(1)

     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 
                                                                                                                                                                                                                                                                                                                                                                                                                                                        (3)
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.
                                                                                                                                                                                                                                                                                                                                          (4)
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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