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Cooley's Anemia

Beta Thalassemia Major

Cooley's anemia is also known as beta-thalassemia major and is the most severe type of beta-thalassemia, characterized by a total absence of beta globin chains in the hemoglobin. It may result in severe anemia, which may require regular blood transfusions.


Presentation

There are three forms of beta thalassemias: beta thalassemia major, beta thalassemia minor, and beta thalassemia intermedia. Thalassemia major and intermedia carry a high risk of complications including gallstones and splenomegaly.

Beta-thalassemia major or Cooley's anemia presents in infancy with severe anemia, failure to thrive, growth retardation, and skeletal deformities. Other common symptoms include diarrhea and irritability. Hepatosplenomegaly is a classic feature of beta thalassemia major. Untreated, beta thalassemia major may lead to heart failure and death. Other features are osteoporosis and venous thrombosis.

Another complication of beta thalassemia major is iron toxicity, resulting from repeated blood transfusions. Iron overload is also induced by the increased gastrointestinal absorption of iron, increased hemolysis and ineffective erythropoiesis seen in beta thalassemia major. Iron overload causes iron deposition in tissues causing severe complications including liver cirrhosis, liver carcinoma, myocardial siderosis, testicular failure and failure of sexual development, pancreatitis and diabetes mellitus, insufficiency of the adrenal, thyroid, and parathyroid glands. Cardiopulmonary complications associated with beta thalassemia major include left ventricular dysfunction, valvulopathies, arrhythmias, pericarditis, and pulmonary hypertension.

In uncomplicated cases, skeletal deformities include genu valgum, frontal bossing, malar bone prominence, depression of the nasal bridge, and maxillae hypertrophy. In regularly transfused patients, growth retardation may be absent.

Splenomegaly
  • Splenomegaly, episodes of jaundice and roentgenologic evidence of bone involvement were prominent features.[jamanetwork.com]
  • —An American Negro male first entered the hospital at the age of 28 months with the clinical findings of dark urine, epistaxis, jaundiced sclerae, splenomegaly, and cardiac enlargement. The laboratory findings revealed:[jamanetwork.com]
  • However, hemoglobin (Hb) levels often decrease over time, splenomegaly appears, and progressive iron overload occurs from increased gastrointestinal iron absorption.[news.weill.cornell.edu]
  • Common symptoms of the disease include fatigue, shortness of breath and an enlarged spleen, called splenomegaly, caused by a buildup of malformed red blood cells within the body.[sciencedaily.com]
  • Thalassemia major and intermedia carry a high risk of complications including gallstones and splenomegaly.[symptoma.com]
Anemia
  • Anemia is a condition of a reduced level of normal red blood cells or the reduced ability of the red blood cells to carry oxygen to tissues. Anemia could be severe in Cooley's anemia.[symptoma.com]
  • Abstract Dilatative cardiomyopathy is a late complication of Cooley's anemia resulting in severe heart failure resistant to conventional medical treatment. Anemia, iron and fluid overload are the main causes of this disease entity.[ncbi.nlm.nih.gov]
  • Abstract The dermatoglyphic analysis of a group of Italiam patients with Cooley's anemia and Cooley's trait shows Cooley's anemia patients to undergo a significant increase of loops on fingers and a corresponding decrease of whorls.[ncbi.nlm.nih.gov]
  • Abstract The profound and life-threatening anemia in patients with Cooley's anemia is ascribed primarily to intramedullary hemolysis (ineffective erythropoiesis), the cause of which is obscure.[ncbi.nlm.nih.gov]
  • Our results suggest that the expression of the gamma gene in Cooley's anemia is similar to that of the newborns.[ncbi.nlm.nih.gov]
Fatigue
  • Thalassemia intermedia cause symptoms of moderate to severe anemia including: Fatigue, Paleness, Slow or delayed growth, Weak bones, Enlarged spleen.[omicsonline.org]
  • Fatigue and being short of breath are two of the more common symptoms. The individual is also likely to be somewhat pale, possibly exhibiting signs of jaundice .[wisegeek.com]
  • Fatigue and being short of breath are two of the more common symptoms. The individual is also likely to be somewhat pale, possibly exhibiting signs of jaundice.[wisegeek.com]
  • Common symptoms of the disease include fatigue, shortness of breath and an enlarged spleen, called splenomegaly, caused by a buildup of malformed red blood cells within the body.[sciencedaily.com]
  • You can also take steps on your own to cope with fatigue, such as choosing a healthy diet and exercising regularly.[pharmacypedia.org]
Pallor
  • The anemia surfaces in the first few months after birth and becomes progressively more severe leading to pallor and easy fatigability, failure to thrive (grow), bouts of fever (due to infections) and diarrhea .[medicinenet.com]
  • The anemia surfaces in the first few months after birth and becomes progressively more severe leading to pallor and easy fatigability, failure to thrive (grow), bouts of fever (due to infections) and diarrhea.[medicinenet.com]
  • Physical findings : • Poor growth/failure to thrive; • Delayed puberty; • Pallor; • Jaundice (yellowish color of the skin or whites of the eyes); • Enlarged spleen, liver or heart; and • Skeletal abnormalities (especially the bones in the face).[secure.ssa.gov]
  • […] hemoglobin S and thalassemia. thal·as·se·mi·a ma·jor [MIM*141800-142310 passim] the syndrome of severe anemia resulting from the homozygous state of one of the thalassemia genes or one of the hemoglobin Lepore genes with onset, in infancy or childhood, of pallor[medical-dictionary.thefreedictionary.com]
  • Common symptoms include pallor, jaundice, leg ulcers, gallstones (cholelithiasis), and abnormal enlargement of the liver and spleen. Moderate to severe skeletal malformations (as described in beta thalassemia major) may also occur.[rarediseases.org]
Delayed Growth and Development
  • Some of the most common ones include: bone deformities, especially in the face dark urine delayed growth and development excessive tiredness and fatigue yellow or pale skin Not everyone has visible symptoms of thalassemia.[healthline.com]
Diarrhea
  • She had symptoms of abdominal pain, vomiting and diarrhea for three days before admission. Blood pressure stabilized after intravenous normal saline rescue.[ncbi.nlm.nih.gov]
  • The anemia surfaces in the first few months after birth and becomes progressively more severe leading to pallor and easy fatigability, failure to thrive (grow), bouts of fever (due to infections) and diarrhea .[medicinenet.com]
  • The anemia surfaces in the first few months after birth and becomes progressively more severe leading to pallor and easy fatigability, failure to thrive (grow), bouts of fever (due to infections) and diarrhea.[medicinenet.com]
  • Other symptoms include diarrhea, growth retardation, irritability, poor mental and social development.[symptoma.com]
  • The infants may also suffer from diarrhea, irritability, recurrent episodes of fever, and other intestinal problems. These children have trouble gaining weight and growing at the rate expected for their age.[news-medical.net]
Tachycardia
  • There was good correlation between hemoglobin levels and tachycardia, intensity of first heart sound, heart murmurs, and ejection systolic clicks. Upstroke time of carotid pulse increased with restoration of normal hemoglobin levels.[ncbi.nlm.nih.gov]
Jaundice
  • Children develop life-threatening anemia, have failure to thrive, and may develop jaundice. People with BT major are prone to complications such as infection, and osteoporosis.[secure.ssa.gov]
  • Splenomegaly, episodes of jaundice and roentgenologic evidence of bone involvement were prominent features.[jamanetwork.com]
  • —An American Negro male first entered the hospital at the age of 28 months with the clinical findings of dark urine, epistaxis, jaundiced sclerae, splenomegaly, and cardiac enlargement. The laboratory findings revealed:[jamanetwork.com]
  • Other symptoms can include, bone deformities, fatigue, growth failure, shortness of breath, and yellow skin (jaundice). Treatment for thalassemia involves regular blood transfusions and helps improve the outcome.[chegg.com]
  • The individual is also likely to be somewhat pale, possibly exhibiting signs of jaundice . An individual suffering with Cooley’s anemia is typically much more subject to periods of irritability than others.[wisegeek.com]
Hepatosplenomegaly
  • Karimi M et al Prevalence of hepatosplenomegaly in beta thalassemia minor subjects in Iran. Eur J Radiol. 2007. doi: 10.1016/j.ejrad.2007.09.027 Google Scholar 8.[link.springer.com]
  • Hepatosplenomegaly is a classic feature of beta thalassemia major. Untreated, beta thalassemia major may lead to heart failure and death. Other features are osteoporosis and venous thrombosis.[symptoma.com]
  • […] t. major and the heterozygous form is called t. minor. thalassemia ma jor the homozygous form of β-thalassemia, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia; hepatosplenomegaly[medical-dictionary.thefreedictionary.com]
  • The fetus can also have other problems including severe anemia, enlargement of the liver and spleen (hepatosplenomegaly), and defects in the heart, urinary system, or genitals.[beaumont.org]
Hepatomegaly
  • Abdominal imaging such as ultrasound scanning, MRI, or CT may show gallstones, liver cirrhosis, and hepatomegaly. Cardiac MRI is the gold standard for evaluating cardiac overload and cardiac indices.[symptoma.com]
  • Hepatomegaly can result from a number of mechanisms; extramedullary erthyropoiesis, hepatitis due to chronic transfusion associated infections, and iron overload.[pathophys.org]
  • Feeding problems, diarrhea, irritability or fussiness, recurrent fevers, abnormal enlargement of the liver (hepatomegaly), and the abnormal enlargement of the spleen (splenomegaly) may also occur.[rarediseases.org]
  • Hematopoietic stem cell transplantation generally results in an excellent outcome in low-risk persons, defined as those with no hepatomegaly, no portal fibrosis on liver biopsy, and regular chelation therapy, or at most, two of these abnormalities. 2[aafp.org]
Osteoporosis
  • Condition or disease Intervention/treatment Anemia, Cooley's Beta-Thalassemia Hematologic Diseases Thalassemia Osteoporosis Iron Overload Hypertension, Pulmonary Drug: Deferoxamine Drug: Deferiprone Drug: Arginine Drug: Sildenafil Drug: Decitabine Show[clinicaltrials.gov]
  • Scientific and clinical advancements have resulted in new iron-chelating drugs, early detection of organ failure, an understanding of adult complications associated with living with thalassemia (osteoporosis, heart failure, growth hormone deficiency,[wiley.com]
  • People with BT major are prone to complications such as infection, and osteoporosis.[secure.ssa.gov]
  • Bone mineral density (compared with age- but not height-matched normal subjects) showed severe osteoporosis Beta thalassemia patients are multiply transfused. Short stature is present in 40%.[endocrine-abstracts.org]
  • This is an overview of endocrinopathies of adult patients with b-thalassaemia major, excluding osteoporosis and fertility issues. This review will focus on emerging evidence in the last 5 years with regards to endocrinopathies in patients with TM.[pagepressjournals.org]
Genu Valgum
  • In uncomplicated cases, skeletal deformities include genu valgum, frontal bossing, malar bone prominence, depression of the nasal bridge, and maxillae hypertrophy. In regularly transfused patients, growth retardation may be absent.[symptoma.com]
  • Some individuals may develop ‘knock knees’ (genu valgum), a condition in which the legs bend inward so that when a person is standing the knees will touch even if the ankles and feet are not.[rarediseases.org]
Frontal Bossing
  • This results in splenomegaly, hepatomegaly, and changes in the bones including frontal bossing and cortical thinning. Diagnosis of Cooley's anemia is necessary because of myriads of overlapping differentials.[symptoma.com]
  • When facial bones are affected it can result in distinctive facial features including an abnormally prominent forehead (frontal bossing), full cheek bones (prominent malar eminence), a depressed bridge of the nose, and overgrowth (hypertrophy) of the[rarediseases.org]
  • Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion). Marked pallor and slight to moderate jaundice. Exercise intolerance, cardiac flow murmur or heart failure secondary to severe anaemia.[patient.info]
Irritability
  • An individual suffering with Cooley’s anemia is typically much more subject to periods of irritability than others. Along with the irritability, there is also the opportunity for more frequent headaches and sleep apnea .[wisegeek.com]
  • An individual suffering with Cooley’s anemia is typically much more subject to periods of irritability than others. Along with the irritability, there is also the opportunity for more frequent headaches and sleep apnea.[wisegeek.com]
  • Other symptoms include diarrhea, growth retardation, irritability, poor mental and social development.[symptoma.com]
  • Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more.[nytimes.com]
  • The infants may also suffer from diarrhea, irritability, recurrent episodes of fever, and other intestinal problems. These children have trouble gaining weight and growing at the rate expected for their age.[news-medical.net]

Workup

Diagnosis of Cooley's anemia can be made on clinical grounds, however, investigations are necessary to confirm the diagnosis and exclude other conditions. Peripheral blood film shows mild microcytic anemia, target cells and poikilocytes, brisk erythropoiesis and increased numbers of erythroblasts with a normal erythrocyte count. Heinz bodies, which indicate denatured hemoglobin, may also be present on a peripheral blood film [5].

Elevated HbA2 on electrophoresis or column chromatography is diagnostic of the beta thalassemia trait. The increased HbA2 may be masked in patients with concomitant iron deficiency and in patients with a delta-beta thalassemia trait. Furthermore HBA2 level is normal in patients with alpha thalassemia.

In cases where the investigations provide inconclusive results, free erythrocyte porphyrin (FEP) tests may be conducted. FEP is normal in patients with the beta thalassemia trait. The level of FEP may, however, be elevated in patients with lead poisoning and iron deficiency. Iron studies including serum iron, transferrin, and ferritin levels may be done to exclude iron deficiency and anemia of chronic disorders as the cause of the anemia.

Further blood tests may reveal indirect hyperbilirubinemia, elevated lactate dehydrogenase (LDH), and low haptoglobin levels. These indicate excessive hemolysis and ineffective erythropoiesis. Other hematological investigations required include bone marrow analysis and determination of the Mentzer index. Bone marrow analysis is necessary to exclude other causes of microcytic anemia such as sideroblastic anemia. The Mentzer index refers to the mean corpuscular volume for each red cell count. Mentzer index less than 13 indicates a diagnosis of the beta thalassemia trait, while a score greater than 13 suggests iron deficiency.

Imaging studies are necessary to determine the presence of complications of Cooley's anemia, particularly skeletal deformities and cardiac complications. Bone imaging reveals an expansion of the bone marrow cavity with thinning out of the bone cortex. This results from chronic stimulation of erythropoiesis. These bony changes are most commonly observed in the skull bones, vertebrae, long bones, and pelvis.

Abdominal imaging such as ultrasound scanning, MRI, or CT may show gallstones, liver cirrhosis, and hepatomegaly. Cardiac MRI is the gold standard for evaluating cardiac overload and cardiac indices [6]. Echocardiography, chest X-rays, and electrocardiogram are necessary to exclude cardiac complications.

Microcytic Anemia
  • Heterozygous gammabeta(0) mice suffer from microcytic anemia. Unlike previously described animal models of beta thalassemia major, homozygous gammabeta(0) mice switch from mouse embryonic globin chains to human fetal gamma globin during fetal life.[ncbi.nlm.nih.gov]
  • Peripheral blood film shows mild microcytic anemia, target cells and poikilocytes, brisk erythropoiesis and increased numbers of erythroblasts with a normal erythrocyte count.[symptoma.com]
  • The early papers by Cooley 2 described the condition as being characterized by a hypochromic microcytic anemia with many distorted erythrocytes which were usually resistant to hemolysis by hypotonic saline solution.[jamanetwork.com]
  • The result is a very hypermetabolic bone marrow with thrombocytosis, leukocytosis and microcytic anemia in the young child prior to the enlargement of their spleen.[thalassemia.com]
  • Diagnosis Most persons with thalassemia trait are found incidentally when their complete blood count shows a mild microcytic anemia.[aafp.org]
Heinz Bodies
  • Heinz bodies, which indicate denatured hemoglobin, may also be present on a peripheral blood film. Elevated HbA2 on electrophoresis or column chromatography is diagnostic of the beta thalassemia trait.[symptoma.com]
  • Six rare mutations, despite being heterozygote, showed hemolytic anemia which is also called, ”dominant-type thalassemia”, and some of them demonstrated Heinz bodies in the red blood cells.[petit.lib.yamaguchi-u.ac.jp]
  • Six rare mutations, despite being heterozygote, showed hemolytic anemia which is also called, "dominant-type thalassemia", and some of them demonstrated Heinz bodies in the red blood cells.[ci.nii.ac.jp]
  • These inclusions are termed Heinz bodies, depicted below.[emedicine.medscape.com]
Thrombocytosis
  • Complications of splenectomy including sepsis and thrombocytosis should be noted and prevented. The red blood cells have a functional molecule called hemoglobin, which carries oxygen in the blood.[symptoma.com]
  • Essential Thrombocytosis – A disorder in which platelets are overproduced, which can lead to both blood clotting and bleeding. Clotting Disorders – Problems affecting the ability to clot blood, leading to excessive bleeding or excessive clotting.[nhoh.com]
  • The result is a very hypermetabolic bone marrow with thrombocytosis, leukocytosis and microcytic anemia in the young child prior to the enlargement of their spleen.[thalassemia.com]
Iron Increased
  • Iron overload is also induced by the increased gastrointestinal absorption of iron, increased hemolysis and ineffective erythropoiesis seen in beta thalassemia major.[symptoma.com]
Hepatocellular Carcinoma
  • Machado, MD, University of Illinois College of Medicine 3:25 PM Renal Aspects of Thalassemia Sunil Bhandari, MBChB, MRCP, FRCP, PhD, M Clin Ed, FHEA, Hull & East Yorkshire Hospitals NHS Trust & Hull York Medical School 3:50 PM Hepatocellular Carcinoma[nyas.org]
  • In addition, with increasing age of the patients, new life-threatening complications are being recognized, including severe thromboembolic events, 10 pulmonary hypertension, 11 hepatocellular carcinoma, 12 and pseudoxanthoma elasticum. 13 Hypogonadotropic[haematologica.org]
  • With increasing length of survival, hepatocellular carcinoma is becoming an increasing problem. [ 15 ] Desferrioxamine can cause toxicity: Local reaction at the site of injection can be severe.[patient.info]

Treatment

Management of beta thalassemia major involves lifelong blood transfusions, however, a bone marrow transplant provides a definitive cure for patients [7]. Iron chelation is considered in patients who receive frequent blood transfusions and have developed iron overload. Iron chelation treatment has greatly reduced mortality from iron overload. Deferoxamine and deferiprone are the most commonly used iron chelators.

The goal of long-term transfusion is to achieve and maintain a hemoglobin level of 9-10g/dL. Regular transfusions help to correct the anemia and suppress endogenous erythropoiesis, which in turn, suppresses extra medullary stimulation. Alloimmunization can be prevented by performing an initial typing of the red blood cells for rhesus and ABO antigens and compatibility. The recommended transfusion regimen includes the administration of leukocyte-poor erythrocytes at 8-15ml/kg of body weight over 1-2 hours.

Bone marrow transplantation is indicated in severe cases and it provides a significant reduction in the patient's requirement for blood transfusion [8]. Emerging medical therapies include gene therapy to deliver the globin gene into the cells and pharmacologic modalities which stimulate the production of fetal hemoglobin.

Allogeneic hematopoietic transplantation may provide a definitive cure for some patients. The first successful allogeneic stem cell transplant was reported in 1982 involving an HLA-identical sibling donor [9]. This procedure is best done by an Italian group of hematologists led by Lucarelli [10]. This group has reported a 90% long-term survival in favorable patients, that is, those of young age, HLA match or compatibility, and those with no organ damage. However, complications of transplantation such as graft versus host disease should be considered and prevented.

Dietary modifications may play a role in the treatment of beta thalassemia major, for example, tea may reduce iron absorption in the intestine and intake of vitamin C may improve the excretion of iron in patients who are on iron chelators. However, some reports have indicated that excessive consumption of vitamin C without concurrent administration of iron chelators may cause life-threatening arrhythmias.

Surgical management of beta thalassemia major involves splenectomy. Splenectomy is not routinely indicated in beta thalassemia minor. Splenectomy is indicated if the annual transfusion requirement of the patient is above 200-220ml RBCs/kg. Splenectomy serves to reduce extra medullary hemopoiesis and reduce the patient's transfusion requirement and, in turn, to prevent iron toxicity. This procedure is recommended only for patients above 6 years old, because of the risk of post-splenectomy sepsis in those younger than 6 years old. Furthermore, vaccination of the patient against pneumococcus, meningococcus, and Hemophilus influenza is essential before the procedure, to minimize the risk of post-splenectomy sepsis caused by these encapsulated organisms. Prophylactic penicillin is necessary because of the aforementioned risk. Of note, also, is that splenectomy may increase the risk of thrombocytosis.

In cases of symptomatic cholelithiasis, cholecystectomy may be considered. This procedure may be performed together with splenectomy.

Prognosis

Prognosis depends on the availability of treatment and patient compliance to treatment. The major factors which cause mortality in Cooley's anemia are severe anemia and iron toxicity.

Etiology

Thalassemias are a result of mutations in the genes responsible for globin chain synthesis. Thalassemias are named according to the defective globin chains. The hemoglobin molecule consists of 2 alpha chains and 2 beta chains with heme molecules attached to each chain; defects in the alpha globin genes cause alpha-thalassemia while defects in the beta globin genes cause beta thalassemia.

Beta-thalassemia is an autosomal recessive disorder caused by a complete absence or a significantly reduced production of the beta-globin protein, referred to as beta-zero and beta-plus thalassemia respectively. The imbalance between the alpha and beta chains of the hemoglobin molecule results in hypochromic anemia [2] [3].

As with 50% of all genetic disorders [4], in Cooley's anemia, there is a mutation in the assembly of the messenger RNA (mRNA). The mutation causes the obliteration of the boundary between the introns and exons of the mRNA. This obliteration results in an abnormal assembly of the mRNA, that involves additional continuous length or breakage of the mRNA length. Although hemoglobin may still be formed normally if all the coding sections of the mRNA are present, the additional fragments result in functional defects of the hemoglobin molecule.

Epidemiology

Thalassemias are amongst the most common genetic disorders, affecting persons of all ethnic groups and regions. The incidence of Cooley's anemia is 1 in 100,000 individuals annually worldwide, but with an incidence rate of 1 in 10,000 in Europe.

Worldwide, 15 million patients suffer from symptomatic thalassemias. Beta thalassemia is more common in the Mediterranean countries including Italy, Spain, and Greece. It also occurs frequently in North Africa, Eastern Europe, and the Middle East, while the incidence of alpha thalassemia is higher in Southeast Asia, Africa, and the middle East.

Sex distribution
Age distribution

Pathophysiology

Insufficient production or total absence of beta globin chains results in the synthesis of an abnormal and functionally impaired hemoglobin. The defective gene in Cooley's anemia is on chromosome 11. The insufficient production of the globin chains results in microcytic anemia. This necessitates repeated blood transfusions to compensate for the lack of red blood cells with beta globin chains. However, excessive blood transfusions result in iron overload, with deposits in the tissues, causing myocardial hemosiderosis and heart failure.

Prevention

As it is a genetic disorder, Cooley's anemia cannot be prevented. However, genetic testing and prenatal diagnosis may be essential for management.

Summary

Thalassemias are a group of hematological disorders caused by defective and insufficient synthesis of the globin chains of the hemoglobin molecule. Mutation of the genes responsible for the synthesis of the alpha chains is called alpha thalassemia and mutation in the genes responsible for the synthesis of the beta chains is called beta thalassemia.

Beta thalassemia is characterized by a mutation of one or both genes responsible for the synthesis of the beta globin chains. If the mutation is heterozygous, it is referred to as beta thalassemia minor or beta thalassemia trait, and if it is homozygous, it is classified as beta thalassemia major or Cooley's anemia. Both genes are located on chromosome 11. Beta thalassemia is inherited as an autosomal recessive disorder.

Beta thalassemia has a worldwide incidence rate of 1 in 100,000 [1]. Beta thalassemia is most common in countries within the Mediterranean region including Greece, Spain, and Italy. It is less commonly found in North Africa and Eastern Europe.

Beta thalassemia minor may be asymptomatic or present with mild to moderate anemia. Cooley's anemia mostly presents with severe anemia, usually beginning at infancy, failure to thrive, irritability, and delayed milestone attainment. In Cooley's anemia, there is increased splenic hemolysis and extramedullary erythropoiesis. This results in splenomegaly, hepatomegaly, and changes in the bones including frontal bossing and cortical thinning.

Diagnosis of Cooley's anemia is necessary because of myriads of overlapping differentials. A peripheral blood film is required and may reveal microcytic anemia with target cells and poikilocytes. Other tests include iron studies, lactate dehydrogenase levels, serum bilirubin, electrophoresis, and free erythrocyte porphyrin test. Imaging studies including cardiac magnetic resonance imaging (cardiac MRI), electrocardiography, and abdominal computed tomography (CT) scans that may be necessary to exclude complications of Cooley's anemia.

Treatment of Cooley's anemia involves regular blood transfusions. However, the major complication of frequent blood transfusions in these patients is iron overload. Iron overload causes iron deposition in various tissues leading to liver cirrhosis, myocardial damage, pancreatic damage, diabetes mellitus, and testicular failure. The definitive treatment of Cooley's anemia is bone marrow transplant.

Surgical treatment of Cooley's anemia involves splenectomy and cholecystectomy. Complications of splenectomy including sepsis and thrombocytosis should be noted and prevented.

Patient Information

The red blood cells have a functional molecule called hemoglobin, which carries oxygen in the blood. Hemoglobin has a basic structure, comprising two pairs of protein chains called globin chains, each pair having an alpha and beta pair, and a heme molecule in each chain. Any defect in this basic structure impairs the functional ability of the hemoglobin molecule and, in turn, of the red blood cell. Conditions which result from an abnormality of the alpha and beta chains are called alpha and beta thalassemias respectively.

Each of the two beta globin chains is coded for by a gene in the chromosomes. If one gene is affected, the condition is called beta thalassemia minor, and beta thalassemia major if both genes are affected. Beta thalassemia major is also referred to as Cooley's anemia.

Cooley's anemia is a genetic disorder, that is, a condition which occurs due to mutations or changes in the genetic coding of a structure. This disorder is transmitted from parents to their offspring. The problem in Cooley's anemia is the production of an abnormal hemoglobin, hence a functionally impaired red blood cell. These abnormal red blood cells also have shortened life-spans, as they are frequently destroyed by an organ called the spleen. This causes the body to try and replenish the lost red blood cells by stimulating the structures ( bone marrow, liver, and spleen) in which red blood cell production occurs.

Symptoms of Cooley's anemia usually present within the first two years of a child's life. Because the red blood cells which are produced in this condition are abnormal and functionally impaired, it results in anemia. Anemia is a condition of a reduced level of normal red blood cells or the reduced ability of the red blood cells to carry oxygen to tissues. Anemia could be severe in Cooley's anemia.

As a result of the anemia, the liver, spleen and bone marrow are stimulated to produce more red blood cells, but this stimulation is excessive, leading to the enlargement of the liver and spleen, and thinning of the bones of the skull, spine, and the long bones. In the skull, the patient presents with a prominent and enlarged forehead referred to as frontal bossing.

Other symptoms include diarrhea, growth retardation, irritability, poor mental and social development. These patients are often treated with frequent blood transfusions, so another set of symptoms to be looked out for in these patients are symptoms of iron overload which results from the excessive breakdown of the hemoglobin molecule in red blood cells from the repeated blood transfusions. The complications of iron excess in the body include heart damage, liver disease, delayed sexual maturity from damage to the testes, and damage to other important organs.

A diagnosis is very important to manage this case. Blood studies are done to check for typical features of the disease such as an abnormal shape of the red blood cells, reduced size of the red blood cells, and signs of hemolysis such as too much bilirubin in the blood.

Other necessary investigations include imaging studies, such as magnetic resonance imaging (MRI), X-rays, or computed tomography (CT) scans to determine the presence of the complications aforementioned.

Treatment of Cooley's anemia is regular blood transfusions to replace the abnormal red blood cells and prevent the stimulation of red blood cell production in the liver and spleen. However, blood transfusion doesn't provide a definitive cure for patients with Cooley's anemia. The main complication with regular blood transfusion is iron overload which may cause damage to a lot of organs including the pancreas, liver, heart, and other glands. However, administration of certain drugs called iron chelators may be necessary to clear iron from the blood stream.

A bone marrow transplant provides a definitive cure for patients with Cooley's anemia and it involves a transplantation of the the primary cells which give rise to red blood cells from a matching donor. However, this procedure has a number of complications.

Surgical removal of the spleen, called splenectomy, is also necessary to treat Cooley's anemia. Splenectomy serves to reduce frequent red blood cell break down, and therefore, reduce a patient's need for blood transfusion. Splenectomy comes with certain risks which should be considered and avoided including infections and formation of blood clots.

References

Article

  1. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010 May 21;5:11.
  2. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011 Sep 29; 118(13):3479-88.
  3. Galanello R, Sanna S, Perseu L, et al. Amelioration of Sardinian beta0 thalassemia by genetic modifiers. Blood. 2009 Oct 29; 114(18):3935-7.
  4. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R. Cardiovascular function and treatment in ß-thalassemia major: a consensus statement from the American Heart Association. Circulation. 2013 Jul 16; 128(3):281-308.
  5. Muncie HL Jr, Campbell J. Alpha and beta thalassemia. Am Fam Physician. 2009 Aug 15;80(4):339-44.
  6. Jacob H, Winterhalter K. Unstable hemoglobins: the role of heme loss in Heinz body formation. Proc Natl Acad Sci U S A. 1970 Mar;65(3):697-701.
  7. Sabloff M, Chandy M, Wang Z, et al. HLA-matched sibling bone marrow transplantation for β-thalassemia major. Blood. 2011 Feb 3;117(5):1745-50.
  8. Thomas ED, Buckner CD, Sanders JE, Papayannopoulou T, Borgna-Pignatti C, De Stefano P. Marrow transplantation for thalassaemia. Lancet. 1982 Jul 31; 2(8292):227-9.
  9. Lucarelli G, Galimberti M, Polchi P. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med. 1993 Sep 16; 329(12):840-4.
  10. Ward AJ, Cooper TA. The pathobiology of splicing. J Pathol. 2010 Jan;220(2):152-63

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Last updated: 2018-06-22 10:57