Generality
Hemophilia is an inherited genetic disorder that affects the normal coagulation process. The affected patient, therefore, is subject to prolonged bleeding, even after trivial traumas or cuts of the skin.
Once the deficient element is established, you can proceed with the most appropriate therapy. Today, medicine has made significant progress and has guaranteed effective and low-risk treatments. At one time, in fact, one could only resort to transfusions of human blood, much more dangerous. Also prevention, as in all diseases, is fundamental and helps to guarantee a good quality of life for haemophilic patients.
Human chromosomes
To understand hemophilia, we need a premise that describes the human chromosome set. Every cell of a healthy human being contains 23 pairs of chromosomes. A pair of these chromosomes is sexual, that is, it determines the sex of the individual; the remaining 22 pairs, instead, are composed of autosomal chromosomes . In all, therefore, the human genome has 46 chromosomes.
CHROMOSOMAL ALTERATIONS
Each pair of chromosomes contains certain genes .
When a mutation occurs in a chromosome, a gene can be defective. This defective gene consequently expresses a defective protein.
When, on the contrary, the number of chromosomes varies, we speak of aneuploidy . In this case, instead of two, the chromosomes can be three (trisomy) or only one (monosomy).
THE SEXUAL CHROMOSOMES
Sexual chromosomes are essential in determining a person's gender, male or female. The woman has, in the cells of her body, two copies of the so-called X chromosome ; the man, on the contrary, presents an X chromosome and a Y chromosome . As for the autosomal chromosomes, also the sexual ones are inherited from the parents: a copy is given by the father, another by the mother. There are several genetic pathologies due to sexual chromosomes. They present either alterations in the chromosomal structure or changes in the number of chromosomes.
What is hemophilia?
Hemophilia is a genetic disorder that alters the normal process of blood clotting and causes prolonged bleeding .
In most cases, the origin of hemophilia is a genetic mutation of sexual chromosome X, transmitted from parents to children. Therefore, like Duchenne muscular dystrophy or color blindness, haemophilia is also part of the group of so-called hereditary diseases linked to sex chromosomes.
THE COAGULATION PROCESS
When an individual gets a superficial cut of the skin, the consequent blood loss is limited and temporary: in fact, in a short time, it can be observed, even with the naked eye, as the blood passes from the fluid state to the solid state. This unique process, called coagulation, is put into practice by platelets and a series of biomolecules (proteins, enzymes and cofactors) of the blood, called coagulation factors, which are activated in cascade. The same process occurs when there is a small internal trauma: the hematoma, which appears after a blow for example, is the blood that has escaped and then solidified.
This ability to form a blood clot is vital, because, without it, the bleeding would be unstoppable.
THE EMOPHILIC INDIVIDUAL
In the individual with haemophilia, coagulation is deficient and does not stop blood loss with the same efficiency and rapidity. Therefore, a cut, even when it is slight, causes prolonged bleeding, with sometimes serious effects.
Causes
The cause of hemophilia is a genetic mutation, affecting the sex chromosome X, which determines the deficiency of one of the coagulation factors.
THE FACTORS OF COAGULATION. Pathogenesis
Coagulation factors are functional for 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, which depend on him, will not be triggered or will be triggered slowly. All this results in a coagulation defect.
The 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 can be seen, the presence of each factor is fundamental for the final purpose. From the site: farmacologiaoculare.com
GENETICS
Hemophilia mainly affects the male sex. But for what reason?
The mutation of the X chromosome, which determines hemophilia, is recessive . This means that the woman, provided with two X chromosomes, manifests the disease only if both her sex chromosomes have changed (a very remote possibility); in fact, when only one X chromosome is mutated, the other healthy compensates for the deficiencies of the first and provides himself 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 is irremediably lacking a fundamental component.
INHERITANCE AND TRANSMISSION
It has been said that hemophilia is an inherited genetic disease.
Figure: the transmission of hemophilia, 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 known as a 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.
- Female daughters are equally likely (50%) to be born healthy or wholly healthy carriers. In fact, they inherit the healthy X chromosome from their father. The other X chromosome, inherited from the mother, can be sick or healthy.
If both parents have a mutated X chromosome.
Figure: the transmission of hemophilia, when both parents carry a mutated X chromosome. All daughters are healthy carriers; males, on the other hand, can be born, with the same probability, or healthy or sick. From the site: infoemofilia.it
Since haemophilia is a disease compatible with life, a sick man can have children. His union with a healthy carrier woman can give life 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 healthy carrier of the disease. It is the maternal X chromosome that determines the health of the male child, because, from the father, they only inherit the Y chromosome.
- Female daughters with the same probability (50%) to be born healthy or sick carriers.
They certainly inherit an X chromosome mutated from the father. The other chromosome, the one of maternal origin, can be healthy or changed.
If only the father is sick.
In this case, his union with a healthy woman has two consequences:
- The male children are all born healthy, because the mutated component is missing from the mother's side.
- The daughters all born healthy carriers, because all receive, from the father, the mutated X chromosome.
THE TYPES OF EMOFILIA
Based on the coagulation factor involved, we distinguish three types of hemophilia:
- Hemophilia A, in which the factor of deficient coagulation is factor VIII .
- Hemophilia B, in which the deficient coagulation factor is factor IX .
- Hemophilia C, in which the deficient coagulation factor is the XI factor .
At this point, a clarification is needed.
Haemophilia C, on the other hand, is an autosomal genetic disease, since the genetic anomaly resides on the autosomal chromosome 4.
Epidemiology
Hemophilia is a rare disease that affects male individuals the most.
According to some statistical data, about 5, 000 males are born with type A haemophilia, while one in 30, 000 males are born with type B haemophilia.
In women, haemophilia, both type A and type B, is rare, since, as we have seen, it requires that both parents carry a mutated chromosome (which is a very remote circumstance).
Type C hemophilia is a case in itself. It is even rarer than the previous ones and affects both males and females with equal probability.
Symptoms and Complications
To learn more: Symptoms Hemophilia
The main symptom of haemophilia (of any type it may be) 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:
- Extended and deep hematomas
- Bleeding within the large joints (knee, hip, ankle, etc.), resulting in pain and joint swelling
- "Spontaneous" hemorrhages and hematomas
- Blood in urine and faeces
- Prolonged bleeding after tooth extraction
- Nose blood
- Irritability (in children of infantile age)
- fatigue
These symptoms do not always occur in the same way: the more the coagulation factor involved in haemophilia is lacking (regardless of the type), the more the aforementioned manifestations will be serious. A useful example to understand what has been said is the following: a patient with haemophilia A, having a very low level of factor VIII in the blood, will have a worse symptomatology than another patient with the same hemophilia but with modest factor VIII levels.
In light of this, based on the amount of coagulation factor present, a slight haemophilia, a moderate haemophilia and a severe haemophilia can be distinguished.
| Degree of severity of hemophilia | Percentage of residual factor in the blood | Distinguishing features |
| mild | 5-50% | Prolonged bleeding in case of severe trauma or injury |
| Moderate | 1-5% | Prolonged bleeding also due to trivial traumas Internal bleeding at the joints |
| Serious | <1% | Spontaneous bleeding |
EMOFILIA LIEVE
Individuals with a clotting factor between 5 and 50% of normal are affected by a mild form of hemophilia. In these circumstances, the disease does not cause any particular problems, except on some occasions. For example, you notice that the bleeding takes longer than usual when you first seriously injure yourself or after the first tooth extraction (in children).
MODERATE EMOFILIA
When hemophilia is moderate, the amount of coagulation factor is very small (between 1 and 5% compared to the normal quota). The consequences of this condition are obvious: the patient manifests, even if the trauma is mild, extensive hematoma, long bleeding and bleeding inside the joints. The latter mainly concern the knees and ankles and cause pain, swelling and a sense of joint stiffness.
SERIOUS EMOFILIA
Figure: Knee of a healthy person (left) and knee of a person with hemophilia (right). From the site: emofilia.it
The coagulation factor dose is less than 1% of the normal quota. Very similar, due to the symptoms manifested, to moderate haemophilia, the severe form is characterized by the patient's predisposition to spontaneous and apparently motive bleeding .
The situation, in these cases, is critical.
HEMOPHILIA DURING CHILDHOOD
During the first years of life, it is not easy to notice that your child is suffering from haemophilia. This is because the child does not move much yet; however, with the first steps and the first inevitable falls (around two years), here are the classic symptoms of hemophilia.
When should I go to the doctor?
- In the presence of prolonged bleeding
- Frequent hematomas, even after minor traumas
- Family history of hemophilia
COMPLICATIONS
When haemophilia causes profound internal bleeding, the main complications affect the muscles, joints and brain .
The limbs swell, it is difficult to move them and there is the feeling that the musculature is numb.
The joints (in particular, knee and ankle) are painful, even after a minimal movement. Furthermore, without any treatment, they progressively deteriorate to the point of developing arthrosis .
Finally, the brain is more exposed to cerebral haemorrhages, following an even trivial head injury. When this happens, urgent action must be taken, as the patient is in danger of life.
Below are the symptoms experienced during a cerebral hemorrhage.
Symptoms of cerebral hemorrhage, in haemophilic patients:
- 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
CONTINUE: Hemophilia - Diagnosis and Treatment ยป
