ACUTE RESPIRATORY DISORDERS What is the purpose of the nose? The purpose of the nose is to warm, clean, and humidify the air you breathe as well as help you to smell and taste. A normal person will produce about two quarts of fluid each day (mucus), which aids in keeping the respiratory tract clean and moist. Tiny microscopic hairs (cilia) line the surfaces of the nasal cavity, helping to brush away particles. Eventually the mucus blanket is moved to the back of the throat where it is unconsciously swallowed. This entire process is closely regulated by several body systems. Structurally, the nose is separated into two passageways (left and right nostrils) by a structure called the septum. Protruding into each breathing passage are bony projections, called turbinates, which help to increase the surface area of the inside of the nose. There are three turbinates on each side of the nose (inferior or lower turbinates, middle turbinates, superior or upper turbinates). The sinuses are four paired, air-filled chambers which empty into the nasal cavity. Their purpose is not really known, but may help to lighten the skull, reducing its weight.
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The purpose of the nose is to warm, clean, and humidify the air you breathe aswell as help you to smell and taste. A normal person will produce about two
quarts of fluid each day (mucus), which aids in keeping the respiratory tract clean
and moist. Tiny microscopic hairs (cilia) line the surfaces of the nasal cavity,
helping to brush away particles. Eventually the mucus blanket is moved to the
back of the throat where it is unconsciously swallowed. This entire process is
closely regulated by several body systems.
Structurally, the nose is separated into two passageways (left and right nostrils)
by a structure called the septum. Protruding into each breathing passage arebony projections, called turbinates, which help to increase the surface area of the
inside of the nose. There are three turbinates on each side of the nose (inferior or
lower turbinates, middle turbinates, superior or upper turbinates). The sinuses
are four paired, air-filled chambers which empty into the nasal cavity. Their
purpose is not really known, but may help to lighten the skull, reducing its weight.
eliminate house plants; and bathe pets frequently or even give away dander-
producing pets.
Avoidance of nasal irritants: Nasal irritants usually do not lead to the typical
immune response seen with classical allergies, but nevertheless they can mimicor make allergies worse, as in vasomotor rhinitis. Examples of these irritants
include cigarette smoke, perfume, aerosol sprays, smoke, smog and car exhaust.
Identifying the possible allergens may be just as hard as avoiding them. In some,
this may be identified by a very careful history taken by their physician. Details of
the patient's possible exposure to allergens or irritant at home or the workplace
may give some clues. In others, even a very detailed history may not reveal a
possible trigger. Therefore, a consultation with an allergy specialist (allergy and
immunologist) may be prudent. The allergy doctor may perform some simple skintests to try to identify common environmental allergies.
What medications can be used to treat rhinitis and post-nasal
drip?
In addition to measures noted above, medications may also be used for the
treatment of rhinitis and post-nasal drip.
For allergic rhinitis and post-nasal drip many medications are used.
Steroid nasal sprays
The experts recommend using intra-nasal glucocorticoids (steroid sprays applied
directly into the nose) as the first line of treatment. Steroids are known to be
potent anti-inflammatory and anti-allergic agents and they are known to relieve
most of the associated symptoms of runny and itchy nose, nasal congestion,
sneezing, and post-nasal drip.
Their use must be monitored and tapered by the prescribing physician as long-term use may have significant side effects. Examples of the nasal steroids
2. Non-sedating or second generation [loratadine (Claritin), cetirizine(Zyrtec)].
Non-sedating antihistamines can have serious drug interactions. Most of
these are found over the counter.
There is also a nasal antihistamine preparation that has been shown to be veryeffective in treating allergic rhinitis, called azelastine nasal (Astelin).
Decongestant sprays
Examples of decongestant sprays include:
oxymetazoline (Afrin), and
phenylephrine (Neo-Synephrine)
Decongestant sprays quickly reduce swelling of nasal tissues by shrinking the
blood vessels. They improve breathing and drainage over the short-term.
Unfortunately, if they are used for more than a few days they can become highly
addictive (rhinitis medicamentosa). Long-term use can lead to serious damage.
Therefore, their use should limited to only 3 to 7 days.
Oral decongestants
Oral decongestants temporarily reduce swelling of sinus and nasal tissues
leading to an improvement of breathing and a decrease in obstruction. They may
also stimulate the heart and raise the blood pressure and should be avoided by
patients who have high blood pressure, heart irregularities,glaucoma, thyroid
problems, or difficulty in urination. The most common decongestant
is pseudoephedrine (Sudafed).
Cromolyn sodium (Nasalcrom)
Cromolyn sodium (Nasalcrom) is a spray helps to stabilize allergy cells (mast
cells) by preventing release of allergy mediators, like histamine. They are most
effective if used before the start of allergy season or prior to exposure to a known
Humans can't live without blood. Without blood, the body's organs couldn't get theoxygen and nutrients they need to survive, we couldn't keep warm or cool off, fight
infections, or get rid of our own waste products. Without enough blood, we'd
weaken and die.
Here are the basics about the mysterious, life-sustaining fluid called blood.
Blood Basics
Two types of blood vessels carry blood throughout our bodies:
1. Arteries carry oxygenated blood (blood that has received oxygen from the
lungs) from the heart to the rest of the body.
2. Blood then travels through veins back to the heart and lungs, where it receives
more oxygen.
As the heart beats, you can feel blood traveling through the body at pulse points —
like the neck and the wrist — where large, blood-filled arteries run close to the
surface of the skin.
The blood that flows through this network of veins and arteries is whole blood,
which contains three types of blood cells:
1. red blood cells (RBCs)
2. white blood cells (WBCs)
3. platelets
In babies and young kids, blood cells are made within the bone marrow (the soft
tissue inside of bones) of many bones throughout the body. But, as kids get older,blood cells are made mostly in the bone marrow of the vertebrae (the bones of the
spine), ribs, pelvis, skull, sternum (the breastbone), and parts of the humerus (the
Anemia due to kidney disease. The kidneys produce erythropoietin, a
hormone that stimulates production of red cells in the bone marrow. Kidney
disease can interfere with the production of this hormone.
Anemia resulting from unusually rapid red blood cell destruction. When
RBCs are destroyed more quickly than normal by disease (a process calledhemolysis), the bone marrow will make up for it by increasing production of new
red cells to take their place. But if RBCs are destroyed faster than they can be
replaced, a person will develop anemia.
Several causes of increased red blood cell destruction can affect kids:
G6PD deficiency. G6PD is an enzyme that helps to protect red blood cells from
the destructive effects of certain chemicals found in foods and medications.
When the enzyme is deficient, these chemicals can cause red cells to hemolyze,
or burst. G6PD deficiency is a common hereditary disease among people of
African, Mediterranean, and Southeast Asian descent.
Hereditary spherocytosis is an inherited condition in which RBCs are
misshapen (like tiny spheres, instead of disks) and especially fragile because of
a genetic problem with a protein in the structure of the red blood cell. This
fragility causes the cells to be easily destroyed.
Autoimmune hemolytic anemia. Sometimes — because of disease or for no
known reason — the body's immune system mistakenly attacks and destroys
RBCs.
Sickle cell anemia, most common in people of African descent, is a hereditary
disease that results in the production of abnormal hemoglobin. The RBCsbecome sickle shaped, they cannot carry oxygen adequately, and they are easily
destroyed. The sickle-shaped blood cells also tend to abnormally stick together,
causing obstruction of blood vessels. This blockage in the blood vessels can
seriously damage organs and cause bouts of severe pain.
Diseases of the White Blood Cells Neutropenia occurs when there aren't enough of a certain type of white blood
cell to protect the body against bacterial infections. People who take certain
chemotherapy drugs to treat cancer may develop neutropenia. Human immunodeficiency virus (HIV) is a virus that attacks certain types of
WBCs (lymphocytes) that work to fight infection. Infection with the virus can
result in AIDS (acquired immunodeficiency syndrome), leaving the body prone
to infections and certain other diseases. Newborns can become infected with the
virus from their infected mothers while in the uterus, during birth, or from
breastfeeding, although HIV infection of the fetus and newborn is usually
On average, the human body contains five litres of blood, and your red blood cells are replaced
every 120 days. Blood diseases can range from anaemia, which is common, to rare disorders
that affect only a few. You can use this section to find out more.
What is a blood test?Blood tests are a very useful diagnostic tool. Blood is made up of several different kinds of cells
and other compounds, including various salts and certain proteins.
The liquid portion of the blood is called plasma. When blood clots outside the body, the blood
cells and some of the proteins become solid. The remaining liquid is called serum, which can be
used in chemical tests and in tests to find out how the immune system fights diseases.
Doctors can take blood samples and grow the infectious organisms that cause an illness to
see exactly what they are through a microscope.
How is a blood test carried out?Blood samples for testing can be taken either from a vein (which carries blood to the heart) or
from an artery (which takes blood away from the heart).If only a few drops of blood are needed (for monitoring blood sugar in diabetes, for example) it
is enough to make a small prick in the tip of the finger and then squeeze the blood out.
Most blood tests are taken from a vein, commonly from those around the elbow. First a cord
(tourniquet) is tied around the upper arm to make the vein prominent. It may be a bit tight, but
this makes it much easier to take the test.
The site of the injection is then cleaned with spirit and then a needle is put into the vein. The
needle will be attached either to a low pressure blood test bottle, or to a syringe where the
plunger is pulled back to create low pressure. When the necessary amount of blood has been
extracted, the needle is removed and a little ball of cotton wool is held over the wound. This
should be pressed for one to two minutes before applying a sticking plaster.If blood is taken from an artery, it is usually extracted from the wrist where there is an artery that
is very close to the skin. This may be slightly uncomfortable, as the artery wall has more pain
nerves in it than the vein wall.
After taking blood from an artery it may be necessary to hold a ball of cotton wool on the place
where the injection was made for about five minutes to stop any bleeding.
Some people are very sensitive to needles and the sight of their own blood and may
feel faint when a blood sample is taken. This is not uncommon and can be reduced by sitting or
lying down while the sample is taken. If you feel faint or think that you might feel faint,
immediately tell the person who is taking blood.
What do doctors examine in the blood?Blood contains two main elements: the fluid that is called plasma and cells. There are three
kinds of cells: red blood cells, white blood cells and platelets. To get the information they needfrom the blood, doctors actually do several tests with the blood sample. These include
measurements of the levels of the cells and a blood smear. A blood smear is a film of blood
placed on a slide to allow doctors to look at the individual cells under a microscope. These tests
are listed below.
Red blood cellsOne of the most important red blood cell tests is used to find out how much haemoglobin there
is in the blood. Haemoglobin carries oxygen around your body. This is called the haemoglobin
concentration or level.
Another important test, the mean corpuscular volume or MCV test, measures the size of the red
blood cells.If a person suffers from anaemia their haemoglobin level will always be less than normal. But
the size of the red blood cells depends on the type of anaemia you have.
A haematocrit test measures the total volume that red blood cells take up in the blood. In
practice, this is done by spinning a test tube of blood until the red blood cells - the heaviest part
of the blood - go to the bottom of the tube. Then their volume is calculated.
Almost all types of anaemia will cause a low haematocrit (a low red blood cell volume), as will
very severe bleeding. A high haematocrit can occur if a person is dehydrated from not drinking
enough fluid or because they are losing fluid as happens with diarrhoea, burns and sometimes
surgery.
If the red blood cells are pale, it can be a sign of iron deficiency anaemia. If they have astrange shape, it may be because of sickle cell anaemia orpernicious anaemia.
Doctors also add stains to the blood smear to test the blood for parasites, for example in the
case of sleeping sickness or malaria. They may also test for bacteria in the case of blood
poisoning.
White blood cells (WBC)The doctor counts the total number of white blood cells and works out how many different types
of white blood cells the patient has. This is called the differential WBC count.
The number of white blood cells may go up and this may be because of a bacterial infection,
bleeding or a burn. More rarely the cause of a raised white count is due to leukaemia, cancer
or malaria. A person may lose white blood cells because they have autoimmune problems - this is where
the antibodies that should fight diseases attack the body instead. Other reasons for loss of white
blood cells include viral infections. More rarely, this can be a side effect of certain kinds of
medication.
Doctors keep an eye on white blood cells to work out how a disease is changing. By monitoring
the blood count in this way they can alter the patient's treatment as necessary.
What are the symptoms of this type of anaemia?If a person is otherwise healthy, it can take some time for the signs of anaemia to appear.
The first symptoms will be tiredness and palpitations (awareness of heartbeat).
Shortness of breath and dizziness (fainting) are also common.
If the anaemia is severe, it can result in angina (chest pain), headache and leg pains(intermittent claudication).
In addition to these general symptoms of anaemia, the following indicate folic acid deficiency:
red, irritated tongue that may appear shiny
reduced sense of taste
indigestion
changed bowel movements and often diarrhoea.
Bowel symptoms are more likely with a lack of folic acid rather than B12 deficiency.
In contrast to B12 deficiency, this type of anaemia doesn't lead to any symptoms in your
nervous system (muscle weakness, tingling in the hands and feet, nerve inflammation).
However, you can be deficient in B12 and folic acid at the same time.
How is anaemia due to a lack of folic acid
diagnosed?A blood sample is taken and sent off to the laboratory. An analysis of the red blood cells is
usually included with the result of the test.
In cases of folic acid deficiency, low levels of folic acid will be registered in the blood. The red
blood cells will be the usual colour, but larger than normal.
How is it treated?Folic acid supplements can reverse this type of anaemia, but your doctor will also look at
treating any underlying cause.The tablets are taken once a day and have few side-effects. They should be taken for at least
four months.
Folic acid tablets are only continued long term if the underlying cause cannot be corrected.
What can be done to avoid folic acid deficiency? Eat a varied diet.
Good sources of folic acid include beans, oatmeal, mushrooms, broccoli, asparagus, beef and
liver.
Consult your GP if you experience any of the above symptoms.
Women should take a folic acid supplement during pregnancy and ideally before conception.
This is because a baby's spinal cord develops very early on in pregnancy. The recommendeddose is 400 micrograms daily, and more if you have had a previous pregnancy complicated by
spina bifida. Your doctor or pharmacist will be able to advise.
Other people also read:Vitamins and minerals – what do they do?: we show you the recommended daily amounts
(RDAs).
Anaemia due to iron deficiency: how is it treated?
Anaemia during pregnancy: find out what can be done to avoid anaemia during pregnancy.
Folic acid supplement: How does it work?
Anaemia due to iron deficiency
What is anaemia?
Good sources of iron
include liver, beef,
wholemeal bread,cereals, eggs and dried
fruit.
You get anaemia when you don't have enough red blood cells. This makes it difficult for your
blood to carry oxygen, causing unusual tiredness and other symptoms.
The number of red blood cells can drop if there is:
a reduction in the number of red blood cells produced
an increase in the loss of red blood cells.
Red blood cells and oxygen
Term watch Artery: takes blood from the heart to the body.
Vein: takes blood back to the heart.
Through its pumping action, the heart propels blood around the body through the arteries.
The red blood cells take up oxygen in the lungs and carry it to all the body's cells. Your cells use
this oxygen to fuel the combustion (burning) of sugar and fat which produces the body's energy.
During this process carbon dioxide is created as a waste product. It binds itself to the red blood
cells that have delivered the oxygen.
The red blood cells then transport the carbon dioxide back to the lungs. We exchange this
carbon dioxide for fresh oxygen by breathing.
This process is called oxidation.Why does a lack of iron cause anaemia?Red blood cells are made in the bone marrow and circulate in the blood. They only have a life
expectancy of about four months.
The body needs iron, vitamin B12 and folic acid (one of the B group of vitamins) to produce
more red blood cells. If there is a lack of one or more of these nutrients, anaemia will develop.
During this process carbon dioxide is created as a waste product. It binds itself to the red blood
cells that have delivered the oxygen.
The red blood cells then transport the carbon dioxide back to the lungs. We exchange this
carbon dioxide for fresh oxygen by breathing.
This process is called oxidation.
Term watch Artery: takes blood from the heart to the body.
Vein: takes blood back to the heart.
Why does vitamin B12 deficiency cause anaemia?Red blood cells are made in the bone marrow and circulate in the blood. They only have a life
expectancy of about four months.
The body needs iron, vitamin B12 and folic acid(one of the B group of vitamins) to produce
more red blood cells. If there is a lack of one or more of these nutrients, anaemia will develop.
Anaemia due to a lack of vitamin B12 is also called pernicious anaemia.
Vitamin B12 is essential for the nervous system, which is why a deficiency can also causeinflammation of the nerves (neuritis) and dementia (mental deterioration).
Elderly people are particularly at risk of vitamin B12 deficiency, although it may also be present
in the young women.
What causes this type of anaemia? Not eating enough foods that contain vitamin B12. A vegetarian or vegan diet can cause
deficiency because vitamin B12 is only found in foods of animal origin, such as meat, fish,
eggs and milk.
Inability of the small intestine to absorb vitamin B12. The stomach produces a substance called
intrinsic factor to absorb vitamin B12 from food. In the UK, the most common cause of B12
deficiency is a lack of intrinsic factor.
What causes a low production of intrinsic factor? Antibodies can form against the cells that produce intrinsic factor. The cells then die, leading to
B12 deficiency and anaemia.
Stomach cancer and ulcers can take up so much room in the stomach that there are too few
cells left to produce intrinsic factor.
Diseases of the small intestine, fish tapeworm and the after-effects of bowel surgery can all
result in the surface of the small intestine being too small to absorb B12 and intrinsic factor
effectively.
What are the symptoms of this type of anaemia?If a person is otherwise healthy, it can take some time for the signs of anaemia to appear.
The first symptoms will be tiredness and palpitations (awareness of heartbeat).
Shortness of breath and dizziness (fainting) are also common.
If the anaemia is severe, it can result in angina (chest pain), headache and leg pains
Hold the tip of your nose for five minutes while breathing through the mouth.
If the bleeding stops and then returns, hold your nose for 8 to 10 minutes. This will allow time
for the blood to clot.
Applying an ice-pack to your nose may help.
Good advice Do not blow your nose for the next 12 hours after the bleeding has stopped. This will help the
dried blood to remain in place.
Do not swallow the blood. It can cause you to become nauseous and vomit, or could conceal a
greater blood loss.
If you frequently suffer from nosebleeds you should seek help from your doctor.
The most likely development The bleeding usually stops if you follow the above instructions.
Heavy bleeding may require hospital treatment and, in rare cases, a blood transfusion.
How is heavy bleeding treated and what kind of
medication can be given?Contact your doctor if the advice described above does not help stop the bleeding.
Initially, the doctor will try to stop the bleeding by using something that will make the blood
vessels contract.
When the bleeding has stopped, the doctor may choose to cauterise the source of the bleeding
with a chemical to prevent it bleeding again.
If the bleeding fails to stop, it may be necessary to put a pack in the nose.
In rare cases, an operation may be necessary to tie off the blood vessel that supplies the
bleeding area.
If the bleeding is caused by another disease, such as increased blood pressure, it is veryimportant to seek treatment to avoid recurrence of nosebleeds.
Nosebleeds can be very intermittent, and between bleeds it may be very difficult to determine
their source. If this occurs it is best to ensure that the nose is inspected during a bleed, which
might mean needing to be assessed 'out of hours' by the on-call GP or local casualty unit.
Acute leukaemiaReviewed by Dr Rachel Green, consultant haematologist
32 What is leukaemia?Leukaemia, or blood cancer, is a disease of unknown cause where the bone marrow produces
large numbers of abnormal cells. This means that the normal marrow is pushed into smaller and
smaller areas, which results in fewer cells being produced and leads to some of the symptoms
There are many types of leukaemia and each of them is classified according to the exact cell
type affected by the disease.
Chronic leukaemia is a slowly progressive form of leukaemia and tends to involve more mature
cell types.
Acute leukaemia is rapidly progressive if not treated and involves more immature cells. It
develops rapidly from the earliest forms of cells in the immature bone marrow cells (blasts). Itrequires urgent medical treatment but is generally responsive to chemotherapy.
Acute leukaemia is a rare disease that is more common in children and young people. However,
their survival rate is better than in older people.
What are the symptoms of acute leukaemia? Sudden appearance of symptoms.
An unnaturally pale complexion (anaemia).
Fatigue.
Pain in the joints. When children are affected, this is sometimes mistaken for growing pains.
Repeated infections, such as sore throats.
Acute leukaemia is also usually accompanied by nosebleeds and bruising easily, often without
any kind of blow or fall.
If any of the above symptoms develop, it is advisable to consult a doctor. Parents are
understandably afraid of leukaemia, but fortunately, the diagnosis often turns out to be
something else entirely, as many other diseases have similar symptoms.
How is acute leukaemia diagnosed?Many forms of leukaemia can be diagnosed by blood tests. Commonly, the acute leukaemia
cell (blasts) can be seen circulating in the blood.
A bone marrow test will also be performed to diagnose the type of cells involved, as this can
help doctors decide on the best choice of treatment.Acute leukaemia is usually easy to diagnose.
How is acute leukaemia treated?Most patients with acute leukaemia will be referred to specialist units for investigation and
treatment.
These days, medical treatments are extremely effective and an ever-increasing number
of children and young people recover completely.
Treatment is usually with chemotherapy given through the veins. In most cases, chemotherapy
is given in courses over four to six months. Each course lasts four to five days. Chemotherapy
kills all fast dividing cells and this includes normal body cells as well as cancer cells.
The normal bone marrow is sensitive to chemotherapy and the blood counts may drop, makingthe patient vulnerable to infection and bleeding. This generally means that the patient has to
remain in hospital for weeks following chemotherapy. However the blood counts will recover
over time. Blood transfusions are likely to be given during this vulnerable period.
Chemotherapy can lead to hair loss, nausea, vomiting and diarrhoea. Doctors will give medicine
to prevent or reduce the vomiting and diarrhoea. Hair loss is not permanent and hair re-grows
should be limited to 1 part per million, but this is often exceeded, especially in developing
countries. Other related organic chemicals also cause aplastic anaemia, including:
toluene (in glues)
the insecticides DDT and lindane
the explosive TNT
the wood preservative PCP petroleum distillates.
Drugs that cause aplastic anaemia may also be related to benzene. The
antibiotic,chloramphenicol and the anti-inflammatory, phenylbutazone are two examples.
Neither is commonly used in Western countries, but because they are cheap to produce, they
are in widespread use in the developing world. Other medicines with a moderate risk of aplastic
anaemia include gold salts and penicillamine (Distamine), used to
treat arthritis, carbamazepine (eg Tegretol) and phenytoin (eg Epanutin), used to
treat epilepsy, and the diuretic acetazolamide (eg Diamox).
A large number of drugs have been associated with occasional cases of aplastic anaemia. Most
of these are useful drugs and cannot easily be replaced. In Britain, doctors use a system calledthe 'yellow-card' scheme to report suspected side effects of drugs, such as aplastic anaemia.
Cytotoxic drugs are those that are designed to be directly toxic to cells in the treatment of
cancer. Some destroy bone marrow cells (for example, in the treatment of leukaemia). Normally
the marrow recovers after a short period. An overdose of these drugs causes severe, prolonged
aplasia.
Radiotherapy (treatment with X-rays) suppresses the bone marrow, and may be intentionally
used to do so in preparation for bone marrow transplantation. The use of these treatments
should be confined to specialised centres where careful monitoring of the blood count takes
place.
Some cases of aplastic anaemia have occurred after viral infections. In particular,hepatitisA, hepatitis B and 'non-A, non-B, non-C' hepatitis have been implicated, and more rarely the
Epstein-Barr virus.
Very rarely aplastic anaemia occurs during pregnancy. It is not clear whether this is just a
coincidence. Sometimes the disease recovers spontaneously at the end of pregnancy.
What is the disease process?Nowadays, treatment of aplastic anaemia is directed on the assumption that the disease is
related to the immune system.
The first evidence for this came from the early days of bone marrow transplantation. Sometimes
the marrow that regrew after the conditioning treatment was of the person's own type rather
than that of the donor. This implied that there had been an immune attack going on in theperson's bone marrow, which was relieved by the intense dampening down of his or her
immune system by the treatment.
Other evidence comes from immunodeficient individuals (ie those with impaired immunity either
through disease or caused by their treatment) who receive a blood transfusion. They sometimes
develop transfusion-related graft-versus-host disease (GvHD) – in other words a rejection
Other possible diagnoses will also be sorted out by the bone marrow. Myelodysplastic
syndrome is one in which there is faulty blood cell production by abnormal bone marrow cells
rather than by the lack of precursor cells. It also causes pancytopenia but the bone marrow is
full of cells that are recognisably abnormal.
Some cases of megaloblastic anaemia (including pernicious anaemia) also have
pancytopenia, but again the bone marrow is characteristically full of cells. The doctor will alsomeasure blood levels of vitamin B12 and folic acid to exclude this possibility.
Any condition that infiltrates the bone marrow can also cause pancytopenia, but these should be
diagnosable by the bone marrow investigation. Likely conditions include lymphoma, myeloma
and secondary cancer.
Occasionally some of these conditions may present with empty bone marrows just like aplastic
anaemia. Experts can sometimes distinguish small numbers of leukaemic cells or
myelodysplastic cells and are therefore able to make the diagnosis of hypoplastic
(underdeveloped) acute leukaemia or hypoplastic myelodysplastic syndrome. Sometimes these
conditions supervene after treatment of the aplastic anaemia, and the assumption is that they
have been there all along.An important supplementary diagnosis is paroxysmal nocturnal haemoglobinuria (PNH). In this
condition the red cells lack a special molecule on their surface that is used to anchor many other
types of protein to the membrane of the red cell - known as the phosphatidylinositol glycan
(GPI) anchor. As a consequence, the red cells are very susceptible to destruction (haemolysis).
It has been known for a long time that the two conditions can occur together. PNH has been
described as occurring in between 15 and 52 per cent of people with aplastic anaemia at
diagnosis. The diagnosis of PNH is important because it can lead to problems with thrombosis
(blood clots) and difficulties with blood transfusion.
What can you do yourself?It is important that you take charge of your illness:
try to find out all you can about aplastic anaemia and the various treatment options.
don't be afraid to ask questions of your doctor and other patients.
you could encourage your friends and family to become blood and bone marrow donors.
join a support group and read about ways to cope.
check with your doctor about what things to avoid like salads and soft cheeses, which carry
some infection risk.
your doctor will also give you advice about how to recognise the first signs of infection.
you should take your temperature regularly.
it is dangerous to live too far from a hospital capable of giving the right sort of supportive care.
before trying complementary therapies, always consult your doctor.
What can your doctor do?The first thing your doctor will do is ask about the various drugs and toxins that could have
caused the disease, and make sure that they are avoided in future.
He will then take blood samples to tissue type you and your close relatives in case a bone
marrow transplant is needed. Severe and very severe aplastic anaemia are life-threatening
conditions that need to be taken very seriously. Leaving the disease untreated is not an option.
Supportive carePatients with mild aplastic anaemia will only require supportive care and often very little of that.
Sometimes all that is needed is to remove the noxious agent and wait to see if spontaneous
recovery will occur.
Even if you are going to receive a bone marrow transplant or immunosuppressive therapy youwill need short-term treatment to protect you from the consequences of pancytopenia.
Infections are the major hazard. This is especially so if you need an indwelling (Hickman-like)
intravenous line. These are catheters that are inserted in to the main veins within the chest and
can be left in place for a long time in order to give chemotherapy drugs repeatedly. In general
prophylactic or 'just in case' antibiotics are not favoured and your best protection is vigilance. A
fever of 38oC lasting more than two hours requires antibiotics in hospital. Your doctors may
change the antibiotics depending on the results of the bacterial investigations or response to
treatment.
Platelet transfusions are given to lessen the risk of bleeding. It is now usual practice to restrict
these to patients who are actually bleeding or those whose platelet count falls to below 10 x
109/L. Platelet transfusions should be screened to ensure they are free of contamination with
cytomegalovirus (CMV) as this virus can interfere with immunity. They should also be depleted
of white blood cells and, if being used after bone marrow transplantation or immunosuppression
they should also be exposed to X-ray sterilisation.
Red cell transfusions should also carry the same provisos, and are given for anaemia severe
enough to be causing symptoms. Patient who require long-term red cell support from repeated
transfusions are at risk from building up excess iron within the body and may require iron-
For patients aged 50 or less with severe or very severe aplastic anaemia who have an HL-Acompatible sibling (ie a 'close match' in tissue type), bone marrow transplantation is the
treatment of choice.
This means that stem cells will be harvested from your brother or sister. This can either be done
in the operating theatre under a general anaesthetic or, increasingly these days, in the day-ward
using a cell separator.
Under general anaesthetic, bone marrow is sucked out of the hipbones on either side through a
hollow needle. About 4 per cent of the marrow is extracted in this way.
Using the cell separator, the donor's arm veins are connected via plastic tubes to a large
machine that works something like a spin dryer. The process separates the stem cells (which
are retained) from the rest of the blood (which is returned to the donor). About 10 litres of blood
are processed on each occasion. In either case the stem cells are transfused into the recipient
just like a bag of blood. Before this happens the patient must receive conditioning treatment to
allow the donor cells to 'take'.
For aplastic anaemia 'non-ablative' conditioning is used. This comprises large doses
of cyclophosphamide (eg Endoxana) and avoids radiotherapy. This preserves fertility, and
reduces the risk of lung disease and secondary malignancy, but increases the risk of rejection.
Graft rejection is prevented by ciclosporin (Neoral) therapy.
Immunosuppressive therapyIn patients over the age of 50 and those without an HL-A compatible sibling,
immunosuppression is the treatment of choice. The best regimen is a combination of anti-
thymocyte globulin (ATG) and ciclosporin. ATG is an antibody which acts against T-lymphocyes
- another type of white cell which is probably involved in the immune attack of the bone marrow.There are data to suggest that patients failing to respond to ATG have a 43 per cent chance of
responding to a second course.
Patients treated by immunosuppression have a much higher risk than those treated by bone
marrow transplantation of developing another disorder of the bone marrow, such as PNH, acute
leukaemia or myelodysplastic syndrome (these are known as 'clonal' marrow disorders). Factors
that increase the risk of these complications are:
age at diagnosis
multiple courses of immunosuppression
previous removal of the spleen
the addition of androgens (male sex hormones, which have been used in some previous
treatment regimes).
Bone marrow transplantation and
immunosuppression comparedThe survival rate for 168 patients transplanted at Seattle between 1978 and 1991 was 69 per
cent at 15 years. The 15-year survival rate for 227 patients treated by immunosuppression was
only 38 per cent. The difference in mortality is attributable to the development of clonal marrow
disorders, but the group treated by immunosuppression was older. Recent papers have
suggested that the outcome for bone marrow transplantation is still improving with 90 per cent
success rates for children and young adults.
Treatment failuresBone marrow transplant from a matched volunteer donor or a partially matched family donor
carries a greater risk of graft failure or severe graft-versus-host disease. The risk is most
acceptable in patients aged less than 20 and should be offered to such patients who fail the first
round of immunosuppressive therapy and to patients under 40 who fail a second round. For
older patients, further courses of ATG are an option, together with androgens, cytokines (small
proteins released by cells which influence the behaviour of other cells) and experimental
therapies.
Living with aplastic anaemia
Patients will need to steel themselves, at least initially, to a life dependent on the localhaematology service. While it is possible to continue working or schooling, there are certain
restrictions. Bodily contact sports must be avoided and a close watch must be kept for infection.
Transfusions will be a regular interruption. Some infections proceed very rapidly and need
instant remedies, hence the need for close contact with the haematology service.
All of the therapies carry side effects. ATG may cause a fever and often leads to 'serum
sickness'. During this phase there may be rashes and joint pains.
Drugs that reduce red cell countHydroxycarbamide: previously known as hydroxyurea, this drug works by interfering with the
cell's metabolism. It is a common treatment for PV and usually needs to be taken daily. Your
blood count will be monitored at least every two to three months. It has relatively few side-
effects including some darkening of skin pigment, mouth and leg ulcers and rarely stomach and
bowel disturbance.
Hydroxycarbamide can damage DNA and may affect fertility, so shouldn't be used by pregnant
women or those trying to conceive. There have been concerns that this medicine may increase
the risk of PV transforming intoacute leukaemia. Though yet to be proven, the chance of this
occurring is likely to be in less than 5 per cent of patients over a period of 10 to 15 years.
Melphalan, busulfan and 32P: these drugs belong to a group medicines called alkylating
agents and used to be the main treatment for PV. They reduce cell count by binding to DNA and
damaging it, preventing complete separation of the two DNA strands at cell division. This means
these medicines can permanently damage fertility and the bone marrow.They increase the risk of PV turning into a form of acute leukaemia, probably in about 5-10 per
cent of patients over 10 years. Busulfan and 32P are still used to treat PV when other drugs
don't work, cause unacceptable side-effects or if you can't take the hydroxycarbamide tablets for
any reason.
Interferon: this is a naturally occurring protein that inhibits the growth of bone marrow cells. It
has to be given by injection, usually three times a week. Interferon is used in some patients with
PV, particularly in young people who want to preserve their fertility. It can be given to pregnant
women.
Interferon has also been reported to control, or reverse, the development of myelofibrosis. It has
many side-effects, including flu-like symptoms, hair loss, depression, liver and thyroidabnormalities: a high proportion of patients who are prescribed this drug will not be able to
continue using it.
Term watch Platelets: small cell fragments that clump together to form blood clots.
Anagrelide: this drug lowers the platelet count, but has only a very modest and unpredictable
effect upon red cells. It appears to work by reducing the size of the platelet-producing cells
within the bone marrow (the megakaryocytes). Anagrelide can only be used to treat PV when
additional means to control the red cells, such as venesection, are used. It is not currently
licensed in the UK as a treatment for PV.
Other treatmentsMost people with PV, with the possible exception of those with increased bleeding risk or a very
high platelet count, will be advised to take aspirin or a similar drug. Aspirin does not lower the
red cell count but can provide some protection against clotting complications by reducing the
'stickiness' of platelets.
Side-effects include bleeding and ulcers in the stomach and small intestine. For this reason,
aspirin is only used with caution if you have a platelet count in excess of 1500 million per ml.
Sometimes drugs that work in a similar manner to aspirin are used instead. Examples
are dipyridamole and clopidogrel. Some patients are also treated with warfarin, especially if
you have recently had a blood clot in a vein or have had multiple clots.
Gout is controlled both by reducing the number of red cells and by using a drug such
as allopurinol to increase excretion of the uric acid crystals that cause the symptoms. An acute
attack of gout is treated with painkillers.The itching associated with PV can be a particularly difficult problem to control. Measures used
include:
avoiding known triggers
soothing creams (aqueous cream with menthol)
histamine antagonists such as ranitidine may help.
It is also important to treat all other risk factors for arterial disease such as smoking, high blood
pressure, diabetes and high cholesterol.
Pregnancy and PVMany of the drug treatments are toxic to sperm and foetus. If you want to start a family, talk to
your haematologist about whether it's possible to change medication.
Women with PV that is treated through venesection alone are likely to need fewer procedures
throughout pregnancy when the blood naturally dilutes.
Pregnancy itself is associated with an increased risk of clotting. For this reason many pregnant
women will also be given aspirin and some will receive the anticoagulant drug heparin to
minimise the risk of clotting.
Long-term outlookThe outlook for PV is influenced significantly by the occurrence of complications - most
particularly those caused by clotting because these are more common and are often the most
serious.The chance of thrombosis increases with a person's age and when there has been a previous
problem caused by clotting.
Those people with PV who do not go on to develop other related diseases probably have a
normal or only slightly reduced life expectancy.
If you go on to develop myelofibrosis or acute myeloid leukaemia, the outlook is not as good.
MyelofibrosisOver a long period of time 20-30 per cent of patients with PV may develop a 'spent phase' of
their disease known as myelofibrosis. How much treatment to reduce red cells influences the
development of this condition is unclear and controversial.
People with myelofibrosis have low blood counts, develop enlarged spleens and are said to beat increased risk of developing acute myeloid leukaemia. Treatment can include:
support of the blood count (sometimes by red cell transfusion)
drugs such as hydroxyurea or interferon
irradiation (X-ray) treatment to reduce spleen size
Depending upon the severity of fibrosis and the effectiveness of treatment, survival is on
average about three years. A few PV patients with myelofibrosis have been treated
experimentally with bone marrow transplantation.
Acute myeloid leukaemiaAcute myeloid leukaemia is associated with a very poor outlook because this form of leukaemia
is often resistant to treatment.
Occasionally good results have been reported in the very few patients who have been treated
with a bone marrow transplant either using:
their own bone marrow (autologous transplant)
a related donor (allogeneic transplant)
a volunteer unrelated donor.
Because of the high risk of mortality, these transplant procedures are not used very often in
acute myeloid leukaemia that develops from PV.
Thrombocytopenia (reduced plateletcount)Written by Dr Claire Harrison, Consultant Haematologist, St Thomas' Hospital,
London and Professor Samuel Machin, Department of Haematology, University College
London Hospital
246 What is thrombocytopenia?Thrombocytopenia is the term for a reduced platelet (thrombocyte) count. It happens whenplatelets are lost from the circulation faster than they can be replaced from the bone marrow
where they are made.
Did you know? All blood cells are created within the bone marrow.
Thrombocytopenia can result from:
a failure of platelet production
an increased rate of removal from blood.
What are platelets?
Platelets are tiny cells that circulate in the blood and whose function is to take part in the clottingprocess.
Inside each platelet are many granules, containing compounds that enhance the ability of
platelets to stick to each other and also to the surface of a damaged blood vessel wall.
The platelet count in the circulating blood is normally between 150 and 400 million per millilitre
of blood. Newborn babies have a slightly lower level, but are normally within the adult range by
three months of age.
Many factors can influence an individual's platelet count including exercise and racial origin. The
average life span of a platelet in the blood is 10 days.
What do platelets do?Platelets are essential in the formation of blood clots to prevent haemorrhage - bleeding from a
ruptured blood vessel.
An adequate number of normally functioning platelets is also needed to prevent leakage of red
blood cells from apparently uninjured vessels.
In the event of bleeding, muscles in the vessel wall contract and reduce blood flow. The
platelets then stick to each other (aggregation) and hold on to the vessel wall (primary
haemostasis). The coagulation factors are then activated, resulting in normally liquid blood
becoming an insoluble clot or glue.
What are the risks of a low platelet count?The main effect of a reduced platelet count is an increased risk of bleeding, but this rarelyoccurs until there are less than 80-100 million platelets per ml.
There is not a close relationship between the number of platelets and the severity of bleeding,
but there is an increasing risk of haemorrhage if platelet numbers fall or if platelet function is
impaired (for example by aspirin, which reduces the 'stickiness' of the platelets).
There is a particularly high risk of spontaneous bleeding once the platelet count drops below 10
million per ml. The bleeding is usually seen on the skin in the form of tiny pin-prick
haemorrhages (purpura), or bruises (ecchymoses) following minor trauma.
Bleeding from the nose and the gums is also quite common. More serious haemorrhage can
occur at the back of the eye (retina), sometimes threatening sight.
The most serious complication, which is potentially fatal, is spontaneous bleeding inside thehead (intracranial) or from the lining of the gut (gastrointestinal).
Types of thrombocytopeniaSpecific types of low platelet count include:
Diminished platelet survival Antibodies in response to drugs, blood transfusion or another disease, eg glandular fever,
malaria.
Unknown cause (ITP).
Clotting disorder (DIC).
Blood disorder (TTP).
Loss of platelets from the circulation
Massive blood transfusion or exchange.
Enlarged spleen.
Artefactual (false) thrombocytopenia
Some people have platelets that stick together due to the presence of proteins in the blood(antibodies) that bind to the platelets.
These antibodies also bind to a chemical in blood that is tested in the lab, giving a falsely low
platelet count. For this reason, it is helpful to repeat the sample in different tubes with different
chemicals.
The platelet count can also be reduced if the blood sample is difficult to take and the blood clots
- thus using up some of the platelets.
Congenital thrombocytopeniaSeveral rare inherited diseases cause low platelet counts. The severity of the thrombocytopenia
varies with the condition and also the individual patient.
In some of these conditions, eg May Hegglin anomaly, bleeding doesn't happen often.In other inherited diseases, eg Bernard Soulier syndrome, the platelets function less well and
lifelong bleeding symptoms can occur.
Defective platelet productionPlatelets are produced within the bone marrow from cells called megakaryocytes.
If there is a problem in the bone marrow, for example due to abnormal cells, then the number of
megakaryocytes will drop, lowering the number of platelets that can be produced.
Examples of abnormal cells accumulating in the bone marrow include:
acute leukaemia where leukaemic cells, or 'blasts', are seen
other abnormal cancer cells such as lymphoma
more rarely, when cancers develop in another part of the body and have spread
(metastasised) to the bone marrow.
Alternatively, there may be something wrong with the platelet production process itself so notenough platelets are formed.
Impaired platelet production can also be due to:
the side-effects of drugs such as chemotherapy (anti-cancer) agents
viral infections such as HIV
metabolic disorders such as shortage of vitamin B12 or folic acid, kidney failure, alcohol.
an abnormality of the bone marrow called myelodysplasia.
Sometimes platelet production is defective because of an abnormality in the cells that make up
the structural parts of the bone marrow, called the stroma. Examples include:
marble bone disease (osteopetrosis). This hereditary condition causes dense, brittle bones at
the expense of bone marrow. myelofibrosis. This causes a massive increase in the amount of fibrous tissue, which impairs
platelet production as well as the production of other blood cells.
Diminished platelet survivalPlatelet numbers fall if they are removed from the circulation more rapidly than they are
produced.
Platelets are removed for several reasons. They may be coated with an antibody, or are
clumped together and then removed.
Antibodies that cause platelet removal can be due to:
infections such as HIV
medicines such as the anti-malaria drug quinine a specific disease in which abnormal production of other antibodies may occur, eg rheumatoid
arthritis, the skin disease systemic lupus erythematosis or the blood disease chronic
lymphocytic leukaemia.
These antibodies can also occur in someone who is otherwise completely well. This is called
idiopathic thrombocytopinea (ITP) - literally, a low platelet count of unknown cause.
Alternatively, the platelets may be used up if the blood clotting process is inappropriately
'switched on'. This condition is known as disseminated intravascular coagulation (DIC).
DIC can result from the following:
in severe infections such as meningitis.
as a complication of pregnancy or labour, eg high blood pressure and pre-eclampsia in some cancers, specifically types of acute myeloid leukaemia andprostate cancer
in some rare blood disorders such as thrombotic thrombocytopenic purpura or haemolytic
uraemic syndrome (sometimes due to food poisoning outbreaks).
Loss of platelets from the circulation Abnormal distribution of platelets: a low platelet count may be due to a build up of platelets
outside the normal blood pool, for example in a patient with a very large spleen.
Dilution of platelets: the platelet count can fall when a patient is transfused with a large
volume of red blood cells that do not contain platelets, because of dilution of normal blood
factors.
How is a low platelet count diagnosed?
Investigation usually starts with a history of symptoms, signs of bleeding or bruising, othermedical problems, recent infections and medications. A blood test is then taken.
In the haematology lab the doctor:
performs a full blood count
examines the blood film under a microscope (see Figure 1)
examines the blood sample in the test tube.
Usually, another full blood count sample is requested to confirm the result and see if it is a
persisting abnormality.
Depending upon the severity of the platelet lack and the likely cause, the person is likely to be
referred to a haematologist at the hospital.
If the platelet count is very low, the person may need to be seen on the same day, and have a
bone marrow test performed.
A bone marrow test is done under local anaesthetic, with samples usually taken from the back
of the pelvis.
This test helps the haematologist to decide if platelets are being produced normally and whether
the rest of the bone marrow appears normal.
Further tests such as genetic tests can also be done on a bone marrow sample.
What treatment is available?The choice of treatment depends upon the severity of the platelet count, its cause and whether
or not there is any bleeding.
Caution In a type of thrombocytopenia called TTP, the use of platelet concentrates is hazardous.
If life-threatening bleeding occurs, eg to the head or bowel, urgent treatment is needed with
platelet concentrates via blood transfusion.
The effect of the concentrates is then monitored by measuring the platelet count and assessing
any continuing bleeding.
The management of acute bleeding also involves treatment of the underlying cause of the low
platelets.
If there is no major bleeding, treatment is aimed at the cause of the low platelet count.