What is Transfusion-Related Acute Lung Injury?
Transfusion reactions are unfortunate events that happen after receiving a transfusion of blood products. These products can include general blood, fresh frozen plasma, platelets, cryoprecipitate, granulocytes, intravenous immune globulin, allogenic and autologous stem cells, and red blood cells packed together. One type of these reactions is Transfusion-related acute lung injury (TRALI).
TRALI is a serious condition that involves sudden, non-heart-related fluid buildup in the lungs, causing a lower level of oxygen in the blood. This usually happens while getting a transfusion or soon after. It’s important to note that in the US, TRALI is the most common cause of death related to transfusions as recorded by the US Food and Drug Administration (FDA). Specifically, the risk of experiencing TRALI is estimated to be 1 in 5000 for red blood cell transfusions, 1 in 2000 for plasma-containing components, and 1 in 400 for transfusions with whole-blood-derived platelets.
TRALI was first identified in the 1950s but was only recognized as a distinct condition in 1983. A diagnosis of TRALI is usually based on a patient’s symptoms and confirmed with X-ray images. TRALI can typically be diagnosed if symptoms occur during or within 6 hours of getting a transfusion and no other causes of acute lung injury are present. Symptoms include fever, low blood pressure, and rapid heart rate. Clinical signs include fluid in both lungs seen on a chest X-ray, no signs of fluid overload in the lung’s blood vessels, and low oxygen levels in the blood. A possible diagnosis of TRALI is made when other causes of acute lung injury are present, and delayed TRALI is diagnosed when symptoms occur from 6 to 72 hours after a transfusion, which can be associated with a greater risk of death.
Before confirming TRALI, other potential diagnoses such as transfusion-related circulatory overload, which can display similar lung-related symptoms, must be excluded. In the US, any incidences of TRALI should be reported to Blood Banking services.
What Causes Transfusion-Related Acute Lung Injury?
: True TRALI, a type of lung injury, should ideally have no risk factors according to its diagnostic criteria. TRALI is caused by harm to the small blood vessels in the lungs due to an overactive response from neutrophils, a type of white blood cell. This response can be triggered by certain types of proteins (HNA or HLA antibodies) present in the donated blood which bind to the recipient’s cells.
Storing blood products can also lead to a buildup of inflammation-causing substances that can trigger TRALI. To understand how this happens, medical professionals use a ‘two-hit’ theory. First, the neutrophils become trapped in the blood vessels of the lungs. Then, these same neutrophils start to harm the layer of cells that line the inside of the blood vessels, causing proteins and fluids to leak into spaces in the lungs where air would normally be.
Risk Factors and Frequency for Transfusion-Related Acute Lung Injury
TRALI, or transfusion-related lung injury, is a condition whose risk can increase due to several factors known as comorbidities. These include being on a ventilator, having a major infection known as sepsis, receiving a large number of blood transfusions, undergoing heart bypass surgery, and having advanced liver disease. Moreover, it has been observed that this condition may occur more often with plasma from female donors, particularly those who have had children and carry certain antibodies. Products containing high quantities of plasma also seem to increase the rate of TRALI.
Patients who are critically ill are more susceptible to TRALI. This is not only because they may receive more blood transfusions, but also due to their illness causing a build-up of immune cells known as neutrophils even before the blood transfusion, which further increases their risk of developing TRALI.
In the United States, TRALI is a major concern as it has been accountable for around 30% of deaths related to transfusions. Despite a decrease in mortality rates over the past ten years, ongoing awareness of this issue is crucial.
- TRALI risk factors include being on a ventilator, having sepsis, receiving multiple transfusions, heart bypass surgery, and advanced liver disease.
- TRALI might occur more with plasma from female donors, especially those who have had children and carry specific antibodies.
- Transfusing products with high plasma content may increase TRALI occurrence.
- Critically ill patients are at a higher risk of TRALI due to receiving more blood transfusions and the presence of high levels of neutrophils before the transfusion.
- TRALI accounts for about 30% of transfusion-related deaths in the US.
- Though mortality rates from TRALI have dropped, continued awareness is essential.
Signs and Symptoms of Transfusion-Related Acute Lung Injury
Before a blood transfusion, it’s important for medical professionals to take a thorough medical history and do a physical exam to understand the patient’s health condition. Usually, a transfusion might be needed if the patient’s hemoglobin, a protein in red blood cells, is below 7, or if the person is bleeding heavily and needs extra red blood cells. In situations where coagulation, or the blood’s ability to clot, is abnormal, FFP (fresh frozen plasma) or cryoprecipitate might be used to correct it before any major procedures or emergency surgery.
Patients can get symptoms of an immune reaction to the transfusion, known as TRALI (Transfusion-related Acute Lung Injury), within the first 6 hours after the transfusion, or from 6 to 72 hours afterwards. Signs of TRALI may include a fever over 100.4 Fahrenheit (or 37 Celsius), low blood pressure and sudden shortness of breath that could need more oxygen or a breathing machine. Patients may appear to be struggling to breathe and may use extra muscles to help their breathing. But, because TRALI isn’t caused by fluid overload or heart-related fluid in the lungs, their neck veins don’t bulge. When their lungs are examined, they might have rales (which sound like crackles) and the breath sounds might be quieter due to fluid buildup in the lungs. It’s important to note, it’s often hard to tell the difference between TRALI and a similar condition, ARDs (Acute Respiratory Distress Syndrome), based on the patient’s symptoms.
Testing for Transfusion-Related Acute Lung Injury
A chest X-Ray can reveal the presence of unusual shadows or “infiltrates” in both lungs. TRALI, a medical condition that affects the lungs, can be recognized through several symptoms. These include sudden shortness of breath, low oxygen levels in the body, fever, low blood pressure, fast heart rate, a lower than normal white blood cell count, a lower than normal platelet count, and fluid build-up in the lungs that’s not caused by heart problems.
It’s worth noting that nearly 30% of people with this condition may have low levels of BNP, a protein that’s usually high when the heart is working too hard. They may also experience a temporary decrease in white blood cells.
Treatment Options for Transfusion-Related Acute Lung Injury
If you experience TRALI, which stands for Transfusion-Related Acute Lung Injury, the first step is to stop the blood transfusion. Then, the blood from your donor will be checked for certain antibodies that might have caused this reaction. These antibodies can go against leukocytes (white blood cells), HLA (human leukocyte antigens which are found on the surface of almost all cells in your body), or against specific neutrophil (a type of white blood cell) antibodies.
In terms of support, the main focus will be on improving your oxygen levels. TRALI behaves quite similarly to a condition known as Acute Respiratory Distress Syndrome (ARDS). In such cases, applying a small volume of air (low tidal volume) during mechanical ventilation (breathing support) is generally the recommended approach since it can help reduce lung damage.
However, the best way to deal with TRALI is to prevent it from happening in the first place. In the United Kingdom, for instance, they were able to reduce the number of TRALI cases by using plasma (the liquid part of the blood) from male donors and by testing female donors for the types of antibodies that heighten the risk of developing TRALI.
Once the transfusion is halted, recovery usually takes between 2 to 4 days, with improvements visible on chest x-rays within 2 to 5 days.
What else can Transfusion-Related Acute Lung Injury be?
If a patient has a transfusion reaction which results in acute shortness of breath and radiographic evidence of fluid in both lungs, doctors may consider transfusion-associated circulatory overload (TACO) as a possible cause. TACO has similar symptoms to another condition called TRALI, but there are certain differences that allow doctors to distinguish between the two.
Patients with TACO may display symptoms such as fever and low blood pressure. Interestingly, TACO can still occur in patients who had a normal fluid balance before getting a transfusion. This is typically seen in patients who have consumed a lot of fluids prior to the transfusion. Symptoms of TACO such as visible neck vein distension are due to overload of fluid in the body.
Additionally, patients with TACO may already have a reduced heart pumping function, which is medically called as reduced ejection fraction. Further, in patients with TACO, pressure in the pulmonary artery might be high (18 mmHg or more), which can lead to a specific type of lung fluid buildup known as cardiogenic pulmonary edema. This condition also results in elevated levels of a biomarker called brain natriuretic peptide. Because of this cardiogenic pulmonary edema, the excess fluid in TACO is commonly low in plasma proteins.
What to expect with Transfusion-Related Acute Lung Injury
Despite intensive treatment, more than 12% of patients don’t recover after being diagnosed with TRALI. Even those who recover tend to have a slow recovery. TRALI, or Transfusion-Related Acute Lung Injury, is a serious lung condition often associated with blood transfusions. It’s important to note that these cases are rare and most people recover from TRALI with appropriate medical care.