Pharmacotherapeutic group: anticoagulants, antithrombotics: ATC code: B01AB02.
Antithrombin, a glycoprotein with a molecular weight of 58 kD containing 432 amino acids, belongs to the serpin group (serine protease inhibitors). It is one of the most important naturally occurring inhibitors of blood coagulation. The most potently inhibited factors are thrombin and factor Xa, but also contact activation factors, intrinsic system factors, and the factor VIIa/tissue factor complex. The activity of antithrombin is markedly enhanced by heparin, and the anticoagulant effects of heparin are dependent on the presence of antithrombin.
Antithrombin contains two functionally important domains. The first contains the reactive centre and provides the cleavage site for proteinases such as thrombin, which is a prerequisite for the formation of a stable proteinase-inhibitor complex. The second is the glycosaminoglycan-binding domain responsible for interaction with heparin and related substances, which accelerates thrombin inhibition. Inhibitor-coagulation enzyme complexes are cleared by the reticuloendothelial system.
Antithrombin activity in adults is 80–120%, and levels in neonates are approximately 40–60%.
⚠️ Warnings
Hypersensitivity reactions of the allergic type may occur, as with the intravenous administration of any protein product. Patients must be closely monitored and carefully observed for any symptoms occurring during the infusion period. Patients should be informed of the early signs of hypersensitivity reactions including generalised urticaria, chest tightness, dyspnoea, hypotension, and anaphylaxis. If these symptoms occur, patients should contact their physician.
In the event of shock, standard medical treatment should be provided.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include careful donor selection, testing of individual donations and plasma pools for specific markers of infection, and the inclusion of effective manufacturing steps for the inactivation or removal of viruses. Despite all these measures, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be totally excluded. This also applies to any unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV, and HCV, and for the non-enveloped virus HAV. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g., haemolytic anaemia).
It is strongly recommended that each time Anbinex is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the product batch.
Vaccination against hepatitis A and B is recommended for patients receiving antithrombin derived from human plasma.
Clinical and biological monitoring when antithrombin is administered concomitantly with heparin:
In order to adjust heparin dosage and to avoid excessive anticoagulation, regular coagulation monitoring (APTT and appropriate anti-FXa activity) should be performed at short intervals, particularly in the first minutes/hours following initiation of antithrombin administration.
Antithrombin levels must be measured daily in order to determine individual dosing, as there is a risk of decreased antithrombin levels resulting from prolonged treatment with unfractionated heparin.
Anbinex 500 IU contains 1.45 mmol (33.35 mg) of sodium per 10 ml (syringe). Anbinex 1000 IU contains 2.90 mmol (66.7 mg) of sodium per 20 ml (syringe). This should be taken into consideration in patients on a sodium-restricted diet.
Paediatric population
Data from clinical trials and systematic reviews regarding the use of antithrombin for the treatment of premature neonates in the unapproved indication of infant respiratory distress syndrome (IRDS) suggest an increased risk of intracranial haemorrhage and mortality in the absence of a demonstrated beneficial effect.
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