Transfusion-related acute lung injury

Prabakaran Sankaralingam*

Consultant, Transfusion Medicine, Kauvery Hospitals, Trichy, Tamil Nadu, India

*Correspondence: prabakaran@uyirthuli.co.in

Background

The transfusion of blood products is occasionally complicated by acute lung injury (ALI), which can progress to the acute respiratory distress syndrome (ARDS).

TRALI, has been defined as new ALI occurring during or within six hours after a transfusion.

Virtually all blood products have been implicated in TRALI. Infusions of whole blood, platelets, packed red blood cells, and fresh frozen plasma are the most commonly identified precipitating causes, but case reports also implicate transfusion of allogeneic stem cells, cryoprecipitate, intravenous immunoglobulin, and granulocytes.

Pathogenesis

Hypotheses: There are three leading theories regarding the cellular and molecular mechanisms underlying the increase in pulmonary vascular permeability that initiates the syndrome of TRALI.

  1. Anti-granulocyte antibodies: This leading theory posits that anti-granulocyte antibodies contained in the donor’s plasma react with antigens on the recipient’s granulocytes to initiate an inflammatory response within the pulmonary microvasculature.
  2. Granulocyte priming: This theory contends that biologically active substances, such as lipids and cytokines contained within the transfusions, have the ability to prime the activity of granulocytes in the pulmonary vasculature, contributing to increased vascular permeability.
  3. Two event hypotheses: A “two-event” hypotheses combining the two above theories has also been proposed. This composite theory holds that recipient granulocytes are primed, either by transfused active substances or by virtue of the patient’s underlying clinical condition. Transfused antibodies then “activate” these functionally hyperactive granulocytes.

Anti-leukocyte antibodies are more likely to be found in blood donated by multiparous women than in blood donated by men, most likely due to sensitization to fetal antigens during pregnancy.

  1. An accumulation of soluble CD40 ligand has been noted in units of stored platelets, and significantly higher levels are found in donor units implicated in clinical cases of TRALI than those without reported transfusion reaction.
    transfusion-related-acute-lung-injury

Fig. 1. The two-hit model of TRALI. The first hit consists of patient factors resulting in priming of the pulmonary neutrophils. Risk factor have been suggested that might function as a first hit. The second hit is the blood transmission resulting in activation of the endothelial cells, and the primed pulmonary neutrophils resulting in capillary leakage, culminating in pulmonary oedema. Some transfusion factors are independent of the type of blood product, whereas others are specific for a type of product. RBC = red blood cells. HLA = human leucocyte antibodies, HNA = human neutrophils antibodies, sCD40L = soluble CD40 ligand, FFP = fresh frozen plasma, PLT = platelet concentrate.

transfusion-related-acute-lung-injury-2

Epidemiology

The incidence of TRALI is not well established. Incidence of TRALI is approximately one case for every 1000 to 2400 units transfused (Fresh Frozen Plasma-FFP > Platelet Concentrate > Packed RBC > SAGM (SAGM is currently the standard additive solution) PRBC > Apheresis Components). However, most survivors recover completely with appropriate supportive care and can receive additional blood products in the future.

Risk factors

TRALI has been reported in an age range between 9 days to 73 years, and equally in both sexes.

  1. Prolonged storage of transfused products,
  2. Use of fresh frozen plasma (FFP), and
  3. The presence of an underlying condition such as recent surgery, cytokine treatment, thrombocytopenia, massive blood transfusion, and active infection have been implicated.

The risk of TRALI does not correlate with the volume of plasma infused or the titer of the anti-leukocyte antibody. Theoretically, leuko-reduced products should pose a lower risk, but no product is known to be truly risk-free.

Clinical Presentation

The characteristic clinical presentation of TRALI is the sudden onset of respiratory distress during or shortly after the transfusion of blood products. Symptoms may be delayed as long as six hours, but usually begin within one to two hours following the infusion.

Fever, tachycardia, and tachypnea are common clinical signs of TRALI; hypotension may be present. Among patients requiring intubation, elevated peak airway pressures and frothy pink airway secretions indicative of pulmonary edema may be observed.

Chest Radiography: reveals bilateral patchy alveolar infiltrates, classically with a normal cardiac silhouette and without effusions, consistent with acute respiratory distress syndrome (ARDS).

 

transfusion-related-acute-lung-injury-3

 

 

Fig. 2. Chest radiographs of patients presenting with transfusion-related acute lung injury (TRALI). Chest radiographs of two patients before (A, C) and (B, D) onset of TRALI. Radiographs A and C show normal pulmonary vasculature with no signs of pulmonary oedema; B and d show infiltrative changes suggestive of pulmonary edema. D shows the classic severe bilateral infiltrative changes that prevent with TRALI; however, frequently such changes are less apparent with chest X rays as shown in B.

Eosinophilia and an acute but transient drop in the peripheral neutrophil count have been reported in association with TRALI, but the cause and significance of these change are unknown.

Resolution often occurs rapidly, even when initial hypoxemia is severe. Most patients can be extubated within 48 h, and chest radiographs typically return to normal within four days, although hypoxemia and pulmonary infiltrates persist up to seven days in a minority of patients. Patients who are slow to recover have no distinguishing features in their initial course. Despite the favorable overall prognosis, the mortality of TRALI is estimated at 5 percent. There are no clear prognostic factors that influence mortality. Survivors usually recover to their baseline pulmonary function without apparent sequelae.

Diagnosis

TRALI should be considered whenever dyspnea, hypoxemia, and pulmonary infiltrates occur during or within 6 h after transfusion of any blood product.

Differential diagnosis of this clinical presentation is:

  1. acute intravascular volume overload,
  2. hemolytic transfusion reactions, or
  3. anaphylaxis due to the transfusion of IgA-containing products to a recipient with IgA deficiency

The finding of granulocyte, leukoagglutinating, or lymphocytotoxic antibodies in serum from either the donor or the recipient may support the diagnosis of TRALI.

Additional supporting serologic results include a decline in C3 or C5a levels 12 to 36 h after the onset of symptoms, followed by a significant rise 4 to 7 days later.

TRALI versus volume overload: Differentiating between TRALI and transfusion-associated circulatory overload (TACO) can be difficult. Findings supporting a diagnosis of TACO include physical findings suggesting volume overload (such as elevated jugular venous pressure), elevated systolic blood pressure near the time when dyspnea developed, a widened pulmonary vascular pedicle on chest radiography, and, if measured, an increase in the circulating level of brain natriuretic peptide (BNP) or NT-Pro-BNP shortly after, and even occasionally before, transfusion.

Treatment

Management of the patient with TRALI is supportive, with the expectation that clinical improvement will occur spontaneously as lung injury resolves. Mechanical ventilation is often required for several days, and a high concentration of inspired oxygen and positive end-expiratory pressure may be required. Milder cases can be managed with supplemental oxygen alone.

Ventilator management should be guided by the same principles (e.g., low tidal volumes and plateau pressures) used in patients with ARDS. Extracorporeal Membrane Oxygenation (ECMO) has been used successfully in a severe case of TRALI following coronary artery bypass surgery.

Administration of a diuretic should be considered when pulmonary edema develops in association with blood product transfusion, particularly when the distinction between TRALI and TACO is uncertain.

Intravenous corticosteroids have been advocated by some studies.

Subsequent use of blood products

The recipient: Individuals who have developed TRALI should receive no further plasma-containing blood products from the implicated donor. Patients who recover from TRALI do not appear to be at increased risk for recurrent episodes following transfusions from other donors; however, published experience is limited.

The donor: Following a case of TRALI, the blood bank and the blood collection facility should investigate the donor

Prevention: Several blood donor management strategies have been proposed as ways to reduce the incidence of TRALI.

  1. Producing FFP only from male donors
  2. Screening previously-pregnant and previously-transfused apheresis donors for HLA antibodies
  3. Improving tests for the detection of white blood cell antibodies
Dr-prabakaran-sankaralingam

Dr. Prabakaran Sankaralingam

Transfusion Medicine

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