Transfusion-Related Acute Lung Injury and the ICU

Platelet transfusion is one of the most crucial therapeutic approaches in Medicine. However, severe and fatal adverse reactions may develop. In addition to their important function in hemostasis, platelets’ role in inflammation has become more evident. Recently, platelets are also recognized as the main source of circulating soluble CD40 ligand (sCD40L, (CD154)), which plays significant roles in hemostasis, platelet activation, clot stability, interactions with other cells, and upregulation of different mediators.

In this review, we will briefly highlight the importance of platelet transfusion, its role in inflammatory and thrombotic transfusion reactions, and visit the most recent findings on sCD40L.

El término TRALI (transfusion related acute lung injury ‘lesión pulmonar aguda producida por transfusión’) fue acuñado en 1985. Es un síndrome clínico relativamente raro, que puede constituir una amenza para la vida y que se caracteriza por insuficiencia respiratoria aguda y edema pulmonar no cardiogénico durante o después de una transfusión de productos hemáticos. Aunque su verdadera incidencia es desconocida se le ha atribuido un caso por cada 5.000 transfusiones de cualquier producto hemático y ha sido la causa más frecuente de muerte relacionada con la transfusión durante 3 años en Estados Unidos. Se han propuesto 2 etiologías. La primera es un episodio mediado por anticuerpos debido a la transfusión de anticuerpos contra el antígeno leucocitario o anticuerpos antigranulocito a pacientes cuyos leucocitos presentan antígenos afines. La segunda es un modelo en el que se precisan 2 eventos: el primero está relacionado con el cuadro clínico del receptor (sepsis, trauma, etc.) que produce activación endotelial y secuestro de neutrófilos, y el segundo es la transfusión de sustancias con capacidad de modificar la respuesta biológica que activa los leucocitos adheridos que produce daño endotelial y aumento de permeabilidad capilar. El tratamiento es de soporte en función de la gravedad del cuadro clínico, y la prevención se centra en 3 estrategias: selección de donantes, actuación sobre el almacenamiento de los productos hemáticos y evitar las transfusiones innecesarias.

The term Transfusion-Related Acute Lung Injury (TRALI) was coined in 1985. It is a relatively rare, life-threatening clinical syndrome characterized by acute respiratory failure and non-cardiogenic pulmonary edema during or following a blood transfusion. Although its true incidence is unknown, a rate 1 out of every 5000 transfusions has been quoted. TRALI has been the most common cause of transfusion-related fatalities during three years in the USA. Two different etiologies have been proposed. The first is a single antibody-mediated event involving the transfusion of anti-HLA or antigranulocyte antibodies into patients whose leukocytes express the cognate antigens. The second is a two-event model: the first event is related to the clinical condition of the patient (sepsis, trauma, etc.) resulting in pulmonary endothelial activation and neutrophil sequestration, and the second event is the transfusion of a biologic response modifier that activates these adherent polymorphonuclear leukocytes resulting in endothelial damage and capillary leak. The patient management is support as needed based on the severity of the clinical picture and strategies to prevent TRALI are focused on: donor-exclusion policies, product management strategies and avoidance of unnecessary transfusions.

To reduce the incidence of transfusion-related acute lung injury (ALI), the American Association of Blood Banks recently recommended rapid implementation of strategies to minimize transfusion of high plasma volume components, fresh frozen plasma and apheresis platelets, from potentially alloimmunized donors, especially females. The objective of this study was to evaluate the effect of transfusing components from male-only vs. female donors on development of ALI, gas exchange, and outcome in critically ill patients.

In this retrospective case-control study, we identified patients who received high plasma volume components from male-only donors and compared them with patients matched by severity of illness, postoperative state, and number of transfusions but who received high plasma volume components from female donors.

Four intensive care units at a tertiary medical center.

Critically ill patients who received >2 units of fresh frozen plasma or apheresis platelets.

None.

From a database of 3,567 patients who received a total of 46,101 units of fresh frozen plasma and 6,251 units of apheresis platelets, we identified 112 patients who received three or more male-only donor components and 112 matched controls. Baseline characteristics, ALI risk factors, and development of ALI were similar between the two groups. Arterial oxygenation (Pao₂/Fio₂) worsened after the female (mean difference −52, 95% confidence interval −14 to −91, p = .008) but not after male-only donor product transfusion (mean difference 22, 95% confidence interval −23 to 67, p = .325). Male-only component recipients had more ventilator-free days (median 28 vs. 27, p = .006) and a trend toward lower hospital mortality rates (14% vs. 24%, p = .054).

In critically ill recipients of high plasma volume components, gas exchange worsened significantly after transfusion of female but not male donor components. Prospective studies are needed to evaluate the effect of recommendations by the American Association of Blood Banks on outcome of transfused critically ill patients.