TRALI is an acute lung injury that occurred within 6 hours after transfusion of blood or its components, for example, freshly 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. Sometimes hyperthermia is observed. The diagnosis is made on the basis of clinical, laboratory and radiological signs of respiratory failure in a patient who has undergone hemotransfusion. Treatment includes termination of transfusion, oxygen therapy, and, if necessary, a ventilator.
ICD 10
T80.8 Other complications associated with infusion, transfusion and therapeutic injection
General information
TRALI syndrome is a transfusion-associated respiratory distress syndrome. This condition was first described in 1951. The frequency of occurrence in men and non-pregnant women is the same, it is 0.4-1.6 cases per 1,000 patients who underwent hemotransfusion. Pathology develops somewhat more often with plasma transfusion. In a number of countries, TRALI is considered the most common complication of transfusion of blood components and ranks 3rd among the causes of mortality associated with blood transfusions.
Causes of TRALI
In the vast majority of cases, the etiological factor is the presence of specific antibodies in the donor’s blood that interact with HLA antigens expressed on the recipient’s leukocyte membranes. The formation of antigen-antibody complexes leads to the activation of neutrophils, triggering 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 shelf life. Risk factors that increase the likelihood of TRALI are pregnancy and diseases requiring massive hemotransfusion – extensive blood loss, hemoblastosis, cytostatic disease.
Pathogenesis
Activated neutrophils begin to secrete inflammatory mediators (cytokines, interleukins, tumor necrosis factor), reactive oxygen species, 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 entails pronounced vasodilation and the development of hypotension.
There is agglutination of neutrophilic leukocytes, that is, their gluing together. The released platelet activation factor stimulates the aggregation of shaped elements and the formation of blood clots. The prevailing lung lesion in TRALI is explained by the fact that about 2/3 of the neutrophil pool is located in the small circulatory circle.
During transfusion of blood containing specific antibodies, a significant part of neutrophils agglutinate and damage the microcirculatory bed of the lungs. Pathoanatomic examination reveals diffuse leukocyte infiltration in the lungs, stasis of polymorphonuclear leukocytes in the pulmonary capillaries, destruction of the pulmonary parenchyma.
Classification
According to the pathogenetic mechanism , there are 2 types of TRALI:
- Immuno-mediated. Caused by the presence of anti-neutrophil antibodies in the components of transfused blood.
- Non-muno-mediated. Damage to the pulmonary endothelium is caused by biologically active substances contained in long-term stored blood.
According to the clinical course , the following varieties of TRALI are distinguished:
- Classic. It is characterized by the rapid appearance of symptoms after transfusion (within 2-6 hours), almost complete resolution of pathological changes and low mortality.
- Deferred. Typically, gradual development (from 6 to 72 hours), absence of fever, slow course and a higher percentage of deaths.
Symptoms of TRALI
The clinical picture of the disease includes signs of pulmonary edema and respiratory failure. At first, breathing becomes 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, the heart rate and respiratory movements increase. Sometimes the body temperature rises to febrile numbers.
The most specific symptom of TRALI is a decrease in blood pressure. Patients develop dizziness, darkening of the eyes, general weakness. With a decrease in the oxygen content in arterial blood of less than 60 mm Hg. the lips, the tip of the nose and fingers acquire a bluish hue, auxiliary muscles are involved in the breathing process – the muscles of the neck, upper shoulder girdle, back. The frequency of respiratory movements is less than 12 per minute. Sometimes there is pathological breathing: Cheyne-Stokes, Biota, etc.
Complications
TRALI is a serious condition, poses a threat to life and requires urgent medical intervention. Without timely diagnosis and treatment, a fatal outcome occurs. The cause of death is almost always acute respiratory failure. With rapidly developing hypoxemia, the patient may lose consciousness.
In patients with a subclinical course and slowly progressive respiratory dysfunction, there is a possibility of hypoxic or hypercapnic coma. Complications are associated with a compensatory increase in cerebral blood flow, increased intracranial pressure and cerebral edema.
Diagnostics
Usually, patients with TRALI are managed by anesthesiologists, resuscitators and transfusiologists. The crucial point in the diagnosis is the presence of a clear connection between hemotransfusion and the appearance of symptoms. To confirm the diagnosis , the following are prescribed:
- Laboratory tests. In a general blood test in patients with immuno-mediated TRALI, transient leukopenia is sometimes noted. The presence of antibodies to HLA and neutrophil alloantigens in the blood of the donor and antileukocyte antigens in the recipient is determined. A typical positive test for cross-lymphotoxicity. The normal level of the cerebral natriuretic peptide makes it possible to exclude left ventricular dysfunction.
- Study of the gas composition of blood. It is characterized by a decrease in the partial pressure of arterial blood oxygen, oxygen fraction on inspiration, respiratory index. During pulse oximetry, a decrease in saturation (oxygen saturation of the blood) is detected.
- X-ray examinations. On the chest X-ray, the picture of pulmonary edema is determined – diffuse infiltration of the lungs up to total darkening of the pulmonary fields. A distinctive feature of these changes is the rapid disappearance during treatment.
- Examination of aspirate from the bronchi. A 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 blood transfusion and its components – hemodynamic overload syndrome (TACO syndrome), anaphylactic transfusion reactions.
TRALI Treatment
All patients should be in the intensive care unit and intensive care unit. The first stage of treatment is the immediate cessation of blood transfusion. This measure 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 benefit of drugs in this pathology.
Traditionally used in the treatment of pulmonary edema, the diuretic furosemide is strictly contraindicated, as are other diuretics, since these medications aggravate arterial hypotension. The remaining methods of treatment are symptomatic and are used depending on the severity of the patient’s condition:
Oxygen therapy. In case of respiratory insufficiency of the first degree, it is sufficient to prescribe oxygen inhalations through a nasal catheter or a facial mask to relieve hypoxemia. With severe respiratory dysfunction, extracorporeal membrane oxygenation is resorted to.
VENTILATOR. Severe respiratory failure is an indication for connecting the patient to a ventilator. Ventilation is carried out in the mode of low respiratory volume and low pressure on inspiration.
Infusion therapy. To correct arterial hypotension, intravenous infusions of colloidal and crystalloid solutions are used through a central catheter under the control of CVD and diuresis.
Vasopressors. If the infusion correction of blood pressure is ineffective, drugs are prescribed that cause vasoconstriction and increased cardiac output – dopamine, norepinephrine.
Prognosis and prevention
TRALI is a severe life-threatening complication of hemotransfusion with an unfavorable prognosis. The mortality rate, according to various data, ranges from 5 to 10%. The predominant number of deaths is caused by plasma transfusion (about 50%). Prevention is of great importance, especially at the stage of harvesting donor blood.
The main preventive measures are the use of washed erythrocytes, screening of donor blood for the presence of antibodies against HLA and the procurement of freshly 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 the donor blood using special filters.
