Drug information of Antithrombin III


Antithrombin III

Drug group: Anticoagulants

A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.

Mechanism of effect

Antithrombin, an alpha2-glycoprotein of molecular weight 58,000, is normally present in human plasma at a concentration of approximately 12.5 mg/dL and is the major plasma inhibitor of thrombin. Inactivation of thrombin by AT occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two, involving an interaction of the active serine of thrombin and an arginine reactive site on AT. AT is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as plasmin.
The neutralization rate of serine proteases by AT proceeds slowly in the absence of heparin, but is greatly accelerated in the presence of heparin. As the therapeutic antithrombotic effect of heparin is mediated by AT, heparin in vivo is ineffective in the absence or near absence of AT.

After administration, Antithrombin III human temporarily replaces the missing AT in patients with hereditary antithrombin deficiency.

Pharmacodynamic

Hereditary AT deficiency causes an increased risk of venous thromboembolism (VTE). During high-risk situations such as surgery or trauma or for pregnant women, during the peri-partum period, the risk of development of VTEs as compared to the normal population in these situations is increased by a factor 10 to 50.
In hereditary antithrombin deficient patients Antithrombin III  restores (normalize) plasma AT activity levels during peri-operative and peri-partum periods.

Pharmacokinetics

Absorption: Therapeutic target plasma concentrations in patients with congenital antithrombin III deficiency range from 80–120% of values in healthy adults. At plasma concentrations ≤70% of normal, increased thrombin generation. Supraphysiologic plasma concentrations (e.g., 150–200% of normal) have increased bleeding risk in patients with sepsis and disseminated intravascular coagulation, not known whether supraphysiologic concentrations increase bleeding risk in patients with congenital antithrombin III deficiency. 

Volume of distribution: Distributed into plasma (39%), extravascular space (49%), and vascular endothelial cells (11%).

Metabolism: <5% metabolized to low molecular weight breakdown products.

Route of elimination: Complexes of antithrombin III with thrombin or other proteinases cleared principally by liver and excreted in urine.

Half life: 2.5 - 3.8 hs

Dosage

Usual Adult Dose for Antithrombin III Deficiency

Dosage of antithrombin III can be calculated from the following formula: {units required (international units) = [desired - baseline AT-III level] × weight (kg) / 1.4}.

Drug contraindications

Known hypersensitivity to goat and goat milk proteins Hypersensitivity to antithrombin, other anticoagulants, or any component of the formulation

Side effects

chest pain , vertigo , hemorrhage , hematoma

Hemarthrosis

• cangrelor, • caplacizumab, • defibrotide, • drotrecogin alfa, • omacetaxine, • ramucirumab, • temsirolimus, • vorapaxar

Alerts

  • Hypersensitivity reactions: Hypersensitivity reactions, including severe hypersensitivity reactions (eg, anaphylaxis), may occur; monitor closely during infusions. If hypersensitivity symptoms occur, discontinue immediately and institute supportive emergency care.
  • Pregnancy: Pharmacokinetics of the recombinant-derived product are influenced by pregnancy; distinct dosing recommendations are provided for pregnant women.
  • Immunogenic potential: Recombinant human AT, also known as antithrombin alfa, is produced by transgenic goats expressing recombinant human AT in their milk, which is then collected and purified. Antibodies against the recombinant antithrombin protein (or goat-milk protein) may theoretically develop and lead to an immunological reaction.
  • Pharmacokinetic differences: Half-life and clearance differ significantly (~7 to 9 times) between the plasma-derived and the recombinant-derived product.

Points of recommendation

  • Tell all of your health care providers that you take antithrombin. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using antithrombin while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Pregnancy level

B

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