Hemophilia: What is it and how does it manifest? Do you know the causes of royal disease?

Hemophilia is a disease that is inherited. This means that it is mostly transmitted from parents to offspring. However, in some cases, the genetic mutation is new, approximately 20-30%.

The disease is manifested by insufficient blood clotting and increased bleeding. This occurs spontaneously in some cases, for no apparent reason, and sometimes as a result of injury. But also, for example, after tooth extraction or after surgery.

It is important to know that the disease is gonosomally recessive, which means that the genes for coagulation factors are located on the X chromosome. As a result, women, or mothers, are carriers, and the disease affects boys. In very rare cases, the disease also affects a woman.

The name of the disease itself originated in 1828, but it was not until a hundred years later that blood plasma began to be used to treat the disease. It is very important not to neglect this treatment, because otherwise there is a risk of bleeding even in a completely banal injury.

Royal disease, was named after it spread to royal families in the 17th and 18th centuries. This is due to heredity and Queen Victoria (1819 - 1901).

What types of hemophilia do we know?

Hemophilia is an incurable disease that causes a defect in the hemocoagulation factor. We know two types of gonosomally transmitted, ie transmitted on sex chromosomes. The third type is autosomal recessive, which is transmitted on asexual chromosomes.

These types are manifested in the same way, and thus by increased bleeding. The intensity of bleeding depends on the degree of involvement. Haemophilia is divided, according to the hemocoagulation factor, into:

• hemophilia A  - if a factor VIII defect is present 
• hemophilia B - this is damage to factor IX
• hemophilia C - coagulation factor XI deficiency

The most common koagulopatickým disease is hemophilia A. In the past, ie until the 1940s, people with this type lived to live an average of 16 years. The main reason was the complications that the disease brings with it. Thanks to the treatment, the survival time is prolonged and the incidence of complications is reduced.

The incidence of haemophilia A is about 5 times more common than type B. The incidence of haemophilia A is reported to be approximately 1: 10,000 and for haemophilia B to be 1: 100,000 inhabitants. 

The disease is relatively rare and the disease only affects men because they have a genetic predisposition to it. While a woman can only be a carrier of disease due to her genetic makeup, even though she has a similar genomic mutation, in men the presence of a defective gene on the X chromosome always means the manifestation of the disease.

In some rare cases, hemophilia can also be caused by an autoimmune response in the body, where antibodies act against several blood clotting factors. Such an autoimmune response and the production of antibodies against one's own body can occur after childbirth or in old age.

Hemophilia is a blood-clotting disease that results from the presence of a defective gene on the X chromosome. This defect leads to reduced clotting function. Or the dysfunction of blood plasma proteins, which are involved in the process of blood clotting. Depending on how severe the deficiency or dysfunction of this protein is, the severity and intensity of the bleeding.

According to the cause, we recognize two main types of hemophilia, namely A and B. They differ in the absence and deficiency of a specific blood clotting factor. The disease as such is caused by a faulty X chromosome, with women having two X chromosomes. While men have only one, the Y chromosome has it.

This means that the disease will inherit disease in a man who has a faulty X chromosome. And he becomes a hemophiliac. If transmitted to a woman, the second healthy X chromosome can compensate for the error of the first. The woman becomes a carrier of hemophilia.

However, hemophilia can also occur spontaneously. This happens in about 20-30% of cases. In that case, the disorder of hemocoagulant factors is caused again and is not the result of transmission from parents to the child.

We also know of other bleeding conditions and blood clotting disorders that can be the cause of the disorder:

• plasma coagulation system
• fibrinolytic system
• platelet function
• vascular wall function

In the case of hemophilia, it is a disorder of hemostasis (an event of cessation of bleeding), which is caused by a disorder of factor VIII, IX, and XI. We know mild, moderate, and severe forms of the disease. The degree depends on the degree of involvement of the given factor.

The table shows the degrees of hemophilia and the distribution according to the percentage of involvement

What is hemostasis?

Hemostasis is a process that has the task of stopping vascular bleeding after an injury. Of course, in order for blood to flow in the blood vessels, it must be in a liquid state. Primary hemostasis is provided by the vessel wall and platelets, which are platelets.

Coagulation factors, inhibitors, and the fibrinolytic system is secondary hemostasis. If the vessel wall is damaged, the vessel in the area will contract. The flow through the vessel is reduced. Platelets begin to clump on part of the exposed vessel wall. A primary plug is formed.

Subsequently, fibrin is formed, which forms a kind of network on the collection plates and strengthens the whole structure. This created a secondary plug. A coagulation cascade is required for fibrin formation. The coagulation factor XIII (FXIII) is responsible for the fact that this fibrin plug does not dissolve.

Hemostasis is a complex and complex process that is not only present when a vessel is damaged. However, if any of its components is disrupted, pathological conditions occur. These are manifested by either increased bleeding or thrombophilia, which is a tendency for excessive thrombus formation (blood clots).

Typical symptoms of hemophilia are impaired blood clotting,  prolonged bleeding time, and excessive bleeding. Bleeding can be external, for example in the case of injuries, but also in the case of tooth extraction or surgery.

The second form is internal bleeding. The most common bleeding is into joints, muscles, hollow organs, especially the digestive system, but also intracranial hemorrhage into the central nervous system (CNS). Prolonged bleeding into joints or muscles and inadequate treatment result in degenerative changes.

These are the main symptoms, and depending on the extent of the clotting factor damage, the disease may have varying degrees. In the mild form, hemophilia is manifested by excessive bleeding during injuries or the aforementioned tooth extraction, or during surgery. 

The moderate form of hemophilia is characterized by significant and intense bleeding in addition to the above conditions, and thus mainly injuries. In severe cases, there is spontaneous bleeding, ie for no apparent reason. The most severe form of hemophilia is recognized in childhood, often after childbirth, when it is very difficult to stop umbilical cord blood bleeding.

In this form,  spontaneous bleeding is very common, for example not only in the joints but also in the mucous membranes, muscles, and body cavities. There is also compression of blood vessels, nerves, and degeneration of joints. For example, nosebleeds are also common.

Main symptoms of hemophilia:

• spontaneous bleeding, for example, epistaxis which is nosebleeds
• increased bleeding even after minor injuries
• bleeding after surgery, even after tooth extraction
• common hematomas
• bleeding is not stopped even by compression, ie surface oppression
• bleeding into joints, muscles and causes degenerative changes
• gastrointestinal bleeding, such as the presence of blood in the stool, such as melena (dark stool, digested blood in the stool)
• bleeding into the excretory system, haematuria, ie blood in the urine
• CNS bleeding

The proportion of bleeding into the joint is most often to the knee, 45%, to the elbow 25%, to the ankles 15 and to the lumbar joint or shoulder 5%. The total proportion of all hemophilia bleeding is 70-80% into the joints. It is about 20% to the muscles. CNS bleeding is less common at less than five percent.

The presence of bleeding conditions, and thus the presence of symptoms, leads to the diagnosis of hemophilia. Subsequently, blood laboratory tests are performed. Prolonged APTT is demonstrated, which is the activated partial thromboplastin time. This prolongs when factors VIII and IX fall below 25%.

Subsequently, the diagnosis is confirmed by determining the activity of coagulation factors VIII and IX. Alternatively, a gene mutation is identified that indicates hemophilia. If a woman with hemophilia is pregnant, a chorionic villus test is also performed to see if transmission to the baby is possible.

Differential diagnosis is also important in bleeding conditions, which aims to rule out other causes of increased bleeding. Von Willebrand's disease, thrombocytopathy, Rendu-Osler's disease, DIC - disseminated intravascular coagulation, and others.

The course of the disease depends on the degree of hemophilia. In the case of a very mild form, a person does not have to find out that he is a hemophiliac during his life. Bleeding may be prolonged in minor injuries. Thus, in mild forms, prolonged bleeding occurs mainly after injuries or surgeries.

The middle form is already characterized by intense bleeding during injuries and procedures, such as tooth extraction in a dentist. And also occasional spontaneous bleeding. Bleeding into the joints also occurs sporadically.

In the most severe form of the disease, spontaneous bleeding very often occurs. For example, nosebleeds, or epistaxis. Bleeding into joints and muscles is common, which causes degenerative complications if treatment is neglected.

Bleeding into the CNS and digestive system is serious. In case of bleeding into the GIT (gastrointestinal system), there is the presence of blood in the stool, namely melena. Melena is a dark to black stool that is stained with digested blood. Blood in the urine may also be associated.