Transfusion medicine for the pediatrician
Section snippets
Screening for infectious disease
Currently, all blood donations are screened for HIV antigen, antibodies to HIV-1 and HIV-2, human T lymphotrophic virus (HTLV I-II), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBC), hepatitis C (HCV), and syphilis. Nucleic acid testing (NAT) [5], used under an investigative new drug license from the US Food and Drug Administration (FDA), uses a transcription-mediated amplification [6] to test for HIV and hepatitis C but not hepatitis B. There are algorithms to define
Viral pathogens/NAT testing
Once an individual has become infected with a viral pathogen, there is a window of time (Fig. 2) during which the viral load is too low, or is intermittently too low, to be detected by pooled sample NAT. Recipients of donated blood products are at highest risk for infection during this window phase. Because NAT testing is so sensitive and there are so few instances of virally infected products, only mathematical models based on research data can predict the risk of infection from a single
Bacterial contamination of blood products
Bacterial sepsis from contaminated blood products is the second leading cause of transfusion-related death (Fig. 4) in the United States today, behind transfusion errors. Between 1990 and 1998, there were 277 reported transfusion-related deaths, 17% of which were due to bacterial contamination. The fact that patients receiving blood transfusions are likely to have complex medical conditions and are frequently immune suppressed contributes to the morbidity of transfusion-related sepsis. The
Emerging pathogens
With the advent of comprehensive donor screening, NAT testing, and perhaps universal leukoreduction, blood transfusion is safer than it was only a decade ago. Pathogens like HIV, HCV, and HBV are a persistent but vanishing risk of transfusion. Infections once considered low risk have become more significant (Table 2). For these low-risk pathogens there are no approved screening tests. The blood supply is protected by accurate history taking and deferral at the time of donation and in some cases
Transfusion-mediated immune modulation
The first well-documented immune effect of transfusion was reported in 1973 by Opeiz et al [57] and showed increased survival of renal allografts in patients who had received allogeneic blood transfusions before transplantation. Since this report, there have been numerous studies and reports of the immune effects of transfusion [58]. Microchimerism has been detected decades following transfusion of whole blood and other products containing viable leukocytes [59]. Transfusion-related graft
Transfusion-related acute lung injury
In August 2001, a letter circulated by the US Department of Health and Human Services warned about the possibility of transfusion-related acute lung injury (TRALI) in transfused patients [65]. There have been 45 reported fatalities since 1992. TRALI is thought to be responsible for 13% of all transfusion fatalities, making it the third leading cause of transfusion-related death. Most deaths have been associated with the administration of fresh frozen plasma, but TRALI has also been reported
Leukoreduction
Leukoreduction was first proposed as a goal for the blood industry in 1995 by the FDA. In January 2001, Guidance for Industry [70] was released, arguing in favor of universal leukocyte reduction. In addition, this document set forth industry standards for quality assurance, quality monitoring, registration, and production licensure. The FDA argument accepted most of the reasoning in favor of leukoreduction: transfusion-associated immunomodulation, bacterial overgrowth, viral reactivation,
Pathogen inactivation
Pathogen inactivation has been a goal of blood banking since the 1940s, when the pasteurization of albumin was used to prevent jaundice following its infusion. For stable products such as albumin, there have been advances since the 1980s, such as solvent/detergent processing to nanofiltration methods, in the processes used to create a safer product. This article does not explore the methods used for the purification of nonlabile blood products, because an excellent review of this topic has
Prolonging red blood cell storage
In 1961, Simon et al [76] demonstrated that adenine could be added to red blood cells to prolong their survival. In 1977, Zuck et al [77] demonstrated that this was a viable method of preservation, convincing the FDA to approve adenine for red blood cell storage. With the removal of plasma and the use of additive solutions (AS-1, AS-3, and CPDA-1, CPDA-2 or CPDA-3), the storage life of blood is currently 42 days. Even with these additive solutions, there continues to be a storage lesion
Summary
In the next decade, many of the methodologies and research reviewed in this article will become clinical practice, making the transfusion of blood products safer and more universally available than they are today. NAT will be standard and will surely be performed on each unit of product, PCR testing for pathogens will evolve, and the pathophysiology and immunology of transfusion-related events such as TRALI and immunomodulation will be elucidated. New methods of preservation and early detection
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