TRALI syndrome is an acute lung injury that occurs within 6 hours after a transfusion of blood or blood components, such as fresh frozen plasma, erythrocyte or platelet mass. The clinical picture consists of symptoms of acute respiratory failure – shortness of breath, cough with the discharge of foamy sputum, arterial hypotension. Hyperthermia is sometimes observed. The diagnosis is made on the basis of clinical, laboratory and radiological signs of respiratory failure in a patient who underwent blood transfusion. Treatment includes discontinuation of transfusion, oxygen therapy, and, if necessary, mechanical ventilation.
TRALI syndrome is a transfusion-associated respiratory distress syndrome . This condition was first described in 1951. The incidence rate in men and non-pregnant women is the same, amounting to 0.4-1.6 cases per 1,000 patients who underwent blood transfusion . Somewhat more often, pathology develops with plasma transfusion . In a number of countries, TRALI syndrome is considered the most common complication of blood transfusion and ranks 3rd among the causes of death associated with blood transfusions.
Causes of TRALI syndrome
In the overwhelming majority of cases, the etiological factor is the presence of specific antibodies in the donor’s blood that interact with the HLA system antigens expressed on the membranes of the recipient’s leukocytes. The formation of antigen-antibody complexes leads to the activation of neutrophils, which trigger a cascade of pathological reactions.
Another reason for the development of pathology is considered to be the entry into the recipient’s body of the decay products of cell membranes – biologically active lipids (lysophosphatidylcholines) contained in donor blood with a long preparation period. Risk factors that increase the likelihood of TRALI syndrome are pregnancy and diseases requiring massive blood transfusion – extensive blood loss, hemoblastosis , cytostatic disease.
Activated neutrophils begin to secrete inflammatory mediators (cytokines, interleukins, tumor necrosis factor), reactive oxygen species, and the proteolytic enzyme elastase. This leads to damage to the endothelial barrier of the pulmonary capillaries, an increase in vascular permeability and plasma sweating. Excessive release of nitric oxide leads to severe vasodilation and the development of hypotension.
Agglutination of neutrophilic leukocytes occurs, that is, their gluing together. The released platelet activating factor stimulates the aggregation of formed elements and the formation of blood clots. The prevailing lung damage in TRALI syndrome is explained by the fact that about 2/3 of the neutrophil pool is in the pulmonary circulation.
When transfusing blood containing specific antibodies, a significant portion of neutrophils agglutinate and damage the microvasculature of the lungs. Pathological examination in the lungs reveals diffuse leukocyte infiltration, stasis of polymorphonuclear leukocytes in the pulmonary capillaries, destruction of the pulmonary parenchyma.
According to the pathogenetic mechanism, there are 2 types of TRALI syndrome:
- Immune-mediated . Caused by the presence of antineutrophilic antibodies in the components of the transfused blood.
- Non-immune-mediated. Damage to the pulmonary endothelium is caused by biologically active substances that are contained in long-term stored blood.
According to the clinical course, the following types of TRALI syndrome are distinguished:
- Classical. It is characterized by the rapid onset of symptoms after transfusion (within 2-6 hours), almost complete resolution of pathological changes and low mortality.
- Deferred. Typically gradual development (6 to 72 hours), no fever, slow progression, and higher death rates.
The clinical picture of the disease includes signs of pulmonary edema and respiratory failure . At first, breathing is difficult on inhalation and exhalation ( shortness of breath of a mixed nature ), then a cough with foamy sputum joins . As the shortness of breath worsens, the patient becomes more agitated, and the heart rate and respiratory rate increase. Sometimes the body temperature rises to febrile digits.
The most specific symptom of TRALI syndrome is a decrease in blood pressure. Patients develop dizziness, darkening in the eyes, general weakness . With a decrease in the oxygen content in arterial blood less than 60 mm Hg. Art. the lips, tip of the nose and fingers acquire a bluish tint, the auxiliary muscles are involved in the breathing process – the muscles of the neck, upper shoulder girdle, and back. Respiratory rate less than 12 per minute. Sometimes abnormal breathing is observed: Cheyne-Stokes, Biota, etc.
TRALI syndrome is a serious, life-threatening condition and requires urgent medical attention. Without timely diagnosis and treatment, death occurs. The cause of death is almost always acute respiratory failure . With rapidly developing hypoxemia, the patient may lose consciousness.
Patients with a subclinical course and slowly progressive respiratory dysfunction are likely to develop hypoxic or hypercapnic coma. Complications are associated with a compensatory increase in cerebral blood flow, increased intracranial pressure and cerebral edema .
Usually, the management of patients with TRALI syndrome is carried out by anesthesiologists-resuscitators and transfusiologists . A decisive moment in diagnosis is the presence of a clear connection between blood transfusion and the onset of symptoms. To confirm the diagnosis, the following are prescribed:
- Laboratory research. In the general analysis of blood in patients with immune-mediated TRALI-syndrome, transient leukopenia is sometimes noted . The presence of antibodies to HLA and alloantigens of neutrophils in the blood of the donor and antileukocyte antigens in the recipient is determined. A positive test for lymphatic cross-over is typical. Normal brain natriuretic peptide levels can rule out left ventricular dysfunction.
- Study of the gas composition of the blood. Characterized by a decrease in the partial pressure of arterial blood oxygen, the fraction of oxygen during inspiration, and the respiratory index. When conducting pulse oximetry , a decrease in saturation (blood oxygen saturation) is detected.
- X-ray examinations. On a chest x-ray , a picture of pulmonary edema is determined – diffuse infiltration of the lungs up to a total darkening of the pulmonary fields. A distinctive feature of these changes is their rapid disappearance during treatment.
- Study of aspirate from the bronchi. Biochemical analysis of the aspirate obtained during bronchoalveolar lavage reveals a high protein content, close to the concentration in serum.
Differential diagnosis is carried out with cardiogenic pulmonary edema , respiratory distress syndrome of a different etiology, pneumonia . It is necessary to distinguish this condition from other complications associated with transfusion of blood and its components – hemodynamic overload syndrome (TACO syndrome), anaphylactic transfusion reactions.
Treatment of TRALI syndrome
All patients must be in the intensive care unit. The first stage of treatment is the immediate cessation of blood transfusion. This event is considered both etiotropic and pathogenetic therapy. The appointment of glucocorticosteroids is theoretically justified to suppress immunological inflammation, but there is no convincing evidence of the benefits of drugs in this pathology.
The diuretic furosemide, traditionally used in the treatment of pulmonary edema, is strictly contraindicated, like other diuretics, since these medications aggravate arterial hypotension. The rest of the treatment methods are symptomatic and are used depending on the severity of the patient’s condition:
- Oxygen therapy . In case of respiratory failure of the 1st degree, to stop hypoxemia, it is sufficient to prescribe oxygen inhalations through a nasal catheter or a face mask. With severe respiratory dysfunction, extracorporeal membrane oxygenation is used.
- Mechanical ventilation . Severe respiratory failure is an indication for connecting the patient to a ventilator. Ventilation is performed in the mode of low tidal volume and low inspiratory pressure.
- Infusion therapy. To correct arterial hypotension, intravenous infusions of colloidal and crystalloid solutions are used through a central catheter under the control of CVP and diuresis.
- Vasopressors. If the infusion correction of blood pressure is ineffective, drugs are prescribed that cause vasoconstriction and increased cardiac output – dopamine, norepinephrine.
Forecast and prevention
TRALI syndrome is a severe life-threatening complication of blood transfusion with a poor prognosis. The mortality rate, according to various sources, ranges from 5 to 10%. The overwhelming majority of deaths are caused by plasma transfusion (about 50%). Prevention is of great importance, especially at the stage of collecting donated blood.
The main preventive measures are the use of washed red blood cells, screening donated blood for anti-HLA antibodies, and procurement of fresh frozen plasma only from male or female donors who have not had a pregnancy. Another way to reduce the risk of TRALI syndrome is to remove leukocytes from donated blood using special filters.