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Blood safety initiatives: implications for blood component availability
It is well recognized that the blood supply is the safest that it has ever been. The probability of acquiring a transfusion-transmitted infection is small. Interventions such as the introduction of highly sensitive laboratory screening methodologies, as well as donor selection with focused health questionnaires, have contributed to this low risk. Yet morbidity from blood transfusions still occurs from a condition called transfusion-related acute lung injury, which now represents the most common cause of transfusion-related morbidity and mortality.
The association between transfusion and lung injury has been recognized since the early 1950s when it was believed to be a hypersensitivity reaction. It has since been called an allergic pulmonary edema or noncardiogenic pulmonary edema, but it was in 1985 that transfusion-related acute lung injury (TRALI) was described as a separate clinical entity.
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The clinical features of pulmonary edema may begin in dependant areas, particularly in the lateral decubitus position, and involve the entire lung field during several hours. Ninety percent of symptoms occur within one to two hours with 100% of cases being defined as occurring within six hours of the onset of transfusion. The radiographic features are in general nonspecific and involve patchy infiltrates initially, but evolve to bilateral alveolar and interstitial infiltrates. The hypotension that accompanies TRALI does not respond well to IV fluids, and pulmonary wedge pressures are generally normal to low.
Respiratory distress
Since the differential diagnosis of respiratory distress with transfusion is quite extensive and includes any acute event unrelated to transfusion — or indeed transfusion-associated circulatory overload, which can produce similar symptoms — a consensus conference was held in Canada to more accurately define TRALI.
Recommendations from this consensus conference were that TRALI should be defined broadly as a new episode of acute lung injury occurring during or within six hours of a transfusion, which is not temporally related to another risk factor (see Table). It can thus be appreciated that the clinical symptoms and signs and routine tests are nonspecific and may make the distinction between TRALI and transfusion-associated circulatory overload sometimes difficult. The important issue is that TRALI, if not recognized and treated (often with ventilator support) expeditiously, is associated with a high mortality, whereas earlier recognition and appropriate intervention has a good prognosis.
The exact incidence of TRALI is uncertain, but it is believed to be one in 5,000 and is associated mostly with plasma-containing units. In the United States, at least 25 million plasma-containing units are transfused annually and thus it is estimated that there are 5,000 cases of TRALI per year with a mortality of about 6%, but potentially much higher.
Consequently, the estimated number of fatal cases of TRALI is about 300 per year, although the actual reported cases of TRALI range from 12 to 21 per year. The reason for the under-diagnosis of this condition is probably related to lack of recognition by physicians and that the current definition may be overly restrictive. It is a condition that physicians do not always recognize since the patients who receive transfusions have multiple comorbidities.
The exact pathogenesis of TRALI is uncertain. In most cases it appears to result because the transfusion recipient has white cells that are damaged by donor antibodies. As a consequence, there is activation and aggregation of the recipients’ leukocytes that subsequently leads to pulmonary capillary leakage and alveolar edema. These donor antibodies are generally directed to human leukocyte antigens, although they can be directed to neutrophil specific antigens. HLA antibodies are common (up to 15% in multiparous women, but rare in men).
The United Kingdom has implemented plasma diversion as a strategy to reduce the incidence of TRALI. The recent update from the United Kingdom study of the “serious hazards of transfusion” (SHOT) noted that of 23 cases of suspected TRALI, analyzed in 2004, 13 were “highly likely” or “probable” and that plasma containing products were the most common offending component. All 13 cases where TRALI was diagnosed as highly likely were the result of donations from women with leukocyte antibodies. These antibodies most likely derive from past pregnancies. As a result of the SHOT data, the National Blood Transfusion Service in Britain now selects plasma donations from men only for fresh-frozen plasma transfusions.
Recent blood banking guidelines recommend that transfusion services and blood providers establish policies for evaluating donors involved in TRALI reactions to minimize reoccurrence. The results of a TRALI event investigation would provide guidance for the management of the TRALI-associated donors.
Standardized management
It is suggested that all plasma containing components from TRALI- associated donors would be recalled and quarantined pending the completion of the investigation. The result would be that plasma-containing blood products from these donors would not be transfused in the future. The strategy, of course, is reactionary and may be associated with many uncertainties. These include the fact that antileukocyte antibodies may be detected in TRALI associated donors, but those specificities are not necessarily compatible with the recipient or that the recipient is unavailable for testing.
There is no standardized agreement on how future donations from such donors should be managed. However, what is under serious consideration in the United States is the fact that more individuals requiring fresh-frozen plasma will most likely receive transfusions from male donors only. This is based on the fact that transfusion of plasma, or blood components containing a high volume of plasma, obtained from previously pregnant woman is thought to carry a higher risk for inducing TRALI. The prevalence of these antibodies has not been fully investigated; however, a study funded by the NHBLI called the Leukocyte Antibody Prevalence Study (LAP) is being undertaken to evaluate the prevalence of these antibodies in women compared with men who either have or have not been transfused.
Strategies to reduce the risk for TRALI from apheresis platelets are also being identified. At this time there is not a licensed test for the screening of antibodies to white cells to prevent TRALI. There are some diagnostic tests being investigated as potential screening tests, however. Options to reduce the risk for TRALI include the suggestion that all plasma transfused into individuals requiring fresh-frozen plasma come almost completely from men.
Removing women from apheresis platelet donor panels would critically and adversely affect the availability of apheresis platelet inventories. Screening platelet apheresis donors for HLA antibodies is being considered, but again the HLA antibodies do not necessarily indicate a likelihood of developing TRALI. The donor losses would substantially compromise platelet availability.
Social altruism
The blood supply for our communities is at a critical crossroads. Five years after Sept. 11, the social altruism of rolling up your sleeves to donate blood is beginning to wane. The demand for blood continues to increase, outpacing the supply of eligible blood donors. National statistics suggest that only 5% of eligible people give blood regularly. Blood centers are undergoing more frequent appeals and the real issue is not blood shortages but donor shortages. There is a critical shortage of healthy volunteer blood donors who understand the importance of giving blood and are willing to take an hour out of their busy days to help someone in need.
The recent story from the Associated Press (“Gender Makes a Difference in Blood Donors,” January 25) highlights the additional pressure as a result of concerns about TRALI. It reports the discussion that plasma transfused into victims of burns, car crashes and other serious conditions will now come almost completely from men.
What does this mean for women blood donors? Should they be turned away? Absolutely not! Indeed, as the article implies, women need to donate now more than ever as blood supplies become more precarious each year. The issue of TRALI and its implications on donor selection makes the blood supply even safer, but represents a significant challenge to providers. Health regulations restrict more and more people from giving blood. Also, like many other enterprises in today’s economy, blood centers are forced to do more with less. It is a community’s responsibility to support the blood supply. Every company, school, business, church and community group should either host a blood drive or encourage members to give blood regularly. It is safe and easy, and there is no substitute for the generous gift of a blood donation to a patient in need.
For more information:
- Ronald Sacher, MD, director of the Hoxworth Blood Center at the University of Cincinnati Academic Health Center, is section editor of Hem/Onc Today’s Transfusion Medicine section.
- Popovsky MA, Davenport RD. Transfusion-related acute lung injury: femme fatale? Transfusion. 2001;41:312-313.
- National Blood Service for England and North Wales. SHOT report, 2000-2001: transfusion related acute lung injury. http://www.blood.co.uk/hospitals/.
- MacLennan S. Update on TRALI: reducing the risk. Blood Matters. Winter 2003/2004;14:5-6. Available online at www.blood.co.uk/hospitals/library/pdf/bm14.pdf. Accessed May 29, 2007.
- AABB. Transfusion related acute lung injury. AABB Association Bulletin. August 11, 2005; #05-09.