August, 1994
Transfusion Transmitted Cytomegalovirus Darrell J. Triulzi, M.D., Medical Director INTRODUCTION Cytomegalovirus (CMV) is a double stranded DNA virus belonging to the herpes virus family. A hallmark of CMV is its ability to establish a latent infection by integrating its DNA into the genome of host peripheral leukocytes. Latently infected donor white blood cells in cellular blood products are capable of transmitting CMV to susceptible recipients. This complication can largely be avoided by defining those patients at risk and using blood products with a low risk of transmitting CMV.
Approximately 50% of volunteer blood donors are CMV seropositive. The
prevalence increases with age and approaches 80% in the elderly. Serostatus is determined
by latex agglutination or EIA analysis and both methods have a false negative rate of
approximately 1 - 5%. Recipient seroconversion studies suggest that only 10% of
seropositive donors are actually infectious. Unfortunately, there are no practical ways of
determining which of the seropositive donors are infectious. Detection of CMV DNA by PCR
in seropositive donors has been highly variable, ranging from 8% to 80%. Risk Factors for CMV Transmission Only cellular blood products (whole blood, red cells, platelets, granulocytes) which contain viable leukocytes are capable of transmitting CMV. Plasma products such as fresh frozen plasma and cryoprecipitate do not transmit this virus. The dose of infected leukocytes transfused is an important risk factor as evidenced by the increasing risk of seroconversion with the number of units transfused unit (0.1 - 0.4%/unit in immunocompetent recipients, 3 - 12%/unit in immunocompromised recipients). The risk of CMV transmission is lower with stored blood products than fresh blood products due to the breakdown of leukocytes. Leukodepleted blood products are associated with a markedly reduced risk for transmitting CMV. Lastly, the immune status of the recipient influences the risk for infection. Clinical Manifestations of CMV Transmitted by Transfusion Transmission of CMV to seronegative immunocompetent individuals may result in primary infection which is usually asymptomatic but may be associated with flu-like symptoms or heterophile negative mononucleosis. The postperfusion syndrome described in the 1960's in cardiac surgery patients was a mononucleosis-like manifestation of CMV infection via transfusion. Posttransfusion CMV infections in a seropositive recipient are usually a result of reactivation of endogenous virus rather than reinfection. Posttransfusion CMV in immunoincompromised patients may be asymptomatic or mild but has the potential to be lethal. Disseminated CMV may involve almost any organ with predilection for the lungs, GI tract and GU tract. Cytomegalic inclusion disease can occur when primary infection occurs in-utero. Indications for CMV Negative Blood Patient groups for which CMV negative blood should be provided include: seronegative low birth weight infants (<1500 grams), seronegative recipients of seronegative organ transplants or bone marrow transplants, intrauterine transfusions in a seronegative woman, and transfusions in a seronegative pregnant woman. Patients in whom a benefit of CMV seronegative products is less well established include seronegative autologous bone marrow transplant patients, seronegative HIV infected patients and seronegative infants on extracorporeal membrane oxygenators. Seropositive patients do not benefit from the use of seronegative blood products. Studies in seropositive neonates have suggested that use of CMV seronegative blood may actually be deleterious due to dilution of protective antibody. Seronegative recipients of a seropositive organ or bone marrow probably do not benefit from seronegative blood products. Concept of CMV "Safe" Blood The high prevalence of seropositivity among blood donors results in limited availability of CMV seronegative blood products. A growing body of data have now convincingly demonstrated that leukocyte depletion using the current 3 log white cell removal filters can markedly reduce the risk of CMV transmission. Units which were CMV PCR positive have been rendered PCR negative with these filters. Equivalence of filtered products and seronegative blood has been shown in clinical studies of CMV infection and disease in neonates and adult autologous and allogeneic bone marrow transplant patients. Products rendered CMV "safe" by filtration can be substituted for seronegative blood products. It is recommended that quality control of the filtration process be performed to ensure adequate white cell removal. Summary CMV can be transmitted by cellular blood products resulting in significant morbidity and mortality in immunocompromised patients. This complication can be prevented by the use of seronegative or filtered blood products in appropriate patient populations. For questions or further information, contact Darrell J. Triulzi, M.D. (412) 209-7304 e-mail: dtriulzi@itxm.org Copies of the Transfusion Medicine Update can be
obtained by contacting
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