Hemophilia - causes (inherited recessive gene), probability of hemophilia, types, symptoms and signs, diagnosis, treatment principles and drugs. Features of hemophilia in children, men and women. Royal illnesses

Hemophilia: causes, manifestations, types, transmission patterns, diagnosis, treatment

Hemophilia is a genetic, inherited disease that is characterized by a change in one gene on the X chromosome. The manifestation of this disease is excessive bleeding and slow blood clotting, so-called coagulation.

This disease affects only males. Hemophilia in men occurs as a result of inheriting the disease from the mother. This means that transmission of the disease occurs via a recessive, X-linked type. Women with this disease are assigned the role of carriers, or conductors. However, it is known rare cases when women also became ill with hemophilia. This is possible when the father has the disease and the mother is a carrier of the hemophilia gene - the daughter of such parents may be born with a similar genetic disorder.

Signs and causes of hemophilia

One misconception is that a person suffering from this gene disease can die from loss of blood from any scratch or cut. This is not entirely true. Indeed, increased profuse bleeding is considered one of the main signs of the disease, but it occurs quite often even in the absence of injury.

The main signs of the disease are:

1. Excessive bleeding that occurs periodically with different localization: blood loss during injuries, during tooth extraction, during medical interventions associated with surgical operations.
2. or gum bleeding, which is very difficult to stop using conventional methods. Spontaneous, accidental occurrence is possible.
3. As a result of receiving easy, not dangerous injury a large hematoma forms.
4. The appearance of hemarthrosis - intra-articular bleeding resulting from damage to joint tissue. This phenomenon is usually accompanied by acute painful sensations, swelling, impaired motor function of the joint. Secondary hemarthrosis can lead to joint deformation and permanent impairment of its mobility.
5. Digestive problems often accompany the disease.
6. Presence of blood in urine and stool - dangerous symptoms hemophilia. Kidney disease is quite common in people with this genetic disorder.
7. The appearance of such may be fatal danger signs like the spinal cord.

Signs of hemophilia in children

In newborns, the disease is expressed in the form of so-called cephalohematomas - large area hematomas in the head area, and bleeding from the cut umbilical cord is also possible.

Children are already born with the disease, but signs of hemophilia may be absent or not clearly expressed in the first months of life. This happens because mother's milk contains substances that can maintain normal blood clotting in the baby.

Causes of hemophilia

Hemophilia is a hereditary disease and affects mainly men. Since the gene responsible for hemophilia is located on the X chromosome, women are carriers and are likely to pass the disease on to their sons. Hemophilia is inherited in a recessive manner, linked to the X chromosome, and since men have only one X chromosome, if the “sick” chromosome is passed on to a male child, the disease will also be inherited.

Doctors can diagnose this genetic abnormality before the baby is born. After birth, hematomas and excessive bleeding from minor injuries will be a clear sign.

The main causes of hemophilia are hereditary factors. IN currently Medicine cannot eliminate the cause of the disease. This is not yet possible, because the disease turned out to be programmed at the genetic level. People with such a serious illness must learn to be extremely careful about their health and carefully follow precautions.

Possible genetic combinations with risk of hemophilia

Healthy father mother is a gene carrier

Father with hemophilia, healthy mother

Father of a hemophiliac mother is a gene carrier

Forms and types of hemophilia

Hemophilia comes in three forms, depending on the severity of the disease:

• Easy. Bleeding appears only after medical intervention associated with surgery or resulting injuries.
• Moderate. Clinical symptoms, characteristic of hemophilia, can appear at an early age. This form is characterized by the occurrence of bleeding as a result of injuries, the appearance of extensive hematomas.
• Heavy. Signs of the disease appear in the first months of a child’s life during the growth of teeth, during the process of active movement of the child when crawling and walking.

Frequent bleeding should alert parents respiratory tract The child has. The occurrence of large hematomas due to a fall and minor injuries are also alarming symptoms. Such hematomas usually increase in size, swell, and when touching such a bruise, the child experiences pain. It takes a long time for hematomas to disappear - on average up to two months.

Hemophilia in children under 3 years of age can manifest itself in the form of hemarthrosis. Most often, they suffer large joints- hip, knee, elbow, ankle, shoulder, wrist. Intra-articular bleeding is accompanied by severe pain syndrome, violations motor functions joints, their swelling, increased body temperature of the child. All these signs of hemophilia should attract the attention of parents.

Types of hemophilia

In addition to forms of severity, there are three subtypes of hemophilia:

1. Hemophilia type “A” is caused by a gene defect in which the patient’s blood lacks the necessary protein - antihemophilic globulin, factor VIII. This type of hemophilia is called classic, and it occurs in 85 percent of all patients.
2. Hemophilia type “B” is caused by insufficient activity of blood clotting factor IX, which causes a disruption in the formation of a secondary coagulation plug.
3. Hemophilia type C is caused by a deficiency of clotting factor XI. Type C is considered the most rare.

Types of hemophilia “A”, “B” and “C” have the same symptoms, but for treatment it is important to diagnose the type of hemophilia, which is possible only with laboratory testing.

Diagnosis and treatment of hemophilia

Despite the fact that the disease is incurable, it is possible to treat hemophilia and control the patient’s condition. Patients receive injections of the missing factor responsible for blood clotting. Therefore, depending on which factor is deficient in the patient’s blood, the doctor treats hemophilia:

• In type A, factor VIII is introduced into the blood.
• With type “B”, factor IX is introduced into the blood.

All clotting factors are produced from blood provided by donors or from the blood of animals raised specifically for this purpose.

At proper therapy If the patient treats his body with care, the life expectancy of a hemophiliac will not differ from the life expectancy of a person without such a pathology.

Video: exercises for patients with hemophilia

Hemophilia and vaccinations

Contrary to popular belief, there is no vaccine against hemophilia itself. Many people confuse the Haemophilus influenzae vaccine with the hemophilia injection. The diseases are in no way related and have completely different natures.

As for routine vaccination, for hemophilia it is a mandatory measure. All children should have necessary vaccinations. It should be noted that vaccinations for hemophilia must be done only subcutaneously, but not intramuscularly. Because intramuscular injections may lead to extensive hemorrhage.

Video: hemophilia, how is modern medicine defeating it?

Hemophilia in women and royalty

Hemophilia in women is extremely rare, and therefore doctors have little data to fully characterize the clinical picture of the disease in females.

It can be stated with certainty that the disease will manifest itself in a woman only when a girl is born from a mother who carries the gene and a hemophiliac father. It is theoretically possible for such parents to give birth to either a boy, with or without the disease, or a carrier girl or a sick girl.

A famous royal and hemophilia conductor was Queen Victoria. Queen Victoria's hemophilia, as far as is known, arose in connection with a gene mutation in her genotype, since nothing is known about the disease in her parents. Scientists admit the theoretical possibility that Queen Victoria's father could not have been Edward Augustus, but any other man who had this disease. However, there is no historical evidence for this. Victoria's son Leopold and some of her grandchildren and great-grandchildren inherited hemophilia. Tsarevich Alexei Romanov also had the disease.

Photo: Family tree of the British royal family, taking into account the incidence of hemophilia

“Royal” disease is sometimes called the disease, and, for the most part, because in royal families marital relations with close relatives were allowed. Therefore, hemophilia among crowned persons was quite common.

Video: Hemophilia - Diseases and Deaths of Kings (“Discovery”)

The problem of hemophilia

There are more than 400 thousand people in the world suffering from this hereditary disease. This means that every 10,000th man has hemophilia.

Medicine has created drugs that can support the life of a hemophiliac at a quality level. And a patient with hemophilia can receive an education, start a family, work - be a full-fledged member of society.

It's heavy genetic disease recognized as the most expensive in the world. Expensive treatment is due to the high cost of medications that are made from donor blood plasma. Annual treatment for one hemophiliac costs approximately 12 thousand dollars.

One of the significant problems of hemophilia is insufficient provision of necessary medicines sick, and this can lead to early disability, usually of young people or children.

There is also a certain risk for patients receiving drugs for treatment: due to the fact that the medicine is made from the blood of donors, infection with hepatitis or HIV is possible.

So, the problem of hemophilia is quite significant. And in this regard, they have already been developed and put into production synthetic drugs VIII and IX factors that do not pose a risk of contracting blood-borne infections. True, their cost is also quite high.

Video: “Secrets of Health” - Hemophilia

Not many people know the real, medically used name of the disease about which we'll talk. For many, it sounds like “Royal disease” or “Bad blood clotting.” In view of the first version of the name, firmly entrenched among the common people, there is even a belief that it is characteristic only of individuals of “blue blood”, and it is unrealistic that it originated among ordinary people who have no kinship with the aristocracy and, especially, the royal family.

Despite all the myths characteristic of hemophilia, its occurrence is more than real for any person, regardless of whether his ancestors belonged to the upper class or not. Hereditary factor still playing key role in diagnosing this disease, but it is not at all a matter of noble origin.

Hemophilia - what is it?

The disease is characterized poor clotting blood. Having received a minor injury, a person suffering from the “royal disease” cannot stop the bleeding for a long time. It's even worse if bleeding occurs during internal organs– in such cases, hemophilia can be fatal.

From time immemorial, doctors from all countries have been interested in what kind of disease this is, what are the causes of its occurrence, and whether it can be eliminated. It was only by the mid-20th century that some answers to these questions began to emerge in the world of medicine.

Difficulties in folding appear due to mutation, which, in turn, arises due to poor heredity. Hemophilia is transmitted at the genetic level, but the disease occurs differently in men and women.

If the female component practically does not notice changes in the body, then men experience all the consequences of the disease, starting from childhood. In children, poor clotting is observed from their first days, and if appropriate treatment measures are not taken, the prognosis is sad - no more than 15 years of life.

In order for blood clotting to occur in a timely manner, it is necessary that 12 types of proteins take part in this process, one of which is absent in patients with hemophilia. Because of this, problems with blood clotting, as well as spontaneous bleeding, predominate.

How does infection occur?

The disease is transmitted exclusively genetically from sick parents (or one of them). There is an opinion that hemophilia is male disease, but that's not true. Hemophilia in women is detected as often as in the male component, but, in most cases, does not manifest itself. Representatives of the fairer sex, in fact, are only conductors (conductors) of the disease.

The probability that a couple in which one of the spouses is sick with the “royal disease” will have infected offspring is about 50%. The hemophilia gene is passed on to both boys and girls. The only difference is that the first group will experience characteristic diseases symptoms, and the second will only be its carrier.

Acquired hemophilia

Cases have been recorded in which the disease was also acquired. But this happens extremely rarely. The most striking example is Queen Victoria. It was she who began to experience difficulties with clotting in later life.

Acquired hemophilia is not possible in children. As a rule, it appears in people over 60 years of age. The development of a disease of this type is extremely rare - in 1 person out of 1000 thousand. Causes of hemophilia recorded in people who have not previously had it:

• taking medications;
• late pregnancy.

But hemophilia can also develop with severe immune diseases. Until now, doctors have not been able to establish other causes of poor blood clotting that occurs in adulthood.

Why do men get sick?

The fact that only males suffer from hemophilia is explained by the number of X chromosomes. Women have 2 of them, men have 1. If infection occurs in women, the gene affects only 1 chromosome. The second female chromosome becomes dominant and does not allow the disease to prevail in the body. Thus, the woman becomes only a carrier.

For men, things are different. Due to the presence of a single X chromosome, the gene provokes the full course of the disease. Its latent state is completely excluded.

Classification of the disease

Hemophilia can be of three types:

• classical (A);
• Christmas disease (B);
• hemophilia "C";

Determining the type depends on which factor necessary for complete blood clotting is missing.

The royal disease - hemophilia type "A" is the most common - ¾ of cases. It occurs due to a deficiency of antihemophilic globulin, which is necessary for the formation of active thrombokinase.

Christmas disease (hemophilia B) occurs less frequently - 13% of cases of blood incoagulability. It is caused by a lack of the plasma component thromboplastin.

The last type of disease - type "C" is extremely rare - in 2% of cases.

The greater the lack of plasma factors necessary for complete blood clotting, the more severe the disease.

At a level of the missing factor of 1%, severe hemorrhagic syndrome. As a rule, this occurs in young children. With this form of the disease, the baby suffers from frequent hemorrhages occurring in muscle tissue, joints and internal organs. Already in the first days of life, the child experiences:

• cephalohematomas;
• bleeding from the umbilical cord (long-term);
• melena;
• frequent and prolonged bleeding when teething (or when changing milk teeth to molars).

In children with hemophilia moderate severity, the plasma factor level is no more than 5%. The disease makes itself felt closer to preschool age. Exacerbations are possible no more than 3 times a year. Hemorrhages occur in muscle tissue and joints.

In mild forms of the disease, the level of plasma factors is always above 5%. The first manifestations appear in school years. Have no bleeding frequent, and do not last long.

Symptoms

Manifestations of the disease occur in children in their first days of life. Bleeding is frequent and prolonged, and occurs in the umbilical cord, in the gums (when teeth erupt). Hematomas and cephalohematomas are formed. At surgical interventions Damage to certain areas occurs, which also leads to prolonged hemorrhage.

Despite high probability manifestations of hemophilia in infancy, it does not always pose a serious threat, since the body is constantly saturated with active thrombokinase, which is enriched in mother’s milk, which promotes rapid blood clotting.

During the period when the child begins to take his first steps, the likelihood of injuries that contribute to bleeding increases significantly. After one year, the child is exposed to:

• nosebleeds;
• subcutaneous hematomas;
• hemorrhages in muscle tissue;
• hemorrhagic diathesis (occurs due to infection in the body).

Gums are particularly prone to bleeding. Those suffering from hemophilia are often anemic.

The most common and pronounced concomitant of the disease is hemarthrosis. The first hemorrhage occurring inside the joints is observed at the age of 1 year. It can occur either after a bruise or spontaneously. This phenomenon is accompanied by severe pain, enlargement of the joint, and swelling of the skin over it. In view of this, the possibility of developing the following ailments cannot be excluded:

• chronic synovitis;
• contracture;
• deforming osteoarthritis.

The development of deforming osteoarthritis contributes to disorders:

• rachiocampsis;
• curvature of the pelvis;
• muscle tissue wasting;
• osteoporosis;
• hallux valgus deformity of the foot.

All this happens due to a violation of the dynamics of the musculoskeletal system. The presence of any of the above points is quite enough to lead to disability.

Hemorrhages may occur in soft tissues. Often you can find bruises on a child’s body that take a very long time to disappear or do not go away at all.

As the blood flows out, it does not clot, forming hematomas. They, in turn, squeeze major arteries, which often leads to paralysis and muscle atrophy. Possible gangrene formation. With all this, the child experiences severe pain.

Hemorrhages in the gastrointestinal tract occur due to the use of medications. And also the reasons are:

• development of ulcers;
• intestinal diseases;
• gastritis.

One of characteristic features hemophilia is delayed bleeding. In other words, it does not occur immediately after injury, but only after a certain time (sometimes it reaches 12 hours).

Treatment

Full recovery of the body with hemophilia is impossible, and the only way To improve the patient’s condition is to periodically take medications that supply the body with concentrates of blood clotting factors 8 and 9. The name of the drug, as well as the dosage, are prescribed based on the severity of the disease.

Inheriting hemophilia means one thing for a person - the need for constant monitoring attending physician. Wherein health care can be either periodic (aimed at preventing the disease) or urgent (in fact).

Taking medications containing concentrates of factors necessary for complete blood clotting occurs no more than 3 times a week, and only for those with a severe form. This helps prevent the development of hemophilic arthropathy, as well as other types of bleeding.

Any surgical actions aimed at direct contact with human skin are accompanied by hemostatic therapy. For minor damage such as skin cut or nosebleeds, a hemostatic sponge is used. It is also necessary to use a pressure bandage and treat the damaged area with thrombin.

Treatment of hemophilia involves constant adherence to a diet. Patients are recommended products enriched with vitamins of groups A, B, C, D.

Inheriting hemophilia condemns a person to the condition constant anxiety. While injuries that may seem minor to the average person, they can be fatal to those who suffer from poor clotting.

Diagnostics

In order to make a diagnosis of hemophilia, the presence of specialists is necessary:

• neonatologist;
• pediatrician;
• hematologist;
• geneticist.

If a child has other diseases related to a certain system of the body, then the presence of a doctor whose duties include their treatment (gastroenterologist, otolaryngologist, orthopedist, neurologist and others) is mandatory.

Married couples who have hemophilia (one or both spouses) are required to undergo medical genetic counseling before planning a child. In this way, it is possible to identify the presence of a defective gene.

When examining a child, the diagnosis is confirmed using laboratory research hemostasis.

Prevention and prognosis

To constantly saturate the blood with the factors necessary for complete blood clotting, the patient must periodically undergo replacement therapy.

If there is a diagnosis, a person is given a special document that states the nature of the disease, its blood type and Rh affiliation. The patient is in protective mode. He needs to constantly visit his doctor.

At mild degree As a rule, life expectancy is not something to worry about. Regarding hemophilia, which has difficult character progress, the quality of life deteriorates every year. This occurs due to constant bleeding.

Hemophilia - hereditary disease, which is transmitted as a recessive trait linked to the X chromosome, caused by a deficiency or molecular abnormalities of blood coagulation factors VIII/IX and characterized by severe massive bleeding of various locations.

Hemophilia as a hereditary disease was described in the Talmud in the 5th century. n. e., however modern knowledge and scientific research on hemophilia dates back to the end of the 20th century. Research conducted in the 1950s showed that there are at least two forms of hemophilia. One of them, the classic one, called hemophilia A, is caused by the absence or deficiency of factor VIII, also known as antihemophilic factor (AGF), or antihemophilic globulin (AGG). Another form, called hemophilia B, is caused by a deficiency of factor IX, also known as antihemophilic factor B, or Christmas factor. Hemophilia A and B are similar in inheritance and clinically indistinguishable.

Inheritance of hemophilia. The genes responsible for the synthesis of factors VIII and IX are located on the X chromosome and, as noted above, are inherited as a recessive trait. According to the rules of inheritance of an X-linked disease, all daughters of a hemophilia patient are obligate carriers of the pathological gene, and all his sons are healthy. In 25% of cases, carriers have a risk of giving birth to a sick boy and in 25% - transmitting girls (if we take all possible children born as 100%).

Epidemiology. According to WHO, hemophilia A occurs in one case per 10 thousand male population, hemophilia B - 1 case per 50 thousand. In Sweden, hemophilia A occurs with a frequency of 2 cases per 10 thousand male population, hemophilia B - 1.3 per 50 thousand (Lethagen S., 2002).

Diagnosis of hemophilia is based on family history, clinical manifestations and laboratory results.

Coagulogram indicators for a/v hemophilia.

Types of hemophilia:

* Hemophilia A - factor VIII deficiency (87–92% among other hemophilias).

* Hemophilia B (Christmas disease) - factor IX deficiency (8–13%).

Hemophilia severity: extremely severe form - 0-1% of the factor, severe form - 1-2%, moderate form - 2-5%, mild form - 5-10%., very mild or latent forms - more than 10%.

Clinical picture. The most typical manifestations of bleeding in hemophilia are hemorrhages in large joints of the extremities, deep subcutaneous, intermuscular and intramuscular hematomas, heavy and prolonged bleeding from injuries, bleeding after invasive manipulations. Less commonly observed are other hemorrhages, such as retroperitoneal hematomas, hemorrhages in the abdominal organs, gastrointestinal bleeding, hematuria and intracranial hemorrhages. Average age, in which hemophilia is diagnosed, in severe cases it is 9 months, in moderate cases it is 22 months. Mild forms of hemophilia are diagnosed later in life, sometimes only after tooth extraction or other invasive procedures. In hemophilia, there is a clear age-related evolution of the symptoms of the disease. In the most severe cases At birth, the child may experience extensive cephalohematomas and bleeding from the umbilical wound. Most often, the first symptoms of the disease are bleeding due to puncture, injection or surgery, as well as from the oral cavity and hemorrhages into soft tissues. The most significant in terms of disability and impaired quality of life are hemorrhages in the joints. They first appear when the child learns to walk. Most often the knee, ankle and elbow joints are affected, less often the shoulder and hip joints. The spine and wrist joints are rarely affected, usually as a result of trauma. Acute hemorrhages in the joints (hematroses), as a rule, occur without visible trauma: the joint becomes rigid, swollen, hot, painful and bent; movement is hindered by stiffness and pain. Individual episodes of joint hemorrhage are relatively harmless, and once the blood is reabsorbed and the swelling subsides, normal joint mobility and function are restored, with virtually no radiological changes observed. After repeated hemorrhages, the joint capsule becomes thickened and changes color under the influence of hemosiderin. The capsule subsequently becomes more and more inflamed. Later stages of arthropathy are characterized by severe fibrosis joint capsule and surrounding soft tissue with very limited joint mobility. The cartilage of the joint degenerates and is destroyed after repeated hemorrhages under the influence of aggressive active proteolytic enzymes and collagenases, its strength decreases, the surface is affected, and after degeneration it is destroyed. Subchondral bone becomes osteoporotic, thin due to bone resorption, and sclerotic due to ossification. Cysts filled with a gelatinous substance may form in the subchondral bone. Clinically, the function of the joint is impaired, flexion and extension of the limb become limited, the joint becomes deformed, expands and takes on an incorrect position when the limb is straightened - atrophy of the surrounding muscles occurs. In cases of severe arthropathy, there may be loss of mobility and ankylosis. Chronic hemophilic arthropathy can be painful, but relatively often joints with severe chronic hemophilic arthropathy are painless. In the absence of adequate replacement therapy, patients become deeply disabled, forced to use crutches and are often confined to wheelchairs.

The most common causes of gastrointestinal bleeding in patients with hemophilia are peptic ulcer stomach, duodenum, esophageal varices, hemorrhoids, the occurrence of which can be provoked by taking non-steroidal anti-inflammatory drugs. However, spontaneous gastrointestinal bleeding also occurs. At the first episode of bleeding, the patient must be examined to identify the cause of this hemorrhage. A serious therapeutic problem in hemophilia is caused by heavy and persistent renal bleeding, which is observed in 14-30% of patients. They can occur either spontaneously or in connection with injuries to the lumbar region, concomitant pyelonephritis, as well as taking aspirin and non-steroidal anti-inflammatory drugs. Hematuria is often accompanied by dysuric symptoms and attacks of renal colic, caused by the formation of blood clots in the urinary tract, which can obstruct tubular tubules and even the ureter, which can lead to temporary hydronephrosis. It is generally accepted that hemophilic renal bleeding is much more difficult to treat than hemorrhages of many other localizations. To achieve adequate hemostasis, patients with hematuria are recommended to administer concentrates of deficient factors twice a day, as well as maintain bed rest until bleeding stops.

Diagnostics. Significant assistance in the diagnosis of hemophilia is provided by identifying the nature of inheritance. The presence of a sex-linked hemorrhagic diathesis is convincing evidence of the presence of hemophilia in the family. This type of inheritance is characteristic of both hemophilia A and hemophilia B (factor IX deficiency), which can only be differentiated using laboratory testing. Tests characterizing the platelet component of hemostasis: platelet count, duration of bleeding and adhesive-aggregation parameters in patients with hemophilia are within normal limits. Characteristic laboratory signs of hemophilia are disturbances in indicators that evaluate internal path activation of blood coagulation, namely: an increase in the clotting time of venous blood (may be within normal limits if the activity of factor VIII or IX is above 15%), an increase in aPTT along with normal values

prothrombin and thrombin time. A decrease in the coagulation activity of factor VIII or IX is a decisive criterion for the diagnosis and differentiation of hemophilia A or B.

Differential diagnosis. Hemophilia A, especially moderate forms of the disease, should be differentiated from von Willebrand disease, which is also characterized by a decrease in the activity of factor VIII, but there is an increase in bleeding time, impaired platelet aggregation with ristomycin, which is associated with a deficiency or qualitative defect of von Willebrand factor.

Treatment of hemophilia.

Treatment is based on replacement therapy to introduce deficient factors. Currently, the following components and blood products are used to relieve hemorrhagic manifestations in this category of patients: fresh frozen plasma, cryoprecipitate, factor VIII concentrates, factor IX preparations. All patients with hemophilia should be treated in specialized hemophilia centers or, if there are none, under the supervision of a hematologist specializing in the treatment of patients with hemorrhagic diathesis. The principles of treatment for hemophilia A and B are identical, the only differences are in the choice of drugs and the replacement therapy regimen. The main therapeutic measures in patients with hemophilia are aimed at replacing the deficient factor both during the period of hemorrhagic manifestations and for preventive purposes. The goal of prophylactic treatment is to prevent the development of hemophilic arthropathy and other severe bleeding.

Prophylactic treatment in the form of regular injections of factor VIII or IX concentrates 2-3 times a week is recommended for all patients with severe hemophilia. When prescribing hemostatic drugs (concentrates of factors VIII or IX, obtained from human plasma or using genetic technology) for replacement purposes, the doctor must remember that after transfusion, the activity of factor VIII in the patient’s blood quickly decreases and after 12 hours only half of the original level remains in circulation. administered dose. Therefore, to completely stop bleeding, repeated transfusions of hemostatic drugs are necessary every 12 hours. The administered factor IX circulates in the recipient’s blood longer - from 18 to 30 hours, so to maintain its hemostatic level, it is enough to administer the drug once a day. The choice of drug and its dose for stopping bleeding in patients with hemophilia are determined by the intensity of hemorrhages or, if the patient requires surgical treatment, by the expected extent of surgical intervention. It is extremely important to emphasize that the effectiveness of treatment largely depends on the timing of the start of hemostatic therapy. The greatest effect is achieved when the drugs are administered within the first hour after signs of bleeding appear. External bleeding from damaged skin, bleeding from the mucous membranes of the nose, and oral cavity can be stopped both by the administration of antihemophilic drugs and by local influences - by treating the bleeding area with thrombin, a tampon moistened with a 5-6% solution of aminocaproic acid, and a pressure bandage. If stitches are necessary, remember that for patients with hemophilia this is an additional injury that can worsen the bleeding. That's why this procedure must be accompanied by the administration of hemostatic agents. Desmopressin and fibrinolysis inhibitor tranexamic acid can be used as additional therapy. These drugs are primarily used to stop minor bleeding, including from the mucous membranes after tooth extraction. Treatment of hemarthrosis: joint puncture - aspiration of blood, injection of hormones into the joint cavity.

Forecast. Patients with moderate hemophilia A usually have no special complications. They develop severe bleeding only after surgical interventions, injuries and injuries. Patients with severe forms of the disease suffer from frequent recurrent bleeding, which leads to irreversible joint deformities - the main cause of their disability. Regular visits of such patients to specialized hemophilia centers, where outpatient treatment with hemostatic drugs is organized, significantly reduces the frequency of bleeding and prevents the development of disabling complications. Although wide application replacement drugs and increased the life expectancy of patients with hemophilia, but deaths from bleeding are not yet a rare occurrence.

Hemophilia is a disease characterized by incoagulability of blood (this is how the word is translated from Greek). The disease is inherited. Bleeding and hemorrhage in this disease are prolonged, sometimes they occur spontaneously, without any apparent reason.

Fatal "legacy"

Any mention of hemophilia is primarily associated with the image of Tsarevich Alexei, the latter’s son Russian Emperor Nicholas II. Alexei had hemophilia, having received it from his mother, Empress Alexandra Feodorovna, who inherited the disease from her mother, Princess Alice, who, in turn, received it from Queen Victoria. Queen Victoria was a carrier of hemophilia, but of her nine children, only one son, Prince Leopold, had hemophilia and died when he was thirty-one, and her daughters, Princesses Alice and Beatrice, were carriers of the disease.

Of Princess Beatrice's four sons, only two had hemophilia, and her daughter, Victoria Eugenie, wife of the King of Spain, passed the disease on to two of her three sons. Princess Alice's son, Frederick, one of seven children who inherited hemophilia, died in three years old. Her sister Irene's two sons were also hemophiliacs, but one of them managed to live safely to the age of 56.

Monarch parents tried as best they could to protect their children from any injuries. For example, the Spanish royal family dressed their two boys in cotton-lined suits; even the trees in the park where children usually played were wrapped in felt. Nicholas II and his family were also forced to take precautions, surrounding themselves with a narrow circle of people initiated into the secret of the disease, and isolating themselves from the outside world with a high iron grille that surrounded the palace park in Tsarskoe Selo. However, this could not protect the prince from bruises and abrasions, and the parents simply fell into despair, realizing that they were constantly living on the brink of disaster.

Many years ago.

The hereditary nature of the disease, transmitted through the maternal line, was indirectly indicated in the Talmud, a set of religious treatises of Judaism, where the following was literally written: “If one mother has two children who die from circumcision, then her third son is free from this circumcision - it doesn’t matter whether he comes from the same father or from another.” And this is not surprising, since the religious rite of circumcision, so important for adherents of Orthodox Judaism, is associated with minor bleeding. Consequently, the Talmud recommended against exposing children who might have a hereditary bleeding disorder to this risk. Until the end of the 19th century, the cause of this strange disease remained unclear. Doctors tried to explain it either by the abnormal development of the walls of blood vessels, which allegedly became too thin, or by hypertension, or by defects in the structure of red blood cells, or by the influence of the pituitary gland.

First pointed out the real reason disease in 1861, Professor Schmidt of the University of Dorpat, creating the enzymatic theory of familial bleeding. Later, his assumptions were confirmed: it turned out that the blood plasma of patients lacks some proteins that are present in healthy people.

Why and how does blood clot?

It is known that blood clotting is a protective reaction of the body. Blood released from the vessels should normally clot within 3-4 minutes. In this case, the blood changes from a liquid state to a jelly-like state. A clot forms, clogging the damaged vessel and stopping the bleeding. In patients with hemophilia, this mechanism of thrombus formation is impaired. The main cells responsible for blood clotting are platelets. When breaking blood vessel the cells with which it is lined from the inside are damaged. Beneath the lining lie long fibers of the main connective tissue protein, collagen, to which platelets are able to adhere. Strong attachment of platelets to the wound surface leads to several important consequences. Firstly, a peculiar ring of microtubules is compressed inside the attached platelet, as a result of which the shape of the cell changes and numerous outgrowths appear on its surface, which helps to secure the platelet in the wound. Secondly, proteins appear on its surface, which are needed for the attachment of new platelets. Figuratively speaking, platelets that have penetrated the wound give a signal: “Here, to us! Needed here emergency help! From platelets rushing to help, they begin to be released biologically active substance- hormone serotonin. Under its influence, due to the contraction of smooth muscles, it begins vascular reaction- local contraction of the lumens of blood vessels (spasm). Finally, platelets adhered to the wound release a substance that stimulates the division of smooth muscle cells. It’s also clear - the edges of the tear must be tightened with the help of muscles.

If a capillary turns out to be damaged, often a pile of platelets “piled” on the damaged site is quite enough to close the rupture site. If the damage is more large vessel, the mechanism of fibrin plug formation is activated. It happens like this. Platelets attached to the wound release a special substance - a contact factor, which triggers a cascade of interactions between various proteins involved in the formation of a blood clot.

The main protein necessary for the formation of a blood clot is fibrinogen. Fibrin monomers resemble Lego blocks, from which you can easily build a long beam. Fibrinogen is a soluble blood plasma protein belonging to the group of globulins, one of the blood clotting factors. Under the action of the enzyme thrombin, it can be converted into fibrin.

The resulting polymer fibrin threads are stabilized by a special protein fibrinase. Thus, a real patch of densely intertwined fibrin threads appears in the wound, which neutralize thrombin. If this did not happen, thrombin could clot all the blood in the body.

It is clear that the fibrin plug cannot exist indefinitely. Quite soon, endothelial cells (a single layer of flat cells lining the inner surface of blood and lymphatic vessels) and smooth muscle cells close the resulting gap in the vessel wall, and then the clot begins to interfere with the restored blood flow. Therefore, it must be removed, and this is done by another participant in the process - the enzyme fibrinolysin. Under its influence, the fibrin thrombus begins to disintegrate and soon disappears completely.

Who has hemophilia?

Hemophilia is passed from parents to children. But it has one interesting feature: only men suffer from hemophilia, and only women pass it on by inheritance. For example, a sick father passes hemophilia to his daughter, who will not have it. external signs disease, but she will pass it on to her son, in whom hemophilia will manifest itself in full. However, those who think: this misfortune never happened in the family - and never will - are mistaken. Alas, this is not always the case. Trouble can come to any family. It has been proven that some patients received hemophilia not by inheritance, but as a result of the so-called sporadic gene mutation - for example, when foreign genetic information of a viral nature is introduced into the hereditary material of the body. Officially, there are 6.5 thousand registered patients with hemophilia in Russia, but in fact, according to doctors, there may be 1.5-2 times more of them.

A severe form of hemophilia can usually manifest itself already in the first year of life - with extensive bruising and an unusual appearance. long bleeding. Lightweight and medium shape often first appear during surgical operations, even such as tooth extraction, in the form of prolonged bleeding.

Even a bruise, which in a healthy person will manifest itself as a bruise at worst, can have a bruise in a hemophiliac patient. severe consequences. Entire “lakes” of blood can form under the skin, inside the skin, between the muscles. And if the knee is bruised, blood can flow into the joint cavity, which leads to limitation and even complete loss mobility, deformation, pain, so a person with hemophilia must be especially careful in everyday life.

Diagnostics

Early identification of a hemophilia carrier is based, first of all, on analysis of the family genealogical tree, measurement of the ratio of coagulant activity of blood factors VIII and IX, von Willebrand factor, as well as DNA analysis. DNA diagnosis is the most accurate, but not always informative. Possible prenatal diagnosis when performing chorionic villus biopsy at 9-11 weeks of pregnancy or puncture amniotic sac at the 12-15th week of fetal development, as well as DNA extraction from fetal cells for its appropriate analysis. Diagnosis of hemophilia A immediately after birth is based on the failure to detect normal factor VIII coagulant activity in the suspected newborn from whom blood is taken from a vein. Diagnosing hemophilia B, or factor IX deficiency, is more difficult because any newborn has low levels of factor IX activity. Low level factor IX can be detected in a newborn up to 6 months, even if the child does not have hemophilia. Puncture of the arteries, jugular, femoral and ulnar veins, as well as circumcision, are contraindicated until the patient has an appropriate factor level.

To clarify the diagnosis of hemophilia, laboratory diagnostics. During the examination, a series of blood tests are performed, the results of which determine the state of the coagulation system.

Manifestations of the disease

Most often, the first manifestations of bleeding in patients with hemophilia develop at the time when the child begins to walk and is exposed to domestic injuries. For some, the first signs of hemophilia appear already in the newborn period, for example in the form of bruises on the body ( subcutaneous hematomas). During breastfeeding Life-threatening bleeding usually does not occur. This can be explained by the fact that human milk contains substances that for the time being prevent the disease from manifesting itself. In general, children with hemophilia are characterized by fragility, pale skin and poorly developed subcutaneous fat layer.

In newborns with hemophilia, extensive cephalohematomas (head hematomas), subcutaneous and intradermal hemorrhages in the buttocks and perineum, late bleeding from a tied umbilical cord in the first 24 hours after birth, and a little later (after 5-7 months) can also easily form. bleeding during teething.

In sick children 1.5-2 years old, even minor injuries are accompanied by bruises on the forehead, limbs, buttocks, and teething, biting the tongue and mucous membrane of the cheeks, injections are accompanied by prolonged, sometimes multi-day (up to 2-3 weeks) bleeding. Hemorrhages in the joints are often observed. Subcutaneous, intermuscular hematomas are extensive, tend to spread, resemble tumors in appearance, and are accompanied by “blooming” (blue color - blue-violet - brown - golden). They also take a very long time to dissolve - within 2 months.

Treatment and prevention

Hemophilia cannot be completely eliminated, but the quality of life of a patient who is constantly receiving treatment does not suffer. Without treatment, hemophilia leads to permanent disability and quite often to premature death. Even at the beginning of the 20th century, the life expectancy of a hemophilia patient was short. Today, with special treatment, a patient with hemophilia can live as long as healthy man. Patients with hemophilia are treated by a hematologist. Currently, a number of drugs are produced that can restore blood clotting in patients with hemophilia. Most of these drugs are dried blood concentrates from healthy people. Treatment with factor concentrates helps maintain the required level of blood clotting. The Russian drug industry uses domestic donor plasma and cryoprecipitate, which are semi-finished products for the production of blood clotting concentrates. They are administered intravenously. Currently, attempts are being made to launch the production of drugs against hemophilia using genetic engineering methods using stem cells.

Treatment for hemophilia also involves injecting the patient's deficient blood clotting factor directly into the patient's vein. Therapy can either prevent bleeding or reduce its consequences, and try to prevent the development of complications. Bleeding stops when enough clotting factor reaches the injured area. If treatment is carried out on early stage, the likelihood of continued bleeding is sharply reduced. If treatment is delayed, bleeding continues and spreads, causing more severe tissue damage, which in turn increases the likelihood of subsequent bleeding. The frequency of use is individual and depends on the severity of the disease and the frequency of exacerbations.

Unfortunately, the disease has not yet been defeated. Treatment for hemophilia is currently available mainly to patients living in developed countries, where highly effective and virus-safe concentrates of blood clotting factors are used. IN Russian Federation There is currently no technology to produce blood products that meet imported analogues. In Russia, the Hematological Department deals with hemophilia problems. science Center RAMS, which has created a special department for outpatient care for patients suffering from hemophilia, with round-the-clock mobile teams. If you need Additional Information relative to existing diagnostic capabilities, contact your nearest hemophilia treatment center or hemophilia community organization where there are appropriate specialists. The concept of comprehensive care in hemophilia treatment centers is an art approach to the treatment of this disease, where the patient's condition is assessed by a multidisciplinary team, which usually consists of a hematologist, orthopedist, nutritionist, infectious disease specialist, social worker, physiotherapist, dentist, rehabilitation specialist, psychologist and genetic consultant. This staff develops a coordinated plan of care for the patient and expects that the plan will be accepted by the patient's local pediatrician.

Hemophilia is considered one of the most expensive diseases in the world, since drugs made from human donor plasma. It is important for patients with hemophilia to know and remember that drugs such as ACETYLSALICYLIC ACID (ASPIRIN), BRUFEN, INDOMETHACIN, butazolidines, ANALGIN are strictly contraindicated for them. Such drugs have the ability to thin the blood and further increase the likelihood of bleeding. For cuts and injuries, a patient with hemophilia immediately requires first aid; the wounds should be cleared of clots and washed with an antibiotic solution. Then apply gauze soaked in one of the hemostatic agents (adrenaline, hydrogen peroxide) and hemostatic sponges. It is also possible to use breast milk and human and animal blood serum. A bleeding wound must be well packed, that is, closed and clamped. And of course, in such cases you should immediately go to the hospital! The next stage of treatment is blood transfusion. Small doses are usually sufficient to stop bleeding. With significant blood loss, the doses of blood transfused increase. Since intramuscular and subcutaneous injections form hematomas; for patients with hemophilia, medications are administered intravenously.

If your child has hemophilia...

• Tell your doctor immediately if your child is injured, even minor. Injuries to the head, neck or abdomen are especially dangerous. If your child is about to surgery or tooth extraction, talk to your doctor about the necessary measures.
• Watch your child carefully, do not miss such signs of extensive internal bleeding such as severe pain (including in the abdomen), swelling of a joint or muscle, limitation of joint movements, blood in the urine, tarry stool and severe headache.
• Since the child is receiving infusions of blood components, there is a risk of contracting hepatitis. The first signs of infection may appear from 3 weeks to 6 months after the child received blood components. Symptoms of the disease: headache, elevated temperature, poor appetite, nausea, vomiting, abdominal pain and pain in the liver (in the hypochondrium and in the center of the abdomen, change in the color of urine darkening) and stool (light gray), jaundice skin and sclera.
• Never give your child ASPIRIN, as it can cause bleeding, as well as drugs such as BRUFEN, INDOMETHACIN, butazolidines, ANALGIN. In any case, before giving your child a new drug, consult your doctor!
• If you have daughters, go to a specialized medical center to check if they are carriers of hemophilia. Sick male family members need psychological help.
• Make sure your child always wears a medical identification bracelet - this is information about the disease and blood type that can come in handy at any moment. It should be in such patients so that emergency conditions Any person providing assistance to such a patient for the first time will find it easier to navigate the situation. Any person with hemophilia should have this information.
• Teach your child to brush their teeth regularly and thoroughly. soft brushes. Avoid tooth extraction.
• Protect your child from injury, but do not impose unnecessary restrictions that would delay his development. Sew padded knee and elbow pads into his clothing to protect his joints in case of falls. Older children should not play contact or traumatic sports (such as football), but they can, for example, swim or play golf.
• Apply cold compresses and ice to the affected area, and lightly to bleeding areas. pressure bandages. To prevent the bleeding from returning, limit your child's activities for 48 hours after the bleeding has stopped. Elevate the injured body part.
• To avoid frequent hospitalizations, you should learn how to administer blood components with clotting factors. Do not hesitate to administer clotting factor concentrate if bleeding begins. Keep the concentrate ready at all times, even while on vacation.
• Make sure your child is regularly examined by a hematologist.
• If bleeding begins, seek medical help immediately!

Hemophilia is a very dangerous diseases. It still leads to high mortality. Therefore, the most important preventive measure- medical and genetic counseling for those getting married. It is not recommended to have children when a hemophilia patient and a woman who is a carrier of hemophilia are married. In a healthy married woman

with a patient with hemophilia, at 14-16 weeks of pregnancy special method transabdominal amniocentesis (puncture of the amniotic sac through the anterior abdominal wall and the wall of the uterus in order to obtain amniotic fluid for research) the sex of the fetus is determined. If the disease is detected, in order to avoid the birth of a sick child, termination of pregnancy is recommended.

For most ignorant people, hemophilia is a so-called royal disease; they know about it only from history: they say, Tsarevich Alexei suffered from it. Due to lack of knowledge, people often believe that ordinary people cannot have hemophilia. There is an opinion that it affects only ancient births. For a long time the same attitude was towards “aristocratic” gout. However, if gout is a nutritional disease, and any person can now be susceptible to it, then hemophilia is a hereditary disease, and any child whose ancestors had such a disease can get it.

What is hemophilia?

The disease is popularly called " liquid blood" Indeed, its composition is pathological, and therefore its ability to coagulate is impaired. The slightest scratch and the bleeding is difficult to stop. However, the internal ones, occurring in the joints, stomach, and kidneys, are much more severe. Hemorrhages in them can be caused even without outside influence and carry dangerous consequences.

Twelve special proteins are responsible for this and must be present in the blood in a certain concentration. The disease hemophilia is diagnosed if one of these proteins is completely absent or present in insufficient concentration.

Types of hemophilia

In medicine, there are three types of this disease.

1. Hemophilia A. Caused by the absence or deficiency of VIII. The most common type of disease accounts for, according to statistics, 85 percent of all cases of the disease. On average, one baby out of 10 thousand turns out to be sick with just such hemophilia.
2. Hemophilia B. With it, there are problems with factor number IX. It is noted as much rarer: the risk of getting it is six times lower than in the case of option A.
3. Hemophilia C. Factor number XI is missing. This variety is unique: it is characteristic of both men and women. Moreover, most often Ashkenazi Jews get sick (which is generally uncharacteristic of any illness: they are usually international and are equally “attentive” to all races, nationalities and nationalities). Manifestations of hemophilia C also stand out from the general clinical picture, therefore last years it has been removed from the list of hemophilias.

It is worth noting that in a third of families this disease occurs (or is diagnosed) for the first time, which becomes a blow for unprepared parents.

Why does the disease occur?

Its culprit is the congenital hemophilia gene, which is located on the X chromosome. Its carrier is a woman, and she herself is not sick, except that frequent nosebleeds may be observed, too heavy menstruation or slower healing small wounds (for example, after the gene is recessive, so not everyone whose mother is a carrier of the disease gets sick. Usually the probability is distributed 50:50. It increases if the father is also sick in the family. Girls become carriers of the gene in mandatory.

Why hemophilia is a male disease

As already mentioned, the hemophilia gene is recessive and is attached to a chromosome designated X. Women have two such chromosomes. If one is affected by such a gene, it turns out to be weaker and is suppressed by the second, dominant one, as a result of which the girl remains only a carrier through which hemophilia is transmitted, but she herself remains healthy. It is likely that at conception both X chromosomes may contain the corresponding gene. However, when the fetus forms its own circulatory system(and this happens in the fourth week of pregnancy) it becomes unviable, and spontaneous abortion (miscarriage) occurs. Since this phenomenon may be caused for various reasons, usually no studies are carried out on self-abortion material, so there are no statistics on this issue.

Another thing is men. They do not have a second X chromosome, it is replaced by a Y. There is no dominant “X”, so if the recessive one manifests itself, then it is the course of the disease that begins, and not its latent state. However, since there are still two chromosomes, the probability of such a plot development is exactly half the chance.

Symptoms of hemophilia

They can appear already at the birth of a child, if the corresponding factor is practically absent in the child’s body, or they can make themselves felt only over time, if there is a deficiency of it.

1. Bleeding in the absence obvious reasons. Often a child is born with bleeding from the nose, eyes, or navel, and it is difficult to stop the bleeding.
2. Hemophilia (photos demonstrate this) manifests itself by the formation of large, edematous hematomas from an absolutely insignificant impact (for example, pressing with a finger).
3. Repeated bleeding from a seemingly healed wound.
4. Increased everyday bleeding: nasal, from the gums, even when brushing your teeth.
5. Hemorrhages in the joints.
6. Traces of blood in urine and feces.

However, such “signs” do not necessarily indicate hemophilia. For example, nosebleeds may indicate weakness in the walls of blood vessels, blood in the urine may indicate kidney disease, and blood in the feces may indicate an ulcer. Therefore, additional research is required.

Detection of hemophilia

In addition to studying the patient's medical history and examining him with the most by different specialists are carried out lab tests. First of all, the presence of all coagulation factors in the blood and their concentration are determined. The time it took for the blood sample to clot is determined. Often these analyzes are accompanied by DNA testing. For more accurate diagnosis may need to be defined:

• thrombin time;
• mixed;
• prothrombin index;
• amount of fibrinogen.

Sometimes more highly specialized data is also requested. It is clear that not every hospital is equipped with the appropriate equipment, so with suspicion of hemophilia they are sent to a blood laboratory.

The disease that accompanies hemophilia (photo)

What is most characteristic of hemophilia is joint bleeding. Medical name- hemoarthrosis. It develops quite quickly, although it is most common in patients with severe forms of hemophilia. They have hemorrhages in the joints without any external influence, spontaneously. In mild forms, trauma is required to provoke hemoarthrosis. The joints affected primarily are those that experience stress, that is, the knee, hip and foot joints. The second in line are the shoulder ones, followed by the elbows. The first symptoms of hemoarthrosis appear in eight-year-old children. Due to joint lesions, most patients become disabled.

Vulnerable organ: kidneys

Hemophilia often causes blood to appear in the urine. This is called hematuria; may be painless, although the symptom still remains alarming. In approximately half of the cases, hematuria is accompanied by acute, prolonged pain. Not uncommon renal colic caused by blood clots pushing through the ureters. Pyelonephritis is most common in patients with hemophilia, followed by hydronephrosis in frequency of occurrence, and last place occupies capillary sclerosis. Treatment for everyone kidney diseases complicated by certain restrictions on medications: They cannot use anything that thins the blood.

Treatment of hemophilia

Unfortunately, hemophilia is incurable disease, which accompanies a person throughout his life. A way has not yet been invented to force the body to produce the necessary proteins if it does not know how to do this from birth. However, achievements modern medicine allow you to maintain the body at a level at which patients with hemophilia, especially in a not very severe form, can lead an almost normal existence. To prevent hematomas and bleeding, regular infusions of solutions of missing coagulation factors are required. They are isolated from the blood of human donors and animals raised for donation. The administration of drugs has a permanent basis as prophylaxis and therapeutic in case of upcoming operation or injury.

In parallel, patients with hemophilia must constantly undergo physical therapy to maintain joint function. In case of hematomas that are too extensive and become dangerous, surgeons perform operations to remove them.

Since transfusions of drugs made from donor blood are required, hemophilia disease increases the risk of contracting viral hepatitis, herpes and - worst of all - HIV. Without a doubt, all donors are checked for the safety of using their blood, but no one can give guarantees.

Acquired hemophilia

In most cases, hemophilia is inherited. However, there are certain statistics of cases when it manifested itself in adults who had not previously suffered from it. Fortunately, such cases are extremely rare - one or two people in a million. Most get the disease when they are over 60 years of age. In all cases, acquired hemophilia is type A. It is noteworthy that the reasons why it appeared were identified in less than half of the patients. Among them cancerous tumors, taking certain medications, autoimmune diseases, very rarely - pathological, with a severe course. Doctors were unable to determine why the others fell ill.

Victorian disease

The first case of an acquired disease is described using the example of Queen Victoria. For a long time it was considered the only one of its kind, since neither before nor for almost half a century after it, hemophilia had not been observed in women. However, in the twentieth century, with the advent of statistics on the acquisition of the royal disease, the queen cannot be considered unique: hemophilia that appeared after birth is non-hereditary and does not depend on the gender of the patient.