FS.3.2.0003.15 Human blood coagulation factor VIII. Plasma clotting factors

The level of VIII factor of blood coagulation from 0 to 1% causes extremely severe form diseases, from 1 to 2% - severe, from 2 to 5% - moderate, above 5% - light form, but with the danger of severe and even fatal bleeding from injuries and surgical interventions Oh.

Among all possible manifestations hemophilia in the first place are hemorrhages in the large joints of the extremities (hip, knee, ankle, shoulder and elbow), deep subcutaneous, intermuscular and intramuscular hemorrhages, abundant and prolonged bleeding with injuries, the appearance of blood in the urine. Other bleeding is somewhat less common, including such severe and dangerous ones as retroperitoneal hemorrhages, hemorrhages in organs abdominal cavity, gastrointestinal bleeding, intracranial hemorrhage (strokes).

With hemophilia, one can quite clearly trace the progression of all manifestations of the disease as the child grows, and later on as an adult. At birth, more or less extensive hemorrhages under the periosteum of the skull bones, subcutaneous and intradermal hemorrhages, late bleeding from the umbilical cord. Sometimes the disease is detected at the first intramuscular injection, which can cause a large, life-threatening intramuscular hematoma. Teething is often accompanied by not very heavy bleeding. In the first years of life, there are often bleeding from the oral mucosa associated with trauma to various sharp objects. When a child learns to walk, falls and bruises are often accompanied by profuse nosebleeds and hematomas on the head. Hemorrhages in the orbit, as well as postorbital hematomas, can lead to loss of vision. In a child who has begun to crawl, hemorrhages in the buttocks are typical. Then, hemorrhages in the large joints of the limbs come to the fore. They appear the earlier, the more severe the hemophilia is. The first hemorrhages predispose to repeated outpourings of blood in the same joints. Everyone has it individual person, suffering from hemophilia, with particular persistence and frequency of hemorrhages, 1-3 joints are affected. Most commonly affected knee joints, followed by ankle, elbow and hip. Hemorrhages in the small joints of the hands and feet (less than 1% of all lesions) and joints between the vertebrae are relatively rare. In each person, depending on the age and severity of the disease, from 1-2 to 8-12 joints are affected.

It is necessary to distinguish between acute hemarthrosis (primary and recurrent), chronic hemorrhagic-destructive osteoarthritis (arthropathy), secondary immune rheumatoid syndrome as a complication of the underlying process.

Acute hemarthrosis is manifested as sudden appearance(often after a minor injury) or a sharp increase in joint pain. The joint is often enlarged, the skin over it is red, hot to the touch. After the first transfusion of blood components, the pain quickly (within a few hours) decreases, and with the simultaneous removal of blood from the joint, it disappears almost immediately.

IV stages of joint damage are distinguished. In I, or early, stage, the volume of the joint may be increased as a result of hemorrhage. In the "cold" period, the function of the joint is not impaired, but with x-ray examination determine characteristics defeat. In stage II, the progression of the process is noted, which is revealed according to the data x-rays. In stage III, the joint sharply increases in size, deforms, often uneven and bumpy to the touch, pronounced hypotrophy of the muscles of the affected leg is determined. The mobility of the affected joints is more or less limited, which is associated both with damage to the joint itself and with changes in muscles and tendons. In this stage, pronounced osteoporosis is formed, fractures inside the joints easily occur. AT femur crater- or tunnel-like destruction of the bone substance, typical for hemophilia, is noted. The patella is partially destroyed. Intra-articular cartilages are destroyed, mobile fragments of these cartilages are found in the joint cavity. Various kinds of subluxations and displacements of bones are possible. In stage IV, the function of the joint is almost completely lost. Joint fractures are possible. With age, the severity and prevalence of damage to the articular apparatus progresses and becomes more severe when hematomas occur around pathologically altered joints.

Secondary rheumatoid syndrome (Barkagan-Egorova syndrome) is a common form of joint damage in patients with hemophilia. For the first time, this syndrome was described in 1969. In many cases, it is viewed by doctors, since it occurs against the background of already existing hemarthrosis and destructive processes characteristic of hemophilia in the joints. Secondary rheumatoid syndrome is accompanied by a chronic inflammatory process (often symmetrical) in the small joints of the hands and feet, which were not previously affected by hemorrhages. Subsequently, as the process progresses, these joints undergo a typical deformation. AT large joints periodically appears strong pain, you can note the pronounced morning stiffness in the joints. Regardless of the appearance of new hemorrhages, the articular process is steadily progressing. At this moment, a blood test reveals the appearance or a sharp increase in the existing laboratory signs inflammatory process, including immunological ones.

In most people with hemophilia, the syndrome appears over the age of 10-14 years. By the age of 20, its frequency reaches 5.9%, and by 30 - up to 13% of all cases of the disease. With age, the prevalence and severity of all joint lesions are steadily progressing, which leads to disability, forcing the use of crutches, wheelchairs and other devices. The progression of joint damage depends on the frequency of acute hemorrhages, the timeliness and usefulness of their treatment (it is very important to conduct an early transfusion of blood and its components), the quality of orthopedic care, correct application physical therapy, physiotherapeutic and balneological effects, choice of profession and a number of other circumstances. All of these issues are currently extremely relevant, as life expectancy in hemophilia has increased dramatically due to the success of corrective treatment.

Extensive and intense subcutaneous, intermuscular, subfascial and retroperitoneal hematomas are very difficult and dangerous. Gradually increasing, they can reach enormous sizes, contain from 0.5 to 3 liters of blood or more, lead to the development of anemia, cause compression and destruction of the surrounding tissues and the vessels that feed them, necrosis. For example, retroperitoneal hematomas often completely destroy large areas pelvic bones(the diameter of the destruction zone can reach 15 cm or more), hematomas on the legs and arms destroy tubular bones, calcaneus. Doom bone tissue leads to the formation of hemorrhages under the periosteum. The process of such bone destruction on radiographs is often mistaken for a tumor process. Often, calcium salts are deposited in hematomas, which sometimes leads to the formation of new bones, which can close the joints and completely immobilize them.

Many hematomas, putting pressure on the nerve trunks or muscles, cause paralysis, sensory disturbances, and rapidly progressive muscle atrophy. Particularly dangerous are extensive hemorrhages in the soft tissues of the submandibular region, neck, pharynx and pharynx. These hemorrhages cause narrowing of the upper respiratory tract and suffocation.

serious problem with hemophilia, they create profuse and persistent renal bleeding, observed in 14-30% of people with this blood disease. These bleedings can occur both spontaneously and in connection with injuries of the lumbar region associated with pyelonephritis. In addition, renal bleeding may occur due to increased excretion calcium in the urine due to bone destruction in hemophilia. The appearance or intensification of such bleeding can be facilitated by taking analgesics (acetylsalicylic acid, etc.), massive blood and plasma transfusions, which leads to additional damage to the kidneys. Renal bleeding is often preceded by prolonged excretion of blood particles in the urine, which can only be detected when laboratory research.

The appearance of blood in the urine is often accompanied by severe urination disorders, as well as a change in the amount of urine excreted (there may be both an increase in its daily volume and a decrease), attacks of renal colic due to the formation of blood clots in the urinary tract. These phenomena are especially intense and pronounced during treatment, when normal condition blood. The cessation of excretion of blood in the urine is often preceded by renal colic, and often a temporary absence of urine output with the appearance of signs of intoxication of the body with toxic metabolic products.

Renal bleeding periodically recurs, which over the years can lead to severe dystrophic-destructive changes in this organ, secondary infection and death from development kidney failure.

Gastrointestinal bleeding in hemophilia, they can be spontaneous, but more often they are caused by taking acetylsalicylic acid(aspirin), butadione and other drugs. The second source of bleeding are obvious or latent gastric ulcers or duodenum, as well as erosive gastritis of various origins. However, diffuse capillary bleeding without any destructive changes in the mucous membrane. These bleedings are called diapedetic. When they appear, the intestinal wall is saturated with blood for a long time, which quickly leads to coma as a result of severe anemia, fainting due to sharp decline blood pressure and death. The mechanism of development of such bleeding remains unclear to date.

Hemorrhages in the abdominal organs mimic various acute surgical diseases - acute appendicitis, intestinal obstruction and etc.

Hemorrhages in the brain and spinal cord and their membranes in hemophilia are almost always associated either with injuries or with the use of drugs that disrupt the function of platelets, which are directly involved in blood clotting. Between the moment of injury and the development of hemorrhage there may be a light interval lasting from 1-2 hours to a day.

characteristic feature hemophilia are prolonged bleeding during injuries and operations. lacerations much more dangerous than linear breaks. Bleeding often does not occur immediately after injury, but after 1-5 hours.

Removal of the tonsils in hemophilia is much more dangerous than abdominal surgery.

Extraction of teeth, especially molars, is often accompanied by many days of bleeding not only from the tooth sockets, but also from hematomas formed at the site of tissue infiltration with novocaine, which leads to the development of anemia. These hematomas cause destruction of the jaw. With hemophilia, teeth are removed against the background of the action of antihemophilic drugs under general anesthesia. Extraction of several teeth is best done at once.

Part of the complications in hemophilia is due to blood loss, compression and destruction of tissues by hematomas, infection of hematomas. large group complications are also associated with immune disorders. The most dangerous of them is the appearance in the blood in in large numbers immune inhibitors ("blockers") factor VIII blood coagulation (or IX), transforming hemophilia into the so-called inhibitory form, in which the main method of treatment - transfusion therapy (transfusion of blood or its components) - almost completely loses its effectiveness. Moreover, repeated administration of antihemophilic drugs often causes a rapid increase in the amount of inhibitor in the blood, as a result of which the transfusion of blood and its components, which initially had some effect, soon becomes useless. The frequency of the inhibitory form of hemophilia, according to different authors, ranges from 1 to 20%, more often from 5 to 15%. With inhibitory forms, platelet function is noticeably impaired, hemorrhages in the joints and excretion of blood in the urine become more frequent, joint damage is significantly higher.

The main method of treatment and prevention of bleeding and hemorrhage of any localization and any origin in hemophilia is the intravenous administration of sufficient doses of blood products containing factor VIII. Factor VIII is variable and practically not preserved in canned blood, natural and dry plasma. For substitution treatment only direct blood transfusions from a donor and blood products with preserved coagulation factor VIII are suitable. Direct blood transfusions from a donor are resorted to only when the doctor does not have any other antihemophilic drugs. Big mistake is a blood transfusion from the mother, as she is a carrier of the disease, and the level of factor VIII in her blood is sharply reduced. In view of short period life of factor VIII in the blood of the recipient (about 6-8 hours), blood transfusions, as well as transfusions of antihemophilic plasma, should be repeated at least 3 times a day. Such blood and plasma transfusions are unsuitable for stopping massive bleeding and reliable cover for various surgical interventions.

An equal volume of antihemophilic plasma is approximately 3-4 times more effective than fresh banked blood. A daily dose of 30-50 ml / kg of body weight of antihemophilic plasma allows for some time to maintain a 10-15% level of factor VIII. The main danger such treatment is an overload of circulatory volume, which can lead to the development of pulmonary edema. The use of antihemophilic plasma in a concentrated form does not change the situation, since a high concentration of the injected protein causes an intensive movement of fluid from the tissues into the blood, as a result of which the volume of circulating blood increases in the same way as when plasma is infused in a normal dilution. Concentrated dry antihemophilic plasma has only the advantage that it contains more concentrated factor VIII of blood coagulation, and in a small volume it is more quickly introduced into the bloodstream. Dry antihemophilic plasma is diluted with distilled water before use. Treatment with antihemophilic plasma is sufficient to stop most acute hemorrhages in the joints (except the most severe ones), as well as to prevent and treat minor bleeding.

The most reliable and effective in hemophilia concentrates of factor VIII of blood coagulation. The most accessible of them is cryoprecipitate. It is a protein concentrate released from plasma by cooling (cryoprecipitation), which contains enough coagulation factors, but few proteins. Low content proteins allows you to enter the drug into the bloodstream in a very large quantities and increase the concentration of factor VIII to 100% or more without fear of circulatory overload and pulmonary edema. Cryoprecipitate must be stored at -20°C, which makes it difficult to transport. When thawed, the drug quickly loses its activity. Dry cryoprecipitate and modern concentrates of factor VIII of blood coagulation are deprived of these shortcomings. They can be stored in a regular refrigerator. Excessive administration of cryoprecipitate is undesirable, since it creates a high concentration of coagulation factors in the blood, as a result of which microcirculation in the organs is disturbed and there is a risk of blood clots and the development of DIC.

All antihemophilic drugs are administered intravenously only by stream, in the most concentrated form and as soon as possible after they are reopened without mixing with other solutions for intravenous administration. One of the main reasons for failure replacement therapy consists in the drip administration of blood products, which does not lead to an increase in the level of coagulation factor VIII in plasma. Until a stable stop of bleeding, you can not use any blood substitutes and blood products that do not contain antihemophilic factors, as this leads to a dilution of factor VIII and a decrease in its concentration in serum.

In case of acute hemorrhages in the joints, temporary (no more than 3-5 days) immobilization (immobilization) of the affected limb in a physiological position, heating of the affected joint (compresses), but not cooling is necessary. early removal the blood poured into the joint not only immediately eliminates pain syndrome, prevents further blood clotting in the joint, but also reduces the risk of development and rapid progression of osteoarthritis. To prevent and treat secondary inflammatory changes after removal of blood, 40-60 mg of hydrocortisone is injected into the joint cavity. Supportive transfusion therapy, given during the first 3-6 days, prevents further bleeding and allows early initiation of exercise therapy, which contributes to faster and full recovery function of the affected limb, prevents muscle atrophy. It is better to develop movements in the affected joint in stages. In the first 5-7 days after removing the bandage, active movements are performed both in the affected joint and in other joints of the limb, gradually increasing the frequency and duration of exercises. From the 6-9th day, they switch to "load" exercises, using bicycle ergometers, pedal gates for hands, elastic traction. From the 11-13th day, in order to eliminate residual stiffness and limit maximum flexion or extension, passive load exercises are performed with caution. Simultaneously with the 5-7th day, physiotherapy is prescribed - hydrocortisone electrophoresis, anodic galvanization.

With hemorrhages in soft tissues, more intensive treatment with antihemophilic drugs is carried out than with hemorrhages in the joints. With the development of anemia, intravenous infusions of erythrocyte mass are additionally prescribed. If there are signs of infection of the hematoma, then antibiotics are immediately prescribed. a wide range actions. Any intramuscular injections for hemophilia are contraindicated, as they can cause extensive hematomas and pseudotumors. Penicillin and its semi-synthetic analogues are also undesirable, since in large doses they increase bleeding.

Early and intensive treatment with antihemophilic drugs contributes to the rapid regression of hematomas. Encapsulated hematomas are removed, if possible, surgically along with the capsule.

External bleeding from damaged skin, nosebleeds and bleeding from wounds in oral cavity they are stopped both by transfusion therapy and by local influences - by treating the bleeding area with drugs that promote blood clotting. In addition, these drugs can be taken orally. Pressure bandages or sutures are applied to the wounds. Similarly, stop bleeding after tooth extraction. When removed chewing teeth a slightly more intensive transfusion therapy is carried out, and the simultaneous removal of several teeth (3-5 or more) requires the introduction of antihemophilic drugs in the first 3 days.

In case of nosebleeds, tight packing should be avoided, since after the removal of the tampons, bleeding often resumes with even greater force. A quick stop of nasal bleeding is usually provided by antihemophilic plasma and antihemophilic drugs and simultaneous irrigation of the nasal mucosa with solutions that promote blood clotting.

A serious danger is represented by renal bleeding, in which intravenous infusions of antihemophilic plasma and cryoprecipitate are ineffective.

Gastrointestinal bleeding is controlled with large doses of clotting factor concentrates. It should be remembered that gastric bleeding is often provoked by taking aspirin, brufen, indomethacin in connection with pain in the joints, toothache or headache. In patients with hemophilia, even a single dose of aspirin can cause stomach bleeding.

In the prevention and treatment of chronic osteoarthritis and other lesions of the musculoskeletal system, it is necessary to provide various ways joint protection and prevention of limb injuries. To do this, foam pads are sewn into clothes around the knee, ankle and elbow joints, and those sports that are associated with jumps, falls and bruises (including cycling and motorcycle riding) are avoided. Importance given as early as possible and full treatment acute hemorrhages in the joints and muscles, intensive year-round physiotherapy exercises. For this, there are special complexes of atraumatic exercises in water, on soft mats and load devices - bicycle ergometers, manual gates. Classes should start in preschool or junior school age, i.e., before severe disorders of the musculoskeletal system developed. Complex therapy supplement with physiotherapeutic (currents high frequency, electrophoresis of glucocorticosteroids) and balneological methods of treatment, primarily mud therapy, brine and radon baths. With frequent and stubbornly recurring hemorrhages in the same joints, X-ray therapy is performed and surgery.

Minimizing the risk of injury and cuts from early childhood is important in the prevention of hemorrhage. Easily breaking toys (including metal and plastic ones), as well as unstable and heavy objects, are excluded from everyday life. Furniture should be with rounded edges, the protruding edges are wrapped with cotton wool or foam rubber, the floor is covered with a pile carpet. Communication and games of patients with girls are preferable, but not with boys. important for the patient right choice professions and places of work.

Prevention of hemophilia has not yet been developed. Determination of the sex of the unborn child by genetic research cells obtained from amniotic fluid, allows you to terminate the pregnancy in a timely manner, but does not show whether the fetus is a carrier of the hemophilia gene. Pregnancy is preserved if the fetus is male, since all the sons of the sick are born healthy. Terminate pregnancy if the fetus is female, since all daughters of hemophilia patients are carriers of the disease.

In female conductors of hemophilia who have a 50% chance of giving birth to an affected child (if the fetus is male), or who are transmitters of hemophilia (if the fetus is female), the birth of only girls transfers the risk of having hemophilia patients in the family from the first generation to the second, at the same time increasing total number disease transmitters.

Introduced for the first time

PHARMACOPIES AUTHORIZATION

real monograph applies to human coagulation factor VIII preparations derived from human plasma for fractionation.

Human blood coagulation factor VIII is a preparation of a protein fraction of human blood containing a glycoprotein complex of blood coagulation factor VIII and, depending on the method of preparation, various amounts of von Willebrand factor.

The activity of the drug after reconstitution under the conditions indicated on the label must be at least 20 IU of factor VIII in 1 ml.

PRODUCTION

For the production of human blood coagulation factor VIII preparations, the blood plasma of healthy donors is used that meets the requirements of the FS “Human Plasma for Fractionation”. The production technology includes the stages of removal or inactivation of infectious agents. If chemical compounds are used in production to inactivate viruses, their concentration should be reduced to a level that does not affect the safety of the drug for patients. No antimicrobial preservatives are used in the manufacturing process. The drug may contain stabilizers (albumin, polysorbate, sodium chloride, sodium citrate, calcium chloride, glycine, lysine, etc.). The drug solution is aseptically packaged into primary packaging by sterilizing filtration, lyophilized and sealed under vacuum or in an inert gas atmosphere.

TESTS

Description

White or pale yellow powder or fluffy solid. The determination is carried out visually.

Authenticity

species specificity

Confirm by the presence of only human serum proteins. The test is carried out by gel immunoelectrophoresis using sera against human, bovine, equine and porcine serum proteins in accordance with. It is permissible to conduct a gel immunodiffusion test in accordance with. As a result of the test, precipitation lines with only serum against human serum proteins should be detected.

FactorVIII

Confirm by the presence of factor VIII activity. The test is carried out by the chromogenic or coagulometric method. The determination is carried out in accordance with.

Time to receive reconstituted drug

No more than 10 minutes (if normative documentation no other instructions). A description of the procedure is given, indicating the solvent used, its volume and dissolution conditions (solvent temperature, need for mixing, etc.).

Water

No more than 2%. The determination is carried out by the method of K. Fisher in accordance with (if there are no other instructions in the regulatory documentation). The method of determination and the amount of sample required for testing are indicated in the regulatory documentation.

Mechanical inclusions

Visible mechanical inclusions should be absent. The determination is carried out in accordance with. The regulatory documentation indicates the name of the solvent, describes the method of recovery and (if necessary) preparation of the drug.

pH

From 6.5 to 7.5. The determination is carried out by the potentiometric method in accordance with.

Osmolality

Not less than 240 mOsm/kg. The determination is carried out in accordance with.

Protein

The quantitative content of protein per vial or ml of the reconstituted solution is indicated in the regulatory documentation. The determination is carried out in accordance with.

coagulation factor activityVIII

The activity of blood coagulation factor VIII per vial or ml of the reconstituted solution is indicated in the regulatory documentation. The determination is carried out by the coagulometric method in accordance with.

Willebrand factor

The activity of the von Willebrand coagulation factor per vial or ml of the reconstituted solution is indicated in the regulatory documentation. The determination is carried out by the method of agglutination or enzyme immunoassay in accordance with .

Stabilizer(s)

Quantitative determination of the stabilizer(s) introduced into the preparation is carried out in accordance with and / or, if there are no other indications in the regulatory documentation.

The permissible limit of the content of the stabilizer(s) must be specified in the regulatory documentation.

Virusinactivating agents

Carry out a quantitative determination of the residual content of the virus-inactivating agent(s) in the preparation in accordance with and / or, if there are no other indications in the regulatory documentation. The permissible limit for the content of the virus-inactivating agent(s) should be specified in the regulatory documentation.

Sterility

The drug must be sterile. The test is carried out in accordance with.

Pyrogenicity or bacterial endotoxins

Must be pyrogen-free or contain bacterial endotoxins in an amount not exceeding 0.03 EU per 1 IU of blood coagulation factor VIII activity.

The test is carried out in accordance with (test dose - not less than 50 IU of blood coagulation factor VIII per 1 kg of animal weight) or in accordance with the method specified in the regulatory documentation.

Virus safety

Hepatitis B surface antigen (HBsAg)

The drug should not contain the surface antigen of the hepatitis B virus. The determination is carried out by the enzyme immunoassay using test systems approved for use in Russian healthcare practice and having a sensitivity of at least 0.1 IU/ml in accordance with the instructions for use.

Antibodies to hepatitis C virus

Antibodies to the hepatitis C virus should be absent. The determination is carried out by enzyme immunoassay using test systems approved for use in Russian healthcare practice and having 100% sensitivity and specificity in accordance with the instructions for use.

Antibodies to human immunodeficiency virus (HIV-1 and HIV-2)and HIV-1 p24 antigen

The drug should not contain antibodies to the human immunodeficiency virus (HIV-1 and HIV-2) and HIV-1 p24 antigen. The determination is carried out by enzyme immunoassay using test systems approved for use in Russian healthcare practice and having 100% sensitivity and specificity in accordance with the instructions for use.

Packageand labeling

X wound

Store in a place protected from light at a temperature of 2 to 8 ° C, unless otherwise indicated in the regulatory documentation.

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Factor VIII of blood coagulation, or, as it is also called antihemophilic globulin A, could not be isolated in its pure form for a long time due to its low concentration in the blood and its susceptibility to hydrolysis reactions.

Factor VIII is synthesized in the liver, kidneys, spleen, and in the squamous cells that line the inside blood vessels- endothelium. It has been proven that leukocytes are also involved in the production of factor VIII. Factor VIII is extremely poorly preserved in canned blood. Unlike many other coagulation factors, it does not react with aluminum hydroxide or barium sulfate and does not settle on their surface. This can be used to separate factor VIII from other clotting factors.

Antihemophilic globulin A consists of three independent partsVIIIk VIII-AG and VIII-vB, moving through the blood as subunits.

heavy hereditary disease- hemophilia, more precisely, one of its varieties (hemophilia A), is precisely associated with a deficiency in the body of factor VIII. This factor can either be completely absent in the patient's blood, or be there in an inferior mutated form, which leads to insufficient blood clotting.

The norm of factor VIII in the blood. Result interpretation (table)

The norm of factor VIII in the blood ordinary people and pregnant women:

If factor VIII is elevated, what does it mean?

There is no data.

If factor VIII is low, what does it mean?

Factor VIII deficiency is severe hereditary pathology and occurs in 1 in 10,000 male newborns. In women, hemophilia almost never appears, although the hemophilia gene is transmitted through the X chromosome. Deficiency of this factor leads to the development of a serious disease - hemophilia A. The main symptoms are extensive hemorrhages in tissues, joints and muscles.

Hemophilia can have three degrees of severity. A mild form is considered a disease in which the activity of factor VIII is reduced to 40-5%.

• At mild form the disease can practically not manifest itself in any way, violations in blood clotting are noticeable only in case of injury or surgical intervention.
• The average form of hemophilia A is a decrease in the activity of factor VIII to 5-1%.
• And a severe form - when the activity of factor VIII is 1% or less.

Bleeding often occurs spontaneously, without any provoking factors. Bleeding into the joints causes inflammation of the articular bag, destruction of the articular cartilage, its replacement connective tissue leading to complete immobility of the joint.

But the most dangerous are bleeding that occurs in spinal cord, peritoneum, pharynx, or in the brain.

In women, bleeding can occur only if the rate of factor VIII in the blood is reduced to 5% or less.

Intramuscular injections with hemophilia are unacceptable.

Approximately 20-30% of patients with hemophilia A develop antibodies to clotting factor 8

Vegetarian capsules prevent complication of hemophilia treatment in mice. September 4, 2014 American scientists have developed a strategy to prevent one of the most serious complications of hemophilia treatment. An approach that uses vegetable capsules to train the immune system to tolerate rather than attack the clotting factor 8 protein. This is encouraging research for preventing one of the most serious complications of hemophilia treatment.

Blood coagulation factor - a target for the treatment of hemophilia

Healthy people have proteins in their blood - clotting factors that help stop bleeding quickly. In patients with hemophilia, these proteins are not enough, so even small bleeding is difficult to stop. The main treatment option for people with severe hemophilia is to receive continuous injections of a blood clotting factor. However, 20 to 30% of people who receive these injections develop antibodies that are inhibitors of the blood clotting factor. Once these inhibitors are formed in patients, it becomes very difficult to treat or prevent future episodes of bleeding.

In the new study, the scientists tried to develop a strategy to prevent the formation of these antibodies. Their approach uses plant cells to teach the immune system to tolerate rather than attack the clotting factor protein. This study offers hope for preventing one of the most serious complications of hemophilia treatment.

The only modern methods treatments to form an inhibitor cost $1 million and are risky for patients. New technology uses the capsules plant-based and has the potential to be cost effective and safe alternative. This could potentially be a way to prevent the formation of antibodies.

Hemophilia A - blood clotting deficiency 8

The study of scientists was focused on, in which there is a deficiency of blood coagulation factor 8, resulting in a defect in the clotting process. Worldwide, approximately one in 7,500 men is born with this disease. After receiving an injection of factor 8, some patients develop antibodies against it. The immune system reacts to this foreign protein as an invader and attacks it.

These antibodies are known as inhibitors in hemophilia. It is due to the formation of antibodies that standard therapy is ineffective in some patients. To prevent an attack immune system coagulation factors, researchers have focused on previous studies that have shown that by exposing the immune system to individual components of a coagulation factor protein, tolerance to the entire protein can be induced. clotting factor 8 consists of a heavy chain and a light chain, each containing three regions. The scientists used the entire heavy chain and the C2 domain of the light chain.

Modified plant material prevents the formation of inhibitors

Scientists have developed a drug and biological delivery platform therapeutic agent based on genetic modification of plants. They then applied the same method to the components of the clotting factor 8 molecule. The scientists first fused the heavy strand of DNA with the cholera toxin DNA coding subunit (a protein that can cross the intestinal wall and enter the bloodstream), and then did the same with C2 DNA. They introduced fusion genes into tobacco chloroplasts such that some plants expressed heavy chain and cholera toxin proteins, while others expressed C2 and cholera toxin proteins. They then crushed the leaves of the plant and suspended them in the solution, mixed with the heavy chain and the C2 domain of the light chain.

The researchers fed the mixed preparation to hemophilia A mice twice a week for two months and compared them to mice fed unmodified plant material. Then they injected mice with an injection of blood clotting factor 8, which people with hemophilia get. As expected, in the control group of mice, high level inhibitors. In contrast, mice that received experimental plant material developed much more low levels inhibitors - an average of 7 times less!

What mechanism?

Scientists have studied certain types signaling molecules - cytokines that send messages to T-cells of the immune system. They found that mice fed the experimental plant had several cytokines associated with the suppression or regulation of immune responses. At the same time, mice in the control group showed more cytokines associated with triggering the immune response. By transferring subsets of regulatory T cells taken from mice fed the experimental plant to normal mice, the scientists were able to suppress the production of inhibitors. It is assumed that T cells are able to provide tolerance in a new population of animals.

Finally, the researchers tried to reverse the formation of the inhibitor. They fed the experimental plant material to mice that had already developed the inhibitors. Compared with the control group of mice, clotting factor 8 was formed more slowly in the group of mice that were fed plant material. In two to three months of feeding, the levels of inhibitors decreased three to seven times.

This new treatment strategy holds promise for preventing and even reversing inhibitor formation in hemophilia A patients who receive injections of factor 8. However, the scientists note that levels of factor 8 inhibitor may re-form (after a period of time if stop giving plant material to animals). With financial support from global pharmaceutical companies, scientists plan to study the effectiveness of capsules containing this plant material in clinical settings.