FS.3.2.0003.15 Human blood coagulation factor VIII. Association of plasma factor VIII levels with the severity of the bleeding disorder

Formula, chemical name: there is 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, resulting in 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 coagulation 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 (range 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 - time of the curve - 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 of 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 blood coagulation factor VIII units is expressed in international units (IU), which are the current World Health Organization standards for blood 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 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, the initial level of activity of blood coagulation factor VIII is determined and how much this activity needs to be increased. The required dose of the drug is calculated using the following formula: required dose = body weight (kg) × desired increase in blood clotting 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 every 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 blood 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 blood 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. In case of 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 prevention of bleeding in patients with severe hemophilia A, the average dose of coagulation factor VIII is 20-40 IU/kg 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 blood coagulation 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 any special requirements for dosing the drug 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 patients with high level coagulation factor VIII inhibitors, drug treatment is ineffective, then alternative therapy should be considered. 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, and 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 of 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.
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, before 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 factor VIII is a known complication of the treatment of patients with hemophilia A. Typically, these factor VIII inhibitors are immunoglobulins G, which act against the procoagulant activity of factor VIII, their level is measured in units of Bethesda per ml of serum blood 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. All patients treated with factor VIII medicinal products should be carefully monitored for the presence of antibodies to 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 patient at the time of first use of factor VIII was 7 months (range 3 days to 67 months), and the average duration of use of factor VIII in a clinical study was 100 days (range 1 to 553 days).
There is information about the existence of a connection 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. Patients with inhibitors of blood coagulation factor VIII may be at increased risk of anaphylaxis with subsequent use of blood coagulation factor VIII. Therefore, the first injection of blood coagulation factor VIII must be carried out according to the prescription of the attending physician under medical supervision in conditions that allow you to provide 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 drugs prepared from human blood or serum include donor selection, screening of individual donations and blood serum pools for specific markers of infectious diseases. medicines effective stages inactivation and removal of microorganisms. 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 blood coagulation factor VIII 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 increased concentration 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 the auxiliary components of the drug).

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 is 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.

Coagulation factor VIII ( Coagulation Factor VIII)

Clinical and pharmacological group

Factor preparation VIII coagulation blood

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. Plasma factor VIII activity is expressed either as a percentage (relative to normal factor levels in human plasma) or in IU (relative to the International Standard for 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 plasma factor 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.

Patients respond to the administration of the drug individually, while there is a different level of recovery in vivo, T 1/2 of blood coagulation factor VIII is characterized by variability. Therefore, during treatment, to regulate the dose and frequency of administration, its level should be monitored. Coagulation factor VIII activity 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 there is no expected increase in factor VIII activity or there is no required hemostatic effect, a 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 lyophilizate

1. The solvent (water for injection) and lyophilisate in closed vials are recommended to be brought to room temperature. If a water bath is used prior to warming the solvent, 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

Data on the interaction of Octanate with other drugs are not available.

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. 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 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.

Factor VIII Test material: blood plasma Determination of factor VIII activity in blood plasma. Factor VIII The analysis detects the activity of factor VIII in blood plasma (in%) Factor ...

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Study Description

Preparation for the study: Blood is taken on an empty stomach Material under study: Taking blood

Factor VIII

Test material: blood plasma

Determination of factor VIII activity in blood plasma.

The assay detects factor VIII activity in blood plasma (in %)

Blood coagulation factor VIII (Antihemophilic globulin) - plays an important role in blood coagulation processes. Factor VIII is synthesized in the liver, spleen, endothelial cells, leukocytes, and kidneys.

Coagulation factor VIII deficiency is found in one of the most severe hereditary diseases - hemophilia A. The disease is transmitted through the female line, but only men suffer from it. The frequency of the disease is 1 per 8-10 thousand of the male population. The disease is characterized by spontaneous, sometimes fatal bleeding, bleeding into the joints, which leads to irreversible damage to the musculoskeletal system and, as a result, to early disability. Patients with hemophilia throughout their lives need replacement therapy with antihemophilic globulin concentrates. The sooner the diagnosis is established and treatment is started, the more likely it is that the patient will be able to lead a full life.

Method

The simplest and most widely used method for determining factor VIII activity is a one-step method based on a linear relationship between factor VIII and clotting time in the APTT test (activated partial thromboplastin time).

Reference values ​​- norm
(Blood coagulation factor 8 (antihemophilic globulin), blood)

Information regarding the reference values ​​of the indicators, as well as the very composition of the indicators included in the analysis, may differ slightly depending on the laboratory!

Norm:

The activity of factor VIII in the blood plasma of a healthy person is 50-150%.

Indications

• Diagnosis of hemophilia.
• Control of replacement therapy in patients with hemophilia A with factor VIII concentrates.
• Diagnosis of thrombophilia due to an increase in the level of factor VIII.

Increasing values ​​(positive result)

• Increased risk of thrombosis

Decreasing values ​​(negative result)

• Factor VIII level less than 1% - a severe form of hemophilia A. With this form of hemorrhage into the joints, muscles and other organs occur with minimal or even imperceptible damage
• The level of factor VIII 1-5% - moderate hemophilia. With this form of hemophilia, bleeding occurs due to obvious minor injuries, also after various operations and tooth extractions.
• Factor VIII level 5-30% - mild hemophilia. In this form of hemorrhage, it usually only follows major injuries, surgery, or tooth extractions. Diagnosis of this form may not be made until adulthood or bleeding after these situations.

Factor VIII (antihemophilic factor A) is a plasma protein essential for proper blood clotting. It is present in plasma in combination with von Willebrand factor (VWF). Factor VIII is a non-enzymatic cofactor in the internal machinery of the blood coagulation system that, in the presence of phospholipids and calcium ions, accelerates the activation of factor X by factor IXa. Hemophilia A, which is a recessively inherited, sex-linked disease, is characterized by congenital factor VIII deficiency. T1 / 2 of factor VIII is 8-12 hours. Von Willebrand factor, on the one hand, protects factor VIII from proteolytic degradation, on the other hand, is involved in platelet adhesion, forming a bridge between the subendothelial layer of blood vessels and platelets. Deficiency of this factor is the cause of von Willebrand disease. After the use of factor VIII, there is an increase in the procoagulant activity of factor VIII in plasma, which can temporarily correct blood clotting disorders in patients with hemophilia A. Factor VIII is obtained from the blood plasma pool of several donors after preliminary testing for HBsAg carriage, the presence of antibodies to HCV and to HIV. Factor VIII concentrate uses various methods (eg, heat inactivation, chemical methods) to inactivate viruses and reduce the risk of infectious disease transmission. Factor VIII is also produced using genetic engineering techniques.

Indications

Prevention and treatment of blood clotting disorders due to congenital (hemophilia A) or acquired deficiency of factor VIII. Von Willebrand disease (drugs containing factor VIII and von Willebrand factor) with factor VIII deficiency.

Contraindications

Hypersensitivity to any of the components of the drug or to animal proteins, such as mice, cattle, or hamsters (depending on the drug). In the event of an allergic or anaphylactic reaction, use should be discontinued immediately. In patients on a low-sodium diet, the sodium content of the preparations must be taken into account. When using therapy using products based on human blood or plasma, the possibility of transmission of infectious agents cannot be completely excluded. This also applies to unknown or newly discovered viruses and other pathogens. Patients with von Willebrand's disease are at risk of developing thrombotic complications; patients with risk factors should be monitored to detect early signs of thrombosis.

drug interaction

No data available. The preparations should not be mixed with other pharmaceuticals.

Unwanted Effects

Often: chills. Less common: Nausea, severe facial flushing, mild fatigue, rash, bruising, sweating, trembling, tremors, fever, leg pain, cold extremities, sore throat and larynx, ear inflammation, abnormal hearing test results, bleeding from nose, pallor, allergic reactions (urticaria, rash, shortness of breath, cough, chest tightness, shortness of breath, hypotension, anaphylaxis). In addition: cyanosis, tachycardia, vomiting, abdominal discomfort, fainting, skin peeling. In 15-30% of patients with severe hemophilia A, a factor VIII inhibitor is produced, especially in the first 20 days of therapy.

Pregnancy and lactation

Dosage and administration

Intravenously. The individual dose depends on the severity of the disease, the location and extent of bleeding, and the clinical condition of the patient. It is recommended to control the heart rate before and during the administration of the drug - in case of an increase in the heart rate, it is necessary to reduce the rate of administration of the drug or stop it for a moment. Hemophilia A. Dose calculation (IU): body weight (kg) x desired factor VIII concentration (% of normal) x 0.5. In case of early hemorrhages in the joints and muscles or bleeding from the mouth, it is necessary to maintain the activity of factor VIII at the level of 20-40% of the usual (IU / dl), inject the drug for 1-3 days every 12-24 hours until the pain stops or healing wounds. For more severe hemorrhages in the joint, muscles, or in the case of a hematoma, it is necessary to maintain the activity of factor VIII at the level of 30-60% of the norm (IU / dl), inject the drug for 3 days or longer every 12-24 hours, until the pain stops and troubleshooting. In severe, life-threatening bleeding, it is necessary to maintain the activity of factor VIII at the level of 60-100% of the norm, administer the drug every 8-24 hours until the threat is eliminated. Minor surgery, including tooth extractions - maintain factor VIII activity at 30-60% of normal (IU/dl), administered every 24 hours until the wound heals, at least every other day. Major surgery - maintain factor VIII activity at 80-100% of normal (IU/dl) before and after surgery, inject until the wound heals every 8-24 hours, and then continue therapy for at least 7 days, maintaining factor VIII activity at the level of 30-60% of the norm (IU / dl). Preventive maintenance therapy - usually 20-40 IU / kg of body weight every 2-3 days; in some patients, especially children, it may be necessary to use higher doses or shorter intervals between injections. It is necessary to monitor the condition of patients for the appearance of factor VIII inhibitors in them, it is recommended to perform appropriate laboratory tests, including to determine the activity of antihemophilic factor (AHF). If the expected plasma AHF activity is not achieved, or if the bleeding has not stopped despite the application of the required dose, an analysis for the presence of a factor VIII inhibitor should be performed. If the inhibitor titer is > 10 BU/mL, factor VIII therapy may not be effective and other therapies should be considered. Von Willebrand disease. Typically, 1 IU/kg von Willebrand factor (vWf) increases the plasma concentration of von Willebrand factor by 0.02 IU/mL (2%). The recommended concentration of von Willebrand factor to achieve is > 0.6 IU/ml (60%) and factor VIII > 0.4 IU/ml (40%). As a rule, to obtain hemostasis, the recommended concentration is 40-80 IU von Willebrand factor / kg body weight and 20-40 IU factor VIII / kg body weight. It may be necessary to administer an initial dose of 80 IU/kg b.w. von Willebrand factor, especially in patients with type 3 von Willebrand disease, which may require higher doses than other types of VWD to achieve adequate levels. For prevention heavy bleeding during or after surgery, the administration of the drug should be started 1-2 hours before surgery, and then re-introduce a certain dose every 12-24 hours. The dose and duration of treatment depends on the clinical condition of the patient, the type and intensity of bleeding, as well as on the concentration von Willebrand factor and factor VIII. In the case of the use of drugs with von Willebrand factor containing factor VIII, long-term treatment may lead to an excessive increase in the concentration of factor VIII. After 24-48 hours of therapy, to prevent an uncontrolled increase in the concentration of factor VIII, the need to reduce the dose and / or increase the interval between doses of the drug should be considered. In the case of von Willebrand disease with factor VIII deficiency, the prevention and treatment of bleeding is based on recommendations for use in hemophilia A.

A set of reagents for determining the activity of the factorVIII blood clotting (FactorVIII-test)according to TU 9398-020-05595541-2009

Designed to determine the activity of factor VIII (f. VIII) of blood coagulation by a one-stage clotting method in the blood plasma of patients in order to diagnose hemophilia A and thrombophilia, in fresh frozen donor plasma (FFP), cryoprecipitate and factor VIII preparations in order to determine their quality.

Factor VIII test designed to work manual method, as well as on automatic and semi-automatic coagulometers capable of recording the formation of a clot in the presence of kaolin.

Factor VIII is a glycoprotein with molecular weight approximately 280,000 daltons, localized in the liver, spleen, and lymphocytes other than plasma. In plasma, factor VIII circulates in a non-covalently bound complex with von Willebrand factor. Factor VIII is activated by thrombin and factor Xa, and is a cofactor of factor IXa during the activation of factor X in the presence of phospholipids and calcium ions.

Factor VIII deficiency causes hemophilia A. Hemophilia A is severe hereditary disease, is characterized by spontaneous, often fatal bleeding, hemorrhage into the joints, leading to early disability. Already with a decrease in the deficient factor to 30% (the norm is 50-150%), the disease manifests itself in latent form and is found after surgical interventions in the form of profuse bleeding. These patients require plasma replacement therapy throughout their lives.

The kit is designed to measure plasma factor VIII activity in patients with hemophilia A, patients with inhibitory form of hemophilia A, patients with thrombophilic conditions due to high levels of factor VIII activity, monitor treatment results and for control testing of antihemophilic drugs (cryoprecipitate).

Method principle:

When substrate-deficient plasma is added to the diluted test plasma, all coagulation factors except f.VIII are corrected. Therefore, the clotting time in the APTT test of a mixture of diluted test and substrate deficient plasma for f.VIII depends only on the activity of f.VIII in the test plasma. The activity of f.VIII is determined by the calibration curve of dilutions of the plasma calibrator with the established activity of f.VIII.

Set composition:

• Erilid, freeze-dried analogue of cephalin - 1 vial;
• Kaolin, suspension in 0.9% sodium chloride solution (5 ml / vial) - 1 vial;
• 0.025M solution of calcium chloride (5 ml/vial) - 1 vial;
• Plasma substrate VIII, freeze-dried (1 ml/vial) - 1 vial;
• Freeze-dried plasma calibrator (1 ml/vial) - 1 vial;
• Concentrated imidazole buffer (5 ml/vial) - 1 vial.

One kit is designed for 20 tests at a consumption of 0.05 ml of reagent per test.

Normal and pathological values ​​of factor VIII activity in the plasma of patients should be monitored using the code KM-2. High activity of factor VIII in cryoprecipitate should be monitored using code KM-8/9.

Code KM-16, can be used to build a calibration graph.

Interpretation of results:

The level of factor VIII activity in plasma in normal and pathological conditions.

The unit of activity is the activity of factor VIII contained in the pool of donor plasma taken from at least 300 healthy male donors. Factor VIII activity is expressed in international units (IU) or as a percentage, with 1 IU/mL corresponding to 100% activity.