Generality
Hemophilia is a hereditary genetic disease, which affects the normal coagulation process. The affected patient is consequently subject to prolonged bleeding, even after trivial trauma or skin cuts.
Having established which element is lacking, we can proceed with the most appropriate therapy. Today, medicine has made considerable progress and has guaranteed effective and low-risk treatments. In fact, once upon a time, only human blood transfusions could be used. Prevention, as in all diseases, is also fundamental and contributes to guaranteeing a good quality of life for haemophilic patients.
Human chromosomes
To understand hemophilia, we need a premise that describes the human chromosomal makeup. Each cell of a healthy human being contains 23 pairs of chromosomes. A pair of these chromosomes is of the sexual type, that is, it determines the sex of the individual; the remaining 22 pairs, on the other hand, are composed of autosomal chromosomes. In all, therefore, the human genome has 46 chromosomes.
ALTERATIONS OF CHROMOSOMES
Each pair of chromosomes contains certain genes.
When a mutation occurs in a chromosome, a gene can be defective. This defective gene, therefore, expresses a defective protein.
Conversely, when the number of chromosomes varies, we speak of aneuploidy. In this case, instead of two, the chromosomes can be three (trisomies) or only one (monosomy).
THE SEXUAL CHROMOSOMES
Sex chromosomes are key in determining a person's sex, male or female. The woman has two copies of the so-called X chromosome in the cells of her body; the man, on the contrary, has an X chromosome and a Y chromosome. As for the autosomal chromosomes, also the sexual ones are inherited from the parents: one copy is donated by the father, another one from the mother. There are several genetic diseases due to the sex chromosomes. They present either alterations in the chromosomal structure or changes in the number of chromosomes.
What is hemophilia?
Hemophilia is a genetic disease that alters the normal blood clotting process and causes prolonged bleeding.
In most cases, the origin of "haemophilia c" is a genetic mutation of the sex chromosome X, transmitted from parents to children. Like Duchenne muscular dystrophy or color blindness, therefore, haemophilia also falls into the group of so-called hereditary diseases related to sex chromosomes.
THE COAGULATION PROCESS
When an individual gets a superficial cut of the skin, the consequent loss of blood is limited and temporary: in fact, in a short time, it is possible to observe, even with the naked eye, how the blood passes from the fluid state to the solid state. This unique process, called coagulation, is carried out by platelets and a series of biomolecules (proteins, enzymes and cofactors) in the blood, called coagulation factors, which are activated in a cascade. The same process occurs when you undergo a small internal trauma: the hematoma, which appears after a blow for example, is the blood that has leaked out and then solidified.
This ability to form a blood clot is vital because, without it, the bleeding would be unstoppable.
THE HEMOPHILIC INDIVIDUAL
In the "individual suffering from haemophilia, coagulation is deficient and does not block blood loss with the same efficiency and speed. Therefore, a cut, even when it is mild, causes" prolonged bleeding, with sometimes serious effects.
Causes
The cause of haemophilia is a genetic mutation, affecting the sex chromosome X, which determines the deficiency of one of the coagulation factors.
THE FACTORS OF COAGULATION. PATHOGENESIS
The clotting factors are functional to their purpose only if they are all present.
The reason is simple. They are activated in a chain ("cascade mechanism"), one after the other. In other words, each factor acts as a trigger for what follows it. Therefore, if a factor is missing or deficient, the following ones depend from him, they will not be triggered or will be activated slowly, all of which results in a coagulation defect.
Coagulation factors are biomolecules (proteins, enzymes and cofactors), produced in part by the liver and circulating in the blood.
The chain mechanism, with which the coagulation factors are activated. As you can see, the presence of each factor is fundamental for the final purpose. From the site: pharmacologiaoculare.com
GENETICS
Hemophilia mainly affects men. But for what reason?
The mutation of the X chromosome, which determines the haemophilia, is of the recessive type. This means that the woman, provided with two X chromosomes, manifests the disease only if both of her sex chromosomes are mutated (very remote possibility); in fact, when only one X chromosome is changed, the other healthy compensates for the deficiencies of the first and provides itself to produce the missing coagulation factor.
Conversely, in humans, the X chromosome is only one (the other is the Y chromosome) and its mutation is fatal and without alternatives. Consequently, the coagulation process irremediably lacks a fundamental component.
INHERITANCE AND TRANSMISSION
It has been said that hemophilia is an inherited genetic disease.
Figure: the transmission of haemophilia, when the mother is a healthy carrier of the disease. From the site: infoemofilia.it
But how does the transmission of the X chromosome between parents and children take place? When are the latter sick?
If the mother is a healthy carrier.
The union between a woman, having only one mutated X chromosome (for this reason called healthy carrier), and a healthy man can have the following consequences:
- Male children are equally likely (50%) to be born healthy or sick.
The Y chromosome inevitably derives from the father; consequently, that X comes from the mother. If it is the changed one, the child will be born affected by the disease. - Daughters are equally (50%) likely to be born healthy or completely healthy carriers. In fact, they inherit the healthy X chromosome from their father. The other X chromosome, inherited from the mother, can be diseased or healthy.
If both parents have a mutated X chromosome.
Figure: the transmission of haemophilia, when both parents carry a mutated X chromosome. All the daughters are healthy carriers, while the boys can be born, with the same probability, either healthy or sick. From the site: infoemofilia.it
Since hemophilia is a disease compatible with life, a sick man can have children. His union with a healthy carrier woman can give rise to:
- Male children with the same probability (50%) of being born healthy or sick.
It is like the case, in which there was only the mother who was a healthy carrier of the disease. It is the maternal X chromosome that determines the health status of the male child, because, from the father, they inherit only the Y chromosome. - Daughters with the same probability (50%) of being born healthy or diseased carriers.
They certainly inherit a mutated X chromosome from their father. The other chromosome, that of maternal origin, can be healthy or mutated.
If only the father is sick.
In this case, his union with a healthy woman has two consequences:
- Male children are all born healthy, because the mutated component on the maternal side is missing.
- The daughters are all born healthy carriers, because they all receive the mutated X chromosome from their father.
Figure: the transmission of haemophilia, when only the father is sick: all the daughters are healthy carriers, all the sons are healthy. From the site: infoemofilia.it
TYPES OF HEMOPHILIA
Based on the coagulation factor involved, three types of haemophilia are distinguished:
- Hemophilia A, in which the deficient coagulation factor is factor VIII.
- Hemophilia B, in which the deficient coagulation factor is factor IX.
- Hemophilia C, in which the deficient coagulation factor is factor XI.
At this point, a clarification must be made.
Hemophilia C, on the other hand, is an autosomal genetic disease, as the genetic anomaly resides on autosomal 4 chromosome.
EPIDEMIOLOGY
Hemophilia is a rare disease that mostly affects males.
According to some statistical data, about one out of 5,000 males is born with type A haemophilia, while one out of 30,000 males is born with type B haemophilia.
In women, haemophilia, both type A and type B, is rare, since, as we have seen, it requires both parents to carry a mutated chromosome (which is a very remote circumstance).
Type C haemophilia is a separate case. It is even rarer than the previous ones and affects both males and females with equal probability.
Symptoms and Complications
For further information: Hemophilia Symptoms
The main symptom of haemophilia (of whatever type it is) is prolonged blood loss, even after a slight external trauma (following a cut, a scratch, etc.) or internal (following a blow, a fall, etc.) To it are added:
- Extensive and deep hematomas
- Hemorrhages within the large joints (knee, hip, ankle, etc.), resulting in joint pain and swelling
- "Spontaneous" haemorrhages and hematomas
- Blood in the urine and feces
- Prolonged bleeding after tooth extraction
- Nosebleed
- Irritability (in infants)
- Fatigue
These symptoms do not always present themselves in the same way: the more the coagulation factor involved in haemophilia is deficient (regardless of type), the more severe the aforementioned manifestations will be. A useful example to understand what has been said is the following: a patient with haemophilia A, who has a very low level of factor VIII in his blood, will have a worse symptom picture than another patient with the same haemophilia but with modest levels of factor VIII.
In light of this, on the basis of the amount of coagulation factor present, we distinguish a "mild haemophilia, a" moderate haemophilia and a "severe haemophilia.
Prolonged bleeding even for trivial trauma
Internal bleeding, at the joints
Mild hemophilia
Individuals with 5 to 50% of normal clotting factor have a mild form of haemophilia. In these circumstances, the disease does not cause particular problems, except on some occasions. For example, we find that bleeding takes longer than usual when we injure ourselves seriously for the first time or after the first tooth extraction (in children).
MODERATE HEMOPHILIA
When hemophilia is moderate, the quantities of coagulation factor are very small (between 1 and 5% of the normal amount). The consequences of this condition are evident: even if the trauma is mild, the patient has extensive hematomas, long bleeding and hemorrhages inside the joints. The latter mainly affect the knees and ankles and cause pain, swelling and a sense of joint stiffness.
SEVERE HEMOPHILIA
Figure: Knee of a healthy person (left) and knee of a person with haemophilia (right). From the site: emofilia.it
The dose of coagulation factor is less than 1% of the normal amount. Very similar, for the symptoms manifested, to moderate haemophilia, the severe form is characterized by the patient's predisposition to spontaneous bleeding and apparently for no reason.
The situation, in these cases, is critical.
HEMOPHILIA DURING CHILDHOOD
During the first few years of life, it is not easy to notice that your child has haemophilia. This is because the baby still doesn't move much; however, with the first steps and the first inevitable falls (around the age of two), the classic symptoms of haemophilia appear.
When to see a doctor?
- In the presence of prolonged bleeding
- Frequent hematomas, even after minor trauma
- Family history of hemophilia
COMPLICATIONS
When hemophilia causes deep internal bleeding, the main complications are in the muscles, joints and brain.
The limbs swell, it is difficult to move them and there is a feeling that the muscles are numb.
The joints (in particular, the knee and ankle) are painful, even after minimal movement. Furthermore, without any treatment, they progressively deteriorate, leading to the development of osteoarthritis.
Finally, the brain is more exposed to cerebral hemorrhages following even a trivial head injury. When this happens, urgent action must be taken, as the patient is in danger of life.
The following are the symptoms experienced during a "brain haemorrhage."
Symptoms of a "cerebral hemorrhage in haemophilia patients:
- Long-lasting headache
- Repeated vomiting
- Double vision
- Neck pain
- Loss of coordination and balance
- Partial or total paralysis of the facial muscles
- Confusion and difficulty in speaking
MORE: Hemophilia - Diagnosis and Treatment "
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