What is Hemolytic Transfusion Reaction?
A transfusion is when whole blood or just a portion of it is given to a patient. Like all medical procedures, transfusions come with their own set of benefits and risks, one such risk being a hemolytic transfusion reaction (HTR). In simpler terms, hemolysis is when red blood cells break open and leak into the bloodstream or other body systems. There are two types of HTRs: immune-mediated and non-immune-mediated.
Immune HTRs usually happen when the patient’s blood doesn’t match with the donated blood. These can be divided into acute and delayed hemolytic reactions. If an acute reaction occurs, it will be within 24 hours of the transfusion. On the other hand, delayed reactions can happen anytime from 24 hours to up to 30 days after the transfusion, with most presenting about 2 weeks later. The severity of the reaction depends on the type and amount of proteins and antibodies involved, along with whether a part of your immune system, known as the complement system, is active.
Non-immune hemolysis can happen due to heat, water imbalance, or physical damage to blood products. These can be caused by human fault or issues within the body itself. Although HTRs are most common with transfusions of red blood cells, they can also happen with other types of blood products like plasma, platelets, a certain type of blood clotting factor called cryoprecipitate, or even with transfusions of whole blood.
What Causes Hemolytic Transfusion Reaction?
Getting a blood transfusion is quite common for both hospital stays and outpatient care in the US. It’s estimated that around 12.5% of hospital patients receive a blood transfusion. This could involve receiving red blood cells (for about 11% of patients) or platelets or plasma (for around 3% of patients). Some patients may receive both, which is why the total percentage is more than 12.5%.
Reactions to blood transfusions can happen, but the likelihood varies a lot based on different hospitals and their reporting requirements. It’s estimated that about 0.1% to 3% of all blood transfusions result in some kind of reaction.
The most common reactions are fever and mild allergic responses, such as a rash, hives, or itchiness. These types of reactions are responsible for approximately 70% to 80% of all adverse events related to blood transfusions. About 7% of all these reactions can be severe, leading to symptoms like difficulty breathing, low blood pressure, unconsciousness, or seeing blood in urine.
Severe reactions tend to happen faster – on average, around 20 minutes after the transfusion. Meanwhile, non-severe reactions typically take longer, around 100 minutes on average. This suggests that it’s important to closely monitor patients for 2 hours after a blood transfusion for any signs of a reaction, while the first hour is especially important to catch any severe reactions.
Reactions where the body breaks down the transfused blood cells, known as hemolytic reactions, are rare and only make up 1% to 3% of all reactions. Causes can include human fault, systems fault or an unrecognized immune incompatibility. Hemolytic reactions can be immune-based (where your body’s immune system reacts to the transfused blood cells) or non-immune-based, and they can be either immediate or delayed. The breakdown of blood cells can also happen inside or outside of blood vessels.
If you’ve had a transfusion before or received multiple transfusions, you might be at a higher risk for a more severe reaction potentially due to a reaction to a foreign substance in the blood (alloimmunization). For these patients, taking preventative measures and using specially treated blood products might be necessary to reduce the risk of a reaction.
Risk Factors and Frequency for Hemolytic Transfusion Reaction
Acute Hemolytic Transfusion Reactions (HTRs) are quite rare, occurring in roughly 1 out of every 70,000 blood transfusions. It’s not certain how often delayed HTRs happen, because most people who have them don’t show symptoms and so these reactions aren’t always reported. The estimates vary for delayed HTRs; the rates range from 1 in 800 transfusions to 1 in 11,000 transfusions. The number of non-immune hemolytic reactions is also unknown, but they’re believed to be very rare. Various systems are in place to try and reduce the number of HTRs caused by human and system faults
Signs and Symptoms of Hemolytic Transfusion Reaction
An acute Hemolytic Transfusion Reaction (HTR) often results in symptoms such as fever, flank pain, and the presence of red or brown urine. These symptoms typically occur within 24 hours of a transfusion, often in the first hour. Other symptoms may include restlessness, chills, discomfort at the infusion site, chest pain, headache, nausea, vomiting, and difficulty breathing. Visible signs may include fever, flushed or swollen skin, rapid heartbeat, low blood pressure, and reddish urine. In later stages, symptoms such as widespread bleeding and reduced urine output due to kidney failure may be observed.
In comparison, the symptoms of delayed transfusion reactions, which occur from 24 hours to 30 days post-transfusion, can be similar but develop more gradually. These reactions tend to involve fever, yellowing of the skin or eyes (jaundice), and signs of anemia such as fatigue and weakness. A delayed HTR rarely results in death, but can increase illness and extend hospital stays. Symptoms such as general fatigue, fever of unknown origin, and signs of anemia might be noticed. Sometimes, the passing of colored urine may be observed much later following a blood transfusion, and kidney failure is less common. Patient death from a delayed HTR is highly rare, but when it happens in patients who are critically ill, it often worsens other severe conditions.
- Acute HTR symptoms (within 24 hours of transfusion):
- Fever
- Flank pain
- Red or brown urine
- Restlessness, chills
- Discomfort at the infusion site
- Chest pain, headache, nausea, vomiting
- Difficulty breathing
- Signs of fever, flushed or swollen skin, rapid heartbeat, low blood pressure
- Widespread bleeding and reduced urine output at later stages
- Delayed HTR symptoms (24 hours to 30 days post-transfusion)
- Fever
- Jaundice
- Signs of anemia such as fatigue, weakness
- Unexplained fall in hemoglobin levels, mild jaundice
- Colored urine may be observed much later
- Less chance of kidney failure
Testing for Hemolytic Transfusion Reaction
If there’s a concern that you might be having an acute (sudden and severe) reaction to a blood transfusion, the transfusion should be stopped immediately. The blood will need to be sent back to the lab for more tests, and you might need further tests as well. Two key tests are the direct and indirect Coombs tests, also known as direct and indirect antibody tests. These are designed to check for a certain type of blood cell damage called immune-mediated hemolysis.
In some situations, free hemoglobin from the transfusion bag may be measured. This is to check for hemolysis or breakdown of red blood cells within the sample transfused. The destruction of red blood cells can cause symptoms similar to those experienced during a blood transfusion reaction. In addition, blood cultures should be taken from both you and the transfusion sample to check for any infection or sepsis, which is a severe and life-threatening reaction to an infection.
In cases of delayed transfusion reactions (when a reaction occurs a few days or even weeks after a blood transfusion), the antibodies in your blood should be retested and compared to a sample taken before the transfusion. This is to check for any new autoantibodies, which are proteins produced by the immune system that mistakenly target and react with a person’s own tissues or organs. This comparison is important in order to prevent similar reactions from happening in the future. The availability of pre-transfusion samples can sometimes vary, as different hospitals have different rules about how long they keep these samples.
Your doctor will also likely order a range of other blood and urine tests. This could include a complete blood count (CBC) with peripheral smear (a test to check your number of blood cells and how they look under a microscope), indirect bilirubin (a test to measure a substance that the liver makes when it breaks down red blood cells), haptoglobin (a protein that binds free hemoglobin released from red blood cells and carries it to the liver), and lactate dehydrogenase (an enzyme that helps produce energy in your cells). They may also test the level of hemoglobin in your urine.
A basic metabolic panel (BMP), which tests your sugars (glucose), electrolytes (sodium, potassium, calcium, chloride, etc.), and kidney function (creatinine, blood urea nitrogen) might also be conducted. And lastly, coagulation studies, which are tests to monitor for Disseminated Intravascular Coagulation (DIC; a condition that causes abnormal blood clotting throughout the body’s vessels), may also be sent off for testing.
Treatment Options for Hemolytic Transfusion Reaction
Hemolytic transfusion reactions, or HTRs, are responses to a blood transfusion that range from mild to severe. These reactions need to be identified and treated swiftly because they can be life-threatening. The first action taken when a HTR is suspected or identified is to stop the blood transfusion immediately.
If someone is showing severe symptoms like low blood pressure, difficulty breathing, or signs of the airway closing, urgent medical action needs to be taken. Medications including steroids, antihistamines (drugs that block the effects of histamines and so reduce allergic reactions) and epinephrine (a hormone used to treat severe allergic reactions) may be given, particularly if the person’s airway is in danger of closing.
In this situation, it’s also very important the person be given fluids, unless there’s a risk of them having too much fluid in their body, which is known as volume overload. The reason for this hydration is it may reduce the risk of potentially serious complications such as kidney damage or a condition known as disseminated intravascular coagulation, which involves abnormal blood clotting throughout the body.
If these treatments are not successful, a procedure known as an exchange transfusion might be used as a last resort. This is when the person’s blood is removed and replaced with fresh blood or plasma. However, an exchange transfusion is only used in severe situations, due to the risks involved with the procedure.
What else can Hemolytic Transfusion Reaction be?
When a doctor is looking at an acute Hemolytic Reaction of Transfusions (HRT), they need to check for multiple eventualities. These could be a variety of reactions or situations including:
- Reactions to the transfusion that are not related to immune response or hemolysis
- Infection from bacteria in the transfused blood
- Hemolysis happening within the transfusion sample
- Anaphylaxis caused by components present in the transfusion or chemicals used to separate blood components
- Transfusion of blood products that have expired
They will also need to rule out other medical conditions that exhibit similar symptoms, such as:
- Transfusion-related acute lung injury (TRALI)
- Acute urticaria, a type of skin rash
- Drug-induced hemolysis- breakdown of red blood cells due to medication
- Angioedema, a skin reaction that causes swelling
- Pulmonary edema, fluid build-up in lungs
- Cold agglutinin disease, a rare autoimmune disease
- DIC, a clotting condition
- Sepsis, a life-threatening infection
- Paroxysmal nocturnal hemoglobinuria, a blood disease that causes your body to destroy its own red blood cells
- Hereditary defects in red blood cells, like in sickle-cell disease or G6PDH deficiency
- Thrombotic thrombocytopenic purpura, a condition that causes blood clots throughout the body
- Mechanical hemolysis, which is caused due to mechanical factors like heart valves or dialysis
What to expect with Hemolytic Transfusion Reaction
Acute Hemolytic Transfusion Reactions (HTRs), which are rapid reactions to a blood transfusion, can pose serious threats to life and need to be identified immediately. It’s also important to detect both acute (quick) and delayed (slow) HTRs, as doing so can help find the antibodies that caused these reactions. Identifying these antibodies can prevent severe reactions from happening in the future.
Possible Complications When Diagnosed with Hemolytic Transfusion Reaction
Transfusion reactions can lead to other health problems. These complications often occur due to autoantibodies – natural substances in the body that increase the possibility of future reactions. Some people may also experience a dramatic drop in blood pressure or issues related to low blood pressure. The blood transfusion can, in unusual cases, cause a condition called ‘volume overload.’ This condition puts too much fluid in your body, leading to problems with your heart and lungs.
Main Complications:
- Presence of autoantibodies leading to future reactions
- Systemic hypotension: Issues due to significantly low blood pressure
- Volume overload: Increased fluid in the body causing heart and lung problems
Preventing Hemolytic Transfusion Reaction
The best way to avoid complications is through prevention, especially when it comes to blood transfusions. This means making sure the right blood product is given to the right patient. If any reactions occur during a blood transfusion, the blood bank must investigate thoroughly, including doing tests to look for antibodies.
For patients at high risk of having a reaction to blood transfusions, preventative treatments can be given. These usually include steroids and antihistamines. It’s also important to regulate the amount of blood transfused, with an aim to keep the hemoglobin (a protein in your red blood cells that carries oxygen) around 7.0 mg/dL for most conditions, or between 8 to 10 mg/dL if the patient is experiencing a heart attack or has decreased blood supply to the heart.
