock, renal failure, or DIC tainer with that of the sealed segments.81if present. The extent of bacterial growth in platelet components correlates with the dura- tion of storage. In recognition of im-Preventive Measures proved platelet function resulting from improved containers and preservatives,Prevention of septic reactions depends in 1983 the FDA increased storage limitsupon reducing or preventing bacterial of platelets at room temperature from 3contamination of components. Careful to 7 days. In 1986, because of reports of Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 585bacterial contamination in platelets Asymptomatic carriers are the sourcestored longer than 5 days, the FDA re- of transfusion-transmitted malaria, al-duced the room temperature storage though the parasite density is very low.limits for platelets to a maximum of 5 Asymptomatic infections rarely persistdays. 84 more than 3 years, but asymptomatic P. Eventually, the use of detection sys- falciparum and P. vivax infections maytems may allow units to be monitored for persist for 5 years, P. ovale for 7 years,contamination at the time of issue. Ap- and P. malariae can remain transmissi-proaches under consideration include ble for the lifetime of the asymptomaticGram’s stain, chemiluminescent probe individual. There are no practical sero-systems, automated cultures, and dem- logic tests to detect transmissible ma-onstration of glucose consumption. 85,86 laria in asymptomatic donors. MalariaOther strategies, such as prestorage leu- transmission is prevented by deferral ofkocyte reduction, use of antibiotics in prospective donors with increased riskthe storage media, and blood gas analysis of infectivity, based on medical andof stored components, are also under in- travel history. AABB Standards22 defers,vestigation. from donation of red cells, persons who have had malaria in the preceding 3 years. Casual travelers to areas in which malaria is endemic are deferred for aMalaria year, but because early or prolonged ex-Malaria is caused by several species of posure may reduce the incidence or se-the intraerythrocytic protozoan genus verity of symptoms, immigrants, refu-Plasmodium. Transmission usually re- gees, or citizens of areas in which thesults from the bite of an anopheles mos- disease is endemic are deferred for 3quito, but infection can follow transfu- years after leaving the area.sion of parasitemic blood. In the UnitedStates, malaria is probably the mostcommonly recognized parasitic compli- Babesiacation of transfusion; the risk in theUnited States is estimated at 0.25 case Clinical Events 87per million transfusions. The species Human babesiosis, caused by the in-involved in transfusion-transmitted ma- traerythrocytic parasite Babesia mi-laria in the United States are P. malariae croti, is the second most commonly re-(40%), P. falciparum (25%), P. vivax ported transfusion-transmitted parasitic 87 88(20%), and P. ovale (15%). Fever, chills, infection. Babesiosis is usually trans-headache, and hemolysis occur a week to mitted by the bite of an infected deerseveral months after the infected trans- tick, from the coastal lands and islandsfusion; morbidity varies but can be se- of northeastern United States includingvere, and deaths have occurred, espe- Martha’s Vineyard, Cape Cod, and Longcially from P. falciparum. Island. Geographic areas of the hosts and Malaria parasites survive for at least a the vectors appear to be expanding,week in components stored at room tem- along with expansion of the deer popula-perature or at 4 C. The parasites can also tion.survive cryopreservation with glycerol The parasite can survive for up to 35and subsequent thawing. Any compo- days at 4 C liquid storage, and has beennent that contains red cells can transmit transmitted by platelet components andinfection, via the asexual form of the cryopreserved red cells. In an area en-intraerythrocytic parasite. demic for babesiosis, the risk of post- Copyright © 2002 by the AABB. All rights reserved.
    • 586 AABB Technical Manualtransfusion babesiosis was found to be flect either immunologic abnormalities0.17% for red cells; no cases were asso- unrelated to syphilis (biologic false-posi-ciated with platelets.89 Symptoms of tives) or inadequately treated syphilistransfusion-transmitted babesiosis are that is more of a threat to the individualoften so mild that the true nature of the being tested than to a potential recipi- 22infection may go undiagnosed; this may ent. The STS is required as an indicatorexplain the small number of cases docu- of potentially high-risk behavior thatmented in the United States. In sympto- makes transmission of other organismsmatic cases, fever develops 1-4 weeks more likely.after infection, sometimes associatedwith chills, headaches, hemolysis, and Chagas’ Diseasehemoglobinuria. Rarely, the infection islife-threatening, due to rapidly progres- American trypanosomiasis, or Chagas’sive hemolytic anemia, renal failure, and disease, is endemic in South and Centraldisseminated intravascular coagulation. America and is caused by the protozoanAsplenic or immunocompromised trans- parasite Trypanosoma cruzi. The humanfusion recipients are at greatest risk.53 host sustains infection after the bite of reduviid bugs (called cone-nosed or “kissing” bugs), which usually exist inPreventive Measures h o l l o w t r e e s , p a l m t r e es , a n d i nAs with malaria, the Babesia carrier thatched-roofed mud or wooden dwell-state may be asymptomatic. Persons ings.with a history of babesiosis are indefi-n i t e l y d e f er r e d , b e c au s e l i f e l o n g Clinical Eventsparasitemia can follow recovery from T. cruzi infects humans whose skin orsymptomatic illness. More restrictive mucosa comes in contact with feces ofpolicies, such as not collecting blood in infected reduviid bugs, usually as theendemic areas in spring and summer result of a bite. Recent infections aremonths, when tick bites are more com- usually either asymptomatic, or the verymon, would probably have only limited mild signs and symptoms go undetected.value. No test is currently under consid- Rarely, the site of entry evolves into aneration for mass screening to detect erythematous nodule called a chagoma,asymptomatic carriers of B. microti. which may be accompanied by lym- phadenopathy. Fever and enlargement ofSyphilis the spleen and liver may follow. Recently infected young children may experienceSyphilis is caused by the spirochete Tre- acute myocarditis or meningoencephali-ponema pallidum a n d i s c h a r a c- tis. Acute infection usually resolvesteristically spread by sexual contact. The without treatment, but persisting low-phase of spirochetemia is brief and the level parasitemia is usual and up to 20-organisms survive only a few days at 4 C, 40% of chronically infected peopleso although transmission by transfusion develop cardiac or gastrointestinalis possible, it occurs very rarely. Syphilis symptoms years or decades later. 90transmission by transfusion is not pre-vented by subjecting the donor blood tostandard serologic tests for syphilis Transfusion Considerations(STS) because seroconversion occurs In urban areas in which the disease iswell after the phase of spirochetemia. endemic, the second most commonMost positive STS results on donors re- means of infection is transmission of T. Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 587cruzi by blood transfusion. This may be- ble, and in two reported cases where thecome a problem in the United States, as donor became ill shortly after donation, 96asymptomatic immigrants from these the recipient did not develop infection.areas become blood donors. Three cases Potential donors who give a history ofof transfusion-transmitted Chagas’ dis- Lyme disease should be completelyease have been reported in the United asymptomatic and should have completed 91States, in New York, Los Angeles, and a full course of antibiotic therapy before 97Texas, all in immunocompromised re- they may be permitted to donate.cipients. An EIA test for antibodies to T. cruzi Parasitic Wormsas well as possibly confirmatory EIA andRIA tests are in development and should There have been occasional reports ofbe submitted for licensure in the near parasitic worm infections transmittedfuture.92,93 Blood centers in areas with by transfusion in countries other than 88many immigrants from Central or South the United States. Microfilariasis is aAmerica have used questionnaires to potential transfusion risk in tropicalidentify potentially infectious donors; zones, acquired by donors through bitesyields have been reassuringly low when by insects carrying Wuchereria ban-donors whose replies indicated risk fac- crofti or Leishmania species.tors were screened by serologic test-ing.91,94,95 At present, it does not appearindicated to defer donors solely on thebasis of questionnaires. Reducing the Risk of Infectious DiseaseToxoplasmosis TransmissionToxoplasmosis is caused by the ubiqui-tous parasite Toxoplasma gondii and in- Inactivation/Destruction of Agents infection has been reported as an unusual Componentstransfusion complication in immuno- The first intervention specifically added 88compromised patients. The disease has to reduce the risk of hepatitis transmis-not been considered a problem in rou- sion was pasteurization (ie, heating totine transfusion practice. 60 C for 10 hours), used for albumin 98 products since 1948. In those rare in- stances when infections have occurredLyme Disease with albumin or plasma protein frac-Lyme disease is the most common tick- tions prepared with this step, the proc-borne disease in the United States. Bor- essing had been compromised. Therelia burgdorferi, the causative spiro- plasma fractionation process used forchete, is transmitted by bites of the deer immunoglobulin products employs coldtick. No transfusion-related cases have ethanol precipitation, which concen-been reported, but chronic subclinical trates HCV in the Factor VIII-rich cryo-infections do occur and experimentally precipitate and other fractions, andinoculated organisms can survive condi- leaves little in the immunoglobulin frac-tions of frozen, refrigerated, or room tion. The immunoglobulin fraction also 96temperature storage. O n t h e o t h er has a high concentration of virus-neu-hand, the phase of spirochetemia seems tralizing antibodies, and the resultingto be associated with symptoms that product has a remarkably low risk of 99would render a potential donor ineligi- virus transmission. Copyright © 2002 by the AABB. All rights reserved.
    • 588 AABB Technical ManualImmunoglobulins tive against nonenveloped agents such as HAV, parvovirus B19, and the Colo-Preparations of immunoglobulin in- rado tick fever virus. Virus inactivationtended for intravenous administration steps have the potential drawback of re-(IVIG) are expected to be similarly free ducing the potency and biologic effec-of disease transmission. However, NANB tiveness of the product. Another concernhepatitis transmission did occur in the is whether virus inactivation steps affect1980’s during initial clinical trials of immunogenicity, especially the induc-IVIG products in the United States and tion of Factor VIII inhibitors in hemo-with routinely manufactured IVIG prod- philiac patients. 100ucts in Europe. In late 1993 and early U n a v o i d ab l e R i s k s o f H u m a n1994, there were numerous reports of Plasma. Many methods are highly effec-HCV infection in US recipients of an tive against enveloped virus, but spo-IVIG preparation from a single manufac- radic reports of viral transmission con-turer, who did not use any virus inacti- tinue to occur, possibly due to accidentvation procedures. During this period, or error during the manufacturing proc-HCV transmission did not occur from ess. The current combination of heatIVIG of other manufacturers or with in- treatment, solvent/detergent treatment, 101tramuscular immunoglobulin. and purification steps with monoclonal antibodies provides clotting factor con- centrates with a risk of transmittingCoagulation Factors hepatitis and HIV that is lower than theUntil recently, clotting factor concen- risk associated with use of cryoprecipi-trates frequently transmitted viral infec- tated Factor VIII derived from individualtions. As the significance of HIV trans- voluntary whole blood donations. Abso-mission became recognized, virus lute safety of products derived from hu-inactivation steps were applied more rig- man plasma may be unattainable; start-orously to concentrates of Factor VIII ing with the safest possible donated 103and other clotting factors. Unfortu- plasma is of primary importance.nately, a large proportion of the hemo- Avoiding Human Plasma. Factor VIIIphiliac population receiving concen- concentrates have been produced by re-trates before processing was improved combinant DNA technology and are li- 104sustained HIV infection. Chronic hepati- censed for use. Batches are producedtis was an additional complication in al- by culture of mammalian cells engi-most all hemophiliacs receiving older neered to secrete Factor VIII into theclotting factor products. 102 supernatant medium, which is purified The thermal instability of Factor by ion-exchange chromatography andVIII made it difficult to develop an ef- immunoaffinity chromatography usingfective heat treatment, until a practical a mouse monoclonal antibody againstapproach was adopted in 1985. Since human Factor VIII. Except for additionthen, many disinfection steps have of human albumin to stabilize Factorbeen introduced and factor concen- VIII, the product is free of human pro-trates are now, in general, very safe teins, HIV, hepatitis viruses, and otherproducts. Each process has its own set unwanted agents.of advantages and disadvantages. Appli-cation of organic solvents and deter- Frozen Plasmagents inactivates viruses with a lipid-containing envelope (eg, HIV, HBV, HCV, Virus inactivation steps, originally de-HTLV, EBV, CMV, HHV-6), but is ineffec- veloped for plasma fractionation, are be- Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 589ing considered for transfusions of frozen a mechanism to encourage recognitionplasma. The options under study include and reporting of possible transfusion-as-organic solvents and detergents, pas- sociated infections. HIV infectionteurization, and use of photochemi- thought to be a result of transfusion 105cals. Solvent/detergent treatment, ef- should also be reported to the supplier,fective against lipid-enveloped viruses, although the interval between transfu-involves addition of 1% Triton X-100 and sion and the recognition of infection or1% tri-n-butyl phosphate (TNBP) to symptoms may be years.pooled plasma, followed by oil extraction Infection in a recipient should be re-of the TNBP and chromatographic ad- ported to the collecting agency so thatsorption of the Triton X-100. To protect donors shown or suspected to be infec-Factor VIII during pasteurization, stabi- tive can be evaluated and recipients oflizers are added and subsequently re- other components from the implicatedmoved by ultrafiltration. Photochemi- or other donations can be contacted and,cals such as methylene blue can be added if necessary, tested. A donor who provesto individual plasma units, which are to have positive results on tests duringthen exposed to visible light. Of these the investigation must be placed on athree approaches, solvent/detergent suitable deferral list.treatment of plasma has been the best The Code of Federal Regulations [21studied and validated. CFR 606.170(b)] requires that fatalities attributed to transfusion complications (eg, hepatitis, AIDS, and hemolytic reac-Processing Cellular Components tions) be reported to the Director, Cen-The use of chemicals to inactivate vi- ter for Biologics Evaluation and Re-ruses in red cell and platelet components search (CBER), Office of Compliance,is actively being studied but is not yet Division of Inspections and Surveil- 106close to clinical application. Most in- lance, 1401 Rockville Pike, Suite 200N,activation protocols evaluated to date HFM-650, Rockville, MD 20852-1448. Ahave employed photochemicals, pho- report should be made by telephonetoreactive compounds added to the (301-594-1191) within one working dayblood component, which is then exposed and a written report should be submittedto light of a specific wavelength. These within 7 days.may act by generating reactive oxygenspecies that inactivate virus or by directeffects on nucleic acid. Management of Posttransfusion InfectionsReporting Transfusion-Associated Implicated DonorsInfections If documented transfusion-associatedUnexplained infectious disease reported hepatitis, HIV, or HTLV-I occurs in a pa-in a transfusion recipient must be inves- tient who received only a single unit,tigated for the possibility of transfusion- that donor must be permanently ex- 22transmitted illness. Hepatitis is ex- cluded from future donations, and thepected to become apparent within 2 name be placed in a file of permanentlyweeks to 6 months if it resulted from deferred individuals. If posttransfusiontransfusion, but even within this inter- viral infection occurs after exposure toval the cause need not necessarily have blood from several donors, it is not nec-been blood-borne infection. Blood cen- essary to exclude all of the potentiallyters and transfusion services must have implicated donors. If only a few donors Copyright © 2002 by the AABB. All rights reserved.
    • 590 AABB Technical Manualare involved, it may be desirable to recall serum globulin or HBIG prophylacti-them to obtain an interim history and cally to prevent posttransfusion hepati- 107,108additional tests. If this is not feasible, a tis ; these agents have not beennotation can be made in each donor’s file shown to prevent posttransfusion hepa-that the individual was one of several titis B, and the available evidence is con-donors (specify the number) involved in flicting about their effect on posttrans- 109,110a case of transfusion-associated viral dis- fusion hepatitis C. If there has beenease, and the names should be included i n a d v e r t e n t t r an s f u s i o n o f k n o w nin a special file of potentially implicated marker-positive blood, or needlestick ex-donors. Donors found to have been im- posure to infectious material, HBIG may 7,111plicated in more than one case of trans- prevent or attenuate infection.fusion-associated viral infection shouldbe appropriately investigated and possi-bly deferred permanently according toprocedures established by the collecting Referencesagency. 1. Anderson KC, Ness PM, eds. Scientific basis of transfusion medicine. Implications for clinical practice. Philadelphia: WB Saunders,Notification 1994. 2. Dodd RY. Adverse consequences of bloodA donor who will be permanently ex- transfusion: Quantitative risk estimates. In:cluded as a future blood donor, because Nance ST, ed. Blood supply: Risks, percep-of a positive test implication in post- tions and prospects for the future. Bethesda,transfusion viral infection, must be no- MD: American Association of Blood Banks, 1994:1-24.tified of this fact. Follow-up testing 3. Menitove JE. Hepatitis. In: Anderson KC,should, ideally, be done by the donor’s Ness PM, eds. Scientific basis of transfusionown physician, and the collecting agency medicine. Implications for clinical practice.should obtain the donor’s consent to re- Philadelphia: WB Saunders, 1994:620-36.lease available information to a desig- 4. Zuckerman AJ. Viral hepatitis. Transfus Med 1993;3:7-19.nated health-care provider. If the donor 5. Simons JN, Pilot-Matias TJ, Leary TP, et al.does not have a physician, a blood bank Identification of two flavivirus-like genomesphysician or other trained staff member in the GB hepatitis agent. Proc Natl Acad Scishould provide initial counseling and ap- USA 1995;92:3401-5.propriate medical referral. The notifica- 6. Alter HJ. Transfusion-transmitted non- A,non-B and hepatitis C infections. In: Rossition process and counseling must be EC, Simon TL, Moss GS, Gould SA, eds. Prin-done with tact and understanding, and ciples of transfusion medicine, 2nd ed. Balti-the fears and concerns of the donor more, MD: Williams and Wilkins, 1995:687-should be addressed. The donor should 98. 7. Dodd RY. Hepatitis. In: Petz LD, Swisher SN,be told clearly why he or she is deferred Kleinman S, et al, eds. Clinical practice ofand, when appropriate, about the possi- transfusion medicine, 3rd ed. New York:bility of being infectious to others. Noti- Churchill Livingstone, 1996:847-73.fication should occur promptly because 8. Koff RS, Seeff LB, Dienstag JL. Transfusion-a delay in notification can delay initia- transmitted hepatitis A, B, and D. In: Rossi EC, Simon TL, Moss GS, Gould SA, eds. Prin-tion of treatment or institution of meas- ciples of transfusion medicine, 2nd ed. Balti-ures to prevent spread to others. more, MD: Williams and Wilkins, 1995:675- 86. 9. Alter HJ. To C or not to C: These are theUse of Immunoglobulins questions. Blood 1995;85:1681-95. 10. Centers for Disease Control. Public HealthIt is not recommended practice to give Service inter-agency guidelines for screeningintramuscular or intravenous immune donors of blood, plasma, organs, tissues and Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 591 semen for evidence of hepatitis B and hepa- 25. Ragni MV, Winkelstein A, Kingsley L, et al. titis C. MMWR 1991;40(RR-4):1-17. 1986 update of HIV seroprevalence, serocon-11. Busch MP. Let’s look at human immunodefi- version, AIDS incidence and immunologic ciency virus look-back before leaping into correlates of HIV infection in patients with hepatitis C virus look-back. Transfusion hemophilia A and B. Blood 1987;70:786-90. 1991;31:655-61. 26. Montagnier L, Gruest J, Chamaret S. Adap-12. Dodd RY. The risk of transfusion-transmit- tation of lymphadenopathy associated virus ted infection. N Engl J Med 1992;327:419-20. (LAV) to replication in EBV-transformed B13. Mannucci PM, Gdovin S, Gringeri A, et al. lymphoblastoid cell lines. Science Transmission of hepatitis A to patients with 1984;225:63-6. hemophilia by factor VIII concentrates 27. Popovic M, Sarngadharan MG, Read E, Gallo treated with organic solvents and detergent RC. Detection, isolation and continuous to inactivate viruses. Ann Intern Med production of cytopathic retrovirus (HTLV- 1994;120:1-7. III) from patients with AIDS and pre-AIDS.14. Alter HJ, Purcell RH, Shih JW, et al. Detec- Science 1984;224:497-500. tion of antibody to hepatitis C virus in 28. Levine AM, Liebman HA. The acquired im- prospectively followed transfusion recipi- munodeficiency syndrome (AIDS). In: Beut- ents with acute and chronic non-A,non-B ler E, Lichtman MA, Coller BS, Kipps TJ, eds. hepatitis. N Engl J Med 1989;321:1494-500. Williams’ hematology, 5th ed. New York:15. Vengelen-Tyler G, Busch M. Decline of trans- McGraw-Hill, 1995:975-97. fusion-associated hepatitis C virus. CBBS 29. Mayer A, Busch MP. Transfusion-transmitted Today 1995;13:17-21. HIV infection. In: Anderson KC, Ness PM,16. Ebeling F, Naukkarinen R, Leikola J. Recom- eds. Scientific basis of transfusion medicine. binant immunoblot assay for hepatitis C vi- Implications for clinical practice. Philadel- rus antibody as predictor of infectivity. Lan- phia: WB Saunders, 1994:659-68. cet 1990;335:982-3. 30. Centers for Disease Control. 1993 Revised17. van der Poel CL, Cuypers HTM, Reesink HW, classification system for HIV infection and et al. Confirmation of hepatitis C virus infec- expanded surveillance and case definition tion by new four-antigen recombinant im- for AIDS among adolescents and adults. munoblot assay. Lancet 1991;337:317-9. MMWR 1992;41(RR-17):1-19.18. Steane EA. Surrogate testing for non-A,non- 31. Brookmeyer R. Reconstruction and future B hepatitis (Memo to AABB Institutional trends of the AIDS epidemic in the United Members). Arlington, VA: American Associa- States. Science 1991; 253:37-42. tion of Blood Banks, February 11, 1987. 32. Centers for Disease Control and Prevention.19. Chambers LA, Popovsky MA. Decrease in re- National HIV serosurveillance summary. Re- ported posttransfusion hepatitis: Contribu- sults through 1992. Volume 3. (Publication tions of donor screening for alanine ami- number HIV/NCID/11-93/036). Atlanta, GA: notransferase and antibodies to hepatitis B US Department of Health and Human Serv- core antigen and changes in the general popu- ices, Public Health Service, 1994. lation. Arch Intern Med 1991;151:2445-8. 33. Marlink R. Biology and epidemiology of HIV-20. Busch MP, Koretitz JJ, Kleinman SH, et al. 2. In: Essex M, Kalengayi M, Kauki P, et al, Declining value of alanine aminotransferase eds. AIDS in Africa. New York: Raven Press, in screening of blood donors to prevent post- 1994:47-65. transfusion hepatitis B and C virus infection. 34. O’Brien TR, George JR, Holmberg SD. Hu- Transfusion 1995;35:903-10. man immunodeficiency virus type 2 infec-21. NIH consensus statement on infectious dis- tion in the United States. Epidemiology, di- ease testing for blood transfusion. Bethesda, agnosis and public health implications. MD: National Institutes of Health, 1995. JAMA 1992;267:2775-79.22. Klein HG, ed. Standards for blood banks and 35. Centers for Disease Control and Prevention. transfusion services, 17th ed. Bethesda, MD: First 500,000 AIDS cases—United States, American Association of Blood Banks, 1996. 1995. MMWR 1995;45:849-53.23. Centers for Disease Control. Pneumocystis 36. Donegan E, Stuart M, Niland JC, et al. Infec- carinii pneumonia among persons with he- tion with human immunodeficiency virus mophilia A. MMWR 1982;31:365-7. type 1 (HIV-1) among recipients of antibody-24. Centers for Disease Control. Possible trans- positive blood donations. Ann Intern Med fusion-associated acquired immune defi- 1990;113:733-9. ciency syndrome (AIDS)—California. 37. Dufoort G, Courouce A-M, Ancelle-Park R, MMWR 1982;31;652-4. Bletry O. No clinical signs 14 years after Copyright © 2002 by the AABB. All rights reserved.
    • 592 AABB Technical Manual HIV-2 transmission via blood transfusion. the safety of the blood supply and, if so, at Lancet 1988;ii:510. what cost? Transfusion 1995;35:536-9.38. Simon F, Puel J, Hammer R, et al. HIV-2 50. Food and Drug Administration. Memoran- infection in two European hemophiliac pa- dum: Recommendation for donor screening tients (abstract). Presented at the Fifth Inter- with a licensed test for HIV-1 antigen. August national Conference on AIDS, June 4-9, 1989. 8, 1995. Rockville, MD: Congressional and Montreal, Canada. Consumer Affairs, 1995.39. Busch MP. Transfusion-associated AIDS. In: 51. Centers for Disease Control and Prevention. Rossi EC, Simon TL, Moss GS, Gould SA, eds. US Public Health Service Guidelines for test- Principles of transfusion medicine, 2nd ed. ing and counseling blood and plasma donors Baltimore, MD: Wi lliams and Wilkins, for human immunodeficiency virus type 1 1995:699-708. antigen. MMWR 1996;45:1-10.40. Busch MP, Young MO, Ward JW, Perkins HA, 52. Food and Drug Administration. Memoran- and the Transfusion Safety Study Group. Risk dum: Additional recommendations for donor of human immunodeficiency virus transmis- screening for a licensed test for HIV-1 anti- sion by transfusions prior to implementing gen. March 14, 1996. Rockville, MD: Congres- of HIV antibody screening in the San Fran- sional and Consumer Affairs, 1996. cisco Bay Area. Transfusion 1991;31:4-11. 53. Dodd RY. Epidemiology of transfusion-trans-41. Lackritz E, Petusen L, Satten G. Current risk mitted diseases. In: Anderson KC, Ness PM, estimates of HIV in the United States (ab- eds. Scientific basis of transfusion medicine. stract). 2nd National Conference on Human Implications for clinical practice. Philadel- Retroviruses and Related Infections. Wash- phia: WB Saunders, 1994:599-619. ington, DC: American Society for Microbiol- 54. Hjelle B. Transfusion-transmitted HTLV-I ogy, 1995:56. and HTLV-II. In: Rossi EC, Simon TL, Moss42. Busch MP. HIV and blood transfusions: Focus GS, Gould SA, eds. Principles of transfusion on seroconversion. Vox Sang 1994;62 (Suppl medicine, 2nd ed. Baltimore, MD: Williams 3):13-18. and Wilkins, 1995:709-16. 55. Sullivan MT, Williams AE, Fang CT, et al.43. Zaaijer HL, Exel-Oehlers PY, Kraaijeveld T, et Transmission of human T-lymphotropic vi- al. Early detection of antibodies to HIV-1 by rus types I and II by blood transfusion. Arch third-generation assays. Lancet 1992;340: Intern Med 1991;151:2043-8. 770-2. 56. Luban NLC. Cytomegalovirus. In: Anderson44. Centers for Disease Control. Interpretive cri- KJ, Ness PM, eds. Scientific basis of transfu- teria used to report Western blot results for sion medicine. Implications for clinical prac- HIV-1-antibody testing—United States. tice. Philadelphia: WB Saunders, 1994:637- MMWR 1991;40:692-5. 53.45. Celum CL, Coombs RW, Jones M, et al. Risk 57. Gunter KC, Luban NLC. Transfusion-trans- factors for repeatedly reactive HIV-1 EIA and mitted cytomegalovirus and Epstein-Barr vi- indeterminate western blots. A population- rus diseases. In: Rossi EC, Simon TL, Moss based case-control study. Arch Intern Med GS, Gould SA, eds. Principles of transfusion 1994;153:1129-37. medicine, 2nd ed. Baltimore, MD: Williams46. Henrard DR, Phillips J, Windsor I, et al. De- and Wilkins, 1995:717-31. tection of human immunodeficiency virus 58. Sayers MH. Cytomegalovirus and other her- type 1 p24 antigen and plasma RNA: Rele- pesviruses. In: Petz LD, Swisher SN, Klein- vance to indeterminate serologic tests. man S, et al, eds. Clinical practice of transfu- Transfusion 1994;34:376-80. sion medicine, 3rd ed. New York: Churchill47. Food and Drug Administration. Memoran- Livingstone, 1996:875-89. dum: Revised recommendations for the pre- 59. Sayers MH, Anderson KC, Goodnough LT, et vention of human immunodeficiency virus al. Reducing the risk for transfusion-trans- (HIV) transmission by blood and blood prod- mitted cytomegalovirus infection. Ann In- ucts. April 23, 1992. Rockville, MD: Congres- tern Med 1992;116:55-62. sional and Consumer Affairs, 1992. 60. Gerna G, Zipeto D, Percivalle E, et al. Human48. Food and Drug Administration. Memoran- cytomegalovirus infection of the major leu- dum: Use of Fluorognost HIV-1 immunofluo- kocyte subpopulations and evidence for in- rescent assay (IFA). April 23, 1992. Rockville, itial viral replication in polymorphonuclear MD: Congressional and Consumer Affairs, leukocytes from viremic patients. J Infect Dis 1992. 1992;166:1236-44.49. Busch MP, Alter HJ. Will human immunode- 61. Hillyer CD, Emmens RK, Zago-Novaretti M, ficiency virus p24 antigen screening increase Berkman EM. Methods for the reduction of Copyright © 2002 by the AABB. All rights reserved.
    • Chapter 26: Infectious Complications of Blood Transfusion 593 transfusion-transmitted cytomegalovirus 75. Esmonde TF, Will RG, Slattery JM, et al. infection: Filtration versus the use of se- Creutzfeldt-Jakob disease and blood transfu- r o n e g a t i v e d o n o r u n i t s . Tr a n s f u s i o n sion. Lancet 1993;341:205-7. 1994;34:929-34. 76. Bohnen NI, Warner MA, Kokmen E, et al.62. Goldman M, Delage G. The role of leukode- Prior blood transfusions and Alzheimer’s pletion in the control of transfusion-trans- disease. Neurology 1994;44:1159-60. mitted disease. Transfus Med Rev 1995;9:9- 77. Food and Drug Administration. Memoran- 19. dum: Precautionary measures to further re-63. Sayers MH. Transfusion-transmitted viral duce the possible risk of transmission of CJD infections other than hepatitis and human by blood and blood products (August 5, immunodeficiency virus infection. Cy- 1995). Rockville, MD: Congressional and tomegalovirus, Epstein-Barr virus, human Consumer Affairs, 1995. herpesvirus 6, and human parvovirus B19. 78. Fratantoni J. CJD: Clarification of the Arch Pathol Lab Med 1994;118:346-9. agency position. As cited in: American Asso-64. Guisti G, Galanti B, Gaeta GB, Gallo C. Eti- ciation of Blood Banks. FDA provides guid- ological, clinical and laboratory data of post- ance on HIV antigen testing, CJD. AABB transfusion hepatitis: A retrospective study Weekly Report 1995;1(9):2. of 379 cases from 53 Italian hospitals. Infec- 79. Sazama K. Bacteria in blood for transfusion. tion 1987;15:111-4. Arch Pathol Lab Med 1994;118:350-65.65 Brown KE, Hibbs JR, Gallinella G, et al. Re- 80. Morrow JW, Braine HG, Kickler TS, et al. sistance to parvovirus B19 infection due to Septic reactions to platelets, a persistent lack of virus receptor (erythrocyte P anti- problem. JAMA 1991;266:555-8. gen). N Engl J Med 1994;330:1192-6. 81. Kim DM, Brecher ME, Bland LA, et al. Visual66. Luban NLC. Human parvoviruses: Implica- identification of bacterially contaminated tions for transfusion medicine. Transfusion red cells. Transfusion 1992;32:221-5. 1994;34:821-7. 82. Haditsch M, Binder L, Gabriel C, et al.67. DiNapoli G, Bucci E. Human parvovirus B19 Yersinia enterocolitica septicemia in autolo- after concentrates for haemophilia (letter). g o u s b l o o d t r a n s f u s i o n . Tr a n s f u s i o n Lancet 1994;343:1566. 1994;34:907-9.68. Williams MD, Cohen BJ, Beddall AC, et al. Transmission of human parvovirus B19 by 83. Sire JM, Michelet C, Mesnard R, et al. Septic coagulation factor concentrates. Vox Sang shock due to Yersinia enterocolitica after 1990;58:177-81. autologous transfusion (letter). Clin Infect Dis 1993;17:954-5.69. Frickhofen N, Abkowitz JL, Safford M, et al. Persistent B19 parvovirus infection in pa- 84. Anderson KC, Lew MA, Gorgone BC, et al. tients infected with human immunodefi- Transfusion-related sepsis after prolonged ciency virus type 1 (HIV-1): A treatable cause platelet storage. Am J Med 1986;81:405-11. of anemia in AIDS. Ann Intern Med 85. Ness PM. Bacterial transmission by transfu- 1990;113:926-33. sion. In: Rossi EC, Simon TL, Moss GS,70. Centers for Disease Control. Transmission of Gould SA, eds. Principles of transfusion Co lo ra d o ti ck fever by blood transf u- medicine, 2nd ed. Baltimore, MD: Williams sion—Montana. MMWR 1975;24:422,427. and Wilkins, 1995:739-45.71. Wahlberg P, Saikkhu P, Brummer-Korvenk- 86. Burstain J, Workman K, Brecher M. Inexpen- ontio M. Tick-borne viral encephalitis in Fin- sive and rapid detection of bacterially con- land. The clinical features of Kumlinge dis- taminated platelets using urine dipsticks e a se du ri n g 1 9 59 - 1 9 82. J Intern Med (abstract). Transfusion 1995;35:645. 1989;225:173-7. 87. Shulman IA. Transmission of parasitic infec-72. Manuelides L. The dimensions of tions by blood transfusion. In: Rossi EC, Creutzfeldt-Jakob disease. Transfusion Simon TL, Moss GS, Gould SA, eds. Princi- 1994;34:915-28. ples of transfusion medicine, 2nd ed. Balti-73. Manuelidis EE, deFigueiredo JM, Kim JH, et more, MD: Williams and Wilkins, 1995:733- al. Transmission studies from blood of Alzhe- 7. imer disease patients and healthy relatives. 88. Shulman IA. Parasitic infections and their Proc Natl Acad Sci USA 1988;85:4898-901. impact on blood donor selection and testing.74. Godec MS, Asher DM, Kozachuk WE, et al. Arch Pathol Lab Med 1994;118:366-70. Blood buffy coat from Alzheimer’s disease 89. Gerber MA, Shapiro ED, Krause PJ, et al. The patients and their relatives does not trans- risk of acquiring Lyme disease or Babesiosis mit spongiform encephalopathy to ham- from blood transfusion. J Infect Dis 1994; sters. Neurology 1994;44:1111-5. 170:231-4. Copyright © 2002 by the AABB. All rights reserved.
    • 594 AABB Technical Manual 90. Schmunis GA. Trypanosoma cruzi, the etio- 101. Centers for Disease Control and Prevention. logic agent of Chagas’ disease: Status in the Outbreak of hepatitis C associated with intra- blood supply in endemic and nonendemic venous immunoglobulin administration— countries. Transfusion 1991;31:547-57. United States, October 1993-June 1994. 91. Appleman MD, Shulman IA, Saxena S, Kirch- MMWR 1994;43:505-9. hoff LV. Use of a questionnaire to identify 102. Makris M, Preston FE. Chronic hepatitis in potential blood donors at risk for infection hemophilia. Blood Rev 1993;7:243-50. w i t h Trypanosoma cruzi. Tra nsf usion 103. Prowse C. Kill and cure. The hope and reality 1993;33:61-4. o f v i r u s i n a c t i v a t i o n . Vo x S a n g 92. Brashear RJ, Winkler MA, Schur JD, et al. 1994;67(Suppl 3):191-6. Detection of antibodies to Trypanosoma 104. Lusher JM, Arkin S, Abildgaard CF, Schwartz cruzi among blood donors in the southwest- RS and the Kogenate Previously Untreated ern and western United States. I. Evaluation Patients Study Group. Recombinant factor of the sensitivity and specificity of an enzyme VIII for the treatment of previously untreated immunoassay for detecting antibodies to T. patients with hemophilia A. Safety, efficacy cruzi. Transfusion 1995;35:213-8. and development of inhibitors. N Engl J Med 93. Winkler MA, Brashear RJ, Hall HJ, et al. De- 1993;328:453-59. tection of antibodies to Trypanosoma cruzi 105. Horowitz B, Prince AM, Horowitz MS, among blood donors in the southwestern and Watklevicz C. Viral safety of solvent-deter- western United States. II. Evaluation of a gent treated blood products. Dev Biol Stand supplemental enzyme immunoassay and ra- 1993;81:147-61. dioimmunoprecipitation assay for confirma- 106. Friedman LI, Stromberg RR, Wagner SJ. Re- t i o n o f s e r o r e a c t i v i t y. Tr a n s f u s i o n ducing the infectivity of blood compo- 1995;35:219-25. nents—what have we learned? In: Nance ST, 94. Tabony L, Chappell C. Prevalence of Try- ed. Blood supply: Risks, perceptions and panosoma cruzi (Chagas’ disease) antibody prospects for the future. Bethesda, MD: and high risk in blood donor populations of Am erican Association of Blood Banks, Texas (abstract). Transfusion 1995;35:645. 1994:139-69. 95. Leiby DA, Lenes BA, Nystrom SR, et al. Sero- prevalence of Trypanosoma cruzi antibodies 107. Alter HJ. The epidemiology and prevention of in blood donors from metropolitan Miami post- transfusion hepatitis. In: Polesky HF, (abstract). Transfusion 1995;35:645. Walker RH, eds. Safety in transfusion prac- 96. Benson K. Bacterial and parasitic infections. tices. Skokie, IL: College of American Pa- In: Petz LD, Swisher SN, Kleinman S, et al, thologists, 1982:1-16. eds. Clinical practice of transfusion medi- 108. Seeff LB. The efficacy of and place for HBIG cine, 3rd ed. New York: Churchill Living- in the prevention of type B hepatitis. In: stone, 1996:891-903. Szmuness W, Alter HJ, Maynard JE, eds. Viral 97. Aoki SY, Holland PV. Lyme disease, another hepatitis: 1981 International Symposium. transfusion risk? Transfusion 1989;29:646- Philadelphia, PA: The Franklin Institute 50. Press, 1982:585-95. 98. Suomela H. Inactivation of viruses in blood 109. Sanchez-Quijano A, Lissen E, Diaz-Torres and plasma products. Transfus Med Rev MA, et al. Prevention of post-transfusion 1993;7:42-57. non-A,non-B hepatitis by nonspecific immu- 99. Centers for Disease Control. Safety of thera- noglobulin in heart surgery patients. Lancet peutic immune globulin preparations with 1988;1:1245-9. respect to transmission of human T- lym- 110. Conrad ME. Prevention of post-transfusion photropic virus type III/lymphadenopathy- hepatitis. Lancet 1988;2:217. associated virus infection. MMWR 111. Kobayashi RH, Stiehm ER. Immunoglobulin 1986;35:231-3. therapy. In: Petz LD, Swisher SN, Kleinman100. Williams PE, Yap PL, Gillon J, et al. Non- S, et al, eds. Clinical practice of transfusion A,non-B hepatitis transmission by intrave- medicine, 3rd ed. New York: Churchill Liv- nous immunoglobulin. Lancet 1988;2:501. ingstone, 1996:985-1010. Copyright © 2002 by the AABB. All rights reserved.