Statement of
The American Association of Blood Banks
Before the Blood Products Advisory Committee

July 22, 2004

Transfusion-related Acute Lung Injury (TRALI)

Presented by Kay R. Gregory, MS, MT(ASCP)SBB
Director, Regulatory Affairs

AABB is an international association dedicated to advancing transfusion and cellular therapies worldwide. Our members include more than 1,800 hospital and community blood centers and transfusion and transplantation services as well as approximately 8,000 individuals involved in activities related to transfusion, cellular therapies and transplantation medicine. For over 50 years, AABB has established voluntary standards for, and accredited institutions involved in, these activities. AABB is focused on improving health through the advancement of science and the practice of transfusion medicine and related biological therapies, developing and delivering programs and services to optimize patient and donor care and safety.

The American Association of Blood Banks (AABB) believes that transfusion-related acute lung injury (TRALI) is a significant transfusion safety concern that merits increased awareness and research. In an effort to educate our members about the clinical and laboratory features of TRALI, AABB has issued guidelines for the management of TRALI and our association considers this a priority transfusion safety matter. We commend the Food and Drug Administration (FDA) for alerting physicians to the risk of TRALI from transfusion of plasma-containing blood products in 2001. However, we are disappointed that the federal government has not done more to advance needed research regarding this important transfusion safety issue since the Blood Products Advisory Committee (BPAC) last addressed TRALI in 2001.

Definitions

In order to allow for the most effective and meaningful research and clinical understanding of this condition, the AABB proposes that a standard uniform definition of TRALI be established and adopted by the medical community and policy makers, including the FDA. Earlier this year, Canadian Blood Services and Hema-Quebec hosted a valuable consensus conference, bringing together the leading experts to discuss the current state of knowledge regarding TRALI. At the end of this conference, the group recommended definitions of TRALI, and “possible TRALI” (see attached definitions).

In general, the group recommended that TRALI should be diagnosed in patients with no acute lung injury (ALI) prior to transfusion who, during or within six hours after transfusion, experienced certain specific criteria. They distinguished “possible TRALI” cases, which would involve patients with the same criteria who also had one or more temporally associated ALI risk factors.

The AABB endorses the definitions set forth during the consensus conference and urges the FDA to adopt these definitions as well. Emerging data and research regarding TRALI should be carefully monitored to determine if refinements to these definitions are necessary over time.

Research

Using the uniform definitions, AABB recommends that additional research be conducted to define the scope of the problem and its mechanisms or pathophysiology. As we proposed to BPAC in 2001, AABB continues to advocate a prospective epidemiologic study to establish the incidence of TRALI. For example, we propose a multi-center study of acute lung problems in the transfusion setting to assess, evaluate, and analyze all pulmonary reactions using a standardized protocol.

The AABB also continues to recommend that the National Heart, Lung and Blood Institute (NHLBI) establish a multi-center study to lead to a better understanding of the mechanisms that cause TRALI. Once the mechanisms of TRALI are better understood, the risk factors in donors and recipients may become apparent.

Donor Deferrals

The AABB continues to believe that more data are needed before establishing donor deferral criteria or other regulatory strategies for TRALI. When a severe clinical reaction has occurred, an antibody has been identified in the donor and the recipient has the corresponding antigen, the preventive measure is relatively clear. In such cases, it is generally agreed that blood from that donor should not ever again be transfused to the same recipient. However, it is not so clear that such a donor should be permanently deferred from donating all blood components. The appropriate preventive measures are even less obvious for the majority of pulmonary reactions that occur in the transfusion setting.

It is important to understand what proportion of the donor population would be affected by proposed deferral criteria or other regulatory strategies, so that the potential impact on the blood supply can be evaluated. These data are especially critical, as we already too frequently face blood shortages in regions across the country. A careful and thorough analysis of the risks and benefits of any donor deferrals or any other regulatory strategy must be completed before taking steps that could unnecessarily hinder patient access to life-saving blood components.

Consensus Conference Definitions

TRALI:

For patients with no Acute Lung Injury (ALI) prior to transfusion, the diagnosis of TRALI is made if, during or within six hours after completion of transfusion, there is:

• Acute onset of respiratory distress
• Hypoxemia, as defined by one of the following:
  • PaO2/FI02<300 mm Hg or
  • Oxygen saturation is <90% on room air or
  • Other clinical evidence
• Bilateral lung infiltration in the chest radiograph
• No evidence of circulatory overload
• No other temporally associated ALI risk factor(s)

“Possible TRALI:”

For patients with no ALI prior to transfusion, the diagnosis of POSSIBLE TRALI is made if, during or within six hours after completion of transfusion, there is:

• Acute onset of respiratory distress
• Hypoxemia, as defined by one of the following:
  • PaO2/FI02<300 mm Hg or
  • Oxygen saturation is <90% on room air or
  • Other clinical evidence
• No evidence of circulatory overload
• Bilateral lung infiltration in the chest radiograph
• One or more temporally associated ALI risk factor(s)

The risk factors for ALI which if pre-existing prior to transfusion distinguish TRALI from “possible TRALI” include:

• Septic shock
• Sepsis
• Aspiration
• Lung contusion
• Pneumonia ICU
• Multiple trauma
• Drug overdose
• Burn injury
• CP bypass
• Inhalation injury
• Acute pancreatitis