Hemophilia and color blindness are inherited as traits. Hemophilia and color blindness

(haemophilia) - a hereditary pathology from the group of coagulopathy, leading to a violation of the synthesis of VIII, IX or XI factors responsible for blood clotting, ending in its insufficiency. The disease is characterized by an increased tendency to both spontaneous and cause hemorrhages: intraperitoneal and intramuscular hematomas, intraarticular (hemarthrosis), bleeding of the digestive tract, inability to coagulate blood with various even minor injuries of the skin.

The disease is relevant in pediatrics, as it is detected in young children, more often in the first year of a baby's life.

The history of the appearance of hemophilia goes deep into antiquity. In those days, it was widespread in society, especially in the royal families of both Europe and Russia. Entire dynasties of crowned males suffered from hemophilia. This is where the terms " crowned hemophilia" And " royal disease».

Examples are well known - Queen Victoria of England suffered from hemophilia, who passed it on to her descendants. Her great-great-grandson was the Russian Tsarevich Alexei Nikolaevich, the son of Emperor Nicholas II, who inherited the “royal illness”.

Etiology and genetics

The causes of the disease are associated with mutations in the gene that is linked to the X chromosome. As a result, there is no antihemophilic globulin and there is a deficiency of a number of other plasma factors that are part of active thromboplastin.

Hemophilia has a recessive type of inheritance, that is, it is transmitted through the female line, but only men get sick with it. Women also have a damaged gene, but they do not get sick, but act only as its carrier, passing on the pathology to their sons.

The appearance of healthy or diseased offspring depends on the genotype of the parents. If the husband is healthy in marriage, and the wife is a carrier, then they have a 50/50 chance of having both healthy and hemophiliac sons. And daughters have a 50% chance of getting the defective gene. In a man suffering from a disease and having a genotype with a mutated gene, and a healthy woman, daughters carrying the gene and completely healthy sons are born. Girls with congenital hemophilia may come from a carrier mother and an affected father. Such cases are very rare, but still occur.

Hereditary hemophilia is detected in 70% of cases of the total number of patients, the remaining 30% account for the detection of sporadic forms of the disease associated with a mutation in the locus. Subsequently, such a spontaneous form becomes hereditary.

Classification

ICD-10 hemophilia code - D 66.0, D67.0, D68.1

Types of hemophilia differ depending on the lack of one or another factor contributing to hemostasis:

Hemophilia type A(classic). It is characterized by a recessive mutation of the F8 gene on the X chromosome. This is the most common type of the disease, occurring in 85% of patients, characterized by congenital deficiency of antihemophilic globulin, leading to a failure in the formation of active thrombokinase.

Christmas sickness or hemophilia type B is associated with a deficiency of factor IX, otherwise called the Christmas factor, the plasma component of thromboplastin, which is also involved in the formation of thrombokinase. This type of disease is detected in no more than 13% of patients.

Rosenthal disease or hemophilia type C(acquired) is distinguished by an autosomal recessive or dominant type of inheritance. In this type, factor XI is defective. It is diagnosed only in 1-2% of the total number of patients.

Concomitant hemophilia- a very rare form with a simultaneous lack of VIII and IX factors.

Hemophilia types A and B are found exclusively in men, type C - in both sexes.

Other varieties, such as hypoproconvertinemia, are very rare, accounting for no more than 0.5% of all patients with hemophilia.

Clinical manifestations

The severity of the clinical course does not depend on the type of disease, but is determined by the level of the deficient antihemophilic factor. There are several forms:

Easy, characterized by the factor level from 5 to 15%. The debut of the disease usually falls on school years, in rare cases after 20 years, and is associated with surgery or injuries. Bleeding is rare and non-intense.

Medium. With a concentration of antihemophilic factor up to 6% of the norm. Appears at preschool age in the form of a moderately pronounced hemorrhagic syndrome, aggravated up to 3 times a year.

heavy exhibited at a concentration of the missing factor up to 3% of the norm. Accompanied by severe hemorrhagic syndrome from early childhood. A newborn baby has prolonged bleeding from the umbilical cord, melena, cephalohematoma. With the development of the child - post-traumatic or spontaneous hemorrhages in the muscles, internal organs, joints. There may be long-term bleeding from eruption or change of milk teeth.

Hidden (latent) the form. With a factor indicator exceeding 15% of the norm.

subclinical. The antihemophilic factor does not decrease below 16-35%.

In young children, bleeding can occur from biting the lips, cheeks, tongue. After infections (chickenpox, influenza, SARS, measles), exacerbations of hemorrhagic diathesis are possible. Due to frequent and prolonged bleeding, thrombocytopenia and anemia of various types and severity are detected.

Characteristic signs of hemophilia:

Hemarthrosis - profuse bleeding into the joints. According to the purity of hemorrhages, they account for 70 to 80%. The ankles, elbows, knees are most often affected, less often the hip, shoulder and small joints of the fingers and toes. After the first hemorrhages in the synovial capsules, the blood gradually resolves without any complications, the function of the joint is fully restored. Repeated bleeding leads to incomplete resorption, the formation of fibrinous clots deposited in the joint capsule and cartilage with their gradual germination by connective tissue. It is manifested by severe pain and limitation of movement in the joint. Recurrent hemarthroses cause obliteration, ankylosis of the joints, hemophilic osteoarthritis and chronic synovitis.

Bleeding into the bone tissue ends with bone decalcification and aseptic necrosis.

Hemorrhages in the muscles and subcutaneous tissue (from 10 to 20%). The blood poured into the muscles or intermuscular spaces does not clot for a long time, therefore it easily penetrates into the fascia and nearby tissues. Clinic of subcutaneous and intramuscular hematomas - poorly absorbed bruises of various sizes. As complications, gangrene or paralysis is possible, appearing as a result of compression of large arteries or peripheral nerve trunks by volumetric hematomas. This is accompanied by severe pain syndrome.

Statistics
On the territory of Russia there are about 15 thousand men with hemophilia, of which about 6 thousand are children. In the world, more than 400 thousand people live with this disease.

Prolonged bleeding from the mucous gums, nose, mouth, different parts of the stomach or intestines, as well as from the kidneys. The frequency of occurrence is up to 8% of the total number of all bleeding. Any medical manipulations or operations, whether it be tooth extraction, tonsillectomy, intramuscular injection or vaccination, end with profuse and prolonged bleeding. Extremely dangerous bleeding from the mucous membrane of the larynx and pharynx, as this can result in airway obstruction.

Hemorrhages in different parts of the brain and meninges lead to disorders of the nervous system and the corresponding symptoms, often ending in the death of the patient.

Hematuria spontaneous or due to trauma to the lumbar. Found in 15-20% of cases. Symptoms and disorders preceding it - urination disorders, pyelonephritis, hydronephrosis, pyeloectasia. Patients pay attention to the appearance of blood in the urine.

Hemorrhagic syndrome is characterized by delayed onset of bleeding. Depending on the intensity of the injury, it may occur after 6-12 hours or later.

Acquired hemophilia is accompanied by a violation of color perception (color blindness). It occurs rarely in childhood, only with myeloproliferative and autoimmune diseases, when antibodies to factors begin to be produced. Only in 40% of patients it is possible to identify the causes of acquired hemophilia, these include pregnancy, autoimmune diseases, taking certain medications, and malignant neoplasms.

If the above manifestations appear, a person should contact a specialized center for the treatment of hemophilia, where he will be prescribed an examination and, if necessary, treatment.

Diagnostics

At the stage of pregnancy planning, future parents can undergo medical genetic counseling with molecular genetic testing and collection of genealogical data.

Perinatal diagnosis consists of amniocentesis or chorin biopsy followed by a DNA study of the obtained cellular material.

The diagnosis is established after a detailed examination and differential diagnosis of the patient.

Mandatory physical examination with examination, auscultation, palpation, collection of family history to identify possible inheritance.

Laboratory studies of hemostasis:

Coagulogram;
- quantitative determination of factors IX and VIII;
- definition of INR - international normalized ratio;
- a blood test to calculate the amount of fibrinogen;
- thromboelastography;
- thrombodynamics;
- prothrombin index;
- calculation of APTT (activated partial thromboplastin time).

The appearance of hemarthrosis in a person requires an x-ray of the affected joint, and hematuria requires an additional study of urine and kidney function. Ultrasound diagnostics is performed for retroperitoneal hemorrhages and hematomas in the fascia of internal organs. If cerebral hemorrhage is suspected, CT or MRI is mandatory.

Differential diagnosis is carried out with Glanzmann's thrombasthenia, thrombocytopenic purpura, von Willebrand's disease, and thrombocytopathy.

Treatment

The disease is incurable, but amenable to hemostatic replacement therapy with concentrates of missing factors. The dose of the concentrate is selected depending on the degree of its deficiency, the severity of hemophilia, the type and severity of bleeding.

It is important to start treatment at the first bleeding. This helps to avoid many complications that require surgical intervention.

Treatment consists of two components - permanent supportive or prophylactic and immediate, with manifestations of hemorrhagic syndrome. Supportive treatment consists of periodic self-administration of antihemophilic factor concentrate. The task of doctors is to prevent the occurrence of arthropathy and bleeding in various parts of the body. In severe hemophilia, the frequency of administration reaches 2-3 times a week for prophylactic treatment and up to 2 times a day for the main one.

The basis of treatment is antihemophilic drugs, blood transfusions and its components.

Hemostatic therapy for hemophilia type A involves the use of cryoprecipitate, an antihemophilic globulin concentrate made from fresh frozen human plasma.
Hemophilia type B is treated by IV administration of PPSB, a complex preparation that includes several factors, including prothrombin, proconvertin, and a component of plasma thromboplastin. In addition, fresh frozen donor plasma is administered.
For hemophilia type C, fresh frozen dry plasma is used.

Symptomatic treatment consists of the appointment of glucocorticoids, angioprotectors. Complemented by physiotherapy. First aid for external bleeding includes local application of a hemostatic sponge, treatment of the wound with thrombin, and the application of a temporary pressure bandage.

As a result of intensive substitution transfusion therapy, an inhibitory form of hemophilia occurs, characterized by the appearance of inhibitors to clotting factors that neutralize the antihemophilic factor administered to the patient, leading to the futility of treatment. The situation is saved by plasmapheresis and the appointment of immunosuppressants.

In case of hemorrhage in the joint, rest is recommended for 3-5 days, non-steroidal anti-inflammatory drugs in tablets and glucocorticoids locally. Surgical treatment is indicated for irreversible dysfunction of the joint, its destruction.

Alternative Treatment

In addition to drug treatment, patients can be treated with traditional medicine. Prevention of bleeding can be carried out with the help of herbs that have an astringent property that helps strengthen the walls of blood vessels. These include yarrow, grape seed extract, blueberries, stinging nettle.

To improve blood coagulation, the following medicinal plants are taken: arnica, coriander, astragalus, dandelion root, Japanese Sophora fruit, and others.

Complications

Complications are divided into groups.

associated with hemorrhages:

a) intestinal obstruction or compression of the ureters by extensive hematomas;
b) deformities of the musculoskeletal system - muscle hypotrophy, cartilage usuration, curvature of the pelvis or spinal column, as a complication of hemophilic osteoarthritis;
c) infection with hematomas;
d) airway obstruction.

Related to the immune system- the appearance of inhibitors of factors that impede treatment.

They are more at risk of contracting HIV infection, herpetic and cytomegalovirus infection and viral hepatitis.

Prevention

There is no specific prevention. Only drug prophylaxis is possible, preventing the occurrence of bleeding. When entering into marriage and planning a pregnancy, it is important to undergo medical genetic counseling with all the necessary examinations.

Forecast

With a mild form, the prognosis is favorable. When severe, it worsens significantly. In general, it depends on the type, severity, timeliness of treatment and its effectiveness. The patient is registered, given disability.

How many live with different types of hemophilia? The mild form does not affect the life expectancy of the patient. Effective and permanent treatment for moderate and severe forms helps the patient live as long as healthy people live. Death occurs in most cases after hemorrhages in the brain.

Any science has its own specific vocabulary, which is quite difficult for an uninitiated person to understand. A vivid confirmation of this is genetics - one of the most difficult sections of biology. Many people have an idea that genes are present in the sex chromosomes of the human body. They not only determine the signs of the sex of a woman and a man, but also affect other features of the functioning of the body. Scientists managed to find out this pattern in the study of a number of diseases. In particular, it was found that such rare diseases as hemophilia and color blindness are recessive traits that carry certain genetic information. In this case, the recessive gene is linked to the X chromosome. Before explaining the essence of this process, it is necessary to make a small explanation. Male cells contain one Y-chromosome, which determines the sex of the male organism, is responsible for the formation of spermatozoa, and one X-chromosome. Female cells contain only two (sometimes three) X chromosomes.

Hemophilia

This disease, which mainly affects men, is a very dangerous pathology. With hemophilia, a person's blood loses its ability to clot. Even a minor wound or small cut in such people can lead to prolonged bleeding. A large loss of blood is a mortal threat to human life. The problem lies in the X chromosome. The gene contained in it can be dominant, which determines blood clotting, or recessive, which does not allow blood to clot normally.

Some women have a recessive gene in one of the X chromosomes, but they do not even suspect that they are its carriers. On the other X chromosome, the dominant gene works as it should, so the blood clots normally. But if a defective gene is found in a man, it is dangerous. After all, men only have one X chromosome. At the same time, a man can receive a recessive gene exclusively from his mother, respectively, a son cannot inherit hemophilia from his father. In general, a woman with hemophilia is an extremely rare occurrence.

As an example, it is worth mentioning Tsarevich Alexei, who suffered from hemophilia, the son of Nicholas II, the last Russian Tsar. He inherited the recessive gene from his mother. It is assumed that Empress Alexandra Feodorovna received the hemophilia gene from her grandmother, Queen Victoria of England, who, according to historians, was its bearer.

color blindness

Another well-known disease is color blindness - color blindness. The development of this pathology occurs according to a similar scenario and is also associated with the presence of a defective gene on the X chromosome. Therefore, in this case, only women are carriers of the recessive gene. A non-colorblind man and a carrier woman have an equal chance of having both a colorblind son and a healthy boy.

In the opposite situation (a healthy mother and a color-blind father), only their daughter can inherit the recessive gene, and you don’t have to worry about the health of your son. And the highest probability of having a daughter with abnormal color perception (more than 50%) occurs when the parents of the unborn child are a couple of a color-blind man and a carrier woman. Indeed, in this case, along with the maternal gene for color blindness, the girl additionally receives a defective paternal X chromosome.

Genes located on the sex chromosomes determine the characteristics that are called sex-linked. This applies not only to hemophilia and color blindness. In particular, as many as 267 traits are transmitted through the X chromosome to humans. Examples are rickets, which cannot be cured with vitamin D, or the birth of a person with brown tooth enamel.

Certainly, genetics is the science of the future. Perhaps someday people will learn how to penetrate a person's hereditary apparatus, be able to protect it from the negative effects of the environment, and even eliminate or replace defective genes. But for this it is necessary to solve many not only scientific, but also moral and ethical problems.

Hemophilia is a blood disease that belongs to the group of hereditary coagulopathy or diathesis. The prevalence of recorded pathology in the world is 1 case per 10 thousand male population. In Russia, there are 7.5 thousand patients with hemophilia, but, according to the statements of public organizations involved in providing care to patients, mild forms are simply not registered, there should be about 12 thousand people who fell ill.

Popular opinion among the people is that a patient with hemophilia can die suddenly from heavy bleeding that cannot be stopped. This is not true and is generated by rumors. However, the risk of death from hemorrhagic stroke, indeed, exceeds the average, since the vulnerability of cerebral vessels is high.

Disability of patients with hemophilia occurs at a young age from extensive hemorrhages in the joints and muscles, followed by the development of contractures.

Causes

The causes of hemophilia are well understood. Characteristic changes of one gene in the X-chromosome were found. It has been established that it is this site that is responsible for the production of the necessary coagulation factors, specific protein compounds.

Each section of the chromosome is responsible for a specific function, mutations cause hereditary diseases

The hemophilia gene does not occur on the Y chromosome. This means that it goes to the fetus from the mother's body. An important feature is the possibility of clinical manifestations only in males.

The hereditary mechanism of transmission of the disease is called "linked" in the family with sex. Similarly, color blindness (loss of the function of distinguishing colors), the absence of sweat glands are transmitted. Scientists tried to answer the question of in which generation the gene mutation occurred by examining the mothers of boys with hemophilia.

It turned out that from 15 to 25% of mothers did not have the necessary damage to the X chromosome. This indicates the occurrence of a primary mutation (sporadic cases) during the formation of the embryo and means the possibility of hemophilia without aggravated heredity. In subsequent generations, the disease will be transmitted as a family.

The specific reason for the change in the genotype of the child has not been identified.

Chances of inheriting the altered gene

70% of hemophilia cases are considered hereditary. Genetic changes are inherited by a recessive type (the dominant type indicates the disease of both parents and the mandatory transmission to children). The role of a woman as a carrier of a mutation is reduced to the transmission of the disease to her sons. A born girl can be a carrier, but not get sick herself.

The probability of having a sick boy in a couple consisting of a healthy man and a carrier mother is 50:50. Rare cases of the disease occur in girls born to a father with hemophilia and a healthy mother. Usually from such a marriage one can expect healthy sons or daughters carrying the changed gene.

Hemophilia in women (girls) is a very rare occurrence. To do this, the child must be born from a father with hemophilia and a carrier mother. In world practice, only 60 similar diseases have been described. The success of modern medicine in prolonging the life of patients suggests an increase in the identification of sick girls in the coming years.

Why is hemophilia called the "royal disease"?

The emergence of the name "royal disease" pathology is obliged to the British Queen Victoria. It was she who served as the ancestor of the altered gene in her children and grandchildren. At the same time, historical evidence of the possibility of Victoria's paternity and mother's connections was checked.

One of Britain's favorite queens had a large and friendly family

Clinical manifestations of hemophilia were found in Victoria's son Leopold, Duke of Albany. Further inheritance went on a recessive basis through daughters and granddaughters. One of the factors that increase the likelihood of the disease is considered to be closely related marriages between cousins in the royal families of Europe.

Thus, the mutating gene went through the Empress Alexander to Tsarevich Alexei Nikolaevich, the son of the last Russian monarch.

Types of hemophilia

Blood clotting is one of the protective reactions of the body against wounds and possible blood loss. In addition to platelets, fibrinogen, actively involved in the formation of blood clots in the vessels, plasma factors are important. They are endowed with the ability to balance the processes of coagulation and anticoagulability as necessary.

Deficiency of one of the necessary factors leads to disruption of the entire system. Hemophilia is directly related to the lack of factors VIII, IX, responsible for the formation of thromboplastin in the first phase of coagulation.

Depending on the type of disorders in the coagulation system caused by mutating regions (loci) of the X chromosome, there are 3 variants of the disease:

Type A - caused by a lack of antihemophilic globulin (factor VIII), which disrupts the synthesis of thrombokinase. The most typical form. It affects up to 85% of patients. The severity is due to bleeding in injuries, operations occurring against the background of a decrease in the concentration of the factor to 5–20% of the normal level.

Type B (Christmas disease) - associated with a lack of synthesis of factor IX, which is responsible for the creation of a secondary coagulating plug in the vessel and the synthesis of thrombokinase, up to 13% of patients are ill.

Type C - occurs in 2% of patients, unlike the previous ones, transmission according to the dominant type is possible, both men and women are ill. Deficiency of factor XI responsible for thromboplastin was revealed. There is a national susceptibility: more characteristic of Ashkenazi Jews. Since the clinical manifestations differ significantly from the classical ones, it was decided to exclude this subspecies from the modern classification.

Up to 0.5% of cases are other types of hemostasis disorders.

Classification according to the severity of the current

The severity of the course of the disease is affected by the degree of deficiency of the listed factors that cause the loss of blood clotting ability. There are degrees:

mild - the concentration of the factor is 6% or more, usually detected at school age, bleeding is rare, low intensity, occurs during injuries, during surgery, during tooth extraction;

moderate - the level of factors ranges from 1 to 5% of the norm, usually the symptoms of hemophilia are detected in the preschool years, moderately pronounced hemorrhagic manifestations (hemorrhages in the joint bags, muscles) are characteristic, erythrocytes are found in the urine test;

severe - the level of deficiency is below 1%, pronounced hemorrhagic manifestations develop already in early childhood, widespread hematomas on the head, increased bleeding from the umbilical cord, black stools (chalk), hematomas occur without any connection with injury, bleeding of the gums during teething is characteristic, the change of dairy to indigenous, hemorrhages in the internal organs are possible.

Clinical signs

For symptoms of hemophilia types A and B are typical:

various hematomas (in the muscles, under the skin, under the muscular fascia, in the retroperitoneal space) are more often associated with a small bruise, every fifth patient has it, they are distinguished by an extensive distribution zone, if the internal nerve trunk or artery is compressed, severe pain appears;

bleeding - from cuts, the hole of the extracted tooth, gums, after surgical interventions, injuries, a delayed character is characteristic (bleeding does not occur immediately after the injury, but after 6-8 hours);

the occurrence of hemarthrosis (70–80% of cases);

hematuria - renal bleeding, detected by the admixture of blood in the urine (from 14 to 20% of cases), occurs spontaneously or after a bruise of the lower back, may be accompanied by attacks of renal colic, leads to hydronephrosis, chronic pyelonephritis;

intestinal bleeding - manifested in 8% of patients with severe hemophilia in the form of a "black" liquid stool, severe dizziness, weakness, can be provoked by taking medications (steroids, analgesics);

hemorrhage in the mesentery - causes an attack of acute pain in the abdomen, cannot be distinguished from appendicitis and peritonitis, sometimes similar to the clinic of acute intestinal obstruction;

hemorrhagic strokes - accompany up to 5% of patients, often occur at a young age, the clinic depends on the localization of the focus.

With hemarthrosis in a child, after a bruise, the joint swells, sharp pains appear, redness of the skin over the affected area, the joint is hot to the touch. In the case of repeated hemorrhages (relapses), chronic inflammation of the joint capsule (synovitis) occurs, which causes osteoarthritis (fusion of the articular surfaces) and changes in the shape of the limb, its length. In the future, the patient may have a curvature of the spinal column, pelvic bones, deformity of the feet and hands, muscle atrophy. This becomes the main cause of disability in childhood.

Diagnostic features

Specialists of different profiles should take part in the diagnosis of the disease: neonatologists in the maternity ward, pediatricians, therapists, hematologists, geneticists. When unclear symptoms or complications appear, consultations of a gastroenterologist, neurologist, orthopedist, surgeon, ENT doctor and other specialists are involved.

The signs identified in the newborn should be confirmed by laboratory methods for the study of coagulability.

Determine the changed parameters of the coagulogram:

clotting and recalcification time;
thrombin time;
activated partial thromboplastin time (APTT);
specific tests for thrombin potential, prothrombin time are carried out.

Diagnosis includes the study of:

thromboelastogram;
carrying out genetic analysis for the level of D-dimer.

Diagnostic value has a decrease in the level of indicators to half the norm or more.

Hemarthrosis must be examined using x-rays. Hematomas with suspected retroperitoneal localization or inside parenchymal organs require ultrasound examination. To detect diseases and damage to the kidneys, a urine test and ultrasound are done.

Hemophilia is treated with replacement therapy. It is impossible to save the patient from the pathology, it is necessary to add or introduce deficient coagulation factors into the patient's body with the help of drugs.

The required dosage depends on the degree of insufficiency, the type and severity of the course of the disease. The need to increase the dose arises in the development of antibodies to the replacement protein complexes.

prophylaxis during periods without signs of hemorrhagic syndrome;
treatment during hemorrhagic manifestations.

Preventive treatment of hemophilia is reduced to the introduction of clotting factors in a maintenance dosage 2-3 times a week. All surgical interventions, including tooth extraction, are carried out "under the guise" of an additional dosage of factors. This helps to prevent the development of joint damage and other hemorrhages.

A mild degree of hemophilia can be seen with small stabbing wounds.

If hemorrhages are manifested by minor external bleeding (cuts, nosebleeds), it is shown:

use of a hemostatic sponge;

treatment of the wound surface with thrombin;

pressure bandage;

local cold;

in case of injury to the limb, ensuring rest with an auxiliary splint.

In the future, the appointment of UHF, light massage, electrophoresis, physiotherapy exercises is required to maintain joint mobility.

In nutrition, you should follow a diet enriched with vitamins C, A, B, D, phosphorus and calcium salts.

In the case of severe bleeding, repeated injections of drugs-substitutes for clotting factors are required.

And. They are obtained from donated human blood or artificially from animal material. Apply fresh frozen plasma, hemostatics, erythromass.

Standard scheme for different types of hemophilia:

A - fresh plasma is needed, a special antihemophilic type of plasma, cryoprecipitate;

B - enough fresh frozen donor plasma, concentrated factor IX;

With - it is possible to be limited only to fresh frozen dry plasma.

When antibodies are formed, plasmapheresis, immunosuppressants are indicated.

All patients receive symptomatic treatment depending on the clinic (for example, anti-inflammatory drugs).

Genetic scientists are developing measures to influence the altered genome of a sick person. So far, only animal experiments have been carried out. Efficiency was obtained using the enzymatic base of adeno-associated viruses. As it turned out, they are able to remove the mutating part of the hemophilia gene and replace it with a healthy one.

The prognosis of life for current hemophiliacs is favorable with constant compliance with the conditions of therapy. Their average life expectancy is the same as that of healthy people.

Frequent transfusions of blood components increase the risk of infection with hepatitis, HIV, herpes, and cytomegalovirus infection. The prognosis worsens with severe rebleeding, untreated.

A healthy woman married to a hemophilic man may have a carrier daughter and pass the disease on to her grandson

How to find out about the possibility of transmitting pathology to children?

Genetic consultations work with spouses who want to have a child. You can pass an interview and examination at the stage of pregnancy planning. Experts analyze known genealogical data. It is impossible to plan the birth of a healthy baby in advance.

During pregnancy, carriage is detected by chorion biopsy using amniocentesis (tissue sampling). The fetus can be diagnosed with hemophilia from the eighth week of pregnancy.

Large perinatal centers accumulate experience in in vitro fertilization after special processing of the material.

Many public organizations have been created around the world that protect patients and explain their problems to the population. Hemophilia Day is held annually on April 17th. Its task is to involve officials from the medical field in the daily difficulties of patients.

3. Sex-linked inheritance. Hemophilia. color blindness

Traits inherited through the X- and Y-chromosomes are called sex-linked. In humans, traits inherited through the Y chromosome can only be in males, and those inherited through the X chromosome can be in individuals of both one and the other sex. A female can be either homozygous or heterozygous for genes located on the X chromosome. And the recessive alleles of her genes appear only in the homozygous state. Since males have only one X chromosome, all genes localized in it, even recessive ones, immediately appear in the phenotype. Such an organism is often called homozygous.

In humans, some pathological conditions are sex-linked. These include, for example, hemophilia. The allele of the gene that controls normal blood clotting (H) and its allele pair, the hemophilia h gene, are located on the X chromosome. The H allele is dominant, the h allele is recessive, so if a woman is heterozygous for this gene (XHXh), she does not develop hemophilia. A man has only one X chromosome. Therefore, if he has the H allele on the X chromosome, then it manifests itself.

If the X chromosome of a man has the allele h, then the man suffers from hemophilia: the X chromosome does not carry the genes that determine the mechanisms of normal blood clotting.

Naturally, the recessive allele of hemophilia in a heterozygous state is found in women even for several generations, until it again appears in any of the males. A woman with hemophilia can only be born from the marriage of a woman heterozygous for hemophilia to a man with hemophilia. Due to the rarity of this disease, this combination is unlikely.

Similarly, color blindness is inherited, that is, such an anomaly of vision when a person confuses colors, most often red with green. Normal color perception is due to a dominant allele located on the X chromosome. Its recessive allelic pair in the homo- and heterozygous state leads to the development of color blindness.

From this it is clear why color blindness is more common in men than in women: men have only one X chromosome, and if it contains a recessive allele that determines color blindness, it necessarily manifests itself. A woman has two X chromosomes: she can be either heterozygous or homozygous for this gene, but in the latter case she will suffer from color blindness.

Anomaly Inheritance Types

Autosomal recessive type of inheritance - when the anomaly is caused by one recessive gene localized in the autosome. Autosomal recessive mutant genes show their visible effect only in the homozygous state, when the animal receives it from each of the parents. The frequency of recessive anomalies increases in populations where inbreeding is used.

It is possible to reliably determine the type of inheritance of many mutations only if the structure and function of the gene in which it occurred is known. Fortunately, genetic research is progressing quite rapidly, and the first laboratories for the genetic diagnosis of diseases have already appeared. However, for a number of mutations, the type of inheritance is fairly well known.

Anomaly Inheritance Types

Determining the type of inheritance of anomalies is important in order to develop breeding methods for their prevention in offspring. The type of inheritance of anomalies is usually determined on the basis of an analysis of pedigrees, in which information about the nature of the anomalies should be recorded. There are three types of inheritance of anomalies: autosomal recessive, autosomal dominant and sex-linked.

With an autosomal recessive type of inheritance, the anomaly is determined by a recessive gene localized in autosomes. This is the most common type of inheritance, which manifests itself to the same extent in males and females. With an autosomal recessive type of inheritance, abnormal offspring usually appear in healthy parents. When we begin to analyze the pedigree, it turns out that such an anomaly was once encountered in the descendants of both parents or their common ancestor.

With an autosomal dominant type of inheritance, the anomaly is due to a dominant gene localized in the autosome. Traits due to dominant genes, as a rule, appear in a homo- and heterozygous state; with a dominant type of inheritance, there is no skipping of generations; each anomalous child has an anomalous parent. Moreover, with this type of inheritance, the anomaly usually occurs in one half of the pedigree.

With a sex-linked type of inheritance, the anomaly manifests itself, as a rule, in individuals of the same sex. This is due to the localization of the mutant gene on the X chromosome. An example of sex-linked inheritance is hemophilia and color blindness in humans.

inheritance rule autosomal recessive traits:

1) offspring with abnormal traits are born from phenotypically normal but heterozygous parents with a frequency of 3:1.

2) all parents of abnormal animals - heterozygous - carriers of the recessive mutant gene.

3) if one of the parents is abnormal and the other is normal, then the offspring will be normal.

4) anomalies with the same frequency appear in females.

Autosomal dominant type of inheritance - manifests itself in the heterozygous state. It is typical for him:

1) direct inheritance by generation. The anomaly is passed from generation to generation without gaps.

2) each anomalous child has an anomalous parent.

3) the probability of the birth of an abnormal offspring, if one of the parents is abnormal, is 50%.

4) manifests itself in males and females, because the gene is located on the autosome. X-linked type of inheritance - genes located on the X chromosome can show a dominant and recessive effect.

It is typical for him:

1) from abnormal fathers, all daughters will be abnormal, and sons will be normal.

2) descendants will be abnormal only when one of the parents has this trait.

3) anomalies appear in every generation. If the mother has anomalies, then the probability of having an abnormal offspring is 50%, regardless of gender.

4) males and females are affected.

Hemophilia(haemophilia) - a hereditary pathology from the group of coagulopathy, leading to a violation of the synthesis of VIII, IX or XI factors responsible for blood clotting, ending in its insufficiency. The disease is characterized by an increased tendency to both spontaneous and cause hemorrhages: intraperitoneal and intramuscular hematomas, intraarticular (hemarthrosis), bleeding of the digestive tract, inability to coagulate blood with various even minor injuries of the skin.

The disease is relevant in pediatrics, as it is detected in young children, more often in the first year of a baby's life.

Etiology and genetics

Classification

ICD-10 hemophilia code - D 66.0, D67.0, D68.1

Types of hemophilia differ depending on the lack of one or another factor contributing to hemostasis:

Concomitant hemophilia- a very rare form with a simultaneous lack of VIII and IX factors.

Hemophilia types A and B are found exclusively in men, type C - in both sexes.

Other varieties, such as hypoproconvertinemia, are very rare, accounting for no more than 0.5% of all patients with hemophilia.

Clinical manifestations

The severity of the clinical course does not depend on the type of disease, but is determined by the level of the deficient antihemophilic factor. There are several forms:

Easy. characterized by a factor level of 5 to 15%. The debut of the disease usually falls on school years, in rare cases after 20 years, and is associated with surgery or injuries. Bleeding is rare and non-intense.

Medium. With a concentration of antihemophilic factor up to 6% of the norm. Appears at preschool age in the form of a moderately pronounced hemorrhagic syndrome, aggravated up to 3 times a year.

Hidden (latent) the form. With a factor indicator exceeding 15% of the norm.

subclinical. The antihemophilic factor does not decrease below 16-35%.

Characteristic signs of hemophilia:

Bleeding into the bone tissue ends with bone decalcification and aseptic necrosis.

Statistics

On the territory of Russia there are about 15 thousand men with hemophilia, of which about 6 thousand are children. In the world, more than 400 thousand people live with this disease.

Hemorrhages in different parts of the brain and meninges lead to disorders of the nervous system and the corresponding symptoms, often ending in the death of the patient.

Hemorrhagic syndrome is characterized by delayed onset of bleeding. Depending on the intensity of the injury, it may occur after 6-12 hours or later.

If the above manifestations appear, a person should contact a specialized center for the treatment of hemophilia, where he will be prescribed an examination and, if necessary, treatment.

Diagnostics

At the stage of pregnancy planning, future parents can undergo medical genetic counseling with molecular genetic testing and collection of genealogical data.

Perinatal diagnosis consists of amniocentesis or chorin biopsy followed by a DNA study of the obtained cellular material.

The diagnosis is established after a detailed examination and differential diagnosis of the patient.

Mandatory physical examination with examination, auscultation, palpation, collection of family history to identify possible inheritance.

Laboratory studies of hemostasis:

- coagulogram;

— quantitative determination of factors IX and VIII;

- definition of INR - international normalized ratio;

- a blood test to calculate the amount of fibrinogen;

- thromboelastography;

- thrombodynamics;

- prothrombin index;

- calculation of APTT (activated partial thromboplastin time).

Differential diagnosis is carried out with Glanzmann's thrombasthenia, thrombocytopenic purpura, von Willebrand's disease, and thrombocytopathy.

Treatment

The disease is incurable, but amenable to replacement hemostatic therapy with concentrates of missing factors. The dose of the concentrate is selected depending on the degree of its deficiency, the severity of hemophilia, the type and severity of bleeding.

It is important to start treatment at the first bleeding. This helps to avoid many complications that require surgical intervention.

The basis of treatment is antihemophilic drugs, blood transfusions and its components.

Hemostatic therapy for hemophilia type A involves the use of cryoprecipitate, an antihemophilic globulin concentrate made from fresh frozen human plasma.

Hemophilia type B is treated by IV administration of PPSB, a complex preparation that includes several factors, including prothrombin, proconvertin, and a component of plasma thromboplastin. In addition, fresh frozen donor plasma is administered.

For hemophilia type C, fresh frozen dry plasma is used.

Alternative Treatment

To improve blood coagulation, the following medicinal plants are taken: arnica, coriander, astragalus, dandelion root, Japanese Sophora fruit, and others.

Complications

Complications are divided into groups.

associated with hemorrhages.

a) intestinal obstruction or compression of the ureters by extensive hematomas;

b) deformities of the musculoskeletal system - muscle hypotrophy, cartilage usuration, curvature of the pelvis or spinal column, as a complication of hemophilic osteoarthritis;

c) infection with hematomas;

d) airway obstruction.

Related to the immune system- the appearance of inhibitors of factors that impede treatment.

They are more at risk of contracting HIV infection, herpetic and cytomegalovirus infection and viral hepatitis.