The Physiotherapy Management of Thalassaemia and Sickle Cell Anaemia
Original Editors - Mariam Hashem
Thalassaemia[edit | edit source]
Thalassaemia is one of the most common inherited diseases. It is defined as an autosomal recessive blood disorder. This means that for the trait or disease to develop, two copies of the abnormal gene must be present, it also has no gender preference.
The disease results from a reduction or absence in the production of globin chains that make up the haemoglobin (Hb) leading to abnormal destruction of erythrocytes and consequently decreased oxygen delivery. As a result, patients have a range of symptoms and complications that impose a large burden on individuals and the healthcare systems.
Thalassaemia is derived from the Greek word "Thalassa" which means ''sea''. It's also referred to as ''Mediterranean Anaemia''. It mainly affects individuals originating from the Mediterranean area, Middle East, Transcaucasia, Central Asia, Indian subcontinent, and Southeast Asia.
There are two types of Thalassaemia: α- and β- depending on the type of the involved globin chain. Alpha Thalassaemia is developed when the alpha gene is affected and likewise, in beta-thalassemia, the globin chain that is affected or the abnormal haemoglobin involved is the beta-globin gen.
The prevalence rate is about 4.4 of every 10000 live births globally and approximately about 5% of all population. It is estimated that there are 270 million carriers of Alpha thalassemia genes. More than 95% of children have alpha thalassemia are Asian, Indian, or Middle Eastern. About 80 to 90 million people are carriers of β-thalassemia genes, that’s about 1% to 1.5% of the worldwide population
Clinically, Thalassemia is classified into three forms:
- Thalassemia major: this is a severe form of anaemia where patients need continuous blood transfusions throughout their lives.
- Thalassemia intermedia: mild to moderate anaemia, patients occasionally need blood transfusions
- Thalassemia minor or trait: patients have mild symptoms and they usually don’t need blood transfusions.
- A person is a carrier when one gene is mutated
- Alpha Thalassaemia Trait: when two genes are mutated leading to mild manifestations
- Alpha Thalassaemia Major: when three genes are mutated leading to moderate to severe symptoms
- Rarely, four genes might be mutated leading to an early death.
Beta haemoglobin chain is formed of two genes:
Beta Thalassaemia Minor develops when one gene is mutated. Patients experience mild symptoms
Cooley's Anaemia or Beta Thalassaemia Major develops when two genes are mutated leading to moderate to severe manifestation
Symptoms & Complications[edit | edit source]
- Brittle bones
- Poor appetite
- Liability to infection
- Dark urine
- Generalized body weakness
- Anaemia due to the deficiency of haemoglobin.
- Hepatosplenomegaly: abnormal enlargement of the abdomen.
- Iron overload as a result of repeated blood transfusion. Consequently, a patient may develop further complications such as:
- Endocrine complications such as diabetes, glucose intolerance, decreased production of growth hormone and hypogonadism
- Cardiac disorders, for example, congestive heart failure or arrhythmias
- Hepatic disorders such as cirrhosis and liability to have HCV
The diagnosis is based on the Red Blood Cells (RBC) count specifically the number of erythrocytes.
Other important tests for the diagnosis of Thalassaemia are genetic testing, haemoglobin electrophoresis and reticulocyte count (the number of young RBCs formed from bone marrow)
Although Thalassaemia has a wide range of symptoms and classifications, there are general principals of medical management.
Accurate diagnosis is crucial. The family history should be documented and studied to help assess relative risks and future decisions of the family. Medical management includes:
- Regular transfusions with observations to prevent unnecessary complications 
- Folic acid supplements are also included in the long term management
- Chelation therapy which refers to the extraction the iron excess to prevent iron overload.
- STEM cell transplantation
- Genetic therapy
- Bone marrow transplantation.
- Psychological therapy
Sickle Cell Anaemia[edit | edit source]
Sickle cell anaemia is an autosomal recessive inherited group of blood disorders characterized by the presences of atypical haemoglobin molecules (haemoglobin S) leading to distortion of erythrocytes red blood cells into a sickle, or crescent, shape. It is characterized by the presences of abnormal haemoglobin, excessive erythrocytes destruction. The crescent or sickle-shaped erythrocytes are approximately 15 microns.
Sickle cell anaemia was diagnosed in 1910 by Dr Ernest who described the red blood cells of a patient with anaemia symptoms as “having the shape of a sickle”
Sickle Cell Anemia is inherited in an autosomal recessive manner due to mutation of the HBB gene leading to Hemoglobin S production
Sickle Cell anaemia mainly affects people with African origins but it has spread globally. The estimated prevalence rate is 250,000 children are born annually with sickle cell anaemia worldwide. Around 1% of all births in Africa are inheriting sickle cell disease, causing 6–15% of all deaths in children younger than 5 years. Autosomal recessive disorders have no gender preference.
Classification[edit | edit source]
There are several types of sickle cell anaemia but the most common are Sickle Cell Anemia (SS), Sickle Hemoglobin-C Disease (SC), Sickle Beta-Plus Thalassemia and Sickle Beta-Zero Thalassemia.
Sickle Hemoglobin-D Disease (Hemoglobin SD), Hemoglobin SE, And Sickle Hemoglobin-O Disease (Hemoglobin SO) are less common and are usually less severe types
|Sickle Cell Anemia (SS), also known as Hemoglobin SS Disease||The child inherits one substitution beta-globin genes (the sickle cell gene) from each parent.||African and Indian descents.||The most common type||The most severe type|
|Sickle Hemoglobin- C Disease (SC) known as Hemoglobin SC Disease||The child inherits haemoglobin beta S gene from one parent and the haemoglobin C gene from the other.||West African, Mediterranean and Middle Eastern descents.||It is the second most common sickle cell anaemia type. Some normal beta haemoglobin is produced but in reduced amounts.||As there is a production of some normal haemoglobin, this leads to less severe form than haemoglobin SS disease.|
|Sickle Beta-Plus Thalassemia Known as Hemoglobin SB+ (Beta) Thalassemia||The child inherits haemoglobin beta S gene from one parent and a haemoglobin beta plus thalassemia gene from the other parent.||Mediterranean and Caribbean descents||Some normal beta haemoglobin is produced but in reduced amounts.||This is a less severe type than haemoglobin SS disease. Symptoms are milder than Sickle Cell Anemia (SS) and Sickle Hemoglobin- C Disease (SC) but complications can still be developed.|
|Sickle beta zero thalassemia||Haemoglobin S is inherited from one parent and haemoglobin beta0 thalassemia gene mutation is inherited from the other parent||Eastern Saudi Arabia||It has similar symptoms Sickle Cell Anemia (SS) type. The body only produces haemoglobin S.||Less severe|
Manifestations[edit | edit source]
The severity of the sickle cell anaemia varies from one person to another. People with sickle cell disease can experience acute and chronic signs, symptoms, and various complications.
Sings and Symptoms:
- Jaundice / Icterus
- Dactylitis (swelling of a finger digit)
- Acute chest syndrome
- Acute pain crisis
- Brain complications eg. a clinical /silent stroke
- Chronic pain
- Delayed growth and puberty
- Eye problems
- Heart problems
- Joint complications
- Kidney complications
- Leg ulcers.
- Liver complications
- Pregnancy complications
Diagnosis[edit | edit source]
The most common blood tests used for Sickle cell Anemia diagnosis are :
- Haemoglobin electrophoresis
- High-performance liquid chromatography (HPLC)
- Deoxyribonucleic acid (DNA) testing
Medical Management [edit | edit source]
Blood Transfusion and STEM cell transplantation are used in the management od Sickle Cell anaemia
Also, Medications are used mainly to reduce the frequency of pain crises in sickle cell anaemia:
- Hydroxyurea (Droxia, Hydrea, Siklos).
- L-glutamine oral powder (Endari).
- Crizanlizumab (Adakveo).
- Pain-relieving medications
- Voxelotor (Oxbryta) -> Improves the anaemia
Role of Physiotherapy in the management of Thalassaemia and Sickle Cell Anaemia[edit | edit source]
Physiotherapy can help in the management of thalassemia and sickle cell anaemia symptoms  Thalassemia was proven to have a negative impact on pain, muscle strength, functional ability and quality of life in terms of physical, emotional, social and school functioning when compared to healthy children.
Benefits of Physical Activity[edit | edit source]
The Center for Disease Control (CDC) recommends
- 60 minutes of physical activity per day for children and adolescents with thalassemia or 12,000 to 15,000 steps/day
- A minimum of 150 minutes of moderate activity (including aerobic, muscle strengthening, and bone-strengthening activities) per week for adults with thalassemia. Or 10 000 steps per day
A study of sickle cell anaemia randomly allocated 40 patients into two groups. One group assigned to follow their normal daily routine and the second group was assigned 40-minute moderate-intensity stationary bicycle workouts three times a week. After eight weeks, biopsies were taken from the thigh muscles of participants. The samples showed that the exercises group had a significant increase in the capillaries density, increase in the number of capillaries around muscle fibre, and increase in the surface area through which oxygen and nutrients can flow between blood and muscle.
Pain Management[edit | edit source]
One of the most common problems affecting patients with thalassemia and sickle cell anaemia is pain.. Physiotherapy can help patients to manage their pain using different techniques and strategies:
Regular breathing can help in reducing catheter pain in children with thalassaemia. Breathing exercises were also found to help with pain during Venipuncture due to its analgesic effect. This effect can also be achieved when combined with spirometry.
Pulmonary Functions[edit | edit source]
Pulmonary functions and lung capacity were found to be reduced in patients with thalassemia and sickle cell anaemia such as forced vital capacity (FVC), forced expiratory flow in the first second (FEV 1) Functional capacity, anaerobic threshold and O2 pulse; indicating a restrictive pulmonary dysfunction
Whole Body Vibration[edit | edit source]
A study of thirty-nine children with β-thalassemia major, Whole body vibration was shown to improve the bone mineral density and functional capacity.
Fluidotherapy[edit | edit source]
Fluidized therapy (Fluidotherapy) it is a high-intensity heat modality consisting of a dry whirlpool of finely divided solid particles suspended in a heated air stream. The mixture has the properties of liquids and provides tactile stimulation while allowing space for performing active range of motion
Hydrotherapy[edit | edit source]
A study investigated a hydrotherapy program consisting of stretching, aerobics and relaxation exercises in warm water( 34°C ) for 45 minutes, twice a week, for 10 sessions. The study reported improvement in muscle strength, quality of life and decrease in pain
References[edit | edit source]
- Autosomal recessive. Medline Plus.
- Medline Plus. Thalassemia [Internet]. US National Library of Medicine. 2020 [cited 2020 Jul 21]. Available from: https://medlineplus.gov/ency/article/000587.htm
- Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harbor perspectives in medicine. 2013 Feb 1;3(2):a011775.
- Lai K, Huang G, Su L, He Y. The prevalence of thalassemia in mainland China: evidence from epidemiological surveys. Scientific reports. 2017 Apr 19;7(1):1-1.
- Saggar SA. Thalassemia: Cultural and Historical Perspectives [Internet]. Science Museum. 2019 [cited 2020 Jul 12]. Available from: https://blog.sciencemuseum.org.uk/thalassemia-cultural-and-historical-perspectives/
- Kora A. The Physiotherapy Management of Thalassaemia and Sickle Cell Anaemia. Physioplus Course 2020
- Aszhari FR, Rustam Z, Subroto F, Semendawai AS. Classification of thalassemia data using random forest algorithm. InJournal of Physics: Conference Series 2020 Mar 1 (Vol. 1490, No. 1, p. 012050). IOP Publishing.
- Cheerva A. What is the global prevalence of alpha thalassemia syndromes? [Internet]. Medscape. 2018 [cited 2020 Jul 18]. Available from: https://www.medscape.com/answers/955496-156159/what-is-the-global-prevalence-of-alpha-thalassemia--thalassemia-syndromes
- Prevalence and Clinical Presentation of Beta Thalassemia [Internet]. HCPLive Network. 2020 [cited 2020 Jul 18]. Available from: https://rarediseases.org/rare-diseases/thalassemia-major/
- Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bulletin of the World Health Organization. 2008;86:480-7.
- What is Thalassemia? . Available from:https://www.youtube.com/watch?v=JxuupecxHO8[last accessed 30/09/2020]
- Thalassemia [Internet]. Mayo Foundation for Medical Education and Research. 2020 [cited 2020 Jul 21]. Available from:https://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/syc-20354995
- Nienhuis AW, Nathan DG. Pathophysiology and clinical manifestations of the β-thalassemias. Cold Spring Harbor perspectives in medicine. 2012 Dec 1;2(12):a011726.
- Clevland Clinic. Thalassemias: Diagnosis and Tests [Internet]. 2020 [cited 2020 Jul 21].Available from: https://my.clevelandclinic.org/health/diseases/14508-thalassemias/diagnosis-and-tests
- Olivieri NF, Brittenham GM. Management of the thalassemias. Cold Spring Harbor perspectives in medicine. 2013 Jun 1;3(6):a011767.
- Allen A, Fisher C, Premawardhena A, Peto T, Allen S, Arambepola M, Thayalsutha V, Olivieri N, Weatherall DBlood. 2010 Dec 9; 116(24):5368-70.
- Robinson IB, Sarnat BG. Roentgen studies of the maxillae and mandible in sickle-cell anemia. Radiology. 1952 Apr;58(4):517-23.
- Winter WP. A Brief History of Sickle Cell Disease [Internet]. Howard University Hospitals. 2020 [cited 2020 Aug 3]. Available from: http://www.sicklecell.howard.edu/ABriefHistoryofSickleCellDisease.htm
- Sickle Cell Anaemia.Available from :https://www.youtube.com/watch?v=ZSpFVPBEeLk&feature=youtu.be (Last access 19/11/2020)
- Mumal I. Inheritance of Sickle Cell Disease [Internet]. Sickle Cell Disease News. 2020 [cited 2020 Aug 3]. Available from: https://sicklecellanemianews.com/inheritance-sickle-cell-anemia/
- Lervolino LG, Baldin PE, Picado SM, Calil KB, Viel AA, Campos LA. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Revista brasileira de hematologia e hemoterapia. 2011 Feb;33(1):49-54.
- Uyoga S, Macharia AW, Mochamah G, Ndila CM, Nyutu G, Makale J, Tendwa M, Nyatichi E, Ojal J, Otiende M, Shebe M. The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study. The Lancet Global Health. 2019 Oct 1;7(10):e1458-66.
- Types of Sickle Cell Disease [Internet]. Sickle Cell Association of the National Capital Area. 2017 [cited 2020 Aug 3]. Available from: http://scancainc.org/learn/types-of-sickle-cell-disease/
- Types of Sickle Cell Anemia [Internet]. Global Blood Therapeutics Inc. 2020 [cited 2020 Aug 3]. Available from: https://sicklecellspeaks.com/understanding-sickle-cell/types-of-sickle-cell/
- Sickle Cell Disease [Internet]. National Heart, Lung and Blood Institute. 2020 [cited 2020 Aug 3]. Available from: https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease
- Diagnostic Screening for Sickle Cell Disease [Internet]. St. Jude Children’s Research Hospital. 2020 [cited 2020 Aug 3]. Available from: https://www.stjude.org/treatment/disease/sickle-cell-disease/diagnosing-sickle-cell.html
- Sickle Cell Anemia [Internet]. Mayo Clinic. 2020 [cited 2020 Aug 3]. Available from: https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/diagnosis-treatment/drc-20355882
- Jadhav D, Agrawal P, Fernandes S, Mathur R, Vishwakarma U, HN R, et al. Thalassemia: Impact of Physiotherapy. Pediatr Hematol Oncol J [Internet]. 2018;3(3):S38. Available from: https://doi.org/10.1016/j.phoj.2018.11.108
- Hakeem GL, Mousa SO, Moustafa AN, Mahgoob MH, Hassan EE. Health-related quality of life in pediatric and adolescent patients with transfusion-dependent ß-thalassemia in upper Egypt (single center study). Health and quality of life outcomes. 2018 Dec 1;16(1):59.
- Preidt R. Time to Rethink Ideas About Exercise, Sickle Cell Disease? [Internet]. HealthDay. 2019 [cited 2020 Jul 22]. Available from: https://www.usnews.com/news/health-news/articles/2019-11-19/time-to-rethink-ideas-about-exercise-sickle-cell-disease
- Goldberg E, Fung E, Gaine S. The Benefits of Exercise [Internet]. Northern California Comprehensive Thalassemia Center. 2017 [cited 2020 Jul 22]. Available from: https://thalassemia.com/exercise-and-thalassemia.aspx#gsc.tab=0
- Heidary H, Bijeh N, Javahery SA, Abrishami F. The effect of eight weeks of aerobic training on hematological indices in β-thalassemia minor patients in kermanshah. The Horizon of Medical Sciences. 2011 Oct 10;17(3):20-8.
- Ballas SK, Darbari DS. Review/overview of pain in sickle cell disease. Complementary Therapies in Medicine. 2020 Mar 1;49:102327.
- Bagheriyan S, Borhani F, Abbaszadeh A, Ranjbar H. The effects of regular breathing exercise and making bubbles on the pain of catheter insertion in school age children. Iranian journal of nursing and midwifery research. 2011;16(2):174.
- Bagheriyan S, Borhani F, Abbaszadeh A, Miri S, Mohsenpour M, Zafarnia N. Analgesic effect of regular breathing exercises with the aim of distraction during venipuncture in school-aged thalassemic children. Iranian Journal of Pediatric Hematology and Oncology. 2012 Sep 10;2(3):116-22.
- Matthie N, Brewer CA, Moura VL, Jenerette CM. Breathing exercises for inpatients with sickle cell disease. Medsurg nursing: official journal of the Academy of Medical-Surgical Nurses. 2015 Jan;24(1):35.
- Al-Jafar H, Al-Feeli A, Alozairi A. Non-conventional pain management for sickle cell disease. Annals of Hematology & Oncology. 2017;4(7):1161.
- El-tagui M, Salama K, Salama HM, Mahmoud MM, Massoud HH, El-batanony M, et al. Spirometry and Cardiopulmonary Exercise Performance in Patients with Thalassemia Major. Med J Ca. 2009;77(1):523–8.
- Vieira AK, Alvim CG, Carneiro MC, Ibiapina CD. Pulmonary function in children and adolescents with sickle cell disease: have we paid proper attention to this problem?. Jornal Brasileiro de Pneumologia. 2016 Dec;42(6):409-15.
- Eid MA, Aly SM. Effect of whole body vibration training on bone mineral density and functional capacity in children with thalassemia. Physiother Theory Pract [Internet]. 2019 Jun 10;1–8. Available from: https://doi.org/10.1080/09593985.2019.1625089
- aetna. Fluidized Therapy (Fluidotherapy) [Internet]. 2019 [cited 2020 Jul 27]. Available from: http://www.aetna.com/cpb/medical/data/400_499/0450.html
- Alcorn R, Bowser B, Henley EJ, Holloway V. Fluidotherapy® and Exercise in the Management of Sickle Cell Anemia: A Clinical Report. Physical therapy. 1984 Oct 1;64(10):1520-2.
- fluidotherapy. Available from:https://www.youtube.com/watch?v=_NAYuPgfgp0[last accessed 30/09/2020]
- Tinti G, Somera R, Valente FM, Domingos CR. Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia. A case report. Genetics and Molecular Research. 2010 Jan 1:360-4.