Transfusion-dependent anemia
Transfusion-dependent anemia is a form of anemia characterized by the need for continuous blood transfusion. It is a condition that results from various diseases, and is associated with decreased survival rates. Regular transfusion is required to reduce the symptoms of anemia by increasing functional red blood cells and hemoglobin count. Symptoms may vary based on the severity of the condition and the most common symptom is fatigue.
Various diseases can lead to transfusion-dependent anemia, most notably myelodysplastic syndromes and thalassemia. Due to the number of diseases that can cause transfusion-dependent anemia, diagnosing it is more complicated. Transfusion dependence occurs when an average of more than 2 units of blood transfused every 28 days is required over a period of at least 3 months. Myelodysplastic syndromes is often only diagnosed when patients become anemic, and transfusion-dependent thalassemia is diagnosed based on gene mutations. Screening for heterozygosity in the thalassemia gene is an option for early detection.
The transfusions itself alleviates the symptoms of anemia, and are used to treat the disease that causes transfusion dependence. The recommended restrictive threshold for blood transfusion is a hemoglobin level of 7 to 8 g/dL, while a more liberal threshold is set at 9 to 10 g/dL. However, more evidence may be required to establish a consensus on the threshold and a personalized approach may be more useful. The main complication of transfusion dependence is iron overloading, which can damage the liver, heart, bone tissue and endocrine glands. Iron chelation therapy is used to treat iron overload and common iron chelators used are deferoxamine, deferiprone and deferasirox. Due to the complications of transfusions dependency, it may be more ideal to directly treat the cause of anemia if possible. However, this might not be suitable for all patients, and some may still rely on frequent blood transfusions for survival. While transfusion-dependent anemia has a poor prognosis, advancement in iron chelation therapy may help increase survival rates.
Signs and symptoms
See more: AnemiaWhen transfusion dependent patients do not receive their transfusion, symptoms of anemia may arise. The most common symptom that patients experience is fatigue, and other symptoms include shortness of breath, dizziness and heart palpitations. Symptoms may vary depending on the severity of the disease. The use of blood transfusions can ease some of these symptoms by replenishing the blood cells and maintain sufficient hemoglobin levels, however, the goal to improve the overall oxygen-carrying capacity has conflicting results.
Causes
There are numerous causes for transfusion dependent anemia, typically due to diseases affecting the blood.Thalassemia
Alpha-thalassemia
is the most severe form of alpha-thalassemia, and individuals with this disease have severe anemia during the fetal stage of development. It has been considered as fatal until advances in treatment were made. Patients that survive hemoglobin Barts hydrops fetalis will become transfusion dependent.Beta-thalassemia
causes decreased functional hemoglobin production, and blood transfusions can be given to maintain a sufficient hemoglobin level. Patients with beta thalassemia major are more affected and are recommended to receive transfusion throughout their lives.Myelodysplastic syndromes (MDS)
Myelodysplastic syndromes are disorders where defective blood cells are produced by an abnormal bone marrow, resulting in anemia. Severe cases may require ongoing transfusions, and around 70% of people with myelodysplastic syndromes become transfusion dependent at some point. Patients who are initially considered to be lower-risk may experience disease progression as a result of becoming dependent on blood transfusion when they become increasingly unresponsive to alternative treatments.Diagnosis
Diagnosis of transfusion dependent anemia is challenging because this anemia is caused by multiple diseases. Therefore, other than diagnosing anemias that require transfusion, diagnosis for the two main causes of transfusion dependent anemia is also important.Transfusion dependent anemia
Diagnosis of transfusion-dependent anemia is similar to the diagnosis of all other kinds of anemia, which primarily depends on one's complete blood count. Units of red blood cells required is examined to diagnose transfusion dependent anemia. Patients that need more than 2 units of red blood cells every 28 days are considered transfusion dependent. Diagnosed patients require frequent and regular transfusion for survival.Myelodysplastic syndromes (MDS)
As 70% of myelodysplastic syndrome patients exhibit transfusion dependent anemia, diagnosis of MDS can also help indicate transfusion dependency. Diagnosis of it is complexed with great diversity of symptoms, and therefore most patients are only diagnosed with myelodysplastic syndromes when seeking clinical advice after experiencing symptoms of anemia.Beta-thalassemia
Beta-thalassemia is a genetic disease mostly caused by beta-globin gene mutations. Clinical diagnosis is based on interpretation of the peripheral blood smear, which examines red blood cell morphology, followed by hemoglobin analysis and confirmed by DNA sequencing. DNA analysis is performed by either mutation-specific detection or genome scanning. Different mutation patterns observed from DNA analysis divide thalassemia patients into three classes: thalassemia major, thalassemia intermedia and thalassemia minor. Another classification was established in 2012 for easier referral of patients that require frequent transfusion for survival, dividing patients into non–transfusion-dependent thalassemia and transfusion-dependent thalassemia by their baseline hemoglobin levels. Thalassemia major is usually manifested in fetus and early life and all patients are transfusion-dependent from birth in order to survive. Anemia experienced by some thalassemia intermedia patients are also regarded transfusion dependent. Therefore, most transfusion-dependent thalassemia patients can be diagnosed within the first few years of life, which severe anemia, differed growth, jaundice and hepatosplenomegaly can be observed. Parameters for confirmation includes baseline hemoglobin level <7g/dL, enlargement of liver and spleen and height in the first 10th percentile.Screening
Thalassemia
Screening programs are available to identify thalassemia patients among the general public. Couples are in particular the target group of screening for early identification of carriers who bear risks of having children with thalassemia. Screenings targeted at them are done by detecting heterozygotes in the thalassemia gene. Whereas screening of fetus is done by one-tube osmotic fragility test, red blood cell tests or dischlorophenol indophenol precipitation tests.Treatment
The primary method to treat transfusion-dependent anemia is by transfusing packed red blood cells. Transfusion is also one of the treatment strategies for beta-thalassemia patients and patients with myelodysplastic syndrome. Although transfusion of red blood cells cannot correct the underlying problems, it can improve anemia conditions.Side effects of treatment
There are considerable side effects associated with the transfusion of red blood cells. Side effects include iron overloading, allergic reactions that lead to skin rashes and infections transmitted through transfusion.The most common side effect is iron overloading, which the severity of overload depends on the frequency, volume, and the amount of blood transfused to the patient. Approximately, 200 to 250 mg of iron is transfused per unit of blood. Iron overloading is resulted because human body cannot excrete excess iron from frequent transfusions, leading to accumulation of iron in blood. Iron in blood causes damage to important organs, such as the heart, liver, bone tissue and endocrine glands. Damage to vital organs leads to morbidities, including cardiovascular diseases and heart failure. The liver is normally involved in iron metabolism and storage and excess iron causes liver diseases, fibrosis and cirrhosis. Complications associated with the endocrine hormones may also occur, including diabetes. The risk of developing transfusion dependency related morbidities increases with patients' ages.
Treatment to reduce iron overloading
To reduce iron overloading in blood, iron chelation therapy is commonly used together with transfusion. Necessity to initiate iron chelation therapy is determined by blood test and transfusion volume. Generally, blood with serum ferritin level that exceed 1000 ug/L and a transfusion of 20 units of red blood cells will require iron chelation therapy along with transfusion.There are three common iron chelators, including deferoxamine, deferiprone and deferasirox.