Anaemia
Introduction
The term anaemia is derived from Ancient Greek for "bloodlessness". It is a condition involving an abnormal reduction haemoglobin content.
Red blood cells (containing haemoglobin) are the means by which oxygen is carried to the various parts of the body.
People who are anaemic develop symptoms caused by the inadequate delivery of oxygen to their body tissues. This can vary from simple fatigue to death according to the nature and severity of the anaemia.
The condition is far more common in women than in men.
There are three primary causes:
1. reduced production of red blood cells, which may result from deficiency in nutrients or hormones, or from disease or other conditions
2. excessive destruction of red blood cells, often a hereditary problem
3. excessive blood loss, such as that caused by gastrointestinal ulcers, heavy menstrual periods, or overdose of aspirin.
The most usual symptoms of anaemia are pallor, shortness of breath, low vitality, dizziness, and digestive disorders.
The most common type of anaemia is iron-deficiency anaemia, which occurs when the body’s need for iron increases, as during certain periods of childhood and in pregnancy, or when there is insufficient iron in the diet.
Pernicious anaemia, a chronic ailment that mostly affects people over 40, is a result of vitamin B12 deficiency. Rather than a diet deficient in the vitamin, this is usually caused by intestinal malabsorption, resulting in decreased B12 uptake.
Sickle-cell anaemia is the result of a hereditary defect in the synthesis of haemoglobin.
Aplastic anaemia occurs when there is severe reduction in red blood corpuscles, and when the bone marrow is unable to regenerate them. Ionising radiation is one possible cause.
Past treatment of the condition has included removal of the spleen, repeated transfusions of blood, and a diet featuring beef or calf’s liver.
Transfusions are still used in cases of acute blood loss; iron supplements for iron-deficiency anaemia and injections of vitamin B12 for pernicious anaemia are often effective. Synthetically manufactured erythropoietin (normally produced by the human kidney) is now used to stimulate the production and growth of red blood cells. Other therapy focuses on curing the underlying causes of the nutritional or hormonal deficiency. Blood transfusions and, increasingly, bone marrow transplants, are necessary forms of treatment for aplastic anaemia patients.
Types of Anaemia
anaemia of B12 deficiency
anaemia of chronic disease
anaemia of folate deficiency
drug-induced immune haemolytic anaemia
haemolytic anaemia
haemolytic anaemia due to g6pd deficiency
idiopathic aplastic anaemia
idiopathic autoimmune haemolytic anaemia
immune haemolytic anaemia
iron deficiency anaemia
megaloblastic anaemia
pernicious anaemia
secondary aplastic anaemia
sickle cell anaemia
Anaemia of B12 deficiency is a decrease in the red cells in the blood caused by a vitamin deficiency.
Vitamin B12 is essential for normal nervous system function and normal red cell, white cell and platelet production. All sources of vitamin B12 come from the diet in animal products, including dairy and eggs.
For vitamin B12 to be absorbed by the body, it must become bound to an intrinsic factor, a protein secreted by cells in the stomach.
Causes of vitamin B12 deficiency include:
dietary (a strict vegetarian diet excluding all meat, fish, dairy products, and eggs)
chronic alcoholism
abdominal or intestinal surgery that eliminates the site of intrinsic factor production or absorption
Crohn's disease intestinal malabsorption disorders
fish tape worm
pernicious anaemia, which is caused by an inherited intrinsic factor deficiency.
Anaemia of B12 deficiency that is caused by a poor diet can be prevented through a well-balanced diet. Prophylactic (preventative) use of vitamin B12 injections can prevent deficiency after surgeries known to result in vitamin B12 deficiency. Anaemia resulting from other causes cannot be prevented, but early diagnosis can limit the severity of the anaemia.
Symptoms include:
loss of appetite
diarrhoea
numbness and tingling of hands and feet
paleness
shortness of breath
fatigue
weakness
sore mouth and tongue
Treatment depends on the cause of the anaemia.
Pernicious anaemia requires life long therapy with vitamin B12 injections.
Anaemia caused by dietary insufficiency of vitamin B12 can be corrected by oral (by mouth) vitamin replacement in combination with a more balanced diet. Initially it may be treated with vitamin B12 injections.
Anaemia caused by malabsorption (inadequate absorption of nutrients from the intestinal tract) is treated with vitamin B12 injections until the condition improves.
Prognosis for this form of anaemia is generally that it is corrected by therapy.
Complications
Central nervous system signs and symptoms may be irreversible if treatment is not initiated within 6 months of the onset of these symptoms. Vitamin B12 affects the maturation of all epithelial cells (cells that form the outer surface of the body and line inner passageways) and a deficiency may cause a false positive pap smear.
Anaemia of chronic disease is an anaemia that develops as a result of long-term infection or disease.
Certain chronic infections and diseases cause several changes in the blood production (haematopoietic) system. These include a slightly shortened red blood cell life span, decreases in the amount of iron that is available in the fluid portions of blood, and decreases in the activity of the bone marrow. In the presence of these three effects a low to moderate grade anaemia develops. The symptoms of the anaemia often go unnoticed in the face of the primary disease.
Conditions associated with the anaemia of infection and chronic diseases include such diverse diseases as chronic bacterial endocarditis, osteomyelitis, juvenile rheumatoid arthritis, rheumatic fever, Crohn's disease, and ulcerative colitis. Chronic renal failure may produce a similar anaemia because it causes reduced levels of erythropoietin, the hormone that stimulates the production of red blood cells in the bone marrow.
Treatment of the underlying disease can prevent or reverse the anaemia. Chronic diseases such as Crohn's disease are difficult to treat and patients may exhibit intermittent anaemia that varies with their condition.
Symptoms include:
presence of a chronic disease or infection
pallor
fatigue
tiredness
headache
lethargy
shortness of breath on exertion
dizziness
Signs and tests:
haematocrit (low normal to below normal)
haemoglobin (low)
reticulocyte count (low to normal)
serum ferritin level (normal to elevated)
serum iron (low)
total iron binding capacity (TIBC) (normal)
This type of anaemia responds to treatment of the primary disease and with successful treatment of the primary disease the anaemia will resolve.
Anaemia of folate deficiency is a decrease in the red cells in the blood caused by folate (folic acid) deficiency.
Folate or folic acid is necessary for red blood cell formation and growth. Dietary sources of folate are found in green leafy vegetables and liver. Some medications such as Dilantin interfere with the absorption of this vitamin. Because folate is not stored in the body in large amounts, a continual dietary supply of this vitamin is needed.
In folate deficiency anaemia, the red cells are abnormally large and are referred to as megalocytes, and in the bone marrow as megaloblasts. Subsequently, this anaemia may be referred to as megaloblastic anaemia
Causes of the anaemia are poor dietary intake of folic acid as in chronic alcoholism, malabsorption diseases such as celiac disease and sprue, and certain medications. A relative deficiency due to increased need for folic acid may occur in the third trimester of pregnancy. Risk factors are a poor diet (seen frequently in the poor, the elderly and in people who do not buy fresh fruits or vegetables), overcooking food, alcoholism, having a history of malabsorption diseases, and pregnancy. The incidence is 4 out of 100,000 people.
Adequate dietary intake in high-risk individuals and folic acid supplementation during pregnancy may help prevent the onset of this anaemia.
Symptoms include:
tiredness
headache
sore mouth and tongue
pallor or jaundice
Signs and tests:
a folate - test
low red blood cell folate level
a CBC
a bone marrow examination
The objective of treatment is to treat the underlying cause of the anaemia, which may be dietary or a malabsorption disease.
Oral or parenteral folic acid supplements may be taken on a short-term basis until the anaemia has been corrected, or in the case of loss of absorption by the intestine, replacement therapy may be lifelong.
Dietary treatment consists of increasing the intake of green leafy vegetables and citrus.
This type of anaemia usually responds well to treatment with correction of the abnormalities within 2 months.
Complications of the condition
Symptoms of anaemia can cause discomfort. In a pregnant woman, folate deficiency has been associated with neural tube defects (such as spina bifida) in the infant.
Drug induced immune haemolytic anaemia is an acquired form of haemolytic anaemia caused by interaction of certain drugs with the red blood cell membrane, resulting in antibody production against the red blood cells and premature red blood cell destruction
Drug-induced immune haemolytic anaemia occurs when certain drugs interact with the red blood cell membrane, causing the cell to become antigenic (the body identifies the cell as tissue not belonging to the body). Antibodies form against the red blood cells. The antibodies combine with the affected red blood cells and result in their premature destruction. The incidence is rare in children.
Drugs that can cause secondary immune haemolytic anaemia are penicillins, cephalosporins, levodopa, methyldopa, mefenamic acid, quinidine, salicylic acid, sulfonamides, Thiazide diuretics, antazoline, chlorpromazine, isoniazid, streptomycin, and Motrin. Drug-induced haemolytic anaemia is most often associated with G6PD deficiency.
If the disorder occurs, the individual should avoid the offending drug and its analogues (similar medications) in the future.
Symptoms:
fatigue
pale colour
shortness of breath
rapid heart rate
yellow skin colour (jaundice)
dark urine
Signs and tests:
A physical examination shows an enlarged spleen.
A direct Coombs' test is positive.
An indirect Coombs' test is positive if the offending drug is added to the test.
Indirect bilirubin levels are elevated.
Serum haptoglobin may be low.
Haemoglobin may be present in the urine.
Haemosiderin may be present in the urine.
Urine and faecal urobilinogen are increased.
An absolute reticulocyte count is elevated.
A CBC shows red blood cell count and haemoglobin are low.
A direct measurement of the red cell longevity by isotope tagging techniques shows a decreased life span. See RBC (nuclear) scan.
Discontinuation of the suspected causative drug may alleviate or control the symptoms. Treatment with prednisone is the first additional therapy that may be tried.
Blood transfusions with carefully typed packed red blood cells may be advised for severe symptoms.
The outcome is expected to be good. The process subsides when the offending agent is eliminated from the body.
Complications:
Death caused by severe anaemia may result but it is very rare.
Transfusion can cause a transfusion reaction.
Haemolytic anaemia refers to any condition causing inadequate number of circulating red blood cells caused by premature destruction of red blood cells. There are a number of specific types of haemolytic anaemia which are described individually elsewhere in this text.
Haemolytic anaemia occurs when the bone marrow is unable to compensate for premature destruction of red blood cells by increasing their production. When the marrow is able to compensate, anaemia does not occur.
There are many types of haemolytic anaemia, which are classified by the location of the defect. The defect may be in the red blood cell itself (intrinsic factor) or outside the red blood cell (extrinsic factor).
Causes of haemolytic anaemia include infection, certain medications, autoimmune disorders, and inherited disorders. Types of haemolytic anaemia include:
aplastic anaemia
secondary aplastic anaemia
haemoglobin SC disease
haemolytic anaemia due to G6PD deficiency
hereditary elliptocytosis
hereditary spherocytosis
hereditary ovalocytosis
idiopathic autoimmune haemolytic anaemia
non-immune haemolytic anaemia caused by chemical or physical agents
secondary immune haemolytic anaemia
sickle cell anaemia
The over all incidence of "haemolytic anaemia" is 4 out of 100,000 people.
Haemolytic anaemia due to G-6-PD deficiency is a hereditary, sex-linked, enzyme defect that results in the breakdown of red blood cells when the person is exposed to the stress of infection or certain drugs.
G-6-PD deficiency is an inheritable x-linked recessive disorder whose primary effect is the reduction of G-6-PD in the red blood cell, with resultant haemolysis of the cell. The ultimate effect of the disease is to produce anaemia, either acute haemolytic or a chronic spherocytic type.
The incidence of G-6-PD is much higher among Afro-Caribbean population affecting males.
The disorder may occasionally affect a few females to a mild degree (depending on their genetic inheritance).
Another type of this disorder can occur in whites who originated in the Mediterranean basin. It, too, is associated with acute episodes of homeless. Episodes are longer and more severe than the other type of disorders.
People with the disorder are not normally anaemic and display no evidence of the disease until the red cells are exposed to an oxidant or stress.
Drugs that can precipitate this reaction include:
antimalarial agents
sulfonamides (antibiotic)
aspirin
nonsteroidal anti-inflammatory drugs (NSAIDs)
nitrofurantoin
quinidine
quinine
others
exposure to certain chemicals such as those in mothballs
The risk of acute haemolytic crisis can be decreased by reviewing the family history for any evidence of haemolytic anaemias or spherocytosis or testing before giving any medications belonging to the above class of chemicals.
The episodes are usually brief, because newly produced (young) red cells have normal G6PD activity.
People with G-6-PD must strictly avoid factors that can precipitate an episode, especially drugs known to cause oxidative reactions.
Genetic counselling or genetic information may be of interest to heterozygous women and affected men.
Symptoms:
fatigue
pale colour
shortness of breath
rapid heart rate
yellow skin colour (jaundice)
dark urine
enlarged spleen
Note: Severe homeless may cause haemoglobinuria.
If the cause is an infection, it should be treated, or if the cause is a drug, the offending agent should be stopped. People with the Mediterranean form or those in haemolytic crisis may occasionally require transfusions.
Spontaneous recovery from haemolytic crises are the normal outcome.
Rarely, death may occur following a severe haemolytic event.
Idiopathic aplastic anaemia is a failure of the bone marrow to properly form all types of blood cells.
Idiopathic aplastic anaemia is a condition that results from injury to the stem cell, a cell that gives rise to other cell types when it divides. Consequently, there is a reduction in all cell types--red blood cells, white blood cells and platelets--with this type of anaemia, which is called pancytopaenia. The cause of idiopathic aplastic anaemia is unknown, but is thought to be an autoimmune process (when the body reacts against its own cells). Causes of other types of aplastic anaemia may be chemotherapy, radiation therapy, toxins, drugs, pregnancy, congenital disorder, or systemic lupus erythematosus.
Symptoms arise as the consequence of bone marrow failure. Anaemia (low red blood cell count) leads to fatigue and weakness. Low white blood cell counts, or neutropaenia, causes an increased risk of infection. Low platelet counts, or thrombocytopaenia, results in bleeding of mucus membranes and skin. The disease may be acute or chronic, and is always progressive. Risk factors are unknown. The incidence is 2 out of 1 million people.
There is no known prevention for idioplastic anaemia.
Symptoms include:
fatigue
pallor
shortness of breath on exertion
rapid heart rate
irregular heartbeat
rash
easy bruising
nose bleeds
bleeding gums
prolonged bleeding
lymph nodes may be enlarged although this is rare
Signs and tests:
A physical examination reveals an enlarged spleen, tenderness of the sternum, and irregular heart rate.
Tests:
CBC that shows low haematocrit and haemoglobin levels
white blood cell count, low
reticulocyte count, low
platelet count, low
bone marrow biopsy, abnormal
bilirubin level, elevated
an abdominal X-ray or CT scan that shows enlarged spleen
a sugar-water (haemolysis) test that shows fragile red blood cells
Mild cases of aplastic anaemia are treated with supportive care. Blood transfusions and platelet transfusions help correct the abnormal blood counts and relieve some symptoms.
Severe aplastic anaemia, as evidenced by very low blood cell counts, is a life-threatening condition. Bone marrow transplant for people 30 and under is indicated for severe disease. For adults over 40, or for those who do not have a matched bone marrow donor, antithymocyte globulin (ATG) is the alternative treatment. ATG is a horse serum that contains antibodies against human T cells and is used in an attempt to suppress the body's immune system, allowing the bone marrow to resume its blood cell generating function. Other medications to suppress the immune system may be used, such as cyclosporine.
Untreated aplastic anaemia is an illness that leads to rapid death. Bone marrow transplantation has been successful in young people, with long term survival of 80%. Older people have a survival rate of 40 to 70%.
Complications of treatment may lead to rejection of bone marrow graft, or severe reaction to ATG.
Idiopathic autoimmune haemolytic anaemia is a disorder resulting from an abnormality of the immune system that destroys red blood cells prematurely. The cause is unknown.
It is an acquired disease that occurs when antibodies form against the person's own red blood cells. In the idiopathic form of this disease, the cause is unknown. There are other types of immune haemolytic anaemias where the cause may result from an underlying disease or medication. Idiopathic autoimmune haemolytic anaemia accounts for one-half of all immune haemolytic anaemias. The onset of the disease may be quite rapid and very serious. Risk factors are not known.
autoimmunehaemolyticanaemia.JPG (39512 bytes)This slide shows a sample of blood from a patient suffering acute autoimmune haemolytic anaemia
There is no known prevention for idiopathic autoimmune haemolytic anaemia, because the cause is unknown.
Symptoms:
fatigue
pale colour
shortness of breath
irregular heartbeat (rapid)
yellow skin colour
dark urine
enlarged spleen
Signs and tests:
positive Coombs' test, direct
Coombs' test, indirect
elevated bilirubin levels
low serum haptoglobin
haemoglobin in the urine
elevated reticulocyte count
low red blood cell count and serum haemoglobin
antithyroid microsomal antibody
antithyroglobulin antibody
Treatment with prednisone is the first therapy that is tried. If prednisone does not improve the condition, a splenectomy (removal of the spleen) may be considered. Immunosuppressive therapy is given if the person does not respond to prednisone and splenectomy. Imuran and Cytoxan have both been used.
Blood transfusions are given with caution, if indicated for severe anaemia, because of the potential that blood may not be compatible and precipitate a reaction.
Adults commonly have long-term disease, but in children the anaemia is usually short-lived.
Complications:
bleeding
infection
Iron deficiency anaemia is a decrease in the red cells of the blood caused by too little iron.
Iron deficiency anaemia is the most common form of anaemia. Approximately 20% of women, 50% of pregnant women, and 3% of men are iron deficient. Iron is an essential component of haemoglobin, the oxygen carrying pigment in the blood. Iron is normally obtained through the food in the diet and by the recycling of iron from old red blood cells.
irondeficiency.JPG (29111 bytes)The causes of iron deficiency are too little iron in the diet, poor absorption of iron by the body, and loss of blood (including from heavy menstrual bleeding). It is also caused by lead poisoning in children. Anaemia develops slowly after the normal stores of iron have been depleted in the body and in the bone marrow. Women, in general, have smaller stores of iron than men and have increased loss through menstruation, placing them at higher risk for anaemia than men. In men and postmenopausal women, anaemia is usually due to gastrointestinal blood loss associated with ulcers or the use of aspirin or nonsteroidal anti-inflammatory medications (NSAIDs).
Note the washed out appearance of the red blood cells in the slide above
High-risk groups include:
women of child-bearing age who have blood loss through menstruation
pregnant or lactating women who have an increased requirement for iron
infants, children, and adolescents in rapid growth phases
people with a poor dietary intake of iron through a diet of little or no meat or eggs for several years.
Risk factors related to blood loss are peptic ulcer disease, long term aspirin use, colon cancer, uterine cancer, and repeated blood donation. The incidence is 2 out of 1000 people.
Prevention:
Dietary sources of iron are red meat, liver, and egg yolks. Flour, bread, and some cereals are fortified with iron. If the diet is deficient in iron, iron should be taken orally. During periods of increased requirements such as pregnancy and lactation, increase dietary intake or take iron supplements.
Symptoms:
pale skin colour (pallor)
fatigue
irritability
weakness
shortness of breath
low blood pressure with position change from lying or sitting to standing (orthostatic hypotension)
sore tongue
brittle nails
unusual food cravings (called pica)
decreased appetite (especially in children)
headache - frontal
Note: There may be no symptoms if anaemia is mild.
Signs and tests:
low haematocrit and haemoglobin in a CBC
low serum ferritin (serum iron) level
transferrin saturation
stool for occult blood (stool guaiac) that reveals blood loss
higher than normal TIBC levels
Treatment:
Identification of the cause of the deficiency is essential. Iron deficiency cannot be overcome by increasing dietary intake alone. Iron supplements are always required.
Oral iron supplements are in the form of ferrous sulphate. The best absorption of iron is on an empty stomach, but many people are unable to tolerate this and may need to take it with food. Milk and antacids may interfere with absorption of iron and should not be taken at the same time as iron supplements. Vitamin C can increase absorption and is essential in the production of haemoglobin.
Supplemental iron is needed during pregnancy and lactation because normal dietary intake cannot supply the required amount.
The haematocrit should return to normal after 2 months of iron therapy, but the iron should be continued for another 6 to 12 months to replenish the body's iron stores, contained mostly in the bone marrow.
Intravenous or intramuscular iron is available for patients when iron taken orally is not tolerated.
Iron-rich foods include raisins, meats (liver is the highest source), fish, poultry, eggs (yolk), legumes (peas and beans), and whole grain bread.
With treatment, the outcome is likely to be good. In most cases the blood counts will return to normal in 2 months.
Complications:
There are usually no complications; however, iron deficiency anaemia may recur, so regular follow-up is encouraged. Children with this disorder may have an increased susceptibility to infection.
Megaloblastic anaemia is a blood disorder characterised by red blood cells that are larger than normal, low white blood count, and low platelet count resulting from a deficiency of folic acid or vitamin B-12.
Deficiencies of vitamin B12 and folic acid are the most common causes of megaloblastic anaemia. Other causes are leukaemia, myelofibrosis, multiple myeloma, certain hereditary disorders, drugs that affect nucleic acid metabolism such as chemotherapy agents (methotrexate), and other causes. Risk factors relate to the causes. (See also pernicious anaemia).
megaloblastic.JPG (22914 bytes)Note the large size of the red blood cells when compared to the white blood cells in this slide showing a blood sample taken from a patient with megaloblastic anaemia.
Adequate intake of vitamin B12 and folic acid is helpful.
Symptoms:
loss of appetite
diarrhoea
tingling and numbness of hands and feet
pale skin colour
tiredness
headaches
sore mouth and tongue
pale skin colour or jaundice
Examination of neurological signs shows abnormal reflexes, decreased position sense, and decreased vibration sense.
Tests include:
CBC results showing low haematocrit with elevated MCV
bone marrow examination
serum LDH
below normal serum B12 level
Schilling test
serum folate level
elevated ferritin
The objective of treatment is to determine the cause of the anaemia, and the treatment depends upon the cause. Anaemias related to vitamin deficiencies are discussed separately.
The outcome is expected to be good with treatment.
Complications vary with the underlying cause
Pernicious anaemia is a form of anaemia caused by a lack of intrinsic factor, a substance needed to absorb vitamin B12 from the gastrointestinal tract.
People with pernicious anaemia lose their ability to make intrinsic factor, a substance that enables vitamin B12 to be absorbed from the intestine. Vitamin B12 deficiency results.
This condition may result from hereditary factors. Congenital pernicious anaemia is inherited as an autosomal recessive disorder.
Pernicious anaemia is also seen in association with some autoimmune endocrine diseases such as type 1 diabetes, hypoparathyroidism, Addison's disease, hypopituitarism, testicular dysfunction, Graves disease, chronic thyroiditis, myasthenia gravis, secondary amenorrhea, vitiligo, and candidiasis. Gradually the deficiency of vitamin B12 affects sensory and motor nerves, causing neurological effects. The anaemia also affects the gastrointestinal system and the cardiovascular system.
The disease can affect all racial groups, but the incidence is higher among people of Scandinavian or Northern European descent. Pernicious anaemia usually does not appear before the age of 30, although a juvenile form of the disease can occur in children. Juvenile or congenital pernicious anaemia is evident before the child is 3 years old.
Risk factors are a history of autoimmune endocrine disorders, a family history of pernicious anaemia, and Scandinavian or Northern European descent. The incidence is 1 out of 1,000 people.
In the infant or young child, pernicious anaemia may be secondary to poor absorption of vitamin B12 caused by some of the following conditions:
defect in absorption
celiac disease (sprue)
methylmalonic aciduria
homocystinuria
tuberculosis treatment with para amino salicylic acid
poor diet in the infant
maternal dietary deficiency while pregnant can cause pernicious anaemia in an infant less than 4 months old
This condition is not preventable. Treatment will prevent continued symptoms.
Symptoms:
shortness of breath
fatigue
pallor
rapid heart rate
loss of appetite
diarrhoea
tingling and numbness of hands and feet (paresthesias)
sore mouth
unsteady gait, especially in the dark
slowing of mental processes
Additional symptoms that may be associated with this disease:
tongue problems
smell, impaired
gums, bleeding
positive Babinski's reflex
loss of deep tendon reflexes
Signs and tests:
Neurological signs or symptoms will develop if the disease goes untreated.
Tests that may indicate pernicious anaemia include:
CBC results that show low haematocrit and haemoglobin with elevated MCV
CBC showing low white blood count and low platelets
low reticulocyte count
bone marrow examination
serum LDH
below normal serum vitamin B-12 level
Schilling test
This disease may also alter the results of the following tests:
TIBC
peripheral smear
leukocyte alkaline phosphatase
gastrin
cholesterol test
bilirubin
Treatment:
Vitamin B12 injections are the definitive treatment for this disorder. When treatment is initiated, 5 to 7 injections may be given in a short span of time. Response to this therapy is usually seen within 48 to 72 hours, so there is usually no need for blood transfusions as a treatment for very low blood counts. Life-long therapy (with vitamin B12 injections every month or two) is needed for this disorder. Oral (by mouth) vitamin B12 is not recommended because it will not produce the desired response (the problem is an inability to ABSORB vitamin B12, not a lack of the vitamin in the diet). A well-balanced diet is essential to provide other components for healthy blood cell development such as folic acid, iron, and vitamin C.
The outcome is usually excellent with treatment.
Complications:
* People with pernicious anaemia may have gastric polyps and have twice the incidence of gastric cancer than the normal population.
* Persistent neurological defects may be present if treatment is delayed.
* Vitamin B12 deficiency affects the appearance of all epithelial cells, therefore an untreated woman may obtain a false positive pap smear.
Sickle-Cell Anaemia, also sickle-cell disease is a hereditary condition in which haemoglobin, an oxygen-carrying protein in the blood is altered. This leads to periodic interruptions in blood circulation. The disease is found predominantly in Afro-Caribbean people; it also occurs in the Middle East and the Mediterranean area.
Symptoms of the condition appear at about six months of age and may include enlargement of the abdomen and heart and painful swelling of the hands and feet. In adolescence, sexual maturation may be delayed. The disturbances in blood flow associated with the disease also dispose affected people to infections and leg ulcers. These symptoms are due to the altered haemoglobin, which changes shape when the amount of oxygen in the blood is reduced for any reason. The red blood cell in which the haemoglobin is contained also changes its shape, from round to crescent (sickle shaped). The sickle-shaped red cells interfere with normal blood flow by plugging up small blood vessels.
sicklecell.JPG (35262 bytes)
Sickle-cell anaemia occurs when an individual inherits a sickle-cell gene from each parent. Programmes have been initiated to detect carriers of the gene, who do not themselves show the trait. Such carriers are informed that a child resulting from the union of two carriers runs a one-in-four risk of having sickle-cell disease.
Therapy for sickle-cell anaemia is largely to allay symptoms. Preventive administration of penicillin to affected children by the age of four months greatly decreases mortality from infections. For this reason, routine screening of new-borns for sickle-cell anaemia is currently carried out in most developed countries.
sickle.gif (213226 bytes)
Sickle-Cell Anaemia
Sickle-cell anaemia arises from a mutation in haemoglobin, the protein that carries oxygen in the bloodstream. A substitution in its amino-acid sequence (valine, where glutamic acid should be) causes the four-chained haemoglobin molecule to form incorrectly when oxygen is low. Defective haemoglobins bind together, forming long rods that stretch the red blood cell into a crescent. These "sickled" red blood cells cannot fit through small blood vessels.
This looping animation shows the process of sickle cell formation.
Thalassaemia, inherited form of anaemia in which there is reduced synthesis of one or more of the four globin chains, usually 2a (alpha) and 2b (beta), which make up haemoglobin in red blood cells.
The function of haemoglobin is to carry oxygen between the lungs and the tissues of the body; in anaemia this is insufficient to meet the oxygen requirements of the tissues (for example, the muscles and the brain).
The word "thalassaemia" is derived from the Greek word for "sea"; the disease was called this because it is more common in people of Mediterranean origin. However, it has been recognised that the disorder is found worldwide. There are several types of this condition, the main forms in adults being broadly characterised as a- or b-thalassaemias according to whether the genes for the a or the b chain are abnormal. The severity of the disease varies according to the precise genetic conformation. They are probably the most commonly inherited disorders of the blood, and the most common disorders to be caused by an abnormality in a single gene.
In thalassaemia, the structure of both haemoglobin chains remains unchanged, but either the a or the b chain is absent—not produced at all—or is produced in reduced quantities because of abnormalities in the genes encoding these proteins. This sets up an imbalance in the amount of the globin in chains being produced with either the a or the b predominating. The chains precipitate in the absence of sufficient chains for them to bind to and this precipitation interferes with the formation of red blood cells. Fewer red blood cells are produced than normal and those that are able to develop include the precipitated haemoglobin chains, so that they do not pass through the capillaries correctly and are prematurely destroyed by the body. This leads to a severe anaemia, and in order to attempt to compensate for it, the bone marrow expands to try to make sufficient red blood cells; the spleen is also enlarged. This can lead to severe deformities of the skull and long bones.
Homozygous b Thalassaemia (Cooley’s Anaemia)
Homozygous thalassaemia, where both copies of the gene for a haemoglobin chain are defective, occurs when no chains are synthesised. The symptoms develop after birth during the first few months of life. If affected patients are correctly diagnosed when babies and treated with regular blood transfusions, they will develop normally during childhood until puberty. However, at puberty a variety of liver, heart, and glandular problems can result from the iron overload caused by the transfusions. Death normally occurs before the age of 30 from cardiac damage. In the absence of transfusion, children die within the first year of life. If they receive insufficient blood transfusions, they tend to develop deformities of the skull and the bones, leading to a characteristic mongoloid appearance; they have enlarged spleens, severe anaemia, and are subject to repeated infections and a tendency to bleed. They also fail to thrive and if they survive to adolescence they run the risk of the same complications of iron overloading as those who are sufficiently transfused.
betathalamajor.JPG (29204 bytes)
Blood sample from a patient suffering homozygous b thalassaemia
Heterozygous b Thalassaemia
Heterozygous thalassaemia occurs when only one copy of the gene for the chain is affected. Sufferers are normally free from symptoms except during pregnancy, when they may become anaemic.
Alpha (a) Thalassaemia
Alpha thalassaemia can lead to two main disorders. The most severe is Bart’s hydrops syndrome; the other is haemoglobin H disease. Bart’s hydrops syndrome occurs when no chains are made, even in the foetus; these infants are usually stillborn at between 28 and 40 weeks, and if born alive, they die within the first hour. Haemoglobin H is produced by four normal b chains. It is formed when some chains are being produced, but not enough. The symptoms are not as severe as for Bart’s hydrops syndrome, but anaemia is present and the spleen is enlarged. Patients usually survive to adult life.