Essay, Research Paper: Hemophilia

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In the human body, each cell contains 23 pairs of chromosomes,

one of each pair inherited through the egg from the mother, and the

other inherited through the sperm of the father. Of these

chromosomes, those that determine sex are X and Y. Females have XX

and males have XY. In addition to the information on sex, 'the X

chromosomes carry determinants for a number of other features of

the body including the levels of factor VIII and factor IX.'1 If

the genetic information determining the factor VIII and IX level is

defective, haemophilia results. When this happens, the protein

factors needed for normal blood clotting are effected. In males,

the single X chromosome that is effected cannot compensate for the

lack, and hence will show the defect. In females, however, only one

of the two chromosomes will be abnormal. (unless she is unlucky

enough to inherit haemophilia from both sides of the family, which

is rare.)2 The other chromosome is likely to be normal and she can

therefore compensate for this defect.

There are two types of haemophilia, haemophilia A and B.

Haemophilia A is a hereditary disorder in which bleeding is due to

deficiency of the coagulation factor VIII (VIII:C)3. In most of the

cases, this coagulant protein is reduced but in a rare amount of

cases, this protein is present by immunoassay but defective.4

Haemophilia A is the most common severe bleeding disorder and

approximately 1 in 10,000 males is effected. The most common types

of bleeding are into the joints and muscles. Haemophilia is severe

if the factor VIII:C levels are less that 1 %, they are moderate if

the levels are 1-5% and they are mild if they levels become 5+%.5

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Those with mild haemophilia bleed only in response to major trauma

or surgery. As for the patients with severe haemophilia, they can

bleed in response to relatively mild trauma and will bleed

spontaneously.

In haemophiliacs, the levels of the factor VIII:C are reduced.

If the plasma from a haemophiliac person mixes with that of a

normal person, the Partial thromboplastin time (PTT) should become

normal. Failure of the PTT to become normal is automatically

diagnostic of the presence of a factor VIII inhibitor. The standard

treatment of the haemophiliacs is primarily the infusion of factor

VIII concentrates, now heat-treated to reduce the chances of

transmission of AIDS.6 In the case of minor bleeding, the factor

VIII:C levels should only be raised to 25% with one infusion. For

moderate bleeding, 'it is adequate to raise the level initially to

50% and maintain the level at greater that 25% with repeated

infusion for 2-3 days. When major surgery is to be performed, one

raises the factor VIII:C level to 100% and then maintains the

factor level at greater than 50% continuously for 10-14 days.'7

Haemophilia B, the other type of haemophilia, is a result of

the deficiency of the coagulation factor IX - also known as

Christmas disease. This sex-linked disease is caused by the reduced

amount of the factor IX. Unlike haemophilia A, the percentage of

it's occupance due to an abnormally functioning molecule is larger.

The factor IX deficiency is 1/7 as common as factor VIII deficiency

and it is managed with factor VIII concentrates. Unlike factor VIII

concentrates which have a half-life of 12 hours, the half-life of

factor IX concentrates is 18 hours. In addition, factor IX
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concentrates contain a number of other proteins, including

activated coagulating factors that contribute to a risk of

thrombosis. Therefore, more care is needed in haemophilia B to

decide on how much concentration should be used.

The prognosis of the haemophiliac patients has been

transformed by the availability of factor VIII and factor IX

replacement. The limiting factors that result include disability

from recurrent joint bleeding and viral infections such as

hepatitis B from recurrent transfusion.8

Since most haemophiliacs are male and only their mother can

pass to them the deficient gene, a very important issue for the

families of haemophiliacs now is identifying which females are

carriers. One way to determine this is to estimate the amount of

factor VIII and IX present in the woman. However, while a low level

confirms the carrier status, a normal level does not exclude it. In

addition, the factor VIII and IX blood levels are known to

fluctuate in people and will increase with stress and pregnancy. As

a result, only a prediction of the carrier status can be given with

this method.

Another method to determine the carrier status in a woman is

to look directly at the DNA from a small blood sample of several

members of the family including the haemophiliacs. In Canada,

modern operations include Chorionic Villous Sampling (CVS) and it

helps analyze the DNA for markers of haemophilia at 9-11 weeks of

pregnancy. (Fig. 1)9 A small probe is inserted through the neck of

the mother womb or through the abdomen under local anaesthetics. A

tiny sample from the placenta is removed and sent for DNA analysis.
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Since this process can be done at 9-11 weeks after pregnancy, the

pregnancy is in it's relatively early stages and a decision by the

mother (and father) to terminate the pregnancy will not be as

physically or emotionally demanding on the mother than if she had

it performed in the late stages of the pregnancy.

Going back to the haemophiliacs, many have become seropositive

for HIV infections transmitted through factor VIII and IX

concentrates and many have developed AIDS. In Canada, the two drugs

currently undergoing clinical testing for treatment of HIV disease

are AZT and DDI. For the use of AZT, the major complication is

suppression of normal bone marrow activity. This results in low red

and white blood cell counts.The former can lead to severe fatigue

and the latter to susceptibility to infections.10 DDI is provided

as a powder, which must be reconstructed with water immediately

prior to use. The most common adverse effect so far is the weakness

in the hands and legs. However, it appears that DDI is free of the

bone marrow.11 AZT and DDI both represent the first generation of

anti-retroviral drug and it is the hope of many people that they

will be followed by less toxic and more effective drugs.

As it can be seen, haemophilia is one of those sex-linked

diseases that must involve the inheritance of both recessive and

deficient chromosomes. It is mostly found in males and since every

male has a Y chromosome, it is a general rule that the male will

not pass it to his male offsprings. Haemophiliacs can have either

inherited the disease or they could have had a mutation. In either

case, these people must try to live a normal life and must avoid

any activities that can result in trauma.

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