Level factor 8 down to 50. Specific specific activity

Study Information

Factor VIII- antihemophilic globulin A. Produced in the liver, spleen, endothelial cells, leukocytes, kidneys. Content factor VIII in plasma - 0.01-0.02 g / l, half-life - 7-8 hours. The minimum level required for hemostasis is 30-35%. Antihemophilic globulin A is involved in the "internal" pathway of prothrombinase formation, enhancing the activating effect of factor IXa (activated factor IX) on factor X. Factor VIII circulates in the blood, being associated with von Willebrand factor.

special instructions: Do not conduct research during acute periods diseases and while taking anticoagulant drugs (after cancellation, at least 30 days must pass). Biomaterial for research must be taken on an empty stomach. At least 8 hours should elapse between the last meal and blood sampling.

GENERAL RULES OF PREPARATION FOR RESEARCH:

1. For most studies, it is recommended to donate blood in the morning, between 8 a.m. and 11 a.m., on an empty stomach (at least 8 hours should elapse between the last meal and blood sampling, you can drink water as usual), on the eve of the study light dinner with limited access fatty foods. For infection tests and emergency investigations, it is acceptable to donate blood 4-6 hours after the last meal.

2. ATTENTION! Special rules for preparing for a number of tests: strictly on an empty stomach, after 12-14 hours of fasting, you should donate blood for gastrin-17, lipid profile(total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, lipoprotein (a), apolipo-proten A1, apolipoprotein B); a glucose tolerance test is performed in the morning on an empty stomach after 12-16 hours of fasting.

3. On the eve of the study (within 24 hours), exclude alcohol, intense physical exercise, taking medications (as agreed with the doctor).

4. 1-2 hours before donating blood, refrain from smoking, do not drink juice, tea, coffee, you can drink still water. Exclude physical stress(running, fast climbing stairs), emotional arousal. It is recommended to rest and calm down 15 minutes before donating blood.

5. You should not donate blood for laboratory research immediately after physiotherapy procedures, instrumental examination, X-ray and ultrasound research, massage and other medical procedures.

6. When monitoring laboratory parameters in dynamics, it is recommended to conduct repeated studies under the same conditions - in the same laboratory, donate blood at the same time of day, etc.

7. Blood for research should be donated before the start of taking medications or no earlier than 10-14 days after they are discontinued. To evaluate the control of the effectiveness of treatment with any drugs, it is necessary to conduct a study 7-14 days after the last dose of the drug.

If you are taking medication, be sure to tell your doctor about it.

Formula, chemical name: no data.
Pharmacological group: hematotropic agents / coagulants (including blood coagulation factors), hemostatics.
Pharmachologic effect: hemostatic, replenishing the deficiency of coagulation factor VIII.

Pharmacological properties

Coagulation factor VIII is a hemostatic drug that is used in hemophilia A. Coagulation factor VIII accelerates the conversion of prothrombin to thrombin and thus promotes fibrin clot formation. When administered to patients with hemophilia, coagulation factor VIII binds to von Willebrand factor in the vessels. Activated coagulation factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. Activated factor X, in turn, converts prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, and a clot may already form. Hemophilia A is a hereditary, sex-related bleeding disorder that is caused by a decrease in blood clotting factor VIII, leading to profuse bleeding into the muscles, joints, internal organs and can be both spontaneous and as a result of surgical interventions or accidental injuries. When conducting substitution treatment the level of blood coagulation factor VIII in the blood serum increases, which makes it possible to temporarily compensate for the insufficiency of blood coagulation factor VIII and reduce the tendency to bleed. The specific activity of blood coagulation factor VIII is at least 100 IU/mg of total protein.
Coagulation factor VIII is a common component of human serum and has the same effect as endogenous factor VIII. After administration of coagulation factor VIII, approximately 2/3 to 3/4 of the drug remains in the bloodstream. The level of activity of blood coagulation factor VIII, which is achieved in the blood serum, should be 80 - 120% of the expected activity of blood coagulation factor VIII. The activity of blood coagulation factor VIII in the blood serum decreases according to the model of biphasic exponential decay. In the first phase, the distribution of blood coagulation factor VIII between intravascular and other body fluids occurs with a half-life of 3-6 hours. In the second, more slow phase, which most likely reflects consumption of coagulation factor VIII, the half-life is 12 hours on average (8 to 20 hours). Which corresponds to the true biological half-life of coagulation factor VIII. In patients with hemophilia A, the average values of the pharmacokinetic parameters of blood coagulation factor VIII are: recovery - 2.4% × IU^-1 × kg; area under the pharmacokinetic curve concentration - curve time - from 33.4 to 45.5% × h × IU ^-1 × kg; the average time spent in the blood - from 16.6 to 19.6 hours; half-life - from 12.6 to 14.3 hours; clearance - from 2.6 to 3.2 ml × h^-1 × kg.

Indications

Therapy and prevention of bleeding in patients with congenital hemophilia A or acquired deficiency of blood coagulation factor VIII, including inhibitory forms (using the method of induction immune tolerance).

Route of administration of coagulation factor VIII and doses

Coagulation factor VIII is administered intravenously after dilution in water for injection. The dose and duration of replacement treatment depends on the severity of factor VIII deficiency, the location and duration of bleeding, and the objective condition of the patient. Treatment should be initiated under the supervision of a physician experienced in the treatment of patients with hemophilia.
The number of units of blood coagulation factor VIII is expressed in international units (IU), which are established by current standards World Organization Health care for coagulation factor VIII. The activity of blood coagulation factor VIII in blood serum is expressed as a percentage (relative to normal level coagulation factor VIII in human serum) or in IU (relative to the international standard for coagulation factor VIII). 1 IU of blood coagulation factor VIII activity is equivalent to the content of blood coagulation factor VIII in 1 ml of normal human blood serum. The calculation of the required dose of the drug is based on empirical data, according to which 1 IU of blood coagulation factor VIII per kg of body weight increases the activity of blood coagulation factor VIII in the blood serum by 1.5 - 2% of normal activity. To calculate the required dose of the drug, determine First level coagulation factor VIII activity and how much this activity needs to be increased. Required dose drug is calculated using the following formula: required dose = body weight (kg) × desired increase in blood coagulation factor VIII (%) (IU / dl) × 0.5. The frequency of use and dosage of the medicinal product should always be aimed at achieving clinical effect in each specific case. In case of bleeding after the start of treatment, the activity of blood coagulation factor VIII should not decrease below the initial level in the blood serum (% of normal concentration) in the appropriate period of time.
With early hemarthrosis, intramuscular bleeding, bleeding oral cavity the required level of coagulation factor VIII is 20-40%, repeated injections of the drug are necessary every 12-24 hours for at least one day until the pain subsides or the source of bleeding heals. With more intense bleeding, intramuscular bleeding or hematomas, the required level of blood coagulation factor VIII is 30-60%, repeated injections of the drug are necessary every 12-24 hours for 3-4 days until the pain subsides and the ability to work is restored. With life-threatening bleeding, the required level of coagulation factor VIII is 60-100%, repeated injections of the drug are necessary every 8-24 hours until the threat disappears completely. For minor surgical interventions, including tooth extraction, the required level of blood coagulation factor VIII is 30 - 60%, it is necessary to administer the drug every 24 hours for at least one day until healing is achieved. For major surgical interventions, the required level of blood coagulation factor VIII is 80-100% (preoperative and postoperative), repeated injections of the drug are necessary every 8-24 hours until the wound heals adequately, then at least one week to maintain the activity of blood coagulation factor VIII at the level 30 - 60%. The required frequency of use and dose of the drug is determined by the attending physician.
During treatment, the level of blood coagulation factor VIII should be assessed to adjust the dose and frequency of repeated injections of the drug. It is necessary to carefully monitor the activity of blood coagulation factor VIII in the blood serum, especially during major surgical interventions. The response to treatment in individual patients may differ, as indicated by differences in the half-life and the degree of recovery of the activity of blood coagulation factor VIII.
For long-term prophylaxis bleeding in patients with severe hemophilia A average dose coagulation factor VIII is 20 - 40 IU / kg of body weight at intervals of 2 - 3 days. In some patients, especially in patients young age, it may be necessary to reduce the interval between injections of factor VIII or increase its dose.
In some patients, after drug therapy, the formation of inhibitors of blood coagulation factor VIII is possible, which may affect the effectiveness of further therapy. If against the background of ongoing therapy there is no expected increase in the activity of blood coagulation factor VIII or there is no required hemostatic effect, it is recommended to consult in a specialized treatment center using the Bethesda test. To eliminate the inhibitor of blood coagulation factor VIII, the induction of immune tolerance can be used, which consists in the daily administration of blood coagulation factor VIII at a concentration that exceeds the blocking ability of the inhibitor (100–200 IU/kg/day, depending on the inhibitor titer). Coagulation factor VIII performs the function of an antigen and provokes an increase in the titer of an inhibitor of blood coagulation factor VIII until tolerance develops, that is, a decrease and further disappearance of the inhibitor. The induction of immune tolerance is carried out continuously and lasts an average of 10 to 18 months. Immune tolerance induction should only be carried out by doctors who are experts in the field of antihemophilic treatment.
Clinical data on the use of coagulation factor VIII in previously untreated patients are limited.
A clinical study involving 15 patients under 6 years of age did not reveal special requirements for drug dosing in children.
It is necessary to monitor the presence of inhibitors of blood coagulation factor VIII in patients. If against the background of ongoing therapy there is no expected increase in the activity of blood coagulation factor VIII or there is no necessary hemostatic effect, then it is necessary to analyze for the presence of inhibitors of blood coagulation factor VIII. If drug treatment is not effective in patients with high levels of factor VIII inhibitors, consideration should be given to alternative therapy. The treatment of these patients should be carried out by doctors who have experience in the treatment of hemophilia.
Interim data are available from an ongoing study in patients undergoing immune tolerance induction with coagulation factor VIII. The dosage regimen is set in a medical institution individually for each patient. Patients with a poor response usually receive factor VIII at a dose of 50-100 IU/kg of body weight every day or every other day, patients with a strong response usually receive factor VIII at a dose of 100-150 IU/kg body weight every 12 hours. Factor VIII inhibitor titers are determined twice every 7 days for the first three months, then factor VIII inhibitor titers are determined every three months during scheduled visits medical institutions to continue treatment. The result of the induction of immune tolerance is determined after three years according to three consecutive criteria, including a negative titer of blood coagulation factor VIII inhibitors, restoration of blood coagulation factor VIII activity, normalization of the half-life of blood coagulation factor VIII. An interim analysis found that of the 69 patients who received coagulation factor VIII as immune tolerance induction, 49 patients completed the study. In patients with successful elimination of the factor VIII inhibitor, the monthly bleeding rate was significantly reduced.
Before intravenous administration, the reconstituted medicinal product should be examined for discoloration and the presence of mechanical impurities. The reconstituted clotting factor VIII solution should be clear or slightly opalescent. Do not use a cloudy clotting factor VIII solution or if there are clots in it. The reconstituted solution of coagulation factor VIII must be used immediately after preparation and only once.
As a precautionary measure, heart rate should be monitored before and during administration of coagulation factor VIII. With a pronounced increase in heart rate, the introduction of blood coagulation factor VIII must be slowed down or stopped.
Any unused clotting factor VIII solution should be disposed of in accordance with current regulations.
As with any drug protein origin, For intravenous administration possible development of reactions hypersensitivity allergic type. In addition to coagulation factor VIII, the medicinal product contains trace amounts of other human plasma proteins. Patients should be informed about early signs hypersensitivity reactions, including generalized and local urticaria, wheezing, pressure sensation chest, hypotension, anaphylaxis. With the development of these symptoms, you should immediately stop using the drug and consult your doctor. With the development of shock, standard anti-shock treatment should be carried out.
With the use of clotting factor VIII in rare cases hypersensitivity reactions or allergic reactions which may include a burning sensation at the injection site, a tingling sensation at the injection site, angioedema, flushing, chills, generalized urticaria, local urticaria, headache, hypotension, lethargy, nausea, tachycardia, restlessness, chest pressure, vomiting, ringing in the ears, wheezing, in some cases, these symptoms may progress, in including, until the development of severe anaphylaxis, including shock.
In patients with hemophilia A, the use of blood coagulation factor VIII may cause inhibitors (antibodies) of blood coagulation factor VIII, which is manifested by an insufficient clinical response to the administration of the drug. In this situation, it is necessary to contact a specialized hematology center. The formation of neutralizing inhibitors (antibodies) of blood coagulation factor VIII is known complication treatment of patients with hemophilia A. Typically, these inhibitors of blood coagulation factor VIII are immunoglobulins G, which act against the procoagulant activity of blood coagulation factor VIII, their level is determined in units of Bethesda per ml of blood serum using a modified method. The risk of forming factor VIII inhibitors correlates with drug use and is highest in the first 20 days of treatment. In rare cases, factor VIII inhibitors may appear after the first 100 days of drug use. Careful monitoring of all patients receiving treatment is necessary. medicines coagulation factor VIII, for the appearance of antibodies to coagulation factor VIII by conducting appropriate laboratory tests And clinical observations. In the ongoing clinical trial in previously untreated patients, 3 of 39 people who received coagulation factor VIII as needed developed factor VIII inhibitors. Two cases were clinically significant, in two other patients, factor VIII inhibitors spontaneously disappeared without changing the dose of the drug. All cases of the formation of inhibitors of blood coagulation factor VIII were observed during therapy as needed for no more than 50 days. There was an initial level of activity of blood coagulation factor VIII less than 1% in 35 previously untreated patients and less than 2% in 4 previously untreated patients. At the time of the interim analysis, coagulation factor VIII had been used for at least 20 days in 34 patients and for at least 50 days in 30 patients. In previously untreated patients who used coagulation factor VIII for prophylaxis, inhibitors of blood coagulation factor VIII were not detected. During the study, 12 previously untreated patients underwent 14 surgical interventions. Average age of the patient at the time of the first use of blood coagulation factor VIII was 7 months (from 3 days to 67 months), and average duration coagulation factor VIII use in a clinical study was 100 days (range 1 to 553 days).
There is information about the existence of a relationship between the formation of inhibitors of blood coagulation factor VIII and allergic reactions, therefore, with the development of allergic reactions, the patient should be examined for the presence of inhibitors of blood coagulation factor VIII. In patients with inhibitors of blood coagulation factor VIII, the risk of anaphylaxis may be increased with subsequent use of blood coagulation factor VIII. Therefore, the first injection of blood coagulation factor VIII must be carried out as prescribed by the attending physician under medical supervision under conditions that allow the necessary medical care with the development of allergic reactions.
Standard measures for the prevention of infectious diseases that may be caused by the use of medicinal products prepared from human blood or serum include the selection of donors, the screening of individual donations and blood serum pools for specific markers of infectious diseases, the introduction of effective stages of inactivation and removal of microorganisms into the production of medicinal products. But when using drugs that are prepared from human blood or serum, the risk of transmission of microorganisms that cause infectious diseases cannot be completely excluded. This also applies to new or unknown microorganisms. These infectious disease prevention measures are considered effective against enveloped viruses (human immunodeficiency virus, hepatitis B virus, hepatitis C virus) and non-enveloped hepatitis A virus. These infectious disease prevention measures may have limited effectiveness against non-enveloped viruses, such as parvovirus B19. Infection, which is caused by parvovirus B19, may have serious consequences for women during pregnancy (infection of the fetus) and patients with immunodeficiency or increased erythropoiesis (for example, with hemolytic anemia). Appropriate vaccination against hepatitis A and B should be considered in patients who regularly and repeatedly receive coagulation factor VIII medicinal products derived from human blood serum.
To establish a link between the patient and the drug lot, it is recommended that each time coagulation factor VIII is used, the name and lot number of the drug be recorded.

When using coagulation factor VIII, care must be taken when performing potentially dangerous species activities that require an increased concentration of attention and speed of psychomotor reactions (including control vehicles, mechanisms), as it is possible to develop headache, tinnitus, hypotension and other adverse reactions which can provide Negative influence to carry out these activities. With the development of such adverse reactions, it is necessary to abandon the performance of potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (including driving vehicles, mechanisms).

Contraindications for use

Hypersensitivity (including to auxiliary components medicinal product).

Application restrictions

Pregnancy, breastfeeding.

Use during pregnancy and lactation

Because hemophilia A is rare in women, experience with the use of factor VIII in women during and during pregnancy breastfeeding absent. Coagulation factor VIII in women during pregnancy and during breastfeeding should be used only if absolute readings when the expected benefit to the mother is higher possible risk for the fetus or child.

Side effects of clotting factor VIII

Nervous system, psyche and sense organs: headache, anxiety, ringing in the ears.
Cardiovascular system, blood (hemostasis, hematopoiesis) and lymphatic system: hypotension, flushing, tachycardia.
Digestive system: nausea, vomiting.
Respiratory system: chest tightness, wheezing.
The immune system: hypersensitivity reactions, anaphylactic shock, allergic reactions, severe anaphylaxis, angioedema, generalized urticaria, local urticaria.
General disorders and reactions at the injection site: burning sensation at the injection site, tingling sensation at the injection site, chills, apathy, fever.
Laboratory indicators: the formation of antibodies to blood coagulation factor VIII in the blood serum.

Interaction of blood coagulation factor VIII with other substances

There are no data on the interaction of blood coagulation factor VIII with other drugs.
Others should not be used medicines with the introduction of clotting factor VIII.

Overdose

There have been no cases of overdose with coagulation factor VIII. It is recommended not to exceed the prescribed dose of coagulation factor VIII.

Trade names of drugs with the active substance clotting factor VIII

Agemfil A
Antihemophilic human factor-M(AHF-M)
beriate
Gemoctin
Hemophilus M
Immunat
Coate-DWI
Coate-HP
Cryobulin TIM 3
cryoprecipitate
LongAit
Octavi
Octanate
fandi
Hemate P
Emoklot D.I.

Combined drugs:
Coagulation factor VIII + von Willebrand factor: Vilate, Hemate® P.

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 treatment of hemophilia. 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 clotting factor injections. 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. The new technique uses capsules on plant-based and has the potential to be a 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 condition. 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 on clotting factors, the researchers focused on previous studies that found that by exposing the immune system individual components coagulation factor protein, it is possible to induce tolerance to the entire protein. 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 therapeutic delivery platform based on plant genetic modification. 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 coding subunit of the cholera toxin DNA (a protein that can cross the intestinal wall and enter the bloodstream), and then did the same with the 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 blood coagulation factor 8. However, the scientists note that levels of blood coagulation factor 8 inhibitor can re-form (after a period of time if stop giving plant material to animals). With financial support from global pharmaceutical companies the scientists plan to study the effectiveness of capsules containing this plant material in a clinical setting.

Coagulation factor VIII ( Coagulation Factor VIII)

Clinical and pharmacological group

Coagulation factor VIII drug

pharmachologic effect

hemostatic drug. Promotes the transition of prothrombin to thrombin and the formation of a fibrin clot.

Pharmacokinetics

In patients with hemophilia, A T 1/2 is 12 hours. The activity of blood coagulation factor VIII decreases by 15% within 12 hours. Blood coagulation factor VIII is thermolabile and is rapidly destroyed when the temperature rises, which leads to a decrease in T 1/2.

Dosage

Octanate is administered intravenously after dilution with water for injection, which is included in the package. Octanate dose and duration replacement therapy depend on the degree of deficiency of blood coagulation factor VIII, the location and duration of bleeding, clinical condition patient.

The dose of the drug is expressed in International Units (IU) in accordance with the accepted WHO standards for blood coagulation factor VIII. The activity of blood coagulation factor VIII in plasma is expressed as either percentage(relative to the normal content of the factor in human plasma), or in IU (relative to International Standard for coagulation factor VIII).

1 IU of coagulation factor VIII is equivalent to 1 ml of normal human plasma. The calculation of the required dose is based on empirically obtained results, according to which 1 IU / kg of blood coagulation factor VIII increases the level of plasma factor by 1.5-2% of the normal content. To calculate the dose required for the patient, the initial level of activity of blood coagulation factor VIII is determined and it is estimated by how much this activity needs to be increased.

Required dose = body weight (kg) × desired increase in clotting factor VIII (%) (IU/dl) × 0.5.

The amount and frequency of application of the drug should always correspond clinical efficacy in each individual case.

In the event of subsequent bleeding, the level of blood coagulation factor VIII activity should not decrease below the initial plasma level (% of normal content) in the appropriate period of time. The following table can be used as a guideline for choosing the dose of coagulation factor VIII for various bleeding and surgical interventions.

Severity of bleeding/type of surgery	Required level of coagulation factor VIII (%)	Frequency of administration and duration of therapy
Bleeding
Early hemarthrosis, intramuscular bleeding, bleeding in the oral cavity	20-40	Repeat every 12-24 hours for at least 1 day until pain is relieved or source of bleeding heals
More extensive hemarthrosis, intramuscular bleeding, or hematoma	30-60	Repeated injections every 12-24 hours for 3-4 days, until pain relief and recovery
life threatening bleeding	60-100	Repeated injections every 8-24 hours, until the complete disappearance of the threat to life
Surgical interventions
Minor, including tooth extraction	30-60	Every 24 hours for at least 1 day until healing is achieved
Large	80-100 (pre- and postoperative)	Repeat injections every 8-24 hours until adequate wound healing, then at least 7 days to maintain clotting factor VIII activity at 30-60%

Patients respond to the administration of the drug individually, while there is different level recovery in vivo, T 1/2 coagulation factor VIII is characterized by variability. Therefore, during treatment, to regulate the dose and frequency of administration, its level should be monitored. The activity of blood coagulation factor VIII should be monitored during replacement therapy, especially during major surgical interventions.

The doses indicated in the table are indicative. The doctor sets the required dose and frequency of use of the drug individually.

With the aim of long-term prevention of bleeding in severe hemophilia A the drug is prescribed at a dose of 20-40 IU / kg of body weight every 2-3 days. In some cases, especially in young patients, it may be necessary to reduce the interval between injections or increase the dose.

Some patients may develop after treatment inhibitory antibodies to coagulation factor VIII, which may affect the effectiveness further treatment. If, against the background of ongoing therapy, the expected increase in factor VIII activity is not observed or the required hemostatic effect is absent, consultation at a specialized treatment center using the Bethesda test is recommended. Immune tolerance induction therapy can be used to eliminate an inhibitor to coagulation factor VIII. Its basis is the daily administration of blood coagulation factor VIII at a concentration exceeding the blocking ability of the inhibitor (100-200 IU/kg/day, depending on the inhibitor titer). Blood coagulation factor VIII, acting as an antigen, provokes an increase in the inhibitor titer until tolerance develops, i.e. until the decrease and subsequent disappearance of the inhibitor. Therapy is continuous and lasts an average of 10 to 18 months. Such treatment should only be carried out by specialists in the field of antihemophilic therapy.

Dissolution of the lyophilisate

1. The solvent (water for injection) and lyophilisate in closed vials are recommended to be brought to room temperature. If before warming the solvent is used water bath, care should be taken to ensure that water does not come into contact with rubber stoppers or vial caps. The temperature of the water bath should not exceed 37°C.

2. Remove the protective caps from the bottles with lyophilisate and water, disinfect the rubber stoppers of both bottles with one of the disinfectant wipes.

3. Release the short end of the double-ended needle from the plastic packaging, pierce the stopper of the water bottle with it and push it down until it stops.

4. Turn the bottle of water over with the needle, release the long end of the double-ended needle, pierce the stopper of the vial with lyophilisate with it and press down until it stops. The vacuum in the lyophilisate vial will draw in the water.

5. Separate the bottle with water together with the needle from the bottle with lyophilisate. The drug will dissolve quickly; to do this, the bottle must be slightly shaken. Only a colorless, transparent or slightly opalescent solution without sediment is allowed for use.

Rules for the preparation and administration of the solution

As a precautionary measure, heart rate should be monitored before and during the administration of Octanate. In the case of a pronounced acceleration of the pulse, slow down or stop the administration of the drug.

After dissolving the concentrate according to the instructions, remove the protective coating from the filter needle and insert it into the bottle with the concentrate. Remove the cap from the filter needle and attach the syringe. Turn the vial with the syringe upside down and draw the solution into the syringe. Injections should be carried out in accordance with the rules of asepsis and antisepsis. Disconnect the filter needle from the syringe and attach the butterfly needle instead.

The solution should be administered intravenously slowly at a rate of 2-3 ml / min.

If more than one bottle of Octanate is used, the syringe and butterfly needle can be reused.

The filter needle is for single use only. Always use a needle with a filter to draw the prepared solution into the syringe.

Any unused solution of the drug should be disposed of in accordance with existing regulations.

Overdose

Despite the fact that symptoms of an overdose of factor VIII were not observed, it is recommended not to exceed the prescribed dose.

drug interaction

There are no data on the interaction of Octanate with other drugs.

Pregnancy and lactation

The use of the drug during pregnancy and lactation is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or infant.

Side effects

Allergic reactions: rarely - angioedema, burning sensation in the injection area, chills, hot flashes, urticaria (including generalized), headache, decreased blood pressure, lethargy, nausea, vomiting, anxiety, tachycardia, chest compression, shortness of breath, fever , feeling of trembling. Very rarely (<1/10 000) эти симптомы могут прогрессировать до развития тяжелой анафилактической реакции, включая шок.

Patients with hemophilia A may develop antibodies (inhibitors) to blood coagulation factor VIII (<1/1000). Наличие ингибиторов приводит к неудовлетворительному клиническому ответу на введение препарата. В таких случаях рекомендуется обращаться в специализированные гематологические/гемофильные центры. Неоходимо обследовать пациента на наличие антител с помощью соответствующих методов (тест Бетезда).

Terms and conditions of storage

The drug should be stored in a place protected from light and out of the reach of children at a temperature of 2 ° to 25 ° C; do not freeze. Shelf life - 3 years.

special instructions

When using the drug, the development of hypersensitivity reactions is possible, as with the use of other injectable drugs of protein origin.

In addition to blood coagulation factor VIII, the drug also contains trace amounts of other blood proteins. Early signs of hypersensitivity reactions are hives, chest tightness, shortness of breath, low blood pressure, and anaphylaxis (a severe allergic reaction). If these symptoms occur, the administration of the drug should be stopped immediately. In case of shock development, modern methods of anti-shock therapy should be used.

In the case of medicinal products derived from human blood or plasma, the possibility of transmission of infectious agents cannot be completely excluded. This also applies to pathogens of unknown diseases. However, the risk of transmission of infectious agents is reduced through the following measures:

- selection of donors through medical interviews and examinations, as well as screening of plasma pools for the presence of hepatitis B virus (HBV) antigens, antibodies to HIV and hepatitis C virus (HCV);

— analysis of plasma pools for the presence of HCV genetic material;

— inactivation/removal procedures included in the manufacturing process that have been validated in a viral model. These procedures are effective for HIV, hepatitis A virus (HAV), HBV, and HCV. Inactivation/removal procedures may be of limited effectiveness against non-enveloped viruses, one of which is parvovirus B19. Parvovirus B19 can cause serious reactions in seronegative pregnant women (intrauterine infection) and in people who are immunocompromised or have an increased production of red blood cells (for example, with hemolytic anemia).

When administering plasma-derived coagulation factor VIII concentrate, vaccination against hepatitis A and hepatitis B is recommended.

In the event of allergic reactions, the patient should be examined for the presence of an inhibitor. Patients with inhibitors of blood coagulation factor VIII may increase the risk of anaphylactic reactions during subsequent treatment with Octanate. Therefore, the first use of the specified drug according to the prescription of the attending physician should be carried out under medical supervision in conditions that ensure the provision of qualified medical care in case of allergic reactions.

Do not use other drugs during the administration of Octanate.

For the introduction of Octanate, only the injection devices included in the package should be used. On the inner surface of some injectable devices, adsorption of blood coagulation factor VIII is possible, which leads to a decrease in the effectiveness of treatment.

Application in childhood

Application is possible according to the dosing regimen.

It is carried out mainly by proteins called plasma coagulation factors. Plasma coagulation factors are procoagulants whose activation and interaction lead to the formation of a fibrin clot.

According to the International Nomenclature, plasma coagulation factors are indicated by Roman numerals, with the exception of von Willebrand, Fletcher and Fitzgerald factors. To indicate the activated factor, the letter "a" is added to these numbers. In addition to the numerical designation, other names of clotting factors are also used - according to their function (for example, factor VIII - antihemophilic globulin), by the names of patients with a newly discovered deficiency of one or another factor (factor XII - Hageman factor, factor X - Stuart-Prauer factor) , less often - by the names of the authors (for example, the von Willebrand factor).

Below are the main blood coagulation factors and their synonyms according to the international nomenclature and their main properties in accordance with the literature and special studies.

Fibrinogen (factor I)

Fibrinogen is synthesized in the liver and cells of the reticuloendothelial system (in the bone marrow, spleen, lymph nodes, etc.). In the lungs, under the action of a special enzyme - fibrinogenase or fibrinodestructase - fibrinogen is destroyed. The content of fibrinogen in plasma is 2 - 4 g / l, the half-life is 72 - 120 hours. The minimum level required for hemostasis is 0.8 g/l.

Under the influence of thrombin, fibrinogen is converted into fibrin, which forms a mesh basis of a thrombus that clogs a damaged vessel.

Prothrombin (factor II)

Prothrombin is synthesized in the liver with the participation of vitamin K. The content of prothrombin in plasma is about 0.1 g / l, the half-life is 48 - 96 hours.

The level of prothrombin, or its functional usefulness, decreases with endogenous or exogenous vitamin K deficiency, when defective prothrombin is formed. The rate of blood clotting is disturbed only when the concentration of prothrombin is below 40% of the norm.

Under natural conditions, during blood coagulation under the action of and, as well as with the participation of factors V and Xa (activated factor X), united by the general term "prothrombinase", prothrombin turns into thrombin. The process of converting prothrombin to thrombin is quite complicated, since during the reaction a number of derivatives of prothrombin, autoprothrombins and, finally, various types of thrombin (thrombin C, thrombin E) are formed, which have procoagulant, anticoagulant and fibrinolytic activity. The resulting thrombin C - the main product of the reaction - contributes to the coagulation of fibrinogen.

Tissue thromboplastin (factor III)

Tissue thromboplastin is a thermostable lipoprotein found in various organs - in the lungs, brain, kidneys, heart, liver, skeletal muscles. The tissues do not contain it in an active state, but in the form of a precursor - prothromboplastin. Tissue thromboplastin, when interacting with plasma factors (VII, IV), is able to activate factor X, participates in the external pathway for the formation of prothrombinase, a complex of factors that convert to thrombin.

Calcium ions (factor IV)

Calcium ions are involved in all three phases of blood coagulation: in the activation of prothrombinase (phase I), the conversion of prothrombin into thrombin (phase II) and fibrinogen into fibrin (phase III). Calcium is able to bind heparin, thereby accelerating blood clotting. In the absence of calcium, platelet aggregation and retraction of the blood clot are impaired. Calcium ions inhibit fibrinolysis.

Proaccelerin (factor V)

Proaccelerin (factor V, plasma AC-globulin or labile factor) is formed in the liver, but, unlike other hepatic factors of the prothrombin complex (II, VII, and X), does not depend on vitamin K. It is easily destroyed. The content of factor V in plasma - 12 - 17 units / ml (about 0.01 g / l), half-life - 15 - 18 hours. The minimum level required for hemostasis is 10-15%.

Proaccelerin is necessary for the formation of internal (blood) prothrombinase (activates factor X) and for the conversion of prothrombin to thrombin.

Accelerin (factor VI)

Accelerin (factor VI or serum AC-globulin) is the active form of factor V. Excluded from the nomenclature of coagulation factors, only the inactive form of the enzyme is recognized - factor V (proaccelerin), which, when traces of thrombin appear, becomes active.

Proconvertin, convertin (factor VII)

Proconvertin is synthesized in the liver with the participation of vitamin K. It remains in stabilized blood for a long time, and is activated by a wetted surface. The content of factor VII in plasma is about 0.005 g / l, the half-life is 4 - 6 hours. The minimum level required for hemostasis is 5-10%.

Convertin, the active form of the factor, plays a major role in the formation of tissue prothrombinase and in the conversion of prothrombin to thrombin. Activation of factor VII occurs at the very beginning of the chain reaction upon contact with a foreign surface. During the clotting process, proconvertin is not consumed and is stored in the serum.

Antihemophilic globulin A (factor VIII)

Antihemophilic globulin A is produced in the liver, spleen, endothelial cells, leukocytes, and kidneys. The content of factor VIII in plasma is 0.01 - 0.02 g / l, the half-life is 7 - 8 hours. The minimum level required for hemostasis is 30-35%.

Antihemophilic globulin A is involved in the "internal" pathway for the formation of prothrombinase, enhancing the activating effect of factor IXa (activated factor IX) on factor X. Factor VIII circulates in the blood, being associated with.

Antihemophilic globulin B (Christmas factor, factor IX)

Antihemophilic globulin B (Christmas factor, factor IX) is formed in the liver with the participation of vitamin K, is thermostable, and remains in plasma and serum for a long time. The content of factor IX in plasma is about 0.003 g/l. The half-life is 7-8 hours. The minimum level required for hemostasis is 20-30%.

Antihemophilic globulin B is involved in the "internal" pathway of prothrombinase formation, activating factor X in combination with factor VIII, calcium ions and platelet factor 3.

Stuart-Prower Factor (Factor X)

Stuart-Prower factor is produced in the liver in an inactive state, activated by trypsin and an enzyme from viper venom. K-vitamin-dependent, relatively stable, half-life - 30 - 70 hours. The content of factor X in plasma is about 0.01 g / l. The minimum level required for hemostasis is 10-20%.

The Stuart-Prower factor (factor X) is involved in the formation of prothrombinase. In the modern blood coagulation scheme, active factor X (Xa) is the central factor in prothrombinase, which converts prothrombin to thrombin. Factor X is converted into the active form under the influence of factors VII and III (external, tissue, prothrombinase formation pathway) or factor IXa together with VIIIa and phospholipid with the participation of calcium ions (internal, blood, prothrombinase formation pathway).

Plasma thromboplastin precursor (factor XI)

The plasma thromboplastin precursor (factor XI, Rosenthal factor, antihemophilic factor C) is synthesized in the liver and is thermolabile. The content of factor XI in plasma is about 0.005 g / l, the half-life is 30 - 70 hours.

The active form of this factor (XIa) is formed with the participation of factors XIIa, and. Form XIa activates factor IX, which is converted to factor IXa.

Hageman Factor (Factor XII, Contact Factor)

Hageman factor (factor XII, contact factor) is synthesized in the liver, produced in an inactive state, the half-life is 50-70 hours. The content of the factor in plasma is about 0.03 g/l. Bleeding does not occur even with very deep factor deficiency (less than 1%).

It is activated upon contact with the surface of quartz, glass, cellite, asbestos, barium carbonate, and in the body - upon contact with the skin, collagen fibers, chondroitin sulfuric acid, micelles of saturated fatty acids. Factor XII activators are also Fletcher's factor, kallikrein, factor XIa, plasmin.

The Hageman factor is involved in the "internal" pathway of prothrombinase formation by activating factor XI.

Fibrin stabilizing factor (factor XIII, fibrinase, plasma transglutaminase)

Fibrin-stabilizing factor (factor XIII, fibrinase, plasma transglutaminase) is determined in the vascular wall, platelets, erythrocytes, kidneys, lungs, muscles, placenta. In plasma, it is in the form of a proenzyme combined with fibrinogen. The active form is converted under the influence of thrombin. It is contained in plasma in an amount of 0.01 - 0.02 g / l, the half-life is 72 hours. The minimum level required for hemostasis is 2-5%.

Fibrin-stabilizing factor is involved in the formation of a dense clot. It also influences the adhesion and aggregation of platelets.

Willebrand factor (antihemorrhagic vascular factor)

The von Willebrand factor (antihemorrhagic vascular factor) is synthesized by the vascular endothelium and megakaryocytes, and is found in plasma and platelets.

The von Willebrand factor serves as an intravascular carrier protein for factor VIII. The binding of von Willebrand factor to factor VIII stabilizes the latter molecule, increases its half-life inside the vessel, and promotes its transport to the site of injury. Another physiological role of the relationship between factor VIII and von Willebrand factor is the ability of von Willebrand factor to increase the concentration of factor VIII at the site of vessel injury. Because circulating von Willebrand factor binds to both exposed subendothelial tissues and stimulated platelets, it directs factor VIII to the lesion, where the latter is needed to activate factor X with the participation of factor IXa.

Fletcher factor (plasma prekallikrein)

Fletcher factor (plasma prekallikrein) is synthesized in the liver. The content of the factor in plasma is about 0.05 g/l. Bleeding does not occur even with very deep factor deficiency (less than 1%).

Participates in the activation of factors XII and IX, plasminogen, converts kininogen to kinin.

Fitzgerald factor (plasma kininogen, Flojek factor, Williams factor)

Fitzgerald factor (plasma kininogen, Flojek factor, Williams factor) is synthesized in the liver. The content of the factor in plasma is about 0.06 g/l. Bleeding does not occur even with very deep factor deficiency (less than 1%).

Participates in the activation of factor XII and plasminogen.

Literature:

Handbook of Clinical Laboratory Research Methods. Ed. E. A. Kost. Moscow, "Medicine", 1975
Barkagan Z. S. Hemorrhagic diseases and syndromes. - Moscow: Medicine, 1988
Gritsyuk A. I., Amosova E. N., Gritsyuk I. A. Practical hemostasiology. - Kyiv: Health, 1994
Shiffman F. J. Blood Pathophysiology. Translation from English - Moscow - St. Petersburg: "Publishing house BINOM" - "Nevsky Dialect", 2000
Handbook "Laboratory research methods in the clinic", ed. prof. V. V. Menshikov. Moscow, "Medicine", 1987
Study of the blood system in clinical practice. Ed. G. I. Kozints and V. A. Makarov. - Moscow: Triada-X, 1997