The association of the level of factor VIII in plasma with the severity of coagulation disorders
Level VIII of the clotting factor from 0 to 1% causes an extremely severe form of the disease, from 1 to 2% - severe, 2 to 5% - moderate, above 5% - light form, but with the risk of severe and even fatal bleeding in traumaand surgical interventions. Among all possible manifestations of hemophilia, hemorrhages to the large joints of the extremities( hip, knee, ankle, shoulder and elbow joints), deep subcutaneous, intermuscular and intramuscular hemorrhages, excessive and prolonged bleeding in trauma, and the appearance of blood in the urine are the first of all possible manifestations of hemophilia. Other bleeding is observed less frequently, including such serious and dangerous as retroperitoneal hemorrhages, hemorrhages in the abdominal organs, gastrointestinal bleeding, intracranial hemorrhages( strokes).
In hemophilia, it is possible to follow quite clearly the progression of all manifestations of the disease as the child grows up, and later an adult. At birth, there may be 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 with the first intramuscular injection, which can cause a large, life-threatening intermuscular hematoma. Teething teeth are often accompanied by not very abundant bleeding. In the first years of life, hemorrhages from the mucous membrane of the oral cavity are often associated with injury by various sharp objects. When a child learns to walk, falls and bruises are often accompanied by copious nosebleeds and bruises on the head. Hemorrhages in the orbit, as well as postorbital hematomas, can lead to loss of vision. The child who started to crawl, typical hemorrhages in the buttocks. Then the hemorrhages to the large joints of the extremities come to the fore. They appear the sooner, the heavier the hemophilia. The first hemorrhages predispose to repeated effusions of blood in the same joints. Each individual person suffering from hemophilia, with particular persistence and frequency of hemorrhages, affects 1-3 joints. The knee joints are most often affected, followed by the ankle, elbow and hip joints. Relatively rare are hemorrhages in the small joints of the hands and feet( less than 1% of all lesions) and joints between the vertebrae. Each person, depending on the age and severity of the disease, affects 1-2 to 8-12 joints.
It is necessary to distinguish acute hemarthrosis( primary and recurrent), chronic hemorrhagic-destructive osteoarthritis( arthropathy), secondary immune rheumatoid syndrome as a complication of the main process.
Acute hemarthrosis manifests as a sudden appearance( often after a minor injury) or a sharp increase in pain in the joint. The joint is often enlarged, the skin above it is red, hot to the touch. After the first transfusion of blood components, the pain quickly( within a few hours) is weakened, and with simultaneous removal of blood from the joint almost immediately passes.
IV stages of joint damage are distinguished. In I, or early, the stage of the joint may be increased as a result of hemorrhage. In the "cold" period, the function of the joint is not disrupted, but the X-ray examination determines the characteristic signs of the lesion. In the II stage there is a progression of the process, which is revealed from the data of X-ray images. In the III stage the joint sharply increases in size, deforms, is often uneven and bumpy to the touch, the expressed hypotrophy of the muscles of the affected leg is determined. The mobility of the affected joints is more or less limited, which is associated with both the involvement of the joint itself and changes in the muscles and tendons. In this stage, a pronounced osteoporosis is formed, fractures within the joints easily appear. In the femur, a typical cranial or tunnel-like destruction of bone substance is noted for haemophilia. The patella is partially destroyed. Intraarticular cartilages are destroyed, moving fragments of these cartilages are found in the joint cavity. There are various kinds of subluxations and bone displacements. In the IV stage, the function of the joint is almost completely lost. There may be fractures inside the joints. With age, the severity and prevalence of the lesion of the articular apparatus progresses and assumes a more severe character when hematomas develop 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 seen by doctors, because it occurs against the background of already existing hemarthrosis and inherent hemophilia of destructive processes in the joints. Secondary rheumatoid syndrome is accompanied by a chronic inflammatory process( often symmetrical) in the small joints of the hands and feet that were previously not affected by hemorrhages. Later, as the process progresses, these joints undergo a typical deformation. In large joints there is a strong pain periodically, it can be noted the expressed morning stiffness in the joints. Regardless of the appearance of new hemorrhages, the joint process is steadily progressing. At this point in the study of blood, there is an appearance or sharp increase in the available laboratory signs of the inflammatory process, including immunological ones.
In most people with hemophilia, the syndrome appears older than 10-14 years. By the age of 20, its frequency reaches 5.9%, and by 30 - up to 13% of all cases. With age, the prevalence and severity of all joint lesions progress steadily, which leads to disability, makes use of crutches, wheelchairs and other adaptations. 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, the correct use of physiotherapy exercises, physiotherapeutic and balneological influences, choice of profession and a number of other circumstances. Currently, all these issues are extremely relevant, as life expectancy in hemophilia has increased dramatically due to the success of corrective treatment.
Extensive and tense subcutaneous, intermuscular, subfascial and retroperitoneal hematomas are very serious and dangerous. Gradually increasing, they can reach huge sizes, contain from 0.5 to 3 liters of blood or more, lead to the development of anemia, cause compression and destruction of surrounding tissues and vessels supplying them, necrosis. For example, retroperitoneal hematomas often completely destroy large areas of pelvic bones( the diameter of the zone of destruction can reach 15 cm or more), hematomas on the legs and hands destroy tubular bones, heel bone. The death of bone tissue leads to the formation of hemorrhages under the periosteum. The process of such destruction of bones on radiographs is often taken for a tumor process. Often, calcium salts are deposited in the hematoma, which sometimes leads to the formation of new bones that can close the joints and completely immobilize them.
Many hematomas, exerting pressure on the nerve trunks or muscles, cause paralysis, impaired sensitivity, rapidly progressing muscle atrophy. Especially dangerous are extensive hemorrhages in the soft tissues of the submaxillary region, neck, throat and pharynx. These hemorrhages cause constriction of the upper respiratory tract and suffocation.
A serious problem with hemophilia is the abundant and persistent renal bleeding observed in 14-30% of individuals with this blood disease. These bleedings can occur both spontaneously, and in connection with trauma of the lumbar region, concomitant pyelonephritis. In addition, renal bleeding may occur due to increased excretion of calcium in the urine due to the destruction of bone tissue in hemophilia. The appearance or intensification of such bleeding can be facilitated by taking analgesics( acetylsalicylic acid, etc.), massive transfusions of blood and plasma, which leads to additional damage to the kidneys. Renal bleeding is often preceded by prolonged discharge of urine from the blood particles, which can be detected only in a laboratory study.
The appearance of blood in the urine is often accompanied by severe urination disorders, as well as a change in the amount of urine released( perhaps both an increase in its daily volume and a decrease), attacks of renal colic caused by the formation of blood clots in the urinary tract. Especially intense and pronounced are these phenomena in the treatment, when the normal state of the blood is temporarily restored. Termination of blood in the urine is often preceded by renal colic, and often a temporary absence of urine with the appearance of signs of intoxication with toxic products of metabolism.
Renal hemorrhages periodically recur, which over the years can lead to severe dystrophic-destructive changes in this organ, secondary infection and death from the development of renal failure.
Gastrointestinal bleeding in hemophilia can be spontaneous, but more often they are caused by the use of acetylsalicylic acid( aspirin), butadione and other drugs. The second source of bleeding is the obvious or hidden leakage of the stomach or duodenum, as well as erosive gastritis of various origin. However, sometimes diffuse capillary bleeding is noted without any destructive changes in the mucous membrane. These hemorrhages are called diapedesis. 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 a sharp decrease in blood pressure and death. The mechanism of development of such bleeding to this day remains unclear.
Hemorrhages in the abdominal cavity mimic various acute surgical diseases - acute appendicitis, intestinal obstruction, etc.
Hemorrhages in the brain and spinal cord and their membranes in hemophilia are almost always associated with injuries or with the use of drugs that disrupt the function of platelets that takedirect participation in blood clotting. Between the moment of injury and the development of a hemorrhage there can be a light interval of from 1 to 2 hours to a day.
A characteristic feature of hemophilia is prolonged bleeding in injuries and operations. Ragged wounds are much more dangerous than linear ruptures. Bleeding often occurs not immediately after an injury, but after 1-5 hours.
The removal of tonsils in hemophilia is much more dangerous than cavitary surgical interventions.
Extraction of teeth, especially molars, is often accompanied by multi-day bleeding not only from the dental holes, but also from the hematomas formed at the site of tissue infiltration with novocaine, which leads to the development of anemia. These hematomas cause destruction of the jaw. When hemophilia, the teeth are removed on the background of the action of antihemophilic drugs under general anesthesia. It is better to remove multiple teeth at the same time.
Part of complications in hemophilia is caused by blood loss, compression and destruction of tissues by hematomas, infection with hematomas. A large group of complications is also associated with immune disorders. The most dangerous of them is the appearance in the blood in a large number of immune inhibitors( "blockers") of factor VIII of blood coagulation( or IX), transforming hemophilia into a so-called inhibitory form, in which the main method of treatment is transfusion therapy( blood or blood transfusion)- almost completely loses its effectiveness. Moreover, the repeated administration of antihemophilic drugs often causes a rapid increase in the amount of inhibitor in the blood, resulting in the transfusion of blood and its components, initially giving some effect, soon becomes useless. The frequency of the inhibitory form of hemophilia, according to different authors, varies from 1 to 20%, more often from 5 to 15%.With inhibitory forms, the function of platelets is noticeably impaired, the hemorrhages in the joints and the discharge of blood in the urine are increasing, the lesion of the joints is significantly higher.
The main method of treatment and prevention of bleeding and hemorrhage of any site 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 the donor and blood preparations with preserved coagulation factor VIII are suitable. Direct blood transfusions from the donor are resorted only when the doctor does not have any other antihemophilic drugs. A gross mistake is the blood transfusion from the mother, since she is the transmitter of the disease, and the level of factor VIII in her blood is sharply reduced. Due to the short period of life of factor VIII in the blood of the recipient( about 6-8 hours), blood transfusions, like transfusions of antihemophilic plasma, should be repeated at least 3 times per day. To stop massive bleeding and reliable cover for various surgical interventions, such blood and plasma transfusions are unsuitable.
The equal volume of antihemophilic plasma is approximately 3-4 times more effective than fresh canned blood. The daily dose of 30-50 ml / kg body weight antihemofilnoy plasma allows for a while to maintain a 10-15% level of factor VIII.The main danger of such treatment is the overload of blood circulation 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 the high concentration of the injected protein causes an intensive movement of fluid from tissues to the blood, as a result of which the volume of circulating blood increases in the same way as when infusing plasma in normal dilution. Concentrated dry antihemophilic plasma has only the advantage that the factor VIII of blood coagulation is more concentrated in it, and in a small volume it is more rapidly introduced into the bloodstream. Dry antihemofilnuyu plasma before drinking diluted with distilled water. Treatment with antihemophilic plasma is quite enough to stop most acute hemorrhages in the joints( except for the most severe), and also for the prevention and treatment of small bleedings.
Concentrates of blood clotting factor VIII are most reliable and effective in hemophilia. The most accessible of them is cryoprecipitate. It is a protein concentrate extracted from the plasma by cooling( cryoprecipitation), which contains a sufficient number of clotting factors, but few proteins. The low protein content allows injecting the drug into the bloodstream in very large quantities and increasing the concentration of factor VIII to 100% or more without fear of overload of blood circulation and pulmonary edema. Cryoprecipitate must be stored at -20 ° C, which makes it difficult to transport it. When thawing, the drug quickly loses its activity. These drawbacks are devoid of dry cryoprecipitate and modern concentrates of blood coagulation factor VIII.They can be stored in a conventional refrigerator. Excessive introduction of cryoprecipitate is undesirable, since it creates a high concentration of clotting factors in the blood, as a result of which microcirculation in organs is disturbed and there is a risk of blood clots and the development of DIC syndrome.
All antihemophilic drugs are administered intravenously only in jet form, in as concentrated a form as possible and as soon as possible after they have been re-opened without mixing with other solutions for intravenous administration. One of the main reasons for the failure of substitution therapy is the drip administration of blood products, which does not lead to an increase in the level of clotting factor VIII in plasma. Until persistent bleeding stops, any blood substitutes and blood products that do not contain antihemophilic factors should not be used, as this leads to dilution of factor VIII and a decrease in serum concentrations.
In case of acute hemorrhages in the joints, temporary immobilization( immobilization) of the affected limb in physiological position is required for not more than 3-5 days, heating of the affected joint( compresses), but not cooling. Early removal of blood flowing into the joint not only immediately removes the pain syndrome, prevents further coagulation of the blood in the joint, but also reduces the threat of development and rapid progression of osteoarthritis. To prevent and treat secondary inflammatory changes after removal of blood into the joint cavity, 40-60 mg of hydrocortisone is administered. Supportive transfusion therapy, which is carried out during the first 3-6 days, prevents further bleeding and allows early initiation of physical therapy, which facilitates a more rapid and complete recovery of the function of the affected limb, prevents muscle atrophy. Movements in the affected joint are best developed step by step. In the first 5-7 days after removal of 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 the exercises. From the 6th to the 9th day they switch to "exercise" exercises, using bicycle ergometers, pedal gates for the arms, elastic thrusts. From the 11th to the 13th day, passive loading exercises are performed with caution to eliminate residual stiffness and limitations of maximum flexion or extension. At the same time, on the 5th-7th day, physiotherapy is prescribed - hydrocortisone electrophoresis, anodic galvanization.
For hemorrhages in soft tissues, treatment with antihemophilic drugs is more intensive than with joint hemorrhages. With the development of anemia, intravenous infusions of erythrocyte mass are additionally prescribed. If there are signs of hematoma infection, antibiotics of a wide spectrum of action are immediately prescribed. Any intramuscular injection with hemophilia is contraindicated, as they can cause extensive hematomas and pseudotumors. Penicillin and its semisynthetic analogues are also undesirable, since in large doses bleeding is increased.
Early and intensive treatment with antihemophilic drugs promotes rapid reverse development of hematomas. The bleeding bruises are removed, if possible, surgically with the capsule.
External bleeding from damaged skin, nosebleeds and bleeding from the wound in the oral cavity is stopped both by transfusion therapy and by local influences - treatment of the bleeding site with drugs that promote blood clotting. In addition, these drugs can be taken orally. On the wound put pressure bandages or stitches. Similarly, bleeding stops after tooth extraction. When chewing teeth are removed, a somewhat more intensive transfusion therapy is performed, and simultaneous removal of several teeth( 3-5 or more) requires the introduction of antihemophilic drugs in the first 3 days.
With nasal bleeding, tight tamponade should be avoided, as after removal of tampons, bleeding often resumes with even greater force. Rapid arrest of nasal bleeding is usually provided by antihemophilic plasma and antihemophilic drugs and simultaneous irrigation of the nasal mucosa by solutions that promote blood clotting.
Renal bleeding is a serious hazard, in which intravenous infusions of antihemophilic plasma and cryoprecipitate are ineffective.
Gastrointestinal bleeding is stopped by large doses of concentrates of coagulation factors. It should be remembered that gastric bleeding is often provoked by admission in connection with pain in the joints, dental or headache of aspirin, brufen, indomethacin. In patients with hemophilia, even a single intake of aspirin can cause gastric bleeding.
In the prevention and treatment of chronic osteoarthritis and other injuries of the musculoskeletal system, it is necessary to provide various ways to protect joints and prevent injuries to the limbs. To do this, in the clothes are sewed foam rubber shields around the knee, ankle and elbow joints, avoid those sports that are associated with jumping, falling and bruising( including riding a bicycle and a motorcycle).Important importance is given to the earliest and most valuable treatment of acute hemorrhages in joints and muscles, intensive year-round therapeutic physical training. For this, there are special complexes of atraumatic exercises in water, on soft mats and load devices - veloergometers, hand gates. Classes should be started in preschool or junior school years, that is, before severe disabilities of the musculoskeletal system developed. Complex therapy is supplemented by physiotherapeutic( high-frequency currents, electrophoresis of glucocorticosteroids) and balneological methods of treatment, primarily mud therapy, crustaceans and radon baths. With frequent and persistently repeated hemorrhages, the same joints undergo X-ray and surgical treatment.
The importance of preventing hemorrhage is minimizing the risk of injuries and cuts from early childhood. Of everyday use, easily broken toys( including metal and plastic), as well as unstable and heavy items are excluded. Furniture should be rounded edges, the exposed edges are wrapped with cotton or foam rubber, the floor is covered with a pile carpet. It is preferable to communicate and play the sick with the girls, and not with the boys. For the patient, the right choice of profession and place of work is important.
Prevention of hemophilia has not yet been developed. Determining the sex of the unborn child by genetic examination of cells derived from the amniotic fluid allows for the timely termination of pregnancy, but does not indicate whether the fetus is the carrier of the hemophilia gene. Pregnancy is preserved if the fetus is male, since all the sons of the sick are born healthy. Interrupt the pregnancy in the case of a female fetus, since all the daughters of patients with hemophilia are the carriers of the disease.
Women who are hemophilic conductors who have a 50% chance of giving birth to a sick child( if they are male fetuses) or being transmitters of hemophilia( if the female fetus), the birth of only girls endangers the appearance of hemophilia in the family from the first generation to the second,while increasing the total number of transmitters of the disease.