Transfusion-dependent anemia

Last updated
A blood bag for blood transfusion Ics-codablock-blood-bag sample.jpg
A blood bag for blood transfusion

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. [1] [2] 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. [3] Various diseases can lead to transfusion-dependent anemia, most notably myelodysplastic syndromes (MDS) and thalassemia. [4] [5] 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. [6] [7] 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. [8]

Contents

The transfusions itself alleviates the symptoms of anemia, and are used to treat the disease that causes transfusion dependence. [9] 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. [10] However, more evidence may be required to establish a consensus on the threshold and a personalized approach may be more useful. [11] The main complication of transfusion dependence is iron overloading, which can damage the liver, heart, bone tissue and endocrine glands. [4] [12] Iron chelation therapy is used to treat iron overload and common iron chelators used are deferoxamine, deferiprone and deferasirox. [9] [13] 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. [13] [3] While transfusion-dependent anemia has a poor prognosis, advancement in iron chelation therapy may help increase survival rates. [13]

Signs and symptoms

See more: Anemia

When 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. [3] 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, [5] however, the goal to improve the overall oxygen-carrying capacity has conflicting results. [14]

Causes

There are numerous causes for transfusion dependent anemia, typically due to diseases affecting the blood.[ citation needed ]

Thalassemia

Alpha-thalassemia

Hemoglobin Barts hydrops fetalis is the most severe form of alpha-thalassemia, and individuals with this disease have severe anemia during the fetal stage of development. [15] It has been considered as fatal until advances in treatment were made. Patients that survive hemoglobin Barts hydrops fetalis will become transfusion dependent. [5]

Beta-thalassemia

Bata-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. [5]

Myelodysplastic syndromes (MDS)

Myelodysplastic syndromes are disorders where defective blood cells are produced by an abnormal bone marrow, resulting in anemia. [4] Severe cases may require ongoing transfusions, and around 70% of people with myelodysplastic syndromes become transfusion dependent at some point. [16] [17] 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. [4]

Diagnosis

Diagnosis of transfusion dependent anemia is challenging because this anemia is caused by multiple diseases. [12] Therefore, other than diagnosing anemias that require transfusion, diagnosis for the two main causes (beta-thalassemia and myelodysplastic syndromes) of transfusion dependent anemia is also important.[ citation needed ]

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. [6] Diagnosed patients require frequent and regular transfusion for survival.[ citation needed ]

Myelodysplastic syndromes (MDS)

As 70% of myelodysplastic syndrome patients exhibit transfusion dependent anemia, [17] diagnosis of MDS can also help indicate transfusion dependency. Diagnosis of it is complexed with great diversity of symptoms, [3] and therefore most patients are only diagnosed with myelodysplastic syndromes when seeking clinical advice after experiencing symptoms of anemia. [4]

Beta-thalassemia

Beta-thalassemia is a genetic disease mostly caused by beta-globin gene mutations. [18] 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. [8] Different mutation patterns observed from DNA analysis divide thalassemia patients into three classes: thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (TI). Another classification was established in 2012 for easier referral of patients that require frequent transfusion for survival, dividing patients into non–transfusion-dependent thalassemia (NTDT) and transfusion-dependent thalassemia (TDT) by their baseline hemoglobin levels. Thalassemia major is usually manifested in fetus and early life (birth to <2 years old) 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 (>5 cm) and height in the first 10th percentile. [8]

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. [8] 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 (identification of red blood cells resistance to hemolysis), [8] red blood cell tests (measurement of mean corpuscular volume and mean corpuscular haemoglobin) or dischlorophenol indophenol precipitation tests (detection of mutation). [8]

Treatment

The primary method to treat transfusion-dependent anemia is by transfusing packed red blood cells. [9] Transfusion is also one of the treatment strategies for beta-thalassemia patients and patients with myelodysplastic syndrome (MDS). [13] Although transfusion of red blood cells cannot correct the underlying problems, it can improve anemia conditions. [3]

Side effects of treatment

There are considerable side effects associated with the transfusion of red blood cells. Side effects include iron overloading, [12] [4] [9] [13] [5] allergic reactions that lead to skin rashes and infections transmitted through transfusion. [4] [12]

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. [9] Approximately, 200 to 250 mg of iron is transfused per unit of blood. [4] [5] Iron overloading is resulted because human body cannot excrete excess iron from frequent transfusions, leading to accumulation of iron in blood. [4] [9] Iron in blood causes damage to important organs, such as the heart, liver, bone tissue and endocrine glands. [4] [13] Damage to vital organs leads to morbidities, including cardiovascular diseases and heart failure. [13] 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. [5] The risk of developing transfusion dependency related morbidities increases with patients' ages. [19]

Treatment to reduce iron overloading

To reduce iron overloading in blood, iron chelation therapy is commonly used together with transfusion. [3] 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. [4] [9]

There are three common iron chelators, including deferoxamine, deferiprone and deferasirox. [5] [9] [13]

The 3D structure of deferoxamine Deferoxamine-3D-vdW.png
The 3D structure of deferoxamine
Deferoxamine

Deferoxamine is injected into the body through the veins and is the most traditional chelation therapy available. [9] This therapy, although effective, especially for patients with heavy iron overload, is considered very inconvenient. The injection has to be performed over a duration of 8 hours, 5–7 times every week. [13] Therefore, low compliance of patients is one of the major concerns of this therapy. Side effects include abnormal growth of bones and kidney damages. [9] [13] Deferoxamine is seldom used alone nowadays, but rather in combination with oral deferiprone to increase the effectiveness in reducing iron overload. [9] [13]

Deferiprone forms a complex with excess iron in blood in a binding ratio of 3 to 1 (3 deferiprone: 1 iron). Formation of this complex reduce iron overloading. Deferiprone-Iron complex.png
Deferiprone forms a complex with excess iron in blood in a binding ratio of 3 to 1 (3 deferiprone: 1 iron). Formation of this complex reduce iron overloading.
Deferiprone

Deferiprone is an oral drug that is ingested by patients three times a day. [13] Although patients are still required to visit the clinic frequently for complete blood count, the administering process by simply oral intake regularly is still less tedious when compared to deferoxamine. [9] It is also effective in reducing cardiac-related diseases due to iron overloading. [9] Major side effects of this drug are to the gastrointestinal system. [9]

Defasirox

Defasirox is also an oral drug to mitigate iron overloading taken one dose per day by patients. [13] It shares similar benefits of convenience with deferiprone when compared to deferoxamine, but however is of the highest cost. Side effects to the gastrointestinal and urinary system are common. [9]

The use of iron chelation therapy is not without concern. It can also cause skeletal changes that leads to bone disorders such as osteoporosis. [13] Therefore, minimizing the need of transfusion when possible is still the best way in reducing iron overload. [5]

Other than physical side effects brought by transfusion, transfusion also poses stress psychologically and financially. Inconvenience brought by frequent transfusion interferes with the normal social lives of patients. As a result, lack of social ties make patients more vulnerable to psychiatric illnesses like depression. [5] The high cost for repeated transfusion can also cause financial burden on the patient and his/her family. Subjection to physical, psychological and financial stresses brought by frequent transfusions and its related morbidities worsen the quality of life of most patients as the disease progresses. [4] [13] [3]

Alternative treatments

As there are a number of drawbacks brought by frequent transfusions, directly treating the cause of anemia (e.g. myelodysplastic syndrome), if available, remains the optimal choice of treatment. [3] Hematopoietic stem cell transplantation is a treatment for thalassemia that minimizes the need of transfusion in long term. [8] [13] However, it is not suitable for patients with organs that have already experienced certain degree of iron overload, and it may only be applicable to strong and young patients. [13] While for transfusion-dependent myelodysplastic syndrome patients, lenalidomide is approved for treating lower-risk patients and hypomethylating agents can be used to treat higher-risk patients. [4]

Prognosis

An International Prognostic Scoring System (IPSS) is specially designed to access the prognosis of myelodysplastic syndrome patients. Scores help to classify patients into low, intermediate-1, intermediate-2 and high risks based on their severity levels. [21] Patients in the lower-risk group generally have a longer survival range of 3–8.8 years, comparied to only 0.8–1.6 years for high-risk patients. [22]

In general, the survival rate of transfusion-dependent anemia patients is increasing. This is due to the improvements in transfusion procedures, mature use of iron chelation therapies to reduce iron overloading, and more experiences in dealing with associated morbidities. [13]

Related Research Articles

<span class="mw-page-title-main">Anemia</span> Medical condition

Anemia or anaemia is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. The name is derived from Ancient Greek: ἀναιμία anaimia, meaning 'lack of blood', from ἀν- an-, 'not' and αἷμα haima, 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe.

<span class="mw-page-title-main">Myelodysplastic syndrome</span> Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

<span class="mw-page-title-main">Thalassemia</span> Medical condition

Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. Symptoms and presentations of thalassemia can change over time.

<span class="mw-page-title-main">Paroxysmal nocturnal hemoglobinuria</span> Medical condition

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of venous blood clot formation, are incompletely understood.

<span class="mw-page-title-main">Hemoglobin A</span> 4f CC w I/ pop m onf

Hemoglobin A (HbA), also known as adult hemoglobin, hemoglobin A1 or α2β2, is the most common human hemoglobin tetramer, accounting for over 97% of the total red blood cell hemoglobin. Hemoglobin is an oxygen-binding protein, found in erythrocytes, which transports oxygen from the lungs to the tissues. Hemoglobin A is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (α2β2). Hemoglobin A2 (HbA2) is a less common adult form of hemoglobin and is composed of two alpha and two delta-globin subunits. This hemoglobin makes up 1-3% of hemoglobin in adults.

<span class="mw-page-title-main">Microcytic anemia</span> Medical condition

Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells. The normal mean corpuscular volume is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic. The MCV is the average red blood cell size.

Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an underlying genetic condition, and aluminium toxicity in people on dialysis. It is used by injection into a muscle, vein, or under the skin.

<span class="mw-page-title-main">Sideroblastic anemia</span> Medical condition

Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies.

<span class="mw-page-title-main">Alpha-thalassemia</span> Thalassemia involving the genes HBA1and HBA2 hemoglobin genes

Alpha-thalassemia is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present.

<span class="mw-page-title-main">Beta thalassemia</span> Thalassemia characterized by the reduced or absent synthesis of the beta globin chains of hemoglobin

Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

Transfusional hemosiderosis is the accumulation of iron in the body due to frequent blood transfusions. Iron accumulates in the liver and heart, but also endocrine organs. Frequent blood transfusions may be given to many patients, such as those with thalassemia, sickle cell disease, leukemia, aplastic anemia, or myelodysplastic syndrome, among others. It is diagnosed with a blood transferrin test and a liver biopsy. It is treated with venipuncture, erythrocytapheresis, and iron chelation therapy.

Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. Hb Barts has an extremely high affinity for oxygen, so it cannot release oxygen to the tissue. Therefore, this makes it an inefficient oxygen carrier. As an embryo develops, it begins to produce alpha-globins at weeks 5–6 of development. When both of the HBA1 and HBA2 genes which code for alpha globins becomes dysfunctional, the affected fetuses will have difficulty in synthesizing a functional hemoglobin. As a result, gamma chains will accumulate and form four gamma globins. These gamma globins bind to form hemoglobin Barts. It is produced in the disease alpha-thalassemia and in the most severe of cases, it is the only form of hemoglobin in circulation. In this situation, a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed.

<span class="mw-page-title-main">Hemosiderosis</span> Iron metabolism disease

Hemosiderosis is a form of iron overload disorder resulting in the accumulation of hemosiderin.

Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction. Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.

<span class="mw-page-title-main">Congenital dyserythropoietic anemia</span> Red blood cell disorder

Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood. CDA may be transmitted by both parents autosomal recessively or dominantly.

Red blood cells (erythrocytes) from donors contain normal hemoglobin (HbA), and transfusion of normal red blood cells into people with sickle cell disease reduces the percentage of red cells in the circulation containing the abnormal hemoglobin (HbS). Although transfusion of donor red blood cells can ameliorate and even prevent complications of sickle cell disease in certain circumstances, transfusion therapy is not universally beneficial in sickle cell disease.

Treatment of the inherited blood disorder thalassemia depends upon the level of severity. For mild forms of the condition, advice and counseling are often all that are necessary. For more severe forms, treatment may consist in blood transfusion; chelation therapy to reverse iron overload, using drugs such as deferoxamine, deferiprone, or deferasirox; medication with the antioxidant indicaxanthin to prevent the breakdown of hemoglobin; or a bone marrow transplant using material from a compatible donor, or from the patient's mother. Removal of the spleen (splenectomy) could theoretically help to reduce the need for blood transfusions in people with thalassaemia major or intermedia but there is currently no reliable evidence from clinical trials about its effects. Population screening has had some success as a preventive measure.

Hemoglobin H (Hb H)Disease, also called alpha-thalassemia intermedia, is a disease affecting hemoglobin, the oxygen carrying molecule within red blood cells. It is a form of Alpha-thalassemia which most commonly occurs due to deletion of 3 out of 4 of the α-globin genes.

Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes.

Anemia is a condition in which blood has a lower-than-normal amount of red blood cells or hemoglobin. Anemia in pregnancy is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during pregnancy. Anemia is an extremely common condition in pregnancy world-wide, conferring a number of health risks to mother and child. While anemia in pregnancy may be pathologic, in normal pregnancies, the increase in RBC mass is smaller than the increase in plasma volume, leading to a mild decrease in hemoglobin concentration referred to as physiologic anemia. Maternal signs and symptoms are usually non-specific, but can include: fatigue, pallor, dyspnea, palpitations, and dizziness. There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality.

References

  1. ↑ Harnan, Sue; Ren, Shiji; Gomersall, Tim; Everson-Hock, Emma S.; Sutton, Anthea; Dhanasiri, Sujith; Kulasekararaj, Austin (2016). "Association between Transfusion Status and Overall Survival in Patients with Myelodysplastic Syndromes: A Systematic Literature Review and Meta-Analysis". Acta Haematologica. 136 (1): 23–42. doi: 10.1159/000445163 . ISSN   0001-5792. PMID   27160308. S2CID   21668806.
  2. ↑ Koutsavlis, Ioannis (2016). "Transfusion Thresholds, Quality of Life, and Current Approaches in Myelodysplastic Syndromes". Anemia. 2016: 1–7. doi: 10.1155/2016/8494738 . ISSN   2090-1267. PMC   4853931 . PMID   27195147.
  3. 1 2 3 4 5 6 7 8 Germing, Ulrich; Oliva, Ester N.; Hiwase, Devendra; Almeida, Antonio (December 2019). "Treatment of Anemia in Transfusion-Dependent and Non-Transfusion-Dependent Lower-Risk MDS: Current and Emerging Strategies". HemaSphere. 3 (6): e314. doi:10.1097/HS9.0000000000000314. ISSN   2572-9241. PMC   6924547 . PMID   31976486.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 Raza, Azra; Ali, Abdullah; Iverson, Nicholas (July 2014). "Developments in the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes: epidemiology, etiology, genetics, and targeted therapies". Advances in Genomics and Genetics. 4: 95–106. doi: 10.2147/AGG.S54184 . ISSN   1179-9870.
  5. 1 2 3 4 5 6 7 8 9 10 Cappellini, Maria Domenica; Cohen, Alan; Porter, John; Taher, Ali; Viprakasit, Vip (2014). Guidelines for the management of transfusion dependent thalassaemia (TDT) (3rd ed.). Nicosia (CY): Thalassaemia International Federation. ISBN   978-9963-717-06-4. OCLC   910948346.
  6. 1 2 Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R.; Valcarcel, David; Silverman, Lewis R.; Skikne, Barry; Santini, Valeria (December 2016). "Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion–dependent anemia and thrombocytopenia". BMC Hematology. 16 (1): 12. doi: 10.1186/s12878-016-0049-5 . ISSN   2052-1839. PMC   4855808 . PMID   27148452.
  7. ↑ Gale, R.P.; Barosi, G.; Barbui, T.; Cervantes, F.; Dohner, K.; Dupriez, B.; Gupta, V.; Harrison, C.; Hoffman, R.; Kiladjian, J.-J.; Mesa, R. (January 2011). "What are RBC-transfusion-dependence and -independence?". Leukemia Research. 35 (1): 8–11. doi:10.1016/j.leukres.2010.07.015. PMC   8215731 . PMID   20692036.
  8. 1 2 3 4 5 6 7 Viprakasit, Vip; Ekwattanakit, Supachai (April 2018). "Clinical Classification, Screening and Diagnosis for Thalassemia". Hematology/Oncology Clinics of North America. 32 (2): 193–211. doi:10.1016/j.hoc.2017.11.006. PMID   29458726.
  9. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Taher, Ali; Saliba, Antoine N.; Harb, Afif (June 2015). "Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions". Journal of Blood Medicine. 6: 197–209. doi: 10.2147/JBM.S72463 . ISSN   1179-2736. PMC   4476479 . PMID   26124688.
  10. ↑ Carless, Paul A.; Henry, David A.; Carson, Jeffrey L.; Hebert, Paul Pc; McClelland, Brian; Ker, Katharine (2010-10-06). Carless, Paul A (ed.). "Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion". The Cochrane Database of Systematic Reviews (10): CD002042. doi:10.1002/14651858.CD002042.pub2. hdl: 1959.13/1313148 . ISSN   1469-493X. PMID   20927728.
  11. ↑ Gu, Yisu; Estcourt, Lise J.; Doree, Carolyn; Hopewell, Sally; Vyas, Paresh (2015-10-05). "Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders". The Cochrane Database of Systematic Reviews. 2015 (10): CD011577. doi:10.1002/14651858.CD011577.pub2. ISSN   1469-493X. PMC   4650197 . PMID   26436602.
  12. 1 2 3 4 Schulz, Vincent P.; Maksimova, Yelena; Lezon-Geyda, Kimberly; Gallagher, Patrick G. (2013-11-15). "The Patient With Transfusion-Dependent Anemia: Diagnosis and Directed Management With Targeted Next Generation Sequencing and Copy Number Analysis". Blood. 122 (21): 3419. doi:10.1182/blood.V122.21.3419.3419. ISSN   0006-4971.
  13. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Pinto, Valeria Maria; Poggi, Maurizio; Russo, Rodolfo; Giusti, Andrea; Forni, Gian Luca (November 2019). "Management of the aging beta-thalassemia transfusion-dependent population – The Italian experience". Blood Reviews. 38: 100594. doi:10.1016/j.blre.2019.100594. PMID   31416718. S2CID   201018588.
  14. ↑ Roberson, Russell S.; Bennett-Guerrero, Elliott (January 2012). "Impact of Red Blood Cell Transfusion on Global and Regional Measures of Oxygenation". Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine. 79 (1): 66–74. doi:10.1002/msj.21284. ISSN   0027-2507. PMC   3261580 . PMID   22238040.
  15. ↑ Jatavan, Phudit; Chattipakorn, Nipon; Tongsong, Theera (2017-03-21). "Fetal hemoglobin Bart's hydrops fetalis: pathophysiology, prenatal diagnosis and possibility of intrauterine treatment". The Journal of Maternal-Fetal & Neonatal Medicine. 31 (7): 946–957. doi:10.1080/14767058.2017.1301423. ISSN   1476-7058. PMID   28277912. S2CID   205831632.
  16. ↑ Melchert, Magda; List, Alan F. (2007-01-01). "Management of RBC-Transfusion Dependence". Hematology. 2007 (1): 398–404. doi: 10.1182/asheducation-2007.1.398 . ISSN   1520-4391. PMID   18024657.
  17. 1 2 Heptinstall, K. (May 2007). "P124 Quality of life (QoL) in myelodysplastic syndromes (MDS): an update of results from US & European patient forums". Leukemia Research. 31: S107. doi:10.1016/S0145-2126(07)70194-7.
  18. ↑ Monni, Giovanni; Peddes, Cristina; Iuculano, Ambra; Ibba, Rosa Maria (2018-02-20). "From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience". Journal of Clinical Medicine. 7 (2): 35. doi: 10.3390/jcm7020035 . ISSN   2077-0383. PMC   5852451 . PMID   29461486.
  19. ↑ Taher, Ali T.; Cappellini, Maria Domenica (2018-10-25). "How I manage medical complications of β-thalassemia in adults". Blood. 132 (17): 1781–1791. doi: 10.1182/blood-2018-06-818187 . ISSN   0006-4971. PMID   30206117.
  20. ↑ PubChem. "Deferiprone". pubchem.ncbi.nlm.nih.gov. Retrieved 2020-04-26.
  21. ↑ Malcovati, Luca; Porta, Matteo Giovanni Della; Pascutto, Cristiana; Invernizzi, Rosangela; Boni, Marina; Travaglino, Erica; Passamonti, Francesco; Arcaini, Luca; Maffioli, Margherita; Bernasconi, Paolo; Lazzarino, Mario (2005-10-20). "Prognostic Factors and Life Expectancy in Myelodysplastic Syndromes Classified According to WHO Criteria: A Basis for Clinical Decision Making". Journal of Clinical Oncology. 23 (30): 7594–7603. doi: 10.1200/JCO.2005.01.7038 . ISSN   0732-183X. PMID   16186598.
  22. ↑ Greenberg, Peter L.; Tuechler, Heinz; Schanz, Julie; Sanz, Guillermo; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M.; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop (2012-09-20). "Revised International Prognostic Scoring System for Myelodysplastic Syndromes". Blood. 120 (12): 2454–2465. doi:10.1182/blood-2012-03-420489. ISSN   0006-4971. PMC   4425443 . PMID   22740453.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.