Willebrand factor (Willebrand factor)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Coagulants (including clotting factors), hemostatics

Included in the formulation
  • Wilfactin
    lyophilizate in / in 
    LSE Biomedication     France
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    Minimal chemist's assortment

    АТХ:

    B.02.B.D.10   Coagulation factor of von Willebrand

    Pharmacodynamics:

    The introduction of von Willebrand factor allows to correct hemostatic deviations in patients with a deficiency of this factor (von Willebrand disease) at two levels:

    The von Willebrand factor restores the adhesion of platelets to the vascular subendothelium at the injury site (it can bind to the subendothelium and the platelet membrane), providing primary hemostasis, which is manifested in a decrease in bleeding time. This effect appears immediately and depends to a large extent on the level of multimerization of the active substance;

    VWF contributes to a delayed correction of the concomitant factor deficiency VIII (produced by the patient's body) stabilizes the content of this factor, preventing its rapid degradation.

    Substitution von Willebrand factor therapy normalizes the coagulation factor index VIII after the first injection. This effect is prolonged and persists during subsequent injections.

    Pharmacokinetics:

    A study of the pharmacokinetics of the drug was performed in 8 patients with a disease Willebrand type 3 method of dosing the ristocetin cofactor (FV: RKo). The maximum concentration of the drug was noted 30-60 minutes after administration. The mean recovery is 2.1 IU / dL / IU / kg of the solution administered. With a single dose of 100 IU / kg, the area under the concentration-time curve is 3444 IU / hour. The average clearance is 3.0 ml / h / kg. The half-life of the drug is in the range of 8 to 14 hours (an average of 12 hours).

    When the drug is administered, an increase in the content of the factor ΦVIII: C occurs gradually and reaches normal values ​​after 6-12 hours. Contents ΦVIII: C increases by an average of 6% (6 IU / dL) per hour. Therefore, even in patients with an initial level of ΦVIII: From below 5% (5 IU / dL), starting at the 6th hour, the level of FVIII: C reaches about 40% (40 IU / dL) and was maintained for 24 hours.

    Indications:

    Prophylaxis and treatment of bleeding (including use before planned and urgent surgical or invasive interventions to reduce blood loss) in patients with von Willebrand disease.

    ICD-10

    III.D65-D69.D68.0   Von Willebrand's Disease

    Contraindications:Hypersensitivity, the drug should not be used in the treatment of hemophilia A because of the low content of factor VIII, age to 6 years (use of the drug in children under 6 years of age has not been studied in clinical studies)., Pregnancy, breast-feeding.
    Carefully:

    Elderly and children's age, liver and kidney disease.

    Pregnancy and lactation:

    The category of recommendations for the FDA is C.

    Contraindicated in pregnancy and lactation.

    Dosing and Administration:

    Prevention of bleeding before routine or emergency surgery and treatment of bleeding (spontaneous or due to trauma).

    In the case of urgent surgical interventions, the drug should be administered an hour before the operation begins.

    In planned surgical interventions, the drug should be administered 12-24 hours before surgery, then re-enter the drug 1 hour before the operation. In such a case, simultaneous administration of the coagulation factor preparation VIII, since the content of the endogenous factor VIII:C to the beginning of the operation already reaches 0.4 IU / ml (40%). Nevertheless, each patient should determine the content of the factor VIII:C.

    With the introduction of a single factor of von Willebrand, the factor VIII: C in the blood plasma increases gradually and reaches a maximum after 6-12 hours. The introduction of the drug does not lead to an immediate increase in the concentration of the factor VIII:C. Therefore, if the initial level of the factor VIII:C in the plasma below the critical, and urgent correction of hemostasis is required (for example, in cases of treatment of bleeding, severe injuries or urgent surgery), then the preparation of the coagulation factor VIII in order to achieve activity factor VIII:C. providing hemostasis. If there is no need for an urgent increase in the content of the factor VIII:C (for example, during planned operations), or if the initial activity of the factor VIII:C in plasma is sufficient to provide hemostasis, then the doctor may decide not to use the coagulation factor preparation VIII together with the first administration of the drug.

    The dose and duration of therapy depend on the clinical condition of the patient, the type and severity of bleeding and the content of von Willebrand factor.

    The dosage regimen in children is calculated taking into account the body weight, that is, it is based on the same principles as in adults.The frequency of drug administration should always depend on the clinical effectiveness in each individual case.

    The first injection.

    For treatment of bleeding or in severe injuries, the drug is administered in doses of 40 to 80 IU / kg in combination with the necessary amount of coagulation factor VIII to achieve an adequate level of activity factor VIII:C. Coagulation factor preparation VIII is administered immediately before surgery or as soon as possible after bleeding or trauma; coagulation factor dose VIII is determined by its initial content in the blood plasma.

    In some cases, the drug should be administered at an initial dose of 80 IU / kg, particularly in patients with type 3 vWD disease, in which maintaining adequate levels of vWF can require higher doses than other types of vWF disease.

    Follow-up treatment.

    If necessary, the treatment should be continued with a suitable dose of 40-80 IU / kg per day, in one or two injections, for one or several days. The dose and frequency of injections should always correspond to the nature of the surgical intervention, the clinical condition of the patient, the content of PV: RQ and FVIII: C in the blood plasma, as well as the type and severity of bleeding.

    Prevention of spontaneous bleeding in patients with disease Willebrand.

    It can be used as a long-term prophylaxis in doses individually tailored for each patient. Administration of the drug in doses from 40 to 60 IU / kg 2-3 times a week can reduce the number of bleeding.

    Side effects:

    From the side immune system: infrequently - hypersensitivity reactions or allergic reactions. In very rare cases, severe anaphylactic reactions (Quincke's edema or anaphylactic shock) can develop.

    Disorders of the psyche: infrequently - anxiety.

    From the side central nervous system: infrequently - headache, drowsiness.

    From the side heart: infrequently - a tachycardia.

    From the side vessels: infrequently - hypotension, hot flashes.

    From the side respiratory system, chest and mediastinal organs: infrequently - shortness of breath.

    From the side GIT: infrequently - nausea, vomiting.

    From the side skin and subcutaneous tissues: infrequently - a rash, generalized urticaria, skin itch, a feeling of "crawling creepy."

    General disorders and reactions at the site of administration: infrequent - burning or tingling at the injection site, chills, a feeling of restraint of breathing, rarely - fever.

    Other: very rarely - the formation of neutralizing antibodies (inhibitors) to the von Willebrand factor, especially in patients with type 3 von Willebrand disease. In a clinical study in 62 patients, 23 of whom were of type 3 vWD, no formation of neutralizing antibodies was observed after administration. The presence is manifested in the form of an inadequate clinical response (the expected level of EF: RBC in the blood plasma is not achieved, or bleeding is difficult to control with an adequate dose of the drug) and may be associated with an increased risk of anaphylactic reactions.

    Overdose:

    Not described.

    Interaction:

    Do not mix with other medications.

    Only polypropylene injection / infusion agents should be used, since the adsorption of human plasma proteins on the internal surfaces of some infusion materials can lead to ineffective treatment.

    Clinically significant drug interactions with other drugs are unknown.

    Special instructions:

    The use of the drug in patients who have not previously received von Willebrand factor therapy has not been studied in clinical studies.

    Patients should be monitored throughout the period of drug administration to identify early signs of allergic or anaphylactic reactions. Patients should be informed of early manifestations of hypersensitivity reactions, including pruritus, urticaria, chest tightness, dyspnoea, hypotension and anaphylactic reactions. If such symptoms appear, discontinue the drug immediately. With anaphylactic shock treatment is conducted in accordance with current recommendations.

    There is a risk of thromboembolic complications, especially in patients with risk factors. Therefore, patients from the risk group should be observed to identify early signs of thrombosis. Prevention of venous thromboembolism should be carried out in accordance with current recommendations.

    After correcting the deficiency of von Willebrand factor, due to possible risk of thrombosis, early signs of thrombosis or disseminated intravascular coagulation should be identified and thromboembolic complications should be prevented in accordance with current recommendations.In patients with von Willebrand disease, especially type 3, neutralizing antibodies (inhibitors) to the von Willebrand factor can be formed. The presence of inhibitors manifests itself in the form of an inadequate clinical response (the expected level of EF: RBC in the blood plasma is not achieved, or bleeding is difficult to control an adequate dose of the drug). If the expected EF: plasma in the plasma is not reached, or if bleeding is difficult to control with an adequate dose, laboratory tests should be conducted to determine the presence of PV inhibitors. In patients with high levels of inhibitors, the use of the drug may not be effective enough and other therapeutic options should be considered. Treatment of such patients should be performed by a doctor with experience in the treatment of blood clotting disorders.

    The presence of inhibitory antibodies to von Willebrand factor may be associated with an increased risk of anaphylactic reactions. Therefore, in all patients with anaphylactic reactions or in case of ineffective treatment, it is necessary to conduct appropriate biological studies to determine the presence of inhibitors.

    Standard measures to prevent the risk of transmission of infectious agents through drugs prepared from human blood or plasma include: clinical selection of donors, screening of individual blood samples and batches of plasma for specific markers of infections. Procedures for inactivation and removal of viruses are included in the production process. However, when using drugs made from human blood or plasma, the risk of transmission of infectious agents can not be completely ruled out. This also applies to unknown or only detectable viruses or other types of infectious agents.

    The drug is effectively protected against enveloped viruses: HIV, hepatitis B and C. There is no full guarantee of protection against non-enveloped viruses - hepatitis A and parvovirus B19. Parvovirus B19 is most dangerous for pregnant women (fetal infection), for people with immunodeficiency and for patients with hemolytic anemia. Patients who are systematically receiving therapy with coagulation factors are recommended to undergo the necessary vaccination against hepatitis A and B. It is strongly recommended that whenever you enter the drug, register the serial number indicated on the vial,to monitor the relationship between the patient and the drug used.

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